Multicenter, cluster-based, superiority trial of a multicomponent lifestyle intervention versus usual care for reducing cardiometabolic risk in individuals with psychotic disorders over 36 months: the LAGOM protocol

Multicenter, cluster-based, superiority trial of a multicomponent lifestyle intervention versus usual care for reducing cardiometabolic risk in individuals with psychotic disorders over 36 months: the LAGOM protocol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Multicenter, cluster-based, superiority trial of a multicomponent lifestyle intervention versus usual care for reducing cardiometabolic risk in individuals with psychotic disorders over 36 months: the LAGOM protocol Hemen Najar, Erik Jedenius, Andreas Fröberg, Anna Olofsson, Caroline Holmbom, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7972355/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Cardiometabolic conditions—including cardiovascular disease, type 2 diabetes, and obesity—are highly prevalent among individuals with psychotic disorders. These conditions contribute substantially to reduced life expectancy, diminished quality of life, and increased societal and economic burdens. Thus, effective, individualized interventions are urgently needed. Outpatient psychiatric clinics offer an ideal setting for such efforts owing to regular patient contact and access to multidisciplinary care. We have developed a comprehensive, clinically integrated program aimed at improving cardiometabolic health, promoting healthier lifestyles, and enhancing quality of life for individuals with psychotic disorders receiving care in Gothenburg. Methods LAGOM is a multicenter, naturalistic, quasi-experimental case‒control trial. A total of 644 adults with psychotic disorders will be recruited from six outpatient clinics at the Department of Psychotic Disorders, Sahlgrenska University Hospital. Two clinics will implement the LAGOM intervention, whereas four will serve as control sites delivering usual care. The intervention is embedded within routine psychiatric care and grounded in behavioral science. It includes comprehensive cardiometabolic risk assessments, two visual motivational tools (QRISK3 and a body composition analyzer), personalized follow-up plans, risk-oriented referrals to primary healthcare, and structured education for patients, relatives, and staff. The intervention is designed to be scalable, sustainable, and tailored to individual patient needs. Discussion If proven superior to usual care, this pragmatic, multicomponent intervention—delivered within routine psychiatric care—could improve cardiometabolic health and quality of life for individuals with psychotic disorders. Embedding the intervention within existing clinical structures enhances its scalability and feasibility and, if effective, could serve as a model for wider implementation. Trial status recruitment started on 27 February 2025 and will be completed on 31 December 2026. The current clinical investigation plan version is 3.1, dated 21 October 2025. Trial registration ClinicalTrials.gov (NCT06781801; date registered: 16 January 2025). Psychotic disorders cardiometabolic risk factors behavior change intervention multicomponent intervention integrated health care pragmatic clinical trial metabolic syndrome cardiovascular disease prevention quality of life cost-effectiveness Figures Figure 1 Background Individuals with schizophrenia and schizophrenia-spectrum disorders (psychotic disorders) face significantly elevated risks of cardiometabolic diseases—including cardiovascular diseases (CVDs), obesity, and type 2 diabetes mellitus—compared with the general population ( 1 ). These conditions contribute to markedly reduced life expectancy; in Sweden, people with psychotic disorders die, on average, 20 years earlier than the general population does ( 2 ). In addition to premature mortality, these diseases negatively impact quality of life ( 3 ) and impose substantial economic burdens due to increased healthcare costs and reduced productivity ( 4 ). Multiple factors contribute to this heightened cardiometabolic risk. These include the inherent nature of the illness, genetic predispositions, the metabolic side effects of psychotropic medications, and unhealthy lifestyle behaviors ( 5 ). Additionally, disparities in healthcare access and inadequate somatic care further exacerbate cardiometabolic vulnerability in this population ( 5 , 6 ). Despite these risks, both individual- and system-level barriers limit the effectiveness of lifestyle interventions and preventive care. At the individual level, cognitive impairments, persistent psychiatric symptoms, and side effects of psychotropic medication hinder the initiation and maintenance of healthy behaviors ( 7 ). At the system level, healthcare professionals frequently rely on brief, generic lifestyle advice that fails to account for the cognitive and functional limitations of this group and imposes the same expectations as those placed on the general population. The Swedish National Board of Health and Welfare has highlighted these shortcomings, calling for more individualized and sustained support to promote effective lifestyle changes ( 8 ). Structural gaps in psychiatric care further limit progress. Although annual physical health checks are recommended in psychiatry, clear guidelines for their implementation are lacking. Knowledge among psychiatrists and other healthcare professionals regarding how to assess cardiometabolic risk factors and lifestyle habits—the core purpose of these checks—varies significantly. Moreover, standardized follow-up routines are lacking or inconsistently applied to ensure that identified risks lead to appropriate interventions. This shortcoming—particularly regarding the need for closer follow-up in patients with known risk factors such as weight gain, hereditary cardiovascular disease, or diabetes—was highlighted by the Swedish National Board of Health and Welfare in its 2022 national evaluation of care and support for schizophrenia and schizophrenia-spectrum disorders ( 9 ). Another gap is the lack of educational programs for both individuals with psychotic disorders and healthcare professionals addressing the interactions among psychosis, lifestyle, and cardiometabolic health. Finally, collaboration between psychiatry and primary healthcare—particularly regarding the identification and follow-up of cardiometabolic risks—needs to be strengthened to improve overall health outcomes in this population. Some clinical trials have demonstrated the potential benefits of tailored interventions in improving cardiometabolic outcomes for people with psychotic disorders. For example, the ACHIEVE trial, an 18-month behavioral weight loss intervention, demonstrated weight loss ( 10 ). Similarly, two 30-month programs—one health-promoting and the other individualized and health-oriented—reported reductions in CVD risk ( 11 ) and diabetes incidence ( 12 ). However, most previous interventions have been constrained by a range of limitations that affect their clinical effectiveness, generalizability, and feasibility in routine psychiatric care. Many were short-term, typically lasting a year or less ( 13 – 17 ), which may not allow sufficient time to achieve meaningful improvements—aside from exceptions such as the CRESSOB study ( 18 ). Several trials applied narrow inclusion criteria ( 10 – 15 , 17 , 18 ) or focused exclusively on individual lifestyle habits ( 10 , 14 , 16 ). Others lacked educational components for patients and healthcare professionals regarding the connection between psychotic disorders, lifestyle, and cardiometabolic health ( 10 – 18 ) or failed to address systemic underdiagnosis and undertreatment of cardiometabolic conditions ( 10 – 16 , 18 ). Only two studies ( 14 , 17 ) reported unusually low patient-to-staff ratios, while most studies ( 10 – 13 , 15 , 16 , 18 ) did not report caseloads at all—an omission that limits the assessment of feasibility and generalizability to real-world psychiatric services, where higher caseloads are the norm. In addition, some interventions rely on resource-intensive strategies that are not feasible in psychiatric settings—such as providing meals ( 10 ), conducting home visits to evaluate cooking and grocery shopping, or delivering in-home physical activity coaching ( 17 ). These factors collectively limit the scalability and long-term impact of such interventions in real-world practice. In response to the limitations observed in previous interventions and routine psychiatric care, the LAGOM trial (Longitudinal Approach to Generate positive cardiometabolic health Outcomes in severe Mental illness) was developed as a feasible, scalable, and fully integrated intervention within psychiatric care. Conducted at the Department of Psychotic Disorders in Gothenburg, LAGOM offers structured education to patients, their relatives, and healthcare professionals on the interplay between psychotic disorders, cardiometabolic health, and lifestyle factors. The program adopts a holistic, person-centered approach with broad inclusion criteria, focusing on overall cardiometabolic risk rather than isolated behaviors. It emphasizes gradual, sustainable lifestyle improvements and spans a 36-month period. LAGOM also addresses underdiagnosis and undertreatment of cardiometabolic conditions through strengthened communication with primary healthcare providers. Despite these strengths, evidence on the effectiveness of long-term, real-world interventions such as LAGOM remains limited. This trial aims to fill that critical knowledge gap. To report this trial in a systematic and transparent way, we used the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2025 ( 19 ). Objectives The overall aim of the trial is to improve cardiometabolic health, promote healthy lifestyles, and enhance quality of life in individuals with psychotic disorders. Primary outcomes To evaluate whether the intervention is superior to usual care in reducing cardiometabolic risk indicators over the 36-month period. Primary endpoints : Differences in the mean changes in the following cardiometabolic risk indicators: Body mass index (BMI) (kg/m 2 ) Waist‒hip ratio (WHR) Systolic blood pressure (SBP) (mm Hg) Diastolic blood pressure (DBP) (mm Hg) Blood samples Plasma glucose (mmol/L) Total cholesterol/high density lipoprotein-cholesterol ratio (TChol/HDL-C ratio) Triacylglycerol/HDL-C ratio (TAG/HDL-C ratio) Secondary outcomes To assess whether the intervention is superior to usual care in reducing the risk of CVD or type 2 diabetes mellitus at 36 months. Secondary endpoints : CVD outcomes: Hazard ratio of incident CVD events and/or differences in the mean change in the CVD risk score will be assessed using the Systematic COronary Risk Evaluation 2 (SCORE2) (20). Diabetes mellitus outcomes: Hazard ratio of incident type 2 diabetes mellitus events. Exploratory outcomes To evaluate whether the intervention is superior to usual care in improving health-related quality of life over the 36-month period. To assess whether the intervention reduces the levels of high-sensitivity C-reactive protein (hs-CRP) and HbA1c over the 36-month period. To conduct a cost analysis per participant and assess cost-effectiveness over the 36-month period, where cost neutrality is considered a positive outcome. To evaluate whether the intervention improves targeted lifestyle behaviors (tobacco smoking, alcohol consumption, physical activity, and dietary habits) over the 36-month period. To explore the number, type, and average time interval between intervention sessions required annually to achieve a change in the targeted lifestyle over the 36-month period. To investigate whether participation in educational sessions by participants and their relatives in the intervention group is associated with positive lifestyle changes over the 36-month period. Exploratory endpoints : Biomarkers Differences in the mean changes in hs-CRP (mg/L) and HbA1c (mmol/mol) Questionnaires Difference in the mean change in the EQ-5D-5L score (quality of life) Difference in the mean change in alcohol consumption (Alcohol Use Disorders Identification Test – Consumption (AUDIT-C), scale 0–12) (21) Difference in the mean change in tobacco smoking per week Difference in the mean change in dietary habits (dietary index) (scale 0–12) (22) Difference in the mean change in physical activity (number of minutes per day) Health economic evaluation: Descriptive cost analysis (average cost per participant) in SEK and EUR Difference in the mean change in quality-adjusted life years (QALYs) between the intervention and control groups Incremental cost-effectiveness ratio (ICER) based on the number of CVD or type 2 diabetes mellitus cases averted and the number of QALYs gained For the intervention group, Effect of the number and type of lifestyle sessions with healthcare professionals on the mean change in lifestyle outcomes Effect of participation in educational sessions (0–3 sessions) on the mean change in lifestyle outcomes Trial design This is a longitudinal, multicenter, naturalistic, multicomponent, parallel-group, quasi-experimental cluster-based trial with a superiority framework. The trial uses a case‒control clinical design with a 1:3 allocation ratio, assigning one participant at the intervention clinics for every three at the control clinics. Clusters are defined at the level of outpatient clinics, with two intervention clinics and four control clinics. Methods Eligibility criteria Inclusion criteria 1. Adults ≥18 years of age meeting the International Classification of Diseases, Tenth Revision (ICD-10) diagnostic criteria for any one of the schizophrenia spectrum disorders (F20-F25 or F28-F29) 2. Ability to provide informed consent Exclusion criteria Having an electrical medical implant such as a pacemaker or other mechanical implants Pregnancy Deemed unsuitable by the investigator (a person may be deemed unsuitable for participation in the trial by the clinical investigation team member based on factors that may affect the ability to participate safely and reliably. These factors may include, but are not limited to, physical disabilities that hinder participation or practical challenges such as long travel distances to the trial site. The assessment is made on an individual basis and aims to ensure both patient safety and trial integrity). Prior participation in the LAGOM trial during a previous inclusion cycle (i.e., participants can only be included once during the trial period). Currently under compulsory care. Trial setting and participant recruitment The trial is being conducted in Gothenburg, Sweden’s second-largest city, at six outpatient psychosis clinics affiliated with Sahlgrenska University Hospital. This hospital hosts the country’s largest department specializing in psychotic disorders and delivers both secondary and tertiary psychiatric care. The clinics serve individuals with psychotic disorders residing in Gothenburg, Mölndal, Partille, Härryda, and Öckerö municipalities, representing a total catchment area of 774,247 inhabitants (Statistics Sweden, December 31, 2024) (23). Two clinics—Centrum (PC) and Mölndal (PM)—were purposefully selected as intervention sites because of practical and organizational constraints. PC employs the project leader, whereas PM shares a health promoter with PC. This health promoter is part of the research team and is responsible for implementing key components of the intervention. Four clinics—Hisingen (PH), Nordost (PNO), Väster (PVV), and Öster (PMÖ)—serve as control sites. Random allocation of clinics was not feasible because of these structural factors. Each participant is enrolled in the trial for 36 months ± 6 months. Eligible patients are identified and screened prior to their scheduled annual physical health checks. A trained representative of the clinical investigation team invites eligible patients to participate during these routine visits. The clinical investigation team comprises healthcare professionals employed at each participating psychosis outpatient clinic, including registered and assistant nurses, occupational therapists, social workers, psychologists, and mental health support workers. These professionals also serve as case managers (CMs), who are responsible for coordinating patients’ overall care across primary care, community services, and other secondary care services, following the resource group assertive community treatment (R-ACT) model (24, 25). The CM-to-patient ratio is approximately 1:34. In addition to the CM, the clinical investigation team includes either a psychiatrist or another attending physician (collectively referred to as "the physician"), as well as a single health promoter working at the intervention clinics. All standard CMs and physicians are involved in the trial’s implementation. Clinics may also host medical trainees (e.g., undergraduate medical students, recent graduates, or residents); however, these individuals will only be actively involved in the trial at the control clinics and will not participate in delivering the intervention. The clinical investigation team provides full oral and written information—via a participant information sheet (PIS)—detailing the trial’s purpose, procedures, eligibility criteria, and potential risks and benefits. Participation is voluntary. Patients are informed that they may withdraw at any time without providing a reason and without consequences for their ongoing care. Patients receive sufficient time to review the PIS, ask questions, and consider participation. If they agree, written informed consent is obtained and signed by both the patient and the clinical investigation team representative. A copy of the signed consent and PIS is provided to the participant, and the consent process is documented in source documents and archived with essential trial materials. The PIS specifies that if a participant withdraws, data already collected and necessary for the trial will continue to be used, but no additional data will be gathered. If new information arises that could significantly affect a participant’s health or care, it will be communicated in writing, and participants may then choose whether to continue. Interpreter-assisted consultations are routinely used at outpatient psychosis clinics and will be employed as needed during the consent process. Since the PIS is available only in Swedish, the following steps are taken to ensure comprehension: Interpreter role: An accredited interpreter provides an oral translation of all trial information into the participant’s preferred language. Adapted delivery: Information is presented in short sections with pauses for questions and clarification, without using technical jargon. Comprehension check: Patients are asked open-ended questions to confirm their understanding (e.g., “Can you explain what the study is about in your own words?”). Support inclusion: If applicable, care staff, such as housing support workers, may attend the session to reinforce understanding. Decision time: Patients are given time to consider participation and may schedule a follow-up discussion before deciding. Patients who, despite these measures, are unable to demonstrate understanding will be considered ineligible, as they do not meet the inclusion criterion: “Able to provide informed consent”. Rescreening is permitted if a patient meets the exclusion criteria at one annual check but not at the next. All clinical investigation team members are trained in standardized procedures for delivering information and obtaining consent, with PIS versions tailored to intervention and control clinics. Recruitment is stratified by birth month to ensure year-round coverage. Although the planned recruitment period is 12 months, extensions may be needed due to scheduling constraints. Recruitment will continue until the target sample size is reached in both the intervention and control clinics. A total of 644 participants will be recruited: Intervention clinics (PC and PM): Targeting 157 participants from a combined patient base of over 650. Control clinics (PH, PNO, PVV, and PMÖ): Targeting 487 participants from a combined patient base of over 2,000. Data collection methods Plans for assessment and collection of outcomes To standardize data collection across intervention and control clinics, a structured medical history protocol—referred to as the worksheet—was developed prior to the trial. The worksheet systematized the information gathered during patients’ annual physical health checks and directly supported the research questions guiding the trial. Previously, data collection varied depending on individual healthcare professionals’ experience levels. All healthcare professionals at the participating clinics received training in using the worksheet to interview patients approximately one year before trial initiation. During annual physical health checks, the CM conducts a structured interview using the worksheet. While data are collected primarily through face‒to‒face interviews, additional sources include remote interviews, medical records, and self-administered questionnaires completed at home. The choice of data collection method depends on the nature and type of information being gathered. The worksheet has two versions—an intervention version (v1.1, 2025-02-21) and a control version (v1.1, 2025-01-16)—and is organized into seven data categories (Additional file 1): Social and background information Medical history Lifestyle habits Results of the physical examination Blood test results Assessment scales Other information To support cost-effectiveness analyses, the worksheet and other trial records also capture detailed data on healthcare consumption and socioeconomic factors. These include psychiatric inpatient care (including compulsory admissions); housing status; employment; extent and duration of sick leave; permanent disability benefits; use of municipal and other support services; and dental care needs and subsidies. For the intervention group only, data are also collected on sessions with internal or external healthcare professionals related to lifestyle behaviors, as well as on emergency room visits and hospital admissions for somatic healthcare. Cost data are derived from the clinic’s standardized cost calculations, and the average cost of municipal services is based on pricing data from the municipalities of Gothenburg. All costs will be inflation-adjusted over the 36-month trial period. QALYs are derived from the EQ-5D-5L forms. This is measured using the EuroQol-5D-5L scale (26), which is completed by the patient either at home or during annual physical health checks and is included in the worksheet. The EuroQol-5D-5L scale has been validated in people with schizophrenia (27). Additionally, data on causes of death are available through clinic and trial records. Measurements Blood pressure and pulse: Blood pressure and pulse were measured on the right arm after 15 minutes of seated rest using the OMRON HEM-907-E7. The device is set to AVERAGE mode, which calculates the mean of two readings taken 60 seconds apart. The P-SET is set to AUTO to automatically adjust the cuff pressure. Cuffs are selected based on arm size and are available in three sizes (medium, large, and extra-large; 22–50 cm range). All CMs are trained in proper device use. Weight: Weight was measured using the SECA 799 scale with participants wearing indoor clothing and no shoes. The values are rounded to the nearest whole number. Body composition: Body fat (%), bone mass (kg), body water (%), muscle mass (kg), and metabolic age are measured using the TANITA DC-430MA. The participants are barefoot and wear indoor clothing; 1 kg is subtracted to account for clothing. Height: Measured wearing socks, without shoes, on a firm, flat surface using a calibrated, wall-mounted stadiometer, with the head in the horizontal plane. Rounded to the nearest whole number. Waist and Hip Circumference: Measured using a flexible, non-stretch, multi-color, dual-sided anthropometric measuring tape (150 cm/59 in). Waist circumference is measured at the midpoint between the lower edge of the rib cage and the iliac crest (typically at the umbilicus) during exhalation. Hip circumference is measured at the widest part over the buttocks. All values are rounded to the nearest whole number. Timing of Measurements: The time of each physical exam is recorded to allow for time-adjusted analyses. All CMs and physicians involved in the trial received standardized training to perform these measurements consistently. Blood tests Blood tests are ordered by the physician via CM as part of routine clinical procedures. Patients receive both oral and written instructions for preparing for the blood tests. These include the following standard recommendations: patients must fast for at least 10 hours before the test. If they choose to drink coffee or tea during the fasting period, they are instructed not to add sugar or milk. Morning medications should be taken only after the blood sample has been collected. Patients are also advised that alcohol consumption and intense physical activity the day before testing may influence the test results. QRISK3 QRISK3 (version 2018.0) is a validated tool for estimating 10-year CVD risk, accounting for psychotic disorders and antipsychotic use as independent risk factors (28). In this trial, the QRISK3 is included only in the intervention worksheet as a visual, motivational aid, illustrating how changes in smoking, weight, blood pressure, and lipids can lower overall risk. It also demonstrates the synergistic effect of multiple small improvements, fostering a shared understanding between participants and healthcare professionals. The QRISK3 is used solely for lifestyle counseling and does not influence clinical decision-making. Body composition analyzer The TANITA DC-430MA is a CE-marked class IIa medical device that uses dual-frequency bioelectrical impedance analysis to measure weight, BMI, body fat, muscle mass, visceral fat, basal metabolic rate, and other composition metrics. It is widely used in medical and research settings for screening and monitoring lifestyle-related conditions. In this trial, it is employed to support lifestyle counseling, in line with its intended purpose, without influencing medical decisions. The results are shared only with participants. Training of the clinical investigation team All the clinical investigation team members attended a one-day workshop on standardized measurements of blood pressure, waist circumference, and height. The staff at the intervention clinics received additional training in the use of the QRISK3 and the TANITA body composition analyzer. Plans to promote participant retention and complete follow‑up A patient-centered approach is embedded throughout all trial procedures and interactions. The CM at each outpatient clinic serves as the primary point of contact for participants and is available to address questions, offer support, and respond to any concerns that may arise during the trial. To minimize participant burden, trial visits—including annual health checks and bimonthly physical examinations—are scheduled, when possible, to coincide with existing clinic or outpatient appointments. Since annual health checks are already part of routine care, integrating research activities into these visits helps reduce additional time commitments. In addition, annual education sessions and bimonthly physical examinations are integral components of the patient-centered approach and are expected to further strengthen participant engagement and retention by fostering ongoing interaction, motivation, and continuity of care. Participants receive travel reimbursements for attending bimonthly physical examinations and annual education sessions. CMs are responsible for maintaining ongoing contact with participants and coordinating the scheduling of all trial-related visits. Research assistants support retention efforts by tracking attendance and assisting with logistical follow-up as needed. This proactive, coordinated approach is intended to support participant engagement and promote long-term retention over the 36-month follow-up period. Confidentiality, data management, and access to data All trial data will be registered, managed, and stored to ensure accurate reporting, interpretation, and verification while maintaining participant confidentiality. This is detailed in a Data Management Plan (DMP) (version 1.0, 2025-02-05) approved by the trial sponsor. At each site, the Principal Investigator (PI)—who also serves as the research nurse—will collect completed worksheets from the CMs and physicians and store them in physical folders organized by participant. Data are gathered using paper-based methods. Within 45 days of the second visit of the annual physical health check, the PI will verify that each worksheet is complete and accurate. Any missing or questionable data will be clarified using information from the participant, CM, physician, or medical records. Once validated, the worksheet will be transferred to a research assistant for data entry into the electronic case report form (eCRF). Data entry into the eCRF will also be completed within 45 days of the second visit. During entry, the research assistant identifies missing or abnormal values, such as swapping weight and height values, reversed blood pressure readings, or inconsistencies (e.g., no somatic illness reported despite the use of antihypertensive or antidiabetic medication). Any such discrepancies are communicated to the responsible CM and physician for clarification and correction, with the aim of preventing similar issues in the future. The eCRF system is managed using Research Electronic Data Capture (REDCap), which serves as the electronic data capture (EDC) tool for this trial. The current version in use is v.14 (dated 30 November 2023), supplied by Gothia Forum and hosted by Region Västra Götaland (VGR-IT). REDCap provides a secure interface for data entry, supports real-time data validation, maintains complete audit trails for tracking data modifications, and enables data export to common statistical packages. It also allows data import from external sources. All data are stored on encrypted servers protected by firewalls, with daily backups and individual user logins secured by two-factor authentication. Access to the REDCap system is restricted to trained and authorized personnel, with role-based permissions (e.g., data editing or read-only access). Once the data have been finalized, a formal "Clean File" decision is documented in a ‘Clean File form’ document. At this point, access to the eCRF will be withdrawn, except for authorized data export. PIs at each site retain access to cleaned datasets from their respective sites and may request access to data from other sites. To ensure confidentiality, each participant is assigned a unique record ID, which is used for all data collection, storage, and analysis. A participant enrollment and identification list is maintained separately, linking each participant’s name and personal identification number to that participant’s record ID. Identifying information is not included in the eCRF at the analysis stage. Paper records and forms containing personal information are stored securely in locked areas at each outpatient clinic and are accessible only to authorized staff. These materials will never be left in public or unsecured spaces. Additionally, results will only be reported at the group level, ensuring that no individual participant can be identified. As part of the trial documentation, all participants receive a journal entry stating their enrollment in the trial and what it entails. The informed consent process complies with applicable data protection and privacy legislation. Participants are fully informed about how their data will be collected, used, and published, and how confidentiality will be protected. The PIS also states that authorized representatives of the sponsor or regulatory authorities may access relevant medical or trial records—including the participant’s medical history—for purposes of data verification. Archiving The sponsor representative and PI will maintain the essential trial documents in the Trial Master File (TMF) and Investigator Site File (ISF), respectively. The sponsor representative will keep all documentation and data for at least 10 years after the trial ends. The PI will archive all local investigation documentation for at least 10 years. Quality assurance and quality control Quality assurance ensures high-quality data collection, whereas quality control detects and addresses data problems promptly. Our quality assurance approach involves 1) creating a flowchart for the intervention; 2) developing intervention and control worksheets; 3) conducting workshops to train data collectors; 4) holding regular meetings with data collectors; 5) maintaining logs of training sessions; and 6) following the manufacturer’s maintenance instructions for the OMRON blood pressure devices, SECA scales, and TANITA body composition analyzers. Our quality control strategy includes 1) monitoring the completed worksheets via research nurses and research assistants; 2) rectifying missing or incorrect worksheet data through research nurses during the first review and through research assistants prior to database entry; 3) tracking data entry delays; and 4) conducting regular meetings with research nurses and assistants to address missing, out-of-range, or illogical data. Harms Safety monitoring, adverse event definitions, reporting procedures, and causality assessment for this clinical trial follow applicable regulatory guidelines. Causality is assessed using a standardized 4-level scale, and all reporting procedures follow applicable regulatory timelines. Full details are described in the Clinical Investigation Plan (CIP), which is publicly available at ClinicalTrials.gov (NCT06781801). The CIP is the formal protocol describing the objectives, design, methodology, monitoring, statistical considerations, and organization of the clinical investigation, as defined in SS-EN ISO 14155:2020. In some documents, this may be referred to simply as the Protocol. Intervention and comparator Control clinics (usual care) Usual care refers to the existing clinical practices for individuals with psychotic disorders in Gothenburg. In Sweden, all citizens are registered with a primary healthcare center, which retains responsibility for managing cardiometabolic risk factors—even for patients who receive ongoing specialist psychiatric care. In Gothenburg, individuals with psychotic disorders receive annual physical health checks at psychosis outpatient clinics as part of usual care. This process typically includes two visits. Annual physical health checks Baseline Visits Visit 1 – The annual physical health check with CM As part of usual care, the CM prepares for the annual physical health check by ordering blood tests, beginning to fill in the worksheet, and sending a letter to the patient with instructions for blood sample preparation. Depending on the case, the CM may also send self-assessment questionnaires to be completed at home (including EQ-5D-5L, AUDIT-C, and a questionnaire on dietary habits). These procedures are part of routine care and are unaffected by participation in the trial. During the visit, the CM completes the control version of the worksheet, performs the physical examination, and ensures that fasting blood tests are conducted. Visit 1 lasts approximately 60 minutes. The blood tests and physical examination provide the cardiometabolic parameters relevant to this trial, as outlined in Table 1. Visit 2 – The annual physical health check with the physician and CM The physician and CM review the worksheet, laboratory, and physical examination results. Visit 2 lasts approximately 60 minutes. Clinical management is guided by the physician’s judgment, which is typically based on reference values for cardiometabolic parameters. The participant, CM, and physician collaborate to determine a suitable management plan based on outpatient clinic’s routines. Usual care may include basic lifestyle advice or referrals to health promoters, dietitians, or primary healthcare professionals. The trial does not modify the delivery of usual care but requires that the two annual visits for each participant occur within a 45-day period. However, it may not always be feasible for patients to complete blood tests or physical examinations on the scheduled days of these visits. To accommodate this, the protocol allows these assessments to be completed up to 45 days after Visit 2. This establishes a visit window of ± 45 days from the second visit. If either the blood tests or physical examinations are completed after Visit 2, a follow-up physician appointment is scheduled to review the results and make appropriate clinical decisions. This visit window is designed to reflect the realities of clinical practice while maintaining consistency in data collection. Continuing Annual Physical Health Checks Follow-up assessments at months 12, 24, and 36 replicate the baseline procedure. Visits 3, 5, and 7 – The annual physical health check with CM The same routine as in Visit 1 (baseline) at the control clinics (Table 1). Visits 4, 6, and 8 – The annual physical health check with the physician and CM The same routine as in Visit 2 (baseline) at the control clinics (Table 1). Patients not enrolled in the trial will continue to receive usual care at the control clinics. Intervention Clinics At the intervention clinics, participants receive enhanced assessments and individualized support integrated into usual care. The intervention follows a structured and manualized approach guided by a flowchart (Figure 1), an intervention-specific worksheet, and a brochure (additional file 2). The brochure describes the project and defines the lifestyle habits adapted for individuals with psychotic disorders. It is designed to support healthcare professionals in delivering interventions consistently and effectively. Together, these tools organize the workflow and ensure systematic implementation across the healthcare professionals involved in care. The intervention is designed to promote cardiometabolic health through individualized assessment, feedback, and follow-up. Location and title of Figure 1 Figure 1. Flowchart Annual physical health checks The annual physical health checks at intervention clinics follow the same two-visit structure as usual care but include additional assessments, motivational tools, and follow-up mechanisms tailored to address cardiometabolic health in patients with psychotic disorders. Baseline Visits Visit 1 – The annual physical health check with CM This visit mirrors the control clinic structure and lasts approximately 60 minutes but includes additional components: The CM uses the intervention version of the worksheet. Body composition is assessed using the TANITA DC-430MA analyzer, as outlined in Table 1. No intervention-specific procedures are initiated before written informed consent is obtained. Visit 2 – The annual physical health check with the physician and CM This visit lasts approximately 60 minutes and has the following additional components compared with usual care: Individualized and comprehensive mapping of cardiometabolic risk and lifestyle habits beyond standard cut-off values. This includes assessment of SCORE2 and metabolic syndrome (29) criteria to provide a contextual estimate of the risk for CVD and diabetes, as well as evaluation of trends in risk factors over time. Assessment of risk behavior in lifestyle habits is linked to the participant’s state of cardiometabolic health as well as to the gains the participants make by stopping their unhealthy lifestyle. The physician fills in the QRISK3 algorithm with the participant. The physician uses the results of visual motivational tools—QRISK3 and the TANITA—to support patient understanding and encourage engagement in lifestyle change and cardiometabolic risk management. The physician, CM, and participant jointly develop a personalized care and follow-up plan. Risk-oriented referrals to internal resources (e.g., health promoters, physiotherapists) for further assessment and support or to external providers (e.g., primary healthcare) to promote appropriate diagnosis and management of cardiometabolic concerns, with an emphasis on individualized care. CMs coordinate and follow up on referrals. Additional intervention components: Coordination, motivational support, and counseling The CM conducts individualized follow-up sessions (15–30 minutes), in person or remotely. Sessions target key lifestyle factors: diet, physical activity, alcohol, and tobacco use. The frequency, content, and delivery mode of the sessions are tailored to the participants’ needs. These sessions ensure engagement with care plans initiated by psychiatry or agreed-upon external healthcare resources (e.g., primary healthcare or dietitians) and support continuity, adherence, and necessary adjustments. The approach emphasizes small, sustainable adjustments that consider cognitive limitations and stress sensitivity. Bi monthly follow-up with physical examination Every two months, participants attend a clinic visit that includes a focused discussion of relevant lifestyle behaviors and a physical examination. The measurements included SBP, DBP, pulse, weight, waist and hip circumference, and body composition, which are assessed using the TANITA analyzer (Table 1). These regular assessments are used to monitor progress and guide individualized adjustments to the care plan. Group education sessions for participants and relatives Once annually, participants and their relatives are invited to a 45-minute in-person education session. A representative from the clinical investigation team will hold the education sessions. Sessions are based on the LAGOM concept and focus on the connection between lifestyle, cardiometabolic health, and psychotic disorders. The participation of relatives is optional; no data are collected from them. Education sessions for staff Internal education seminars are held biannually. These address the interplay between cardiometabolic risk, psychotic disorders, and lifestyle habits. Seminars are grounded in the LAGOM framework and promote consistent, evidence-based practice among healthcare professionals. Ongoing data collection and adherence The intervention includes a structured plan for monitoring implementation fidelity and patient adherence: The CM is responsible for documentation during annual check-ups. Contact with referred services is tracked. Follow-ups aim to reinforce intervention goals and evaluate effectiveness. The CM documents the number and type of sessions with internal and external resources in the worksheet at the next annual health check, based on self-reports and medical and trial records. Continuing annual physical health checks Participants undergo follow-up assessments at months 12, 24, and 36, which replicate the baseline procedures: Visits 8, 15, and 22 – The annual physical health check with the CM The same routine as in Visit 1 (baseline) at the intervention clinics (Table 1). Visits 9, 16, and 23 – The annual health check with the physician and the CM The same routine as in Visit 2 (baseline) at the intervention clinics (Table 1). Visits 3–7, 10–14, and 17–21 : Bimonthly physical examinations, as outlined in Table 1. Participants initially deemed ineligible may be rescreened. Patients not enrolled in the trial at intervention clinics continue to receive usual care. Awareness of Assignment Due to the nature of the intervention, both participants and healthcare professionals are aware of the clinic assignment. Location and title of Table 1 Table 1. Schedule of enrollment, interventions, and assessments Criteria and procedures for participant withdrawal or discontinuation Participants have the right to withdraw from the trial at any time without providing a reason and without any impact on their ongoing or future treatment. If a participant discontinues the trial, follow-up and care will continue in accordance with the outpatient clinic’s routines. Individual participant discontinuation may occur under the following circumstances: Enrollment in violation of the inclusion or exclusion criteria (inappropriate enrollment) Withdrawal of informed consent Pregnancy Receipt of an electronic medical implant (e.g., pacemaker) or other mechanical implants Relocation to another city or country, or registration at a different outpatient clinic When available, the reason for discontinuation will be documented in the eCRF. Patient engagement Members of the Schizophrenia Association in Gothenburg were involved in revising the intervention flowchart and brochure, as well as in both the development and revision of the worksheets prior to the start of the trial. They have also reviewed the content and structure of the educational sessions for participants and their relatives to help ensure that the sessions are relevant, understandable, and appropriately tailored to participants’ needs. Patients and/or the public were not involved in the reporting or dissemination plans of this research. Sample size The estimated number of participants required to meet the trial objectives is based on thresholds for clinical significance. To be clinically significant, the difference in the mean value between the intervention and control groups should be at least 1 kg/m 2 in BMI (30), 1 cm in waist circumference or 0.01 units in WHR (31), 10 mm Hg in SBP (32), 2 mm Hg in DBP (33), 1 unit in the TAG/HDL-C ratio (34, 35), 1 unit in the TChol/HDL-C ratio (36), or 1 mmol/L in plasma glucose (37). Table 2 presents the sample size calculation. Among the approximately 2,650 patients listed at the six psychosis outpatient clinics in Gothenburg, 157 participants will be recruited from the intervention clinics, and 487 will be recruited from the control clinics. This accounts for an estimated 40% dropout rate, a type I error rate of 0.05, 80% statistical power, and an allocation ratio of 1:3 (intervention to control). The sample size was calculated using the statistical package STATA (StataNow/SE 19.5). Statistical and health economic analysis plan The trial involves longitudinal comparisons both within and between the intervention and control groups. Primary outcome analysis Cardiometabolic indicators — BMI, WHR, SBP, DBP, the TAG/HDL-C ratio, the TChol/HDL-C ratio, and plasma glucose — will be analyzed using linear mixed-effects regression models for repeated measures. Data will be drawn from assessments conducted within a ±45-day window surrounding the physician-led annual physical health check. Sensitivity analyses will examine the impact of: Including cardiometabolic data collected outside the predefined visit window. Outliers, by comparing models with and without their inclusion. Missing data and dropouts. Secondary and exploratory outcome analysis Cardiovascular risk (SCORE2): Analyzed using linear regression. Time-to-event outcomes (e.g., incident or recurrent cardiovascular events and incident type 2 diabetes mellitus): Analyzed using Cox proportional hazards regression and Kaplan–Meier survival estimates. Quality of life (EQ-5D-5L): Analyzed using linear mixed-effects regression models for repeated measures. Inflammatory and metabolic markers (hs-CRP and HbA1c): Analyzed using linear mixed-effects regression models for repeated measures. Lifestyle behaviors (physical activity, dietary habits, alcohol consumption, and tobacco smoking): Analyzed using linear mixed-effects regression models in a dose–response framework, where the number of lifestyle-related sessions with internal or external healthcare professionals is used as the predictor variable (instead of a binary intervention indicator). Lifestyle behaviors — including smoking status (number of cigarettes per week), AUDIT-C score, dietary index, and time spent in physical activity — and the effects of educational sessions (exclusively for the intervention group) will also be assessed using linear mixed effects regression models for repeated measures. All primary, secondary, and exploratory outcomes will be tested using two-sided statistical tests with a Type I error rate (α) of 0.05. All models will be adjusted for potential cofounders, including site, age, sex, and any baseline covariates not balanced between groups. Health economic analysis The health economic evaluation will consist of three components: Descriptive cost analysis Direct and indirect costs will be calculated and reported in both SEK and EUR. Costs will be indexed to the clinical trial’s end date. QALYs Derived from EQ-5D-5L scores (5-dimensional scale) and analyzed using linear mixed-effects regression models for repeated measures. ICER The ICER will be calculated based on cost per: Case of CVD averted, Case of type 2 diabetes mellitus averted, and QALY gained based on EQ-5D-5L scores normalized to a [0, 1] interval. Sensitivity analyses will test the robustness of the cost-effectiveness model using a ±20% variation in key input parameters. Trial management costs will be excluded from the analysis. However, the model will incorporate the additional time required to deliver the intervention (e.g., more frequent or longer visits), alongside the time spent on usual care. Achieving cost neutrality for both direct and indirect costs will be viewed as a positive outcome. Missing Data A two-step strategy is in place to minimize the occurrence of missing data. Initial Review: The PI reviews the completed worksheets after the second visit of the annual physical health check to identify any missing or inconsistent entries. Follow-up Review: A research assistant then performs a secondary check. Both checks are conducted within 45 days of the second visit of the annual physical health check, unless delayed owing to limited staff availability and scheduling constraints during summer, Christmas, or national holidays. In addition to manual review, the eCRF includes built-in validation checks for missing values and implausible entries. To inform our handling of missing data during analysis, we will evaluate: Level of missing data: item-level, construct-level, and person-level; Missing data mechanism: whether the data are missing completely at random (MCAR), missing at random (MAR), or missing not at random (MNAR) (42). Based on this assessment, appropriate handling strategies will be applied, such as Full Information Maximum Likelihood (FIML), Multiple Imputation (MI), or listwise/pairwise deletion. Sensitivity analyses will be performed to assess how missing data may influence results and to evaluate the robustness of the selected handling methods. Monitoring The trial will be monitored by an independent monitor from the Scandinavian Clinical Research Organisation (SCRO), which is appointed by the sponsor. Monitoring will take place before the trial begins, during its conduct, and after its completion to ensure compliance with the CIP, Good Clinical Practice (GCP), SS-EN ISO 14155:2020, and applicable ethical and regulatory requirements, including the Declaration of Helsinki. The monitor is independent of the PI and trial site staff. Purpose and approach According to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use–Good Clinical Practice (ICH-GCP) and applicable regulations, the sponsor is responsible for ensuring the trial is quality-controlled through monitoring. The monitor must have access to all trial materials, and site staff must allocate time for monitoring activities. Monitoring is risk-based and guided by a Monitoring Plan (version 1.0, dated 24 February 2025), approved by the trial sponsor, developed before the start of the trial, and subject to adjustment based on changes to the trial or updated risk assessments. The sponsor has assessed this trial as low-risk, allowing for a reduced intensity of monitoring. This classification is based on the absence of known risks with the investigational devices (QRISK3 algorithm and body composition analyzer) and the fact that the trial is embedded in routine clinical practice, where risks are no greater than usual care. The main potential burden is the possibility of additional visits for the intervention group; to mitigate this, participants are exempt from visit costs and receive transportation support. Given the potential clinical benefits—improved detection and management of cardiometabolic risk factors, enhanced quality of life, and cost-effective care for individuals with psychotic disorders—the expected benefits clearly outweigh the minimal risks. Continuous internal quality control will be conducted by the sponsor’s research team to ensure adherence to the CIP and data integrity. Monitoring ensures: The rights, safety, and well-being of trial participants are protected. Data collected are accurate, complete, and consistent with source documents. The trial was conducted in accordance with the approved protocol, GCP, and applicable ethical and regulatory requirements, such as the Declaration of Helsinki. Participant confidentiality As described in the informed consent form, participants explicitly consent to allow authorized representatives of the sponsor, including the monitor and relevant regulatory authorities, access to relevant parts of their medical and trial records—including medical history—for purposes of data verification. This is communicated clearly during recruitment through both oral and written information. Access will also be granted for regulatory inspections. Monitoring visits SCRO's monitor will conduct the following types of monitoring visits across the six sites in Gothenburg: Study initiation visit: Verifies staff training and site readiness prior to participant enrollment. Confirms the availability of all essential documents and procedures. Ensures that the ISF is complete. Four initiation visits are conducted: one for the two intervention sites and three for the four control sites. Monitoring and Source Data Verification Conducted at four to six planned visits per site during the trial period. Includes review of informed consent forms, source data, inclusion/exclusion criteria, QRISK3 and TANITA results, and physical examination variables (e.g., weight, blood pressure). Twenty percent of records at each site will be reviewed, with 100% verification for all serious adverse events (SAEs) in the intervention group. Ensures that the eCRF is completed correctly and queries are issued as needed. A source data verification agreement is signed prior to participant inclusion at each site. Site closure visits: Occurs after the last participant completes the trial and a Clean File has been declared. The sponsor representative will confirm when a site is ready for closure. Verifies final documentation (e.g., Clean File documents, signed logs, informed consents). Remote Monitoring: Includes review of eCRF data entry and query management after the first 20 participants at each site complete baseline visits. All monitoring activities will be conducted according to the monitoring plan developed by the sponsor, which includes a predefined schedule and standard procedures. Documentation and follow-up After each visit, the monitor will issue a monitoring report within 10 working days. The report will detail monitoring findings, proposed actions, and responsible parties. It is signed by both the monitor and the sponsor representative and stored in the TMF and ISF. Signed originals are maintained by the sponsor representative and will be archived after trial closure. TMF and ISF management and oversight Gothia Forum at Sahlgrenska University Hospital supported the preparation of both the TMF and ISF in collaboration with the sponsor representative. Ongoing management of the TMF will be coordinated with the sponsor representative, while each trial site is responsible for maintaining its own ISF. Essential documents will be maintained throughout the trial, with appropriate archiving procedures implemented at its conclusion. The SCRO monitor will oversee the completeness, accuracy, and regulatory compliance of both files in accordance with the monitoring plan. Source data and access to documentation The PI at each site is responsible for maintaining source documents for every participant throughout the trial. Prior to trial initiation at each individual site, the definition and location of source data were determined in collaboration with the monitor and documented in the Source Data Location Agreement , which is included in the ISF. This agreement specifies what constitutes source data at each site (e.g., medical records, worksheets). In cases where certain data are not documented elsewhere, the worksheet has been designated as the source document, as agreed upon with the monitor and documented in the Source Data Location Agreement. Access to all trial-related documentation—including medical records, worksheets, eCRFs, and other trial documentation—will be provided for monitoring and other quality control activities. CIP version Version: Version 3.0/Amendment 1 (dated 10 June 2025) Replaces: Version 2.0 (dated 6 December 2024) Revision The substantial modification involves a change of PI at two outpatient clinics (PNO and PMÖ). In addition, a clarification has been added specifying that both Visit 1 and Visit 2 are part of the annual physical health check, with both visits occurring within a 45-day window. Each visit will last approximately 60 minutes. Additional minor, nonsubstantial changes have also been made to the CIP and the PISs. Rationale The PI changes are necessary due to leadership updates at the respective clinics. The clarification regarding visit structure and timing was made to ensure consistency and transparency across all participating sites. Minor adjustments to the CIP and PIS were implemented to improve clarity and alignment with current trial procedures. Version: Version 3.1 (dated 21 October 2025) Replaces: Version 3.0 (dated 10 June 2025) Revision This version includes minor, nonsubstantial updates to improve clarity, consistency, and completeness: • “Care as usual” changed to “usual care” throughout the document. • “Intervention group” and “control group” revised to “intervention clinics” and “control clinics,” respectively, where applicable. • Table 1: “Eating habits” changed to “Dietary habits.” • Table 1: Timing of data collection for “Questions about participation in educational sessions and lifestyle sessions” specified at baseline, 12 months, 24 months, and 36 months. • Section 6.3.2 (Exclusion Criteria): Clarified wording for “Deemed unsuitable for inclusion at the discretion of the investigator” and “Previous participation in the clinical trial.” Rationale These updates were made to enhance clarity, ensure internal consistency, and provide complete documentation of data collection and eligibility procedures. All changes are minor and nonsubstantial, with no impact on the study design, methodology, or participant safety. Protocol amendments Any amendments to the CIP are developed and agreed upon by the sponsor in consultation with the coordinating investigator. Substantial amendments—defined as changes that may impact participant safety, the scientific value of the trial, or the conduct of the trial—must be submitted to and approved by the Swedish Ethical Review Authority and/or the Swedish Medical Products Agency before implementation. Nonsubstantial amendments that do not affect participant safety or trial integrity are documented in writing, dated, and filed in both the TMF and the ISF, with notification to relevant parties as required. All amendments are tracked through version control and documented in the Version history described in the Ethics approval, consent, and compliance section, ensuring full traceability of changes and their rationale. Updated versions of the CIP and related trial materials are distributed to all participating sites, and site staff are trained on the changes before implementation. Deviations from the protocol Investigators may not deviate from the protocol except to protect a participant’s rights, safety, or well-being in emergency circumstances. All such deviations must be documented with an explanation and reported to the sponsor representative as soon as possible. The sponsor representative will review the deviations and, when applicable, report them to the Swedish Medical Products Agency and/or the Swedish Ethical Review Authority. Insurance The participants in the trial will be covered by Swedish Patient Insurance and liability insurance. End of the trial The trial will conclude when the last participant has completed the final scheduled visit (Visit 8 at the control clinics and Visit 23 at the intervention clinics; see Table 1 for the visit schedule). The sponsor representative will notify the Swedish Medical Products Agency within 15 days after the end of the trial and send the trial report within 1 year after the end of the trial, including an easily understandable summary. Trial organization The trial is being conducted at six psychosis outpatient clinics (sites) in Gothenburg. Each site has a PI and research assistant. The two intervention sites also share a health promoter. Together, these staff form the core research team, which is responsible for the integrity and progress of the trial. Roles and Responsibilities: • The main author of this article (HN) represents the sponsor, Region Västra Götaland, and serves as the coordinating investigator leading the project. HN oversees implementation, conducts interviews, performs data analysis and manuscript preparation, and holds regular site meetings. • The PIs, specialist nurses in psychiatric care, coordinate site activities, maintain the ISF, and train CMs on trial procedures (e.g., eligibility screening, consent, physical exams). They also conduct interviews and manage delegation logs, training records, participant scheduling, and subject enrollment and identification logs. At intervention sites, PIs provide additional training on QRISK3, TANITA, and other intervention-specific routines. Duties may be delegated to co-PIs as needed. • Research assistants support data entry, error checking, eligibility screening, attendance tracking, trial material management, and sending out health check invitations. At intervention sites, they also handle transport logistics. • The health promoter (intervention sites) coordinates bimonthly follow-up visits, which include physical examinations, patient scheduling, attendance tracking, and screening for adverse events. While the health promoter typically conducts these visits, other members of the clinical investigation team may perform them when needed, following training provided by the health promoter. Each visit includes cardiometabolic monitoring, motivational support, and guidance on individualized care adjustments. All bimonthly visits—including cancellations—are documented, and each consultation is categorized by focus area to support the evaluation of adherence and program fidelity. Trial status At the time of the first manuscript submission, research ethics approval had been obtained for the trial. Participant enrollment began on 27 February 2025 at PC, the site of the coordinating investigator. Enrollment subsequently commenced at PH [27 February 2025], PM [5 March 2025], PVV [6 March 2025], PMÖ [16 September 2025], and PNO [17 September 2025]. Recruitment across all sites is expected to be completed by December 2026. Discussion This investigator-initiated trial evaluates the effectiveness of LAGOM—a multicomponent, real-world intervention—in reducing cardiometabolic risk among individuals with psychotic disorders over 36 months. The core hypothesis is that a pragmatic, personalized program integrated into routine psychiatric care can lead to clinically meaningful improvements in cardiometabolic health. Delivered through outpatient psychosis clinics in Gothenburg, LAGOM comprises five key components: ( 1 ) individualized, holistic cardiometabolic risk assessment that goes beyond isolated risk factor management; ( 2 ) structured education for patients, relatives, and staff; ( 3 ) risk-oriented referrals to primary healthcare to address underdiagnosis and undertreatment of cardiometabolic concerns; ( 4 ) the use of visual motivational tools to strengthen patient engagement; and ( 5 ) regular follow-ups to reinforce continuity and adherence. LAGOM was developed in response to persistent challenges in both research and clinical settings, particularly the underdiagnosis and undertreatment of cardiometabolic risk among individuals with psychotic disorders. Rather than creating new services, the intervention reorients existing workflows—such as CM follow-ups and patient education—toward systematic management of cardiometabolic and lifestyle-related health risks. Cardiometabolic risk is mapped using methods already employed in psychiatric care, and referrals align with regional protocols. Education sessions, previously focused on psychosis, are adapted to include lifestyle and cardiometabolic health. Similarly, staff training builds on existing professional development structures. The intervention fits within current roles, ensuring both scalability and sustainability. Personalized and integrated into daily practice, LAGOM aims to enhance early risk detection, patient engagement, and team capacity, potentially reducing morbidity, premature mortality, and healthcare costs. If superior to usual care, LAGOM has the potential to serve as a scalable model for addressing cardiometabolic health in one of mental healthcare’s most underserved and high-risk populations. A central theoretical premise is that CVD risk factors interact synergistically rather than additively. Prior work has shown that combined risk factors have greater-than-additive effects on subclinical atherosclerosis and acute myocardial infarction risk. For example, Golden et al. reported that the combined effect of hypertension, hypertriacylglycerolemia, hyperinsulinemia, low HDL-C, and hyperglycemia resulted in an excess carotid intimal-medial thickness of 71 µm—compared with an expected additive increase of only 55 µm—indicating a synergistic impact on subclinical atherosclerosis ( 43 ). Similarly, the INTERHEART study found that the combination of smoking, diabetes, hypertension, elevated apoB/apoA1 ratio, and abdominal obesity increased the odds of acute myocardial infarction to 68.5, as opposed to an additive prediction of just 12.1 ( 44 ). This understanding—of synergistic rather than additive effects—forms one of the conceptual foundations of the LAGOM intervention and is particularly relevant for individuals with psychotic disorders, where metabolic syndrome and co-occurring CVD risk factors are highly prevalent ( 45 ). Risk estimation tools such as SCORE2, along with monitoring whether an individual meets the criteria for metabolic syndrome, reflect this synergistic model by integrating multiple interacting risk factors into a single contextualized estimate. These approaches provide clinically meaningful ways to communicate overall cardiometabolic risk and facilitate shared understanding and decision-making between healthcare professionals and patients. Motivation is the second cornerstone of LAGOM intervention, grounded in the capability, opportunity, motivation–behavior (COM-B) model and self-determination theory (SDT). The intervention targets reflective motivation while supporting autonomy, competence, and relatedness ( 46 , 47 ). Education for patients and relatives clarifies the link between psychosis, lifestyle behaviors, and cardiometabolic risk, helping reduce resistance and build intentions by explaining why change matters ( 46 ). Parallel staff training reinforces the rationale behind interventions, supporting both engagement and professional purposes. LAGOM operationalizes SDT through concrete practices: competence is supported via small goals accepted by patients, tangible health metrics (e.g., laboratory results, physical examination results), and structured education; relatedness is fostered through warm, supportive clinical interactions and shared understanding; and autonomy is encouraged through choice-driven changes and non-coercive sharing of rationale. The evidence suggests that when people feel capable and understand the benefits of a behavior—key aspects of empowerment—internal motivation and long-term adherence improve ( 47 , 48 ). This foundation enables patients not only to understand the consequences of unhealthy habits but also to take ownership of change. The intervention draws from the “small steps” approach, where tiny, sustainable changes create behavioral momentum and long-term identity shifts ( 49 , 50 ). This behavioral strategy emphasizes small, concrete, and achievable actions—such as walking for five minutes instead of aiming for a full workout or reducing smoking by one cigarette rather than quitting abruptly—to build self-efficacy and foster early success ( 49 , 50 ). LAGOM intentionally avoids pressuring participants with population-level guidelines; instead, it makes behaviors more achievable by breaking them down and anchoring them in personally meaningful goals. To complement the motivational work, two visual and tangible tools—QRISK3 and the TANITA body composition analyzer—are included as exploratory supports for shared understanding and direct feedback. Although their motivational effect is not yet firmly established in this population, these tools may assist individuals with impaired executive functioning by simplifying complex health information, visually illustrating cardiometabolic risk, and providing structure to conversations between patients and healthcare professionals. QRISK3, in particular, offers a comprehensive risk assessment that highlights how modest improvements across multiple domains may yield meaningful long-term benefits. The integration of these tools builds on successful local experience with feedback-informed care, where a digital dashboard facilitated co-production between patients and healthcare professionals and enhanced patient engagement in health monitoring ( 51 ). Strengths and Limitations This trial has several strengths that enhance its clinical relevance, feasibility, and potential for real-world impact. It is grounded in well-established behavioral frameworks (COM-B and SDT) while being adapted to local workflows and organizational conditions in psychiatric outpatient care. Importantly, LAGOM targets both patients and healthcare professionals—an uncommon dual approach that supports sustained behavior change, professional engagement, and intervention fidelity—while also addressing the well-documented gap in awareness of the links between psychosis, lifestyle, and cardiometabolic health through structured education. Unlike many previous trials that were short-term, narrowly focused, or dependent on resource-intensive strategies, LAGOM is designed as a long-term (36-month), scalable, and sustainable intervention integrated into routine psychiatric services. It emphasizes comprehensive, individualized cardiometabolic risk management rather than targeting isolated risk factors or single lifestyle behaviors. Broad inclusion criteria improve generalizability and ensure applicability to the diverse patients seen in everyday clinical practice. By repurposing existing roles and responsibilities—such as CM follow-up, referral pathways to primary care, and patient education—the intervention is achievable within standard patient-to-staff ratios and resource constraints. It also facilitates early detection and follow-up of cardiometabolic conditions by strengthening collaboration with primary healthcare, addressing underdiagnosis and undertreatment. The intervention is ecologically valid, as it operates within existing care structures without adding external personnel. Its personalized approach, which is aligned with each participant’s motivation, values, and readiness for change, enhances relevance and engagement. Contamination between groups is unlikely due to clear staff role separation, and the cluster design supports implementation fidelity across sites. Some limitations warrant acknowledgment. The nonrandomized, cluster-assigned design introduces risks of selection bias, allegiance bias, and residual confounding. To mitigate these concerns, outcome models will include multivariable adjustments for prespecified baseline covariates (e.g., age, sex, baseline risk, and socioeconomic status). Although such adjustments cannot replace randomization or eliminate unmeasured confounding, they improve internal validity and strengthen interpretability. Intervention sites were selected based on staff involvement, whereas control clinics continued with usual care. Although this limits causal inference, it enhances feasibility and reflects the complexities of real-world care. Rather than isolating individual variables—which is often neither feasible nor meaningful in this context—LAGOM assesses the combined effect of interrelated components embedded in routine practice. This approach provides insight into associations rather than isolated efficacies. A subtle limitation is that standardizing data collection via worksheets may unintentionally influence practice. Although protocols remain unchanged, the act of documenting cardiometabolic questions could prompt more proactive management. In summary, while LAGOM’s design limits causal inference, it supports feasibility testing, strengthens fidelity, and aligns with everyday clinical practice. The trial offers important insights into embedding structured lifestyle interventions within health services for a high-risk population. If superior to usual care, LAGOM may improve quality of life, reduce premature mortality, and provide a scalable, practice-embedded model for cardiometabolic prevention within routine psychiatric care. Abbreviations Abbreviation Term/Explanation ALT Alanine Aminotransferase ALP Alkaline Phosphatase AST Aspartate Aminotransferase AUDIT-C Alcohol Use Disorders Identification Test - Consumption BMI Body mass index CIP Clinical Investigation Plan CM Case manager COM-B Capability, Opportunity, Motivation – Behavior CVD Cardiovascular disease DBP Diastolic blood pressure DMP Data Management Plan eCRF Electronic Case Report Form EDC Electronic Data Capture EQ-5D-5L EQ: EuroQol (the research group that developed it); 5D: Five Dimensions of health; 5L: Five Levels of severity for each dimension fP-TAG fasting plasma triacylglycerol FIML Full Information Maximum Likelihood GCP Good Clinical Practice HbA1c Hemoglobin A1c, also known as glycated hemoglobin HDL-C High density lipoprotein-cholesterol hs-CRP High-sensitivity C-reactive protein ICD-10 International Classification of Diseases, Tenth Revision. ICER Incremental cost-effectiveness ratio ICH-GCP International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use- Good Clinical Practice ISF Investigator Site File LAGOM Longitudinal Approach to Generate positive cardiometabolic health Outcomes in severe Mental illness MAR Missing At Random MCAR Missing Completely At Random MI Multiple Imputation MNAR Missing Not At Random PC Psychosis outpatient clinic Centrum PH Psychosis outpatient clinic Hisingen PI Principal Investigator PIS Participant Information Sheet PM Psychosis outpatient clinic Mölndal PMÖ Psychosis outpatient clinic Öster PNO Psychosis outpatient clinic Nordost PVV Psychosis outpatient clinic Väster QALYs Quality-Adjusted Life Years R-ACT Resource-group Assertive Community Treatment REDCap Research Electronic Data Capture SAEs Serious Adverse Events SBP Systolic blood pressure SCORE2 Systematic COronary Risk Evaluation 2 SDT Self-Determination Theory TChol Total cholesterol TMF Trial Master File WHR Waist-hip ratio Declarations Ethics approval and consent to participate The trial is conducted in accordance with the CIP, the ethical principles of the Declaration of Helsinki, the principles of SS-EN ISO 14155:2020, and all applicable national and international regulations. These measures ensure both participant safety and data quality. The trial commenced only after the required regulatory and ethical reviews were completed with non-negative outcomes, in compliance with the Medical Device Regulation (MDR) and national legislation. Any additional requirements imposed by the Ethics Committee or regulatory authorities are implemented accordingly. The protocol (version 2.0), worksheets, PISs, informed consent forms, and all other trial materials were approved by the Swedish Medical Products Agency on 6 November 2024 (Dnr: 5.1-2024-92319) and the Swedish Ethical Review Authority on 18 December 2024 (Dnr: 2024-07362-01). The first substantial amendment to the protocol (version 3.0/Amendment 1), which replaces version 2.0, was approved by the Swedish Ethical Review Authority on 25 June 2025 (Dnr: 2025-04238-02) and by the Swedish Medical Products Agency on 1 July 2025 (Dnr: 5.1-2024-92319 [5.1.1-2025-050512]). Individual written informed consent to participate is obtained from all eligible patients prior to enrollment. All clinical investigation team members received training in Good Clinical Practice (GCP) and trial procedures before initiating data collection. The trial is registered at ClinicalTrials.gov (NCT06781801; date registered: 16 January 2025). Consent for publication Not applicable. Dissemination policy The trial is registered at ClinicalTrials.gov, and summary-level results will be submitted for publication in peer-reviewed scientific journals. The first results are expected to be available in 2027. Findings will also be shared at national and international conferences, through meetings with regional health authorities, and via various media channels. Trial participants are informed that they may obtain trial results through the site’s PI once available. The trial also includes collaboration with the Schizophrenia Association in Gothenburg to facilitate communication of results to broader audiences. All abstracts and publications will adhere to the authorship criteria recommended by the International Committee of Medical Journal Editors (ICMJE). The full trial CIP is available at ClinicalTrials.gov (NCT06781801). Availability of data and materials In accordance with the trial’s CIP, individual participant data from this trial are not publicly available due to privacy and data protection regulations. All data are handled in compliance with the General Data Protection Regulation (EU 2016/679; GDPR) and relevant Swedish legislation, and are stored securely at Region Västra Götaland. Participants in the trial are coded with a specific record ID. Competing interests The authors declare that they have no competing interests. This is an investigator-initiated trial without any assistance or input from any company. Funding The trial has received funding from the Gothenburg Society of Medicine, Sahlgrenska University Hospital’s (SU) foundations, and the Wilhelm and Martina Lundgren Science Fund. The trial is sponsored by Region Västra Götaland. The sponsor and funders have no influence on the trial design, conduct, data analysis or interpretation, manuscript writing, or dissemination of results. The funders have no direct involvement in the trial. Authors’ contributions HN, EJ, ZZ, and ChHo conceived the trial design, selected outcome measures, developed the statistical analysis plan, and secured funding. EJ conceptualized and led the health economic evaluation. CaHo, ChHa, ESB, EW, EA, and LK served as site leaders (PIs), overseeing all aspects of trial implementation, supported by research assistants AO, CKB, EH, NK, and SH. Material preparation and data collection were carried out by HN, AO, CaHo, CKB, ChHa, ESB, EH, EW, EA, JG, LK, NK, and SH. AF, LL, LR, and PR provided expert intellectual input to refine and finalize trial implementation. LR also supported submissions to the Swedish Medical Products Agency and the Swedish Ethical Review Authority. HN drafted the initial manuscript, incorporating critical feedback from all co-authors. All authors have read, edited, and approved the final manuscript. Acknowledgements We are sincerely grateful to all participants and to the staff at the six psychosis outpatient clinics in Gothenburg for their essential contributions to this research. We thank the members of the Schizophrenia Association in Gothenburg for their valuable input on the intervention flowchart, brochure, and the development and revision of the worksheet prior to the start of the trial. They also reviewed the content and structure of the educational sessions for participants and their relatives. We would like to thank Kristina Annerbrink for her support in engaging physicians across all trial sites, and Catharina Jedenius, who served as care unit manager at PC and PM at the start of the trial, for her key role in enabling trial feasibility across the intervention clinics. We also extend our appreciation to all care unit managers—Jennie Culbert, Matilda Hansson, Mickela Larsson, Maria Persson, and Marie Wennergren—for their efforts in facilitating the implementation of the trial across their respective sites. We also acknowledge Specialist Nurse in Psychiatric Care Lisa Magnusson and Physiotherapist Martina Gustafsson for their contributions to the initial draft of the trial brochure. Writing assistance was provided using ChatGPT and Copilot. References Druss BG, Zhao L, Von Esenwein S, Morrato EH, Marcus SC. Understanding excess mortality in persons with mental illness: 17-year follow up of a nationally representative US survey. Med Care. 2011;49(6):599–604. 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Tables Table 1 Schedule of enrollment, interventions, and assessments Collected data Baseline Every 12 Every 24 Every 36 other months other months other months month ± 60 month ± 60 month ± 60 ± 14 days ± 14 days ± 14 days days Visits days Visits days Visits Visits 8 + 9* Visits 15 + 16* Visits 22 + 23* 3–7* 10–14* 17–21* Visits Visits Visits 3 + 4 5 + 6 7 + 8 Visit 1 Visit 2 # Check for eligibility X Informed consent X Inquire about adverse event* X X X X X X Social and background questions X X X X Medical anamnesis X X X X Questions about participation in educational sessions and lifestyle sessions* X X X X Lifestyle questionnaires • Alcohol habits according to AUDIT-C • Tobacco habits • Dietary habits • Physical activity X X X X Blood tests P-high-sensitivity CRP (mg/L) X X X X fP-Triacylglycerol (mmol/L) X X X X P-HDL-cholesterol (mmol/L) X X X X P-LDL-cholesterol (mmol/L) X X X X P-Total cholesterol (mmol/L) X X X X P-non-HDL-cholesterol (mmol/L) X X X X fP-Glucose (mmol/L) X X X X B-HbA1c (mmol/mol) X X X X P-Kreatinin (µmol/L) X X X X P-ALT (µkat/L) X X X X P-AST (µkat/L) X X X X P-ALP (µkat/L) X X X X P-bilirubin (µmol/L) X X X X Physical examination Height (cm) X X X X Weight according to SECA 799 (kg) X X X X X X X Waist circumference (cm) X X X X X X X Hip circumference (cm) X X X X X X X Systolic blood pressure mmHg X X X X X X X Diastolic blood pressure mmHg X X X X X X X Pulse (bpm) X X X X X X X Assessment scales EQ-5D-5L X X X X Fulfillment of criteria of metabolic syndrome* X X X X SCORE2* X X X X QRISK3* X X X X Measurements according to TANITA body composition analyzer* • Weight (kg) • Total body fat mass (kg) • Total body water mass (kg) • Total body muscle mass (kg) • Bone mass (kg) • Metabolic age X X X X X X X * Only intervention clinics. # Visit 2 complements Visit 1 by ensuring completeness of the data collected during the first visit. This allows the physician to base decisions on a full assessment. Eligibility screening is always completed during Visit 1, while informed consent may be obtained at either Visit 1 or Visit 2. Table 2. Sample size calculation per group Variable Standard deviation (reference) Expected mean difference Significance level (two-tailed) Power (%) Expected dropout (%) Required Sample Size (Intervention Group) Required Sample Size (Control Group) WHR 0.08 (38) 0.03 0.05 80 40 125 389 BMI 4.5 (39) 1.5 0.05 80 40 157 487 SBP 14.4 (38) 10 0.05 80 40 37 115 DBP 9 (40) 3 0.05 80 40 157 487 TAG/HDL-C ratio 0.9 (41) 1 0.05 80 40 15 47 TChol/HDL-C ratio 1.1 (41) 1 0.05 80 40 24 74 Glucose 0.8 (39) 1 0.05 80 40 14 42 Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.pdf Additionalfile2.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 28 Feb, 2026 Reviewers agreed at journal 17 Feb, 2026 Reviews received at journal 16 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviews received at journal 04 Feb, 2026 Reviewers agreed at journal 02 Feb, 2026 Reviewers agreed at journal 27 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers invited by journal 16 Jan, 2026 Editor assigned by journal 30 Oct, 2025 Submission checks completed at journal 30 Oct, 2025 First submitted to journal 28 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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class=\"CitationRef\"\u003e1\u003c/span\u003e). These conditions contribute to markedly reduced life expectancy; in Sweden, people with psychotic disorders die, on average, 20 years earlier than the general population does (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In addition to premature mortality, these diseases negatively impact quality of life (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) and impose substantial economic burdens due to increased healthcare costs and reduced productivity (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMultiple factors contribute to this heightened cardiometabolic risk. These include the inherent nature of the illness, genetic predispositions, the metabolic side effects of psychotropic medications, and unhealthy lifestyle behaviors (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Additionally, disparities in healthcare access and inadequate somatic care further exacerbate cardiometabolic vulnerability in this population (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite these risks, both individual- and system-level barriers limit the effectiveness of lifestyle interventions and preventive care. At the individual level, cognitive impairments, persistent psychiatric symptoms, and side effects of psychotropic medication hinder the initiation and maintenance of healthy behaviors (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). At the system level, healthcare professionals frequently rely on brief, generic lifestyle advice that fails to account for the cognitive and functional limitations of this group and imposes the same expectations as those placed on the general population. The Swedish National Board of Health and Welfare has highlighted these shortcomings, calling for more individualized and sustained support to promote effective lifestyle changes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStructural gaps in psychiatric care further limit progress. Although annual physical health checks are recommended in psychiatry, clear guidelines for their implementation are lacking. Knowledge among psychiatrists and other healthcare professionals regarding how to assess cardiometabolic risk factors and lifestyle habits\u0026mdash;the core purpose of these checks\u0026mdash;varies significantly. Moreover, standardized follow-up routines are lacking or inconsistently applied to ensure that identified risks lead to appropriate interventions. This shortcoming\u0026mdash;particularly regarding the need for closer follow-up in patients with known risk factors such as weight gain, hereditary cardiovascular disease, or diabetes\u0026mdash;was highlighted by the Swedish National Board of Health and Welfare in its 2022 national evaluation of care and support for schizophrenia and schizophrenia-spectrum disorders (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Another gap is the lack of educational programs for both individuals with psychotic disorders and healthcare professionals addressing the interactions among psychosis, lifestyle, and cardiometabolic health. Finally, collaboration between psychiatry and primary healthcare\u0026mdash;particularly regarding the identification and follow-up of cardiometabolic risks\u0026mdash;needs to be strengthened to improve overall health outcomes in this population.\u003c/p\u003e \u003cp\u003eSome clinical trials have demonstrated the potential benefits of tailored interventions in improving cardiometabolic outcomes for people with psychotic disorders. For example, the ACHIEVE trial, an 18-month behavioral weight loss intervention, demonstrated weight loss (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Similarly, two 30-month programs\u0026mdash;one health-promoting and the other individualized and health-oriented\u0026mdash;reported reductions in CVD risk (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) and diabetes incidence (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, most previous interventions have been constrained by a range of limitations that affect their clinical effectiveness, generalizability, and feasibility in routine psychiatric care. Many were short-term, typically lasting a year or less (\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), which may not allow sufficient time to achieve meaningful improvements\u0026mdash;aside from exceptions such as the CRESSOB study (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Several trials applied narrow inclusion criteria (\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) or focused exclusively on individual lifestyle habits (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Others lacked educational components for patients and healthcare professionals regarding the connection between psychotic disorders, lifestyle, and cardiometabolic health (\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14 CR15 CR16 CR17\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) or failed to address systemic underdiagnosis and undertreatment of cardiometabolic conditions (\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14 CR15\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Only two studies (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) reported unusually low patient-to-staff ratios, while most studies (\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) did not report caseloads at all\u0026mdash;an omission that limits the assessment of feasibility and generalizability to real-world psychiatric services, where higher caseloads are the norm. In addition, some interventions rely on resource-intensive strategies that are not feasible in psychiatric settings\u0026mdash;such as providing meals (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), conducting home visits to evaluate cooking and grocery shopping, or delivering in-home physical activity coaching (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). These factors collectively limit the scalability and long-term impact of such interventions in real-world practice.\u003c/p\u003e \u003cp\u003eIn response to the limitations observed in previous interventions and routine psychiatric care, the LAGOM trial (Longitudinal Approach to Generate positive cardiometabolic health Outcomes in severe Mental illness) was developed as a feasible, scalable, and fully integrated intervention within psychiatric care. Conducted at the Department of Psychotic Disorders in Gothenburg, LAGOM offers structured education to patients, their relatives, and healthcare professionals on the interplay between psychotic disorders, cardiometabolic health, and lifestyle factors. The program adopts a holistic, person-centered approach with broad inclusion criteria, focusing on overall cardiometabolic risk rather than isolated behaviors. It emphasizes gradual, sustainable lifestyle improvements and spans a 36-month period. LAGOM also addresses underdiagnosis and undertreatment of cardiometabolic conditions through strengthened communication with primary healthcare providers. Despite these strengths, evidence on the effectiveness of long-term, real-world interventions such as LAGOM remains limited. This trial aims to fill that critical knowledge gap.\u003c/p\u003e \u003cp\u003eTo report this trial in a systematic and transparent way, we used the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2025 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall aim of the trial is to improve cardiometabolic health, promote healthy lifestyles, and enhance quality of life in individuals with psychotic disorders.\u003c/p\u003e\n\u003cp\u003ePrimary outcomes\u003c/p\u003e\n\u003cp\u003eTo evaluate whether the intervention is superior to usual care in reducing cardiometabolic risk indicators over\u0026nbsp;the 36-month period.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePrimary endpoints\u003c/em\u003e: Differences in the mean changes in the following cardiometabolic risk indicators:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eBody mass index (BMI) (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/li\u003e\n \u003cli\u003eWaist‒hip ratio (WHR)\u003c/li\u003e\n \u003cli\u003eSystolic blood pressure (SBP) (mm Hg)\u003c/li\u003e\n \u003cli\u003eDiastolic blood pressure (DBP) (mm Hg)\u003c/li\u003e\n \u003cli\u003eBlood samples\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003ePlasma glucose (mmol/L)\u003c/li\u003e\n \u003cli\u003eTotal cholesterol/high density lipoprotein-cholesterol ratio (TChol/HDL-C ratio)\u003c/li\u003e\n \u003cli\u003eTriacylglycerol/HDL-C ratio (TAG/HDL-C ratio)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eSecondary outcomes\u003c/p\u003e\n\u003cp\u003eTo assess whether the intervention is superior to usual care in reducing the risk of CVD or type 2 diabetes mellitus at 36 months.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSecondary endpoints\u003c/em\u003e:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eCVD outcomes: Hazard ratio of incident CVD events and/or\u0026nbsp;differences in the mean change in the CVD risk score will be assessed using the Systematic COronary Risk Evaluation 2 (SCORE2) (20).\u003c/li\u003e\n \u003cli\u003eDiabetes mellitus outcomes:\u0026nbsp;Hazard ratio of incident type 2 diabetes mellitus events.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eExploratory outcomes\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eTo evaluate whether the intervention is superior to usual care in improving health-related quality of life over the 36-month period.\u003c/li\u003e\n \u003cli\u003eTo assess whether the intervention reduces\u0026nbsp;the levels of high-sensitivity C-reactive protein (hs-CRP) and HbA1c over the 36-month period.\u003c/li\u003e\n \u003cli\u003eTo conduct a cost analysis per participant and assess cost-effectiveness over the 36-month period, where cost neutrality is considered a positive outcome.\u003c/li\u003e\n \u003cli\u003eTo evaluate whether the intervention improves targeted lifestyle behaviors (tobacco smoking, alcohol consumption, physical activity, and dietary habits) over the 36-month period.\u003c/li\u003e\n \u003cli\u003eTo explore the number, type, and average time interval between intervention sessions required annually to achieve a change in the targeted lifestyle over the 36-month period.\u003c/li\u003e\n \u003cli\u003eTo investigate whether participation in educational sessions by participants and their relatives in the intervention group is associated with positive lifestyle changes over the 36-month period.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cem\u003eExploratory endpoints\u003c/em\u003e:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eBiomarkers\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003eDifferences in the mean changes in hs-CRP (mg/L) and HbA1c (mmol/mol)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eQuestionnaires\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003eDifference in the mean change in the EQ-5D-5L score (quality of life)\u003c/li\u003e\n \u003cli\u003eDifference in the mean change in alcohol consumption (Alcohol Use Disorders Identification Test \u0026ndash; Consumption (AUDIT-C), scale 0\u0026ndash;12) (21)\u003c/li\u003e\n \u003cli\u003eDifference in the mean change in tobacco smoking per week\u003c/li\u003e\n \u003cli\u003eDifference in the mean change in dietary habits (dietary index) (scale 0\u0026ndash;12) (22)\u003c/li\u003e\n \u003cli\u003eDifference in the mean change in physical activity (number of minutes per day)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eHealth economic evaluation:\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003eDescriptive cost analysis (average cost per participant) in SEK and EUR\u003c/li\u003e\n \u003cli\u003eDifference in the mean change in quality-adjusted life years (QALYs) between the intervention and control groups\u003c/li\u003e\n \u003cli\u003eIncremental cost-effectiveness ratio (ICER) based on the number of CVD or type 2 diabetes mellitus cases averted and the number of QALYs gained\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eFor the intervention group,\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003eEffect of the number and type of lifestyle sessions with healthcare professionals on the mean change in lifestyle outcomes\u003c/li\u003e\n \u003cli\u003eEffect of participation in educational sessions (0\u0026ndash;3 sessions) on the mean change in lifestyle outcomes\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp id=\"_Toc160723075\"\u003e\u003cstrong\u003eTrial design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a longitudinal, multicenter, naturalistic, multicomponent, parallel-group, quasi-experimental cluster-based trial with a superiority framework. The trial uses a case‒control clinical design with a 1:3 allocation ratio, assigning one participant at the intervention clinics for every three at the control clinics. Clusters are defined at the level of outpatient clinics, with two intervention clinics and four control clinics.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eEligibility criteria\u003c/p\u003e\n\u003cp\u003eInclusion criteria\u003c/p\u003e\n\u003cp\u003e1. Adults \u0026ge;18 years of age meeting the International Classification of Diseases, Tenth Revision (ICD-10) diagnostic criteria for any one of the schizophrenia spectrum disorders (F20-F25 or F28-F29)\u003c/p\u003e\n\u003cp\u003e2. Ability to provide informed consent\u003c/p\u003e\n\u003cp\u003eExclusion criteria\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eHaving an electrical medical implant such as a pacemaker or other mechanical implants\u003c/li\u003e\n \u003cli\u003ePregnancy\u003c/li\u003e\n \u003cli\u003eDeemed unsuitable by the investigator (a person may be deemed unsuitable for participation in the trial by the clinical investigation team member based on factors that may affect the ability to participate safely and reliably. These factors may include, but are not limited to, physical disabilities that hinder participation or practical challenges such as long travel distances to the trial site. The assessment is made on an individual basis and aims to ensure both patient safety and trial integrity).\u003c/li\u003e\n \u003cli\u003ePrior participation in the LAGOM trial during a previous inclusion cycle (i.e., participants can only be included once during the trial period).\u003c/li\u003e\n \u003cli\u003eCurrently under compulsory care.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eTrial setting and participant recruitment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial is being conducted in Gothenburg, Sweden\u0026rsquo;s second-largest city, at six outpatient psychosis clinics affiliated with Sahlgrenska University Hospital. This hospital hosts the country\u0026rsquo;s largest department specializing in psychotic disorders and delivers both secondary and tertiary psychiatric care. The clinics serve individuals with psychotic disorders residing in Gothenburg, M\u0026ouml;lndal, Partille, H\u0026auml;rryda, and \u0026Ouml;cker\u0026ouml; municipalities, representing a total catchment area of 774,247 inhabitants (Statistics Sweden, December 31, 2024) (23).\u003c/p\u003e\n\u003cp\u003eTwo clinics\u0026mdash;Centrum (PC) and M\u0026ouml;lndal (PM)\u0026mdash;were purposefully selected as intervention sites because of practical and organizational constraints. PC employs the project leader, whereas PM shares a health promoter with PC. This health promoter is part of the research team and is responsible for implementing key components of the intervention. Four clinics\u0026mdash;Hisingen (PH), Nordost (PNO), V\u0026auml;ster (PVV), and \u0026Ouml;ster (PM\u0026Ouml;)\u0026mdash;serve as control sites. Random allocation of clinics was not feasible because of these structural factors.\u003c/p\u003e\n\u003cp\u003eEach participant is enrolled in the trial for 36 months \u0026plusmn; 6 months. Eligible patients are identified and screened prior to their scheduled annual physical health checks. A trained representative of the clinical investigation team invites eligible patients to participate during these routine visits.\u003c/p\u003e\n\u003cp\u003eThe clinical investigation team comprises healthcare professionals employed at each participating psychosis outpatient clinic, including registered and assistant nurses, occupational therapists, social workers, psychologists, and mental health support workers. These professionals also serve as case managers (CMs), who are responsible for coordinating patients\u0026rsquo; overall care across primary care, community services, and other secondary care services, following the resource group assertive community treatment (R-ACT) model (24, 25). The CM-to-patient ratio is approximately 1:34. In addition to the CM, the clinical investigation team includes either a psychiatrist or another attending physician (collectively referred to as \u0026quot;the physician\u0026quot;), as well as a single health promoter working at the intervention clinics.\u003c/p\u003e\n\u003cp\u003eAll standard CMs and physicians are involved in the trial\u0026rsquo;s implementation. Clinics may also host medical trainees (e.g., undergraduate medical students, recent graduates, or residents); however, these individuals will only be actively involved in the trial at the control clinics and will not participate in delivering the intervention.\u003c/p\u003e\n\u003cp\u003eThe clinical investigation team provides full oral and written information\u0026mdash;via a participant information sheet (PIS)\u0026mdash;detailing the trial\u0026rsquo;s purpose, procedures, eligibility criteria, and potential risks and benefits. Participation is voluntary. Patients are informed that they may withdraw at any time without providing a reason and without consequences for their ongoing care.\u003c/p\u003e\n\u003cp\u003ePatients receive sufficient time to review the PIS, ask questions, and consider participation. If they agree, written informed consent is obtained and signed by both the patient and the clinical investigation team representative. A copy of the signed consent and PIS is provided to the participant, and the consent process is documented in source documents and archived with essential trial materials.\u003c/p\u003e\n\u003cp\u003eThe PIS specifies that if a participant withdraws, data already collected and necessary for the trial will continue to be used, but no additional data will be gathered. If new information arises that could significantly affect a participant\u0026rsquo;s health or care, it will be communicated in writing, and participants may then choose whether to continue.\u003c/p\u003e\n\u003cp\u003eInterpreter-assisted consultations are routinely used at outpatient psychosis clinics and will be employed as needed during the consent process. Since the PIS is available only in Swedish, the following steps are taken to ensure comprehension:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eInterpreter role: An accredited interpreter provides an oral translation of all trial information into the participant\u0026rsquo;s preferred language.\u003c/li\u003e\n \u003cli\u003eAdapted delivery: Information is presented in short sections with pauses for questions and clarification, without using technical jargon.\u003c/li\u003e\n \u003cli\u003eComprehension check: Patients are asked open-ended questions to confirm their understanding (e.g., \u0026ldquo;Can you explain what the study is about in your own words?\u0026rdquo;).\u003c/li\u003e\n \u003cli\u003eSupport inclusion: If applicable, care staff, such as housing support workers, may attend the session to reinforce understanding.\u003c/li\u003e\n \u003cli\u003eDecision time: Patients are given time to consider participation and may schedule a follow-up discussion before deciding.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003ePatients who, despite these measures, are unable to demonstrate understanding will be considered ineligible, as they do not meet the inclusion criterion: \u0026ldquo;Able to provide informed consent\u0026rdquo;. Rescreening is permitted if a patient meets the exclusion criteria at one annual check but not at the next. All clinical investigation team members are trained in standardized procedures for delivering information and obtaining consent, with PIS versions tailored to intervention and control clinics.\u003c/p\u003e\n\u003cp\u003eRecruitment is stratified by birth month to ensure year-round coverage. Although the planned recruitment period is 12 months, extensions may be needed due to scheduling constraints. Recruitment will continue until the target sample size is reached in both the intervention and control clinics.\u003c/p\u003e\n\u003cp\u003eA total of 644 participants will be recruited:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eIntervention clinics (PC and PM): Targeting 157 participants from a combined patient base of over 650.\u003c/li\u003e\n \u003cli\u003eControl clinics (PH, PNO, PVV, and PM\u0026Ouml;): Targeting 487 participants from a combined patient base of over 2,000.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eData collection methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePlans for assessment and collection of outcomes\u003c/p\u003e\n\u003cp\u003eTo standardize data collection across intervention and control clinics, a structured medical history protocol\u0026mdash;referred to as the worksheet\u0026mdash;was developed prior to the trial. The worksheet systematized the information gathered during patients\u0026rsquo; annual physical health checks and directly supported the research questions guiding the trial. Previously, data collection varied depending on individual healthcare\u0026nbsp;professionals\u0026rsquo; experience levels.\u003c/p\u003e\n\u003cp\u003eAll healthcare\u0026nbsp;professionals at the participating clinics received training in using the worksheet to interview patients approximately one year before trial initiation.\u003c/p\u003e\n\u003cp\u003eDuring annual physical health checks, the CM conducts a structured interview using the worksheet. While data are collected primarily through face‒to‒face interviews, additional sources include remote interviews, medical records, and self-administered questionnaires completed at home. The choice of data collection method depends on the nature and type of information being gathered.\u003c/p\u003e\n\u003cp\u003eThe worksheet has two versions\u0026mdash;an intervention version (v1.1, 2025-02-21) and a control version (v1.1, 2025-01-16)\u0026mdash;and is organized into seven data categories (Additional file 1):\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eSocial and background information\u003c/li\u003e\n \u003cli\u003eMedical\u0026nbsp;history\u003c/li\u003e\n \u003cli\u003eLifestyle\u0026nbsp;habits\u003c/li\u003e\n \u003cli\u003eResults of\u0026nbsp;the physical examination\u003c/li\u003e\n \u003cli\u003eBlood test results\u003c/li\u003e\n \u003cli\u003eAssessment scales\u003c/li\u003e\n \u003cli\u003eOther information\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTo support cost-effectiveness analyses, the worksheet and other trial records also capture detailed data on healthcare consumption and socioeconomic factors. These include psychiatric inpatient care (including compulsory admissions); housing status; employment; extent and duration of sick leave; permanent disability benefits; use of municipal and other support services; and dental care needs and subsidies.\u003cbr\u003e\u0026nbsp;For the intervention group only, data are also collected on sessions with internal or external healthcare professionals related to lifestyle behaviors, as well as on emergency room visits and hospital admissions for somatic healthcare.\u003c/p\u003e\n\u003cp\u003eCost data are derived from the clinic\u0026rsquo;s standardized cost calculations, and the average cost of municipal services is based on pricing data from the municipalities of Gothenburg. All costs will be inflation-adjusted over the 36-month trial period. QALYs are derived from the EQ-5D-5L forms. This is measured using the EuroQol-5D-5L scale\u0026nbsp;(26), which is completed by the patient either at home or during annual physical health checks and is included in the worksheet. The EuroQol-5D-5L scale has been validated in people with schizophrenia (27). Additionally, data on causes of death are available through clinic and trial records.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMeasurements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eBlood pressure and pulse:\u003cbr\u003eBlood pressure and pulse were measured on the right arm after 15 minutes of seated rest using the OMRON HEM-907-E7. The device is set to \u003cem\u003eAVERAGE\u003c/em\u003e mode, which calculates the mean of two readings taken 60 seconds apart. The \u003cem\u003eP-SET\u003c/em\u003e is set to \u003cem\u003eAUTO\u003c/em\u003e to automatically adjust the cuff pressure. Cuffs are selected based on arm size and are available in three sizes (medium, large, and extra-large; 22\u0026ndash;50 cm range). All CMs are trained in proper device use.\u003c/li\u003e\n \u003cli\u003eWeight:\u003cbr\u003eWeight was measured using the SECA 799 scale with participants wearing indoor clothing and no shoes. The values are rounded to the nearest whole number.\u003c/li\u003e\n \u003cli\u003eBody composition:\u003cbr\u003eBody fat (%), bone mass (kg), body water (%), muscle mass (kg), and metabolic age are measured using the TANITA DC-430MA. The participants are barefoot and wear indoor clothing; 1 kg is subtracted to account for clothing.\u003c/li\u003e\n \u003cli\u003eHeight:\u003cbr\u003eMeasured wearing socks, without shoes, on a firm, flat surface using a calibrated, wall-mounted stadiometer, with the head in the horizontal plane. Rounded to the nearest whole number.\u003c/li\u003e\n \u003cli\u003eWaist and Hip Circumference:\u003cbr\u003eMeasured using a flexible, non-stretch, multi-color, dual-sided anthropometric measuring tape (150 cm/59 in). Waist circumference is measured at the midpoint between the lower edge of the rib cage and the iliac crest (typically at the umbilicus) during exhalation. Hip circumference is measured at the widest part over the buttocks. All values are rounded to the nearest whole number.\u003c/li\u003e\n \u003cli\u003eTiming of Measurements:\u003cbr\u003eThe time of each physical exam is recorded to allow for time-adjusted analyses.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAll CMs and physicians involved in the trial\u0026nbsp;received standardized training to perform these measurements consistently.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBlood tests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc200092620\"\u003eBlood tests are ordered by the physician via CM as part of routine clinical procedures. Patients receive both oral and written instructions for preparing for the blood tests. These include the following standard recommendations:\u0026nbsp;\u003c/span\u003epatients must fast for at least 10 hours before the test. If they choose to drink coffee or tea during the fasting period, they are instructed not to add sugar or milk. Morning medications should be taken only after the blood sample has been collected. Patients are also advised that alcohol consumption and intense physical activity the day before testing may influence the test results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eQRISK3\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQRISK3 (version 2018.0) is a validated tool for estimating 10-year CVD risk, accounting for psychotic disorders and antipsychotic use as independent risk factors (28).\u003c/p\u003e\n\u003cp\u003eIn this trial, the QRISK3 is included only in the intervention worksheet as a visual, motivational aid, illustrating how changes in smoking, weight, blood pressure, and lipids can lower overall risk. It also demonstrates the synergistic effect of multiple small improvements, fostering a shared understanding between participants and healthcare professionals. The QRISK3 is used solely for lifestyle counseling and does not influence clinical decision-making.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBody composition analyzer\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe TANITA DC-430MA is a CE-marked class IIa medical device that uses dual-frequency bioelectrical impedance analysis to measure weight, BMI, body fat, muscle mass, visceral fat, basal metabolic rate, and other composition metrics. It is widely used in medical and research settings for screening and monitoring lifestyle-related conditions. In this trial, it is employed to support lifestyle counseling, in line with its intended purpose, without influencing medical decisions. The results are shared only with participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTraining of\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ethe\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eclinical investigation team\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the clinical investigation team members attended a one-day workshop on standardized measurements of blood pressure, waist circumference, and height. The staff at the intervention clinics received additional training in the use of the QRISK3 and the TANITA body composition analyzer.\u003c/p\u003e\n\u003cp\u003ePlans to promote participant retention and complete follow‑up\u003c/p\u003e\n\u003cp\u003eA patient-centered approach is embedded throughout all trial procedures and interactions. The CM at each outpatient clinic serves as the primary point of contact for participants and is available to address questions, offer support, and respond to any concerns that may arise during the trial.\u003c/p\u003e\n\u003cp\u003eTo minimize participant burden, trial visits\u0026mdash;including annual health checks and bimonthly physical examinations\u0026mdash;are scheduled, when possible, to coincide with existing clinic or outpatient appointments. Since annual health checks are already part of routine care, integrating research activities into these visits helps reduce additional time commitments.\u003c/p\u003e\n\u003cp\u003eIn addition, annual education sessions and bimonthly physical examinations are integral components of the patient-centered approach and are expected to further strengthen participant engagement and retention by fostering ongoing interaction, motivation, and continuity of care.\u003c/p\u003e\n\u003cp\u003eParticipants receive travel reimbursements for attending bimonthly physical examinations and annual education sessions. CMs are responsible for maintaining ongoing contact with participants and coordinating the scheduling of all trial-related visits. Research assistants support retention efforts by tracking attendance and assisting with logistical follow-up as needed.\u003c/p\u003e\n\u003cp\u003eThis proactive, coordinated approach is intended to support participant engagement and promote long-term retention over the 36-month follow-up period.\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc160723093\"\u003e\u003cstrong\u003eConfidentiality, data management, and access to data\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc200092609\"\u003eAll trial data will be registered, managed, and stored to ensure accurate reporting, interpretation, and verification while maintaining participant confidentiality. This is detailed in a Data Management Plan (DMP) (version 1.0, 2025-02-05) approved by the trial sponsor.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eAt each site, the Principal Investigator (PI)\u0026mdash;who also serves as the research nurse\u0026mdash;will collect completed worksheets from the CMs and physicians and store them in physical folders organized by participant. Data are gathered using paper-based methods. Within 45 days of the second visit of the annual physical health check, the PI will verify that each worksheet is complete and accurate. Any missing or questionable data will be clarified using information from the participant, CM, physician, or medical records. Once validated, the worksheet will be transferred to a research assistant for data entry into the electronic case report form (eCRF).\u003c/p\u003e\n\u003cp\u003eData entry into the eCRF will also be completed within 45 days of the second visit. During entry, the research assistant identifies missing or abnormal values, such as swapping weight and height values, reversed blood pressure readings, or inconsistencies (e.g., no somatic illness reported despite the use of antihypertensive or antidiabetic medication). Any such discrepancies are communicated to the responsible CM and physician for clarification and correction, with the aim of preventing similar issues in the future.\u003c/p\u003e\n\u003cp\u003eThe eCRF system is managed using Research Electronic Data Capture (REDCap), which serves as the electronic data capture (EDC) tool for this trial. The current version in use is v.14 (dated 30 November 2023), supplied by Gothia Forum and hosted by Region V\u0026auml;stra G\u0026ouml;taland (VGR-IT). REDCap provides a secure interface for data entry, supports real-time data validation, maintains complete audit trails for tracking data modifications, and enables data export to common statistical packages. It also allows data import from external sources. All data are stored on encrypted servers protected by firewalls, with daily backups and individual user logins secured by two-factor authentication. Access to the REDCap system is restricted to trained and authorized personnel, with role-based permissions (e.g., data editing or read-only access).\u003c/p\u003e\n\u003cp\u003eOnce the data have been finalized, a formal \u0026quot;Clean File\u0026quot; decision is documented in a \u0026lsquo;Clean File form\u0026rsquo; document. At this point, access to the eCRF will be withdrawn, except for authorized data export. PIs at each site retain access to cleaned datasets from their respective sites and may request access to data from other sites.\u003c/p\u003e\n\u003cp\u003eTo ensure confidentiality, each participant is assigned a unique record ID, which is used for all data collection, storage, and analysis. A participant enrollment and identification list is maintained separately, linking each participant\u0026rsquo;s name and personal identification number to that participant\u0026rsquo;s record ID.\u0026nbsp;Identifying information is not included in the eCRF at the analysis stage. Paper records and forms containing personal information are stored securely in locked areas at each outpatient clinic and are accessible only to authorized staff. These materials will never be left in public or unsecured spaces. Additionally, results will only be reported at the group level, ensuring that no individual participant can be identified. As part of the trial documentation, all participants receive a journal entry stating their enrollment in the trial and what it entails.\u003c/p\u003e\n\u003cp\u003eThe informed consent process complies with applicable data protection and privacy legislation. Participants are fully informed about how their data will be collected, used, and published, and how confidentiality will be protected. The PIS also states that authorized representatives of the sponsor or regulatory authorities may access relevant medical or trial records\u0026mdash;including the participant\u0026rsquo;s medical history\u0026mdash;for purposes of data verification.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eArchiving\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;sponsor representative\u0026nbsp;and\u0026nbsp;PI\u0026nbsp;will\u0026nbsp;maintain\u0026nbsp;the\u0026nbsp;essential trial documents in the Trial Master File (TMF) and Investigator Site File (ISF), respectively. The sponsor representative will keep all documentation and data for at least 10 years after the trial ends. The PI will archive all local investigation documentation for at least 10 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuality assurance and quality control\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQuality assurance ensures high-quality data collection, whereas quality control detects and addresses data problems promptly.\u003c/p\u003e\n\u003cp\u003eOur quality assurance approach involves 1) creating a flowchart for the intervention; 2) developing intervention and control worksheets; 3) conducting workshops to train data collectors; 4) holding regular meetings with data collectors; 5) maintaining logs of training sessions; and 6) following the manufacturer\u0026rsquo;s maintenance instructions for the OMRON blood pressure devices, SECA scales, and TANITA body composition analyzers.\u003c/p\u003e\n\u003cp\u003eOur quality control strategy includes 1) monitoring the completed worksheets via research nurses and research assistants; 2) rectifying missing or incorrect worksheet data through research nurses during the first review and through research assistants prior to database entry; 3) tracking data entry delays; and 4) conducting regular meetings with research nurses and assistants to address missing, out-of-range, or illogical data.\u003c/p\u003e\n\u003cp id=\"_Toc200092623\"\u003e\u003cstrong\u003eHarms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSafety monitoring, adverse event definitions, reporting procedures, and causality assessment for this clinical trial follow applicable regulatory guidelines. Causality is assessed using a standardized 4-level scale, and all reporting procedures follow applicable regulatory timelines. Full details are described in the Clinical Investigation Plan (CIP), which is publicly available at ClinicalTrials.gov (NCT06781801). The CIP is the formal protocol describing the objectives, design, methodology, monitoring, statistical considerations, and organization of the clinical investigation, as defined in SS-EN ISO 14155:2020. In some documents, this may be referred to simply as the Protocol.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention and comparator\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eControl clinics (usual care)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsual care refers to the existing clinical practices for individuals with psychotic disorders in Gothenburg. In Sweden, all citizens are registered with a primary healthcare center, which retains responsibility for managing cardiometabolic risk factors\u0026mdash;even for patients who receive ongoing specialist psychiatric care.\u003c/p\u003e\n\u003cp\u003eIn Gothenburg, individuals with psychotic disorders receive annual physical health checks at psychosis outpatient clinics as part of usual care. This process typically includes two visits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnnual\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ephysical health checks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline Visits\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisit 1 \u0026ndash; The annual physical health check with CM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs part of usual care, the CM prepares for the annual physical health check by ordering blood tests, beginning to fill in the worksheet, and sending a letter to the patient with instructions for blood sample preparation. Depending on the case, the CM may also send self-assessment questionnaires to be completed at home (including EQ-5D-5L, AUDIT-C, and a questionnaire on dietary habits). These procedures are part of routine care and are unaffected by participation in the trial.\u003c/p\u003e\n\u003cp\u003eDuring the visit, the CM completes the control version of the worksheet, performs the physical examination, and ensures that fasting blood tests are conducted. Visit 1 lasts approximately 60 minutes. The blood tests and physical examination provide the cardiometabolic parameters relevant to this trial, as outlined in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisit 2 \u0026ndash; The annual physical health check with the physician and CM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe physician and CM review the worksheet, laboratory, and physical examination results. Visit 2 lasts approximately 60 minutes. Clinical management is guided by the physician\u0026rsquo;s judgment, which is typically based on reference values for cardiometabolic parameters. The participant, CM, and physician collaborate to determine a suitable management plan based on outpatient clinic\u0026rsquo;s routines. Usual care may include basic lifestyle advice or referrals to health promoters, dietitians, or primary\u0026nbsp;healthcare professionals.\u003c/p\u003e\n\u003cp\u003eThe trial does not modify the delivery of usual care but requires that the two annual visits for each participant occur within a 45-day period.\u003c/p\u003e\n\u003cp\u003eHowever, it may not always be feasible for patients to complete blood tests or physical examinations on the scheduled days of these visits. To accommodate this, the protocol allows these assessments to be completed up to 45 days after Visit 2. This establishes a visit window of \u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e45 days from the second visit. If either the blood tests or physical examinations are completed after Visit 2, a follow-up physician appointment is scheduled to review the results and make appropriate clinical decisions. This visit window is designed to reflect the realities of clinical practice while maintaining consistency in data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContinuing Annual Physical Health Checks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFollow-up assessments at months 12, 24, and 36 replicate the baseline procedure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisits 3, 5, and 7 \u0026ndash; The annual\u0026nbsp;physical health check with CM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;same\u0026nbsp;routine\u0026nbsp;as\u0026nbsp;in\u0026nbsp;Visit\u0026nbsp;1\u0026nbsp;(baseline)\u0026nbsp;at the control clinics (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisits 4, 6, and 8 \u0026ndash; The annual\u0026nbsp;physical health check with the physician and CM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;same\u0026nbsp;routine\u0026nbsp;as\u0026nbsp;in\u0026nbsp;Visit\u0026nbsp;2\u0026nbsp;(baseline)\u0026nbsp;at the control clinics (Table 1).\u003c/p\u003e\n\u003cp\u003ePatients not enrolled in the trial will continue to receive usual care at the control clinics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention Clinics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the intervention clinics, participants receive enhanced assessments and individualized support integrated into usual care. The intervention follows a structured and manualized approach guided by a flowchart (Figure 1), an intervention-specific worksheet, and a brochure (additional file 2). The brochure describes the project and defines the lifestyle habits adapted for individuals with psychotic disorders. It is designed to support healthcare professionals in delivering interventions consistently and effectively. Together, these tools organize the workflow and ensure systematic implementation across the healthcare professionals involved in care. The intervention is designed to promote cardiometabolic health through individualized assessment, feedback, and follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLocation and title of Figure 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 1. Flowchart\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnnual\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ephysical health checks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe annual physical health checks at intervention clinics follow the same two-visit structure as usual care but include additional assessments, motivational tools, and follow-up mechanisms tailored to address cardiometabolic health in patients with psychotic disorders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline Visits\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisit 1 \u0026ndash; The annual physical health check with CM\u003c/strong\u003e\u003cbr\u003eThis visit mirrors the control clinic structure and lasts approximately 60 minutes but includes additional components:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eThe CM uses the intervention version of the worksheet.\u003c/li\u003e\n \u003cli\u003eBody composition is assessed using the TANITA DC-430MA analyzer, as outlined in Table 1.\u003c/li\u003e\n \u003cli\u003eNo intervention-specific procedures are initiated before written informed consent is obtained.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eVisit 2 \u0026ndash; The annual physical health check with the physician and CM\u003c/strong\u003e\u003cbr\u003eThis visit lasts approximately 60 minutes and has the following additional components compared with usual care:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eIndividualized and comprehensive mapping of cardiometabolic risk and lifestyle habits beyond standard cut-off values. This includes assessment of SCORE2 and metabolic syndrome\u0026nbsp;(29) criteria to provide a contextual estimate of the risk for CVD and diabetes, as well as\u0026nbsp;evaluation of trends in risk factors over time.\u003c/li\u003e\n \u003cli\u003eAssessment of risk behavior in lifestyle habits is linked to the participant\u0026rsquo;s state of cardiometabolic health as well as to the gains the participants make by stopping their unhealthy lifestyle.\u003c/li\u003e\n \u003cli\u003eThe physician fills in the QRISK3 algorithm with the participant.\u003c/li\u003e\n \u003cli\u003eThe physician uses the results of visual motivational tools\u0026mdash;QRISK3 and the TANITA\u0026mdash;to support patient understanding and encourage engagement in lifestyle change and cardiometabolic risk management.\u003c/li\u003e\n \u003cli\u003eThe physician, CM, and participant jointly develop a personalized care and follow-up plan.\u003c/li\u003e\n \u003cli\u003eRisk-oriented referrals\u0026nbsp;to internal resources (e.g., health promoters, physiotherapists) for further assessment and support or to external providers (e.g., primary healthcare)\u0026nbsp;to promote appropriate diagnosis and management of cardiometabolic concerns, with an emphasis on individualized care. CMs coordinate and follow up on referrals.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAdditional intervention components:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eCoordination,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003emotivational support, and counseling\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cul\u003e\n \u003cli\u003eThe CM conducts individualized follow-up sessions (15\u0026ndash;30 minutes), in person or remotely.\u003c/li\u003e\n \u003cli\u003eSessions target key lifestyle factors: diet, physical activity, alcohol, and tobacco use.\u003c/li\u003e\n \u003cli\u003eThe frequency, content, and delivery mode of the sessions are tailored to the participants\u0026rsquo; needs.\u003c/li\u003e\n \u003cli\u003eThese sessions ensure engagement with care plans initiated by psychiatry or agreed-upon external healthcare resources (e.g., primary healthcare or dietitians) and support continuity, adherence, and necessary adjustments.\u003c/li\u003e\n \u003cli\u003eThe approach emphasizes small, sustainable adjustments that consider cognitive limitations and stress sensitivity.\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eBi\u003c/strong\u003e\u003cstrong\u003emonthly\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;follow-up with\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ephysical examination\u003c/strong\u003e\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/li\u003e\n \u003cli\u003eEvery two months, participants attend a clinic visit that includes a focused discussion of relevant lifestyle behaviors and a physical examination.\u003c/li\u003e\n \u003cli\u003eThe measurements included SBP, DBP, pulse, weight, waist and hip circumference, and body composition, which are assessed using the TANITA analyzer (Table 1).\u003c/li\u003e\n \u003cli\u003eThese regular assessments are used to monitor progress and guide individualized adjustments to the care plan.\u003col start=\"3\"\u003e\n \u003cli\u003e\u003cstrong\u003eGroup education sessions for participants and relatives\u003c/strong\u003e\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/li\u003e\n \u003cli\u003eOnce annually, participants and their relatives are invited to a 45-minute in-person education session.\u003c/li\u003e\n \u003cli\u003eA representative from the clinical investigation team will hold the education sessions.\u003c/li\u003e\n \u003cli\u003eSessions are based on the LAGOM concept and focus on the connection between lifestyle, cardiometabolic health, and psychotic disorders.\u003c/li\u003e\n \u003cli\u003eThe participation of relatives is optional; no data are collected from them.\u003col start=\"4\"\u003e\n \u003cli\u003e\u003cstrong\u003eEducation sessions for staff\u003c/strong\u003e\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/li\u003e\n \u003cli\u003eInternal education seminars are held biannually.\u003c/li\u003e\n \u003cli\u003eThese address the interplay between cardiometabolic risk, psychotic disorders, and lifestyle habits.\u003c/li\u003e\n \u003cli\u003eSeminars are grounded in the LAGOM framework and promote consistent, evidence-based practice among healthcare professionals.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eOngoing data collection and adherence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe intervention includes a structured plan for monitoring implementation fidelity and patient adherence:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe CM is responsible for documentation during annual check-ups.\u003c/li\u003e\n \u003cli\u003eContact with referred services is tracked.\u003c/li\u003e\n \u003cli\u003eFollow-ups aim to reinforce intervention goals and evaluate effectiveness.\u003c/li\u003e\n \u003cli\u003eThe CM documents the number and type of sessions with internal and external resources in the worksheet at the next annual health check, based on self-reports and medical and trial records.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eContinuing annual physical health checks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants undergo follow-up assessments at months 12, 24, and 36, which replicate the baseline procedures:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisits\u0026nbsp;8,\u0026nbsp;15,\u0026nbsp;and\u0026nbsp;22\u0026nbsp;\u0026ndash;\u0026nbsp;The\u0026nbsp;annual\u0026nbsp;physical\u0026nbsp;health\u0026nbsp;check\u0026nbsp;with\u0026nbsp;the\u0026nbsp;CM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe same routine as in Visit 1 (baseline) at the intervention clinics (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisits 9, 16, and 23 \u0026ndash; The annual health check with the physician and the CM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe same routine as in Visit 2 (baseline) at the intervention clinics (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisits 3\u0026ndash;7, 10\u0026ndash;14, and 17\u0026ndash;21\u003c/strong\u003e: Bimonthly physical examinations, as outlined in Table 1.\u003c/p\u003e\n\u003cp\u003eParticipants initially deemed ineligible may be rescreened. Patients not enrolled in the trial at intervention clinics continue to receive usual care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAwareness of Assignment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to the nature of the intervention, both participants and healthcare professionals are aware of the clinic assignment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLocation and title of Table 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc200092599\"\u003eTable 1. Schedule of enrollment, interventions, and assessments\u003c/span\u003e\u003c/p\u003e\n\u003cp skip=\"true\"\u003e\u003cstrong\u003eCriteria and procedures for participant withdrawal or discontinuation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants have the right to withdraw from the trial at any time without providing a reason and without any impact on their ongoing or future treatment.\u003c/p\u003e\n\u003cp\u003eIf a participant discontinues the trial, follow-up and care will continue in accordance with the outpatient clinic\u0026rsquo;s routines.\u003c/p\u003e\n\u003cp\u003eIndividual participant discontinuation may occur under the following circumstances:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eEnrollment in violation of the inclusion or exclusion criteria (inappropriate enrollment)\u003c/li\u003e\n \u003cli\u003eWithdrawal of informed consent\u003c/li\u003e\n \u003cli\u003ePregnancy\u003c/li\u003e\n \u003cli\u003eReceipt of an electronic medical implant (e.g., pacemaker) or other mechanical implants\u003c/li\u003e\n \u003cli\u003eRelocation to another city or country, or registration at a different outpatient clinic\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWhen available, the reason for discontinuation will be documented in the eCRF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient engagement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMembers of the Schizophrenia Association in Gothenburg were involved in revising the intervention flowchart and brochure, as well as in both the development and revision of the worksheets prior to the start of the trial. They have also reviewed the content and structure of the educational sessions for participants and their relatives to help ensure that the sessions are relevant, understandable, and appropriately tailored to participants\u0026rsquo; needs.\u003c/p\u003e\n\u003cp\u003ePatients and/or the public were not involved in the reporting or dissemination plans of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe estimated number of participants required to meet the trial objectives is based on thresholds for clinical significance. To be clinically significant, the difference in the mean value between the intervention and control groups should be at least 1 kg/m\u003csup\u003e2\u003c/sup\u003e in BMI (30), 1 cm in waist circumference or 0.01 units in WHR (31), 10 mm Hg in SBP (32), 2 mm Hg in DBP (33), 1 unit in the TAG/HDL-C ratio (34, 35), 1 unit in the TChol/HDL-C ratio (36), or 1 mmol/L in plasma glucose (37).\u003c/p\u003e\n\u003cp\u003eTable 2 presents the sample size calculation. Among the approximately 2,650 patients listed at the six psychosis outpatient clinics in Gothenburg, 157 participants will be recruited from the intervention clinics, and 487 will be recruited from the control clinics. This accounts for an estimated 40% dropout rate, a type I error rate of 0.05, 80% statistical power, and an allocation ratio of 1:3 (intervention to control). The sample size was calculated using the statistical package STATA (StataNow/SE 19.5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical and health economic analysis plan\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial involves longitudinal comparisons both within and between the intervention and control groups.\u003c/p\u003e\n\u003cp id=\"_Toc160723103\"\u003ePrimary\u0026nbsp;outcome analysis\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eCardiometabolic indicators \u0026mdash; BMI, WHR, SBP, DBP, the TAG/HDL-C ratio, the TChol/HDL-C ratio, and plasma glucose \u0026mdash; will be analyzed using linear mixed-effects regression models for repeated measures. Data will be drawn from assessments conducted within a \u0026plusmn;45-day window surrounding the physician-led annual physical health check.\u003c/li\u003e\n \u003cli\u003eSensitivity analyses will examine the impact of:\u003cul type=\"circle\"\u003e\n \u003cli\u003eIncluding cardiometabolic data collected outside the predefined visit window.\u003c/li\u003e\n \u003cli\u003eOutliers, by comparing models with and without their inclusion.\u003c/li\u003e\n \u003cli\u003eMissing data and dropouts.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eSecondary and exploratory outcome analysis\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eCardiovascular risk (SCORE2): Analyzed using linear regression.\u003c/li\u003e\n \u003cli\u003eTime-to-event outcomes (e.g., incident or recurrent cardiovascular events and incident type 2 diabetes mellitus): Analyzed using Cox proportional hazards regression and Kaplan\u0026ndash;Meier survival estimates.\u003c/li\u003e\n \u003cli\u003eQuality of life (EQ-5D-5L): Analyzed using linear mixed-effects regression models for repeated measures.\u003c/li\u003e\n \u003cli\u003eInflammatory and metabolic markers (hs-CRP and HbA1c): Analyzed using linear mixed-effects regression models for repeated measures.\u003c/li\u003e\n \u003cli\u003eLifestyle behaviors (physical activity, dietary habits, alcohol consumption, and tobacco smoking): Analyzed using linear mixed-effects regression models in a dose\u0026ndash;response framework, where the number of lifestyle-related sessions with internal or external healthcare professionals is used as the predictor variable (instead of a binary intervention indicator).\u003c/li\u003e\n \u003cli\u003eLifestyle behaviors \u0026mdash; including smoking status (number of cigarettes per week), AUDIT-C score, dietary index, and time spent in physical activity \u0026mdash; and the effects of educational sessions (exclusively for the intervention group) will also be assessed using linear mixed effects regression models for repeated measures.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAll primary, secondary, and exploratory outcomes will be tested using two-sided statistical tests with a Type I error rate (\u0026alpha;) of 0.05. All models will be adjusted for potential cofounders, including site, age, sex, and any baseline covariates not balanced between groups.\u003c/p\u003e\n\u003cp\u003eHealth economic analysis\u003c/p\u003e\n\u003cp\u003eThe health economic evaluation will consist of three components:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eDescriptive cost analysis\u003cul type=\"circle\"\u003e\n \u003cli\u003eDirect and indirect costs will be calculated and reported in both SEK and EUR.\u003c/li\u003e\n \u003cli\u003eCosts will be indexed to the clinical trial\u0026rsquo;s end date.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eQALYs\u003cul type=\"circle\"\u003e\n \u003cli\u003eDerived from EQ-5D-5L scores (5-dimensional scale) and analyzed using linear mixed-effects regression models for repeated measures.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eICER\u003cul type=\"circle\"\u003e\n \u003cli\u003eThe ICER will be calculated based on cost per:\u003cul type=\"square\"\u003e\n \u003cli\u003eCase of CVD averted,\u003c/li\u003e\n \u003cli\u003eCase of type 2 diabetes mellitus averted, and\u003c/li\u003e\n \u003cli\u003eQALY gained based on EQ-5D-5L scores normalized to a [0, 1] interval.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eSensitivity analyses will test the robustness of the cost-effectiveness model using a \u0026plusmn;20% variation in key input parameters. Trial management costs will be excluded from the analysis. However, the model will incorporate the additional time required to deliver the intervention (e.g., more frequent or longer visits), alongside the time spent on usual care. Achieving cost neutrality for both direct and indirect costs will be viewed as a positive outcome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMissing Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA two-step strategy is in place to minimize the occurrence of missing data.\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eInitial Review: The PI reviews the completed worksheets after the second visit of the annual physical health check to identify any missing or inconsistent entries.\u003c/li\u003e\n \u003cli\u003eFollow-up Review: A research assistant then performs a secondary check. Both checks are conducted within 45 days of the second visit of the annual physical health check, unless delayed owing\u0026nbsp;to limited staff availability and scheduling constraints during summer, Christmas, or national holidays.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eIn addition to manual review, the eCRF includes built-in validation checks for missing values and implausible entries.\u003c/p\u003e\n\u003cp\u003eTo inform our handling of missing data during analysis, we will evaluate:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eLevel of missing data: item-level, construct-level, and person-level;\u003c/li\u003e\n \u003cli\u003eMissing data mechanism: whether the data are missing completely at random (MCAR), missing at random (MAR), or missing not at random (MNAR) (42).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eBased on this assessment, appropriate handling strategies will be applied, such as Full Information Maximum Likelihood (FIML), Multiple Imputation (MI), or listwise/pairwise deletion. Sensitivity analyses will be performed to assess how missing data may influence results and to evaluate the robustness of the selected handling methods.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMonitoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial will be monitored by an independent monitor from the Scandinavian Clinical Research Organisation (SCRO), which is appointed by the sponsor. Monitoring will take place before the trial begins, during its conduct, and after its completion to ensure compliance with the CIP, Good Clinical Practice (GCP), SS-EN ISO 14155:2020, and applicable ethical and regulatory requirements, including the Declaration of Helsinki. The monitor is independent of the PI and trial site staff.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePurpose and approach\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use\u0026ndash;Good Clinical Practice (ICH-GCP) and applicable regulations, the sponsor is responsible for ensuring the trial is quality-controlled through monitoring. The monitor must have access to all trial materials, and site staff must allocate time for monitoring activities. Monitoring is risk-based and guided by a Monitoring Plan (version 1.0, dated 24 February 2025), approved by the trial sponsor, developed before the start of the trial, and subject to adjustment based on changes to the trial or updated risk assessments.\u003c/p\u003e\n\u003cp\u003eThe sponsor has assessed this trial as low-risk, allowing for a reduced intensity of monitoring. This classification is based on the absence of known risks with the investigational devices (QRISK3 algorithm and body composition analyzer) and the fact that the trial is embedded in routine clinical practice, where risks are no greater than usual care. The main potential burden is the possibility of additional visits for the intervention group; to mitigate this, participants are exempt from visit costs and receive transportation support.\u003c/p\u003e\n\u003cp\u003eGiven the potential clinical benefits\u0026mdash;improved detection and management of cardiometabolic risk factors, enhanced quality of life, and cost-effective care for individuals with psychotic disorders\u0026mdash;the expected benefits clearly outweigh the minimal risks. Continuous internal quality control will be conducted by the sponsor\u0026rsquo;s research team to ensure adherence to the CIP and data integrity.\u003c/p\u003e\n\u003cp\u003eMonitoring ensures:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eThe rights, safety, and well-being of trial participants are protected.\u003c/li\u003e\n \u003cli\u003eData collected are accurate, complete, and consistent with source documents.\u003c/li\u003e\n \u003cli\u003eThe trial was conducted in accordance with the approved protocol, GCP, and applicable ethical and regulatory requirements, such as the Declaration of Helsinki.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant confidentiality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs described in the informed consent form, participants explicitly consent to allow authorized representatives of the sponsor, including the monitor and relevant regulatory authorities, access to relevant parts of their medical and trial records\u0026mdash;including medical history\u0026mdash;for purposes of data verification. This is communicated clearly during recruitment through both oral and written information. Access will also be granted for regulatory inspections.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMonitoring visits\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSCRO\u0026apos;s monitor will conduct the following types of monitoring visits across the six sites in Gothenburg:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eStudy initiation visit:\u003cul type=\"circle\"\u003e\n \u003cli\u003eVerifies staff training and site readiness prior to participant enrollment.\u003c/li\u003e\n \u003cli\u003eConfirms the availability of all essential documents and procedures.\u003c/li\u003e\n \u003cli\u003eEnsures that the ISF is complete.\u003c/li\u003e\n \u003cli\u003eFour initiation visits are conducted: one for the two intervention sites and three for the four control sites.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eMonitoring and Source Data Verification\u003cul type=\"circle\"\u003e\n \u003cli\u003eConducted at four\u0026nbsp;to six planned visits per site\u0026nbsp;during the trial period.\u003c/li\u003e\n \u003cli\u003eIncludes review of informed consent forms, source data, inclusion/exclusion criteria, QRISK3 and TANITA results, and physical examination variables (e.g., weight, blood pressure).\u003c/li\u003e\n \u003cli\u003eTwenty percent\u0026nbsp;of\u0026nbsp;records at each site will be reviewed, with 100% verification for all\u0026nbsp;serious adverse events (SAEs) in the intervention group.\u003c/li\u003e\n \u003cli\u003eEnsures that the\u0026nbsp;eCRF is\u0026nbsp;completed correctly and queries are issued as needed.\u003c/li\u003e\n \u003cli\u003eA source data verification agreement is signed prior to participant inclusion at each site.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eSite closure visits:\u003cul type=\"circle\"\u003e\n \u003cli\u003eOccurs after the last participant completes the trial and a Clean File has been declared.\u003c/li\u003e\n \u003cli\u003eThe sponsor representative will confirm when a site is ready for closure.\u003c/li\u003e\n \u003cli\u003eVerifies final documentation (e.g., Clean File documents, signed logs, informed consents).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eRemote Monitoring:\u003cul type=\"circle\"\u003e\n \u003cli\u003eIncludes review of eCRF data entry and query management after the first 20 participants at each site complete baseline visits.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAll monitoring activities will be conducted according to the monitoring plan developed by the sponsor, which includes a predefined schedule and standard procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDocumentation and follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter each visit, the monitor will issue a monitoring report within 10 working days. The report will detail monitoring findings, proposed actions, and responsible parties. It is signed by both the monitor and the sponsor representative and stored in the TMF and ISF. Signed originals are maintained by the sponsor representative and will be archived after trial closure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTMF and ISF management and oversight\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGothia Forum at Sahlgrenska University Hospital supported the preparation of both the TMF and ISF in collaboration with the sponsor representative. Ongoing management of the TMF will be coordinated with the sponsor representative, while each trial site is responsible for maintaining its own ISF. Essential documents will be maintained throughout the trial, with appropriate archiving procedures implemented at its conclusion. The SCRO monitor will oversee the completeness, accuracy, and regulatory compliance of both files in accordance with the monitoring plan.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource data and access to documentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe PI at each site is responsible for maintaining source documents for every participant throughout the trial. Prior to trial initiation at each individual site, the definition and location of source data were determined in collaboration with the monitor and documented in the \u003cstrong\u003eSource Data Location Agreement\u003c/strong\u003e, which is included in the ISF. This agreement specifies what constitutes source data at each site (e.g., medical records, worksheets).\u003c/p\u003e\n\u003cp\u003eIn cases where certain data are not documented elsewhere, the worksheet has been designated as the source document, as agreed upon with the monitor and documented in the Source Data Location Agreement.\u003c/p\u003e\n\u003cp\u003eAccess to all trial-related documentation\u0026mdash;including medical records, worksheets, eCRFs, and other trial documentation\u0026mdash;will be provided for monitoring and other quality control activities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCIP version\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVersion: Version 3.0/Amendment 1 (dated 10 June 2025)\u003c/p\u003e\n\u003cp\u003eReplaces: Version 2.0 (dated 6 December 2024)\u003c/p\u003e\n\u003cp\u003eRevision\u003c/p\u003e\n\u003cp\u003eThe substantial modification involves a change of PI at two outpatient clinics (PNO and PM\u0026Ouml;). In addition, a clarification has been added specifying that both Visit 1 and Visit 2 are part of the annual physical health check, with both visits occurring within a 45-day window. Each visit will last approximately 60 minutes. Additional minor, nonsubstantial changes have also been made to the CIP and the PISs.\u003c/p\u003e\n\u003cp\u003eRationale\u003c/p\u003e\n\u003cp\u003eThe PI changes are necessary due to leadership updates at the respective clinics. The clarification regarding visit structure and timing was made to ensure consistency and transparency across all participating sites. Minor adjustments to the CIP and PIS were implemented to improve clarity and alignment with current trial procedures.\u003c/p\u003e\n\u003cp\u003eVersion: Version 3.1 (dated 21 October 2025)\u003c/p\u003e\n\u003cp\u003eReplaces: Version 3.0 (dated 10 June 2025)\u003c/p\u003e\n\u003cp\u003eRevision\u003c/p\u003e\n\u003cp\u003eThis version includes minor, nonsubstantial updates to improve clarity, consistency, and completeness:\u003c/p\u003e\n\u003cp\u003e\u0026bull; \u0026ldquo;Care as usual\u0026rdquo; changed to \u0026ldquo;usual care\u0026rdquo; throughout the document.\u003c/p\u003e\n\u003cp\u003e\u0026bull; \u0026ldquo;Intervention group\u0026rdquo; and \u0026ldquo;control group\u0026rdquo; revised to \u0026ldquo;intervention clinics\u0026rdquo; and \u0026ldquo;control clinics,\u0026rdquo; respectively, where applicable.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Table 1: \u0026ldquo;Eating habits\u0026rdquo; changed to \u0026ldquo;Dietary habits.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u0026bull; Table 1: Timing of data collection for \u0026ldquo;Questions about participation in educational sessions and lifestyle sessions\u0026rdquo; specified at baseline, 12 months, 24 months, and 36 months.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Section 6.3.2 (Exclusion Criteria): Clarified wording for \u0026ldquo;Deemed unsuitable for inclusion at the discretion of the investigator\u0026rdquo; and \u0026ldquo;Previous participation in the clinical trial.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eRationale\u003c/p\u003e\n\u003cp\u003eThese updates were made to enhance clarity, ensure internal consistency, and provide complete documentation of data collection and eligibility procedures. All changes are minor and nonsubstantial, with no impact on the study design, methodology, or participant safety.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProtocol amendments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAny amendments to the CIP are developed and agreed upon by the sponsor in consultation with the coordinating investigator. Substantial amendments\u0026mdash;defined as changes that may impact participant safety, the scientific value of the trial, or the conduct of the trial\u0026mdash;must be submitted to and approved by the Swedish Ethical Review Authority and/or the Swedish Medical Products Agency before implementation. Nonsubstantial amendments that do not affect participant safety or trial integrity are documented in writing, dated, and filed in both the TMF and the ISF, with notification to relevant parties as required.\u003c/p\u003e\n\u003cp\u003eAll amendments are tracked through version control and documented in the Version history described in the Ethics approval, consent, and compliance section, ensuring full traceability of changes and their rationale. Updated versions of the CIP and related trial materials are distributed to all participating sites, and site staff are trained on the changes before implementation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeviations from the protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInvestigators may not deviate from the protocol except to protect a participant\u0026rsquo;s rights, safety, or well-being in emergency circumstances.\u003cbr\u003e\u0026nbsp;All such deviations must be documented with an explanation and reported to the sponsor representative as soon as possible. The sponsor representative will review the deviations and, when applicable, report them to the Swedish Medical Products Agency and/or the Swedish Ethical Review Authority.\u003c/p\u003e\n\u003cp id=\"_Toc200092617\"\u003e\u003cstrong\u003eInsurance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc200092598\"\u003eThe\u0026nbsp;participants\u0026nbsp;in\u0026nbsp;the\u0026nbsp;trial\u0026nbsp;will\u0026nbsp;be\u0026nbsp;covered\u0026nbsp;by\u0026nbsp;Swedish\u0026nbsp;Patient\u0026nbsp;Insurance and liability insurance.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEnd of the trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial will conclude when the last participant has completed the final scheduled visit (Visit 8 at the control clinics and Visit 23 at the intervention clinics; see Table 1 for the visit schedule). The sponsor representative will notify the Swedish Medical Products Agency within 15 days after the end of the trial and send the trial report within 1 year after the end of the trial, including an easily understandable summary.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial organization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial is being conducted at six psychosis outpatient clinics (sites) in Gothenburg. Each site has a PI and research assistant. The two intervention sites also share a health promoter. Together, these staff form the core research team, which is responsible for the integrity and progress of the trial.\u003c/p\u003e\n\u003cp\u003eRoles and Responsibilities:\u003c/p\u003e\n\u003cp\u003e\u0026bull; The main author of this article (HN) represents the sponsor, Region V\u0026auml;stra G\u0026ouml;taland, and serves as the coordinating investigator leading the project. HN oversees implementation, conducts interviews, performs data analysis and manuscript preparation, and holds regular site meetings.\u003c/p\u003e\n\u003cp\u003e\u0026bull; The PIs, specialist nurses in psychiatric care, coordinate site activities, maintain the ISF, and train CMs on trial procedures (e.g., eligibility screening, consent, physical exams). They also conduct interviews and manage delegation logs, training records, participant scheduling, and subject enrollment and identification logs. At intervention sites, PIs provide additional training on QRISK3, TANITA, and other intervention-specific routines. Duties may be delegated to co-PIs as needed.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Research assistants support data entry, error checking, eligibility screening, attendance tracking, trial material management, and sending out health check invitations. At intervention sites, they also handle transport logistics.\u003c/p\u003e\n\u003cp\u003e\u0026bull; The health promoter (intervention sites) coordinates bimonthly follow-up visits, which include physical examinations, patient scheduling, attendance tracking, and screening for adverse events. While the health promoter typically conducts these visits, other members of the clinical investigation team may perform them when needed, following training provided by the health promoter. Each visit includes cardiometabolic monitoring, motivational support, and guidance on individualized care adjustments. All bimonthly visits\u0026mdash;including cancellations\u0026mdash;are documented, and each consultation is categorized by focus area to support the evaluation of adherence and program fidelity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the time of the first manuscript submission, research ethics approval had been obtained for the trial. Participant enrollment began on 27 February 2025 at PC, the site of the coordinating investigator. Enrollment subsequently commenced at PH [27 February 2025], PM [5 March 2025], PVV [6 March 2025], PM\u0026Ouml; [16 September 2025], and PNO [17 September 2025]. Recruitment across all sites is expected to be completed by December 2026.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis investigator-initiated trial evaluates the effectiveness of LAGOM\u0026mdash;a multicomponent, real-world intervention\u0026mdash;in reducing cardiometabolic risk among individuals with psychotic disorders over 36 months. The core hypothesis is that a pragmatic, personalized program integrated into routine psychiatric care can lead to clinically meaningful improvements in cardiometabolic health. Delivered through outpatient psychosis clinics in Gothenburg, LAGOM comprises five key components: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) individualized, holistic cardiometabolic risk assessment that goes beyond isolated risk factor management; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) structured education for patients, relatives, and staff; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) risk-oriented referrals to primary healthcare to address underdiagnosis and undertreatment of cardiometabolic concerns; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) the use of visual motivational tools to strengthen patient engagement; and (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) regular follow-ups to reinforce continuity and adherence.\u003c/p\u003e \u003cp\u003eLAGOM was developed in response to persistent challenges in both research and clinical settings, particularly the underdiagnosis and undertreatment of cardiometabolic risk among individuals with psychotic disorders. Rather than creating new services, the intervention reorients existing workflows\u0026mdash;such as CM follow-ups and patient education\u0026mdash;toward systematic management of cardiometabolic and lifestyle-related health risks. Cardiometabolic risk is mapped using methods already employed in psychiatric care, and referrals align with regional protocols. Education sessions, previously focused on psychosis, are adapted to include lifestyle and cardiometabolic health. Similarly, staff training builds on existing professional development structures. The intervention fits within current roles, ensuring both scalability and sustainability. Personalized and integrated into daily practice, LAGOM aims to enhance early risk detection, patient engagement, and team capacity, potentially reducing morbidity, premature mortality, and healthcare costs. If superior to usual care, LAGOM has the potential to serve as a scalable model for addressing cardiometabolic health in one of mental healthcare\u0026rsquo;s most underserved and high-risk populations.\u003c/p\u003e \u003cp\u003eA central theoretical premise is that CVD risk factors interact synergistically rather than additively. Prior work has shown that combined risk factors have greater-than-additive effects on subclinical atherosclerosis and acute myocardial infarction risk. For example, Golden et al. reported that the combined effect of hypertension, hypertriacylglycerolemia, hyperinsulinemia, low HDL-C, and hyperglycemia resulted in an excess carotid intimal-medial thickness of 71 \u0026micro;m\u0026mdash;compared with an expected additive increase of only 55 \u0026micro;m\u0026mdash;indicating a synergistic impact on subclinical atherosclerosis (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). Similarly, the INTERHEART study found that the combination of smoking, diabetes, hypertension, elevated apoB/apoA1 ratio, and abdominal obesity increased the odds of acute myocardial infarction to 68.5, as opposed to an additive prediction of just 12.1 (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). This understanding\u0026mdash;of synergistic rather than additive effects\u0026mdash;forms one of the conceptual foundations of the LAGOM intervention and is particularly relevant for individuals with psychotic disorders, where metabolic syndrome and co-occurring CVD risk factors are highly prevalent (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Risk estimation tools such as SCORE2, along with monitoring whether an individual meets the criteria for metabolic syndrome, reflect this synergistic model by integrating multiple interacting risk factors into a single contextualized estimate. These approaches provide clinically meaningful ways to communicate overall cardiometabolic risk and facilitate shared understanding and decision-making between healthcare professionals and patients.\u003c/p\u003e \u003cp\u003eMotivation is the second cornerstone of LAGOM intervention, grounded in the capability, opportunity, motivation\u0026ndash;behavior (COM-B) model and self-determination theory (SDT). The intervention targets reflective motivation while supporting autonomy, competence, and relatedness (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). Education for patients and relatives clarifies the link between psychosis, lifestyle behaviors, and cardiometabolic risk, helping reduce resistance and build intentions by explaining \u003cem\u003ewhy\u003c/em\u003e change matters (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). Parallel staff training reinforces the rationale behind interventions, supporting both engagement and professional purposes.\u003c/p\u003e \u003cp\u003eLAGOM operationalizes SDT through concrete practices: competence is supported via small goals accepted by patients, tangible health metrics (e.g., laboratory results, physical examination results), and structured education; relatedness is fostered through warm, supportive clinical interactions and shared understanding; and autonomy is encouraged through choice-driven changes and non-coercive sharing of rationale. The evidence suggests that when people feel capable and understand the benefits of a behavior\u0026mdash;key aspects of empowerment\u0026mdash;internal motivation and long-term adherence improve (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). This foundation enables patients not only to understand the consequences of unhealthy habits but also to take ownership of change. The intervention draws from the \u0026ldquo;small steps\u0026rdquo; approach, where tiny, sustainable changes create behavioral momentum and long-term identity shifts (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e). This behavioral strategy emphasizes small, concrete, and achievable actions\u0026mdash;such as walking for five minutes instead of aiming for a full workout or reducing smoking by one cigarette rather than quitting abruptly\u0026mdash;to build self-efficacy and foster early success (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e). LAGOM intentionally avoids pressuring participants with population-level guidelines; instead, it makes behaviors more achievable by breaking them down and anchoring them in personally meaningful goals.\u003c/p\u003e \u003cp\u003eTo complement the motivational work, two visual and tangible tools\u0026mdash;QRISK3 and the TANITA body composition analyzer\u0026mdash;are included as exploratory supports for shared understanding and direct feedback. Although their motivational effect is not yet firmly established in this population, these tools may assist individuals with impaired executive functioning by simplifying complex health information, visually illustrating cardiometabolic risk, and providing structure to conversations between patients and healthcare professionals. QRISK3, in particular, offers a comprehensive risk assessment that highlights how modest improvements across multiple domains may yield meaningful long-term benefits. The integration of these tools builds on successful local experience with feedback-informed care, where a digital dashboard facilitated co-production between patients and healthcare professionals and enhanced patient engagement in health monitoring (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e).\u003c/p\u003e"},{"header":"Strengths and Limitations","content":"\u003cp\u003eThis trial has several strengths that enhance its clinical relevance, feasibility, and potential for real-world impact. It is grounded in well-established behavioral frameworks (COM-B and SDT) while being adapted to local workflows and organizational conditions in psychiatric outpatient care. Importantly, LAGOM targets both patients and healthcare professionals\u0026mdash;an uncommon dual approach that supports sustained behavior change, professional engagement, and intervention fidelity\u0026mdash;while also addressing the well-documented gap in awareness of the links between psychosis, lifestyle, and cardiometabolic health through structured education.\u003c/p\u003e \u003cp\u003eUnlike many previous trials that were short-term, narrowly focused, or dependent on resource-intensive strategies, LAGOM is designed as a long-term (36-month), scalable, and sustainable intervention integrated into routine psychiatric services. It emphasizes comprehensive, individualized cardiometabolic risk management rather than targeting isolated risk factors or single lifestyle behaviors. Broad inclusion criteria improve generalizability and ensure applicability to the diverse patients seen in everyday clinical practice. By repurposing existing roles and responsibilities\u0026mdash;such as CM follow-up, referral pathways to primary care, and patient education\u0026mdash;the intervention is achievable within standard patient-to-staff ratios and resource constraints. It also facilitates early detection and follow-up of cardiometabolic conditions by strengthening collaboration with primary healthcare, addressing underdiagnosis and undertreatment.\u003c/p\u003e \u003cp\u003eThe intervention is ecologically valid, as it operates within existing care structures without adding external personnel. Its personalized approach, which is aligned with each participant\u0026rsquo;s motivation, values, and readiness for change, enhances relevance and engagement. Contamination between groups is unlikely due to clear staff role separation, and the cluster design supports implementation fidelity across sites.\u003c/p\u003e \u003cp\u003eSome limitations warrant acknowledgment. The nonrandomized, cluster-assigned design introduces risks of selection bias, allegiance bias, and residual confounding. To mitigate these concerns, outcome models will include multivariable adjustments for prespecified baseline covariates (e.g., age, sex, baseline risk, and socioeconomic status). Although such adjustments cannot replace randomization or eliminate unmeasured confounding, they improve internal validity and strengthen interpretability.\u003c/p\u003e \u003cp\u003eIntervention sites were selected based on staff involvement, whereas control clinics continued with usual care. Although this limits causal inference, it enhances feasibility and reflects the complexities of real-world care. Rather than isolating individual variables\u0026mdash;which is often neither feasible nor meaningful in this context\u0026mdash;LAGOM assesses the combined effect of interrelated components embedded in routine practice. This approach provides insight into associations rather than isolated efficacies.\u003c/p\u003e \u003cp\u003eA subtle limitation is that standardizing data collection via worksheets may unintentionally influence practice. Although protocols remain unchanged, the act of documenting cardiometabolic questions could prompt more proactive management.\u003c/p\u003e \u003cp\u003eIn summary, while LAGOM\u0026rsquo;s design limits causal inference, it supports feasibility testing, strengthens fidelity, and aligns with everyday clinical practice. The trial offers important insights into embedding structured lifestyle interventions within health services for a high-risk population. If superior to usual care, LAGOM may improve quality of life, reduce premature mortality, and provide a scalable, practice-embedded model for cardiometabolic prevention within routine psychiatric care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTerm/Explanation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eAlanine Aminotransferase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eALP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eAlkaline Phosphatase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eAspartate Aminotransferase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eAUDIT-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eAlcohol Use Disorders Identification Test - Consumption\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eBody mass index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eCIP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eClinical Investigation Plan\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eCM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eCase manager\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eCOM-B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eCapability, Opportunity, Motivation \u0026ndash; Behavior\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eCVD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eCardiovascular disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eDBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eDiastolic blood pressure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eDMP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eData Management Plan\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eeCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eElectronic Case Report Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eEDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eElectronic Data Capture\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eEQ-5D-5L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eEQ: EuroQol (the research group that developed it); 5D: Five Dimensions of health; 5L: Five Levels of severity for each dimension\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003efP-TAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003efasting plasma triacylglycerol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eFIML\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eFull Information Maximum Likelihood\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eGCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eGood Clinical Practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eHbA1c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eHemoglobin A1c, also known as glycated hemoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eHDL-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eHigh density lipoprotein-cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ehs-CRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eHigh-sensitivity C-reactive protein\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eICD-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eInternational Classification of Diseases, Tenth Revision.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eICER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eIncremental cost-effectiveness ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eICH-GCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eInternational Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use-\u0026nbsp;Good Clinical Practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eISF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eInvestigator Site File\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eLAGOM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eLongitudinal Approach to Generate positive cardiometabolic health Outcomes in severe Mental illness\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eMAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eMissing At Random\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eMCAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eMissing Completely At Random\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eMultiple Imputation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eMNAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eMissing Not At Random\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003ePsychosis outpatient clinic Centrum\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003ePsychosis outpatient clinic Hisingen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003ePrincipal Investigator\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eParticipant Information Sheet\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003ePsychosis outpatient clinic M\u0026ouml;lndal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePM\u0026Ouml;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003ePsychosis outpatient clinic \u0026Ouml;ster\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003ePsychosis outpatient clinic Nordost\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003ePVV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003ePsychosis outpatient clinic V\u0026auml;ster\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eQALYs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eQuality-Adjusted Life Years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eR-ACT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eResource-group Assertive Community Treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eREDCap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eResearch Electronic Data Capture\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eSAEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eSerious Adverse Events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eSBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eSystolic blood pressure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eSCORE2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eSystematic COronary Risk Evaluation 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eSDT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eSelf-Determination Theory\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eTChol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eTotal cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eTMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eTrial Master File\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3841%;\"\u003e\n \u003cp\u003eWHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.6159%;\"\u003e\n \u003cp\u003eWaist-hip ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial is conducted in accordance with the CIP, the ethical principles of the Declaration of Helsinki, the principles of SS-EN ISO 14155:2020, and all applicable national and international regulations. These measures ensure both participant safety and data quality. The trial commenced only after the required regulatory and ethical reviews were completed with non-negative outcomes, in compliance with the Medical Device Regulation (MDR) and national legislation. Any additional requirements imposed by the Ethics Committee or regulatory authorities are implemented accordingly.\u003c/p\u003e\n\u003cp\u003eThe protocol (version 2.0), worksheets, PISs, informed consent forms, and all other trial materials were approved by the Swedish Medical Products Agency on 6 November 2024 (Dnr: 5.1-2024-92319) and the Swedish Ethical Review Authority on 18 December 2024 (Dnr: 2024-07362-01). The first substantial amendment to the protocol (version 3.0/Amendment 1), which replaces version 2.0, was approved by the Swedish Ethical Review Authority on 25 June 2025 (Dnr: 2025-04238-02) and by the Swedish Medical Products Agency on 1 July 2025 (Dnr: 5.1-2024-92319 [5.1.1-2025-050512]).\u003c/p\u003e\n\u003cp\u003eIndividual written informed consent to participate is obtained from all eligible patients prior to enrollment. All clinical investigation team members received training in Good Clinical Practice (GCP) and trial procedures before initiating data collection. The trial is registered at ClinicalTrials.gov (NCT06781801; date registered: 16 January 2025).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDissemination policy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial is registered at ClinicalTrials.gov, and summary-level results will be submitted for publication in peer-reviewed scientific journals. The first results are expected to be available in 2027. Findings will also be shared at national and international conferences, through meetings with regional health authorities, and via various media channels.\u003c/p\u003e\n\u003cp\u003eTrial participants are informed that they may obtain trial results through the site\u0026rsquo;s PI once available. The trial also includes collaboration with the Schizophrenia Association in Gothenburg to facilitate communication of results to broader audiences.\u003c/p\u003e\n\u003cp\u003eAll abstracts and publications will adhere to the authorship criteria recommended by the International Committee of Medical Journal Editors (ICMJE).\u003c/p\u003e\n\u003cp\u003eThe full trial CIP is available at ClinicalTrials.gov (NCT06781801).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with the trial\u0026rsquo;s CIP, individual participant data from this trial are not publicly available due to privacy and data protection regulations. All data are handled in compliance with the General Data Protection Regulation (EU 2016/679; GDPR) and relevant Swedish legislation, and are stored securely at Region V\u0026auml;stra G\u0026ouml;taland. Participants in the trial are coded with a specific record ID.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests. This\u0026nbsp;is\u0026nbsp;an\u0026nbsp;investigator-initiated\u0026nbsp;trial\u0026nbsp;without\u0026nbsp;any\u0026nbsp;assistance\u0026nbsp;or\u0026nbsp;input\u0026nbsp;from\u0026nbsp;any company.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial has received funding from the Gothenburg Society of Medicine, Sahlgrenska University Hospital\u0026rsquo;s (SU) foundations, and the Wilhelm and Martina Lundgren Science Fund. The trial is sponsored by Region V\u0026auml;stra G\u0026ouml;taland. The sponsor and funders have no influence on the trial design, conduct, data analysis or interpretation, manuscript writing, or dissemination of results. The funders have no direct involvement in the trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHN, EJ, ZZ, and ChHo conceived the trial design, selected outcome measures, developed the statistical analysis plan, and secured funding. EJ conceptualized and led the health economic evaluation. CaHo, ChHa, ESB, EW, EA, and LK served as site leaders (PIs), overseeing all aspects of trial implementation, supported by research assistants AO, CKB, EH, NK, and SH. Material preparation and data collection were carried out by HN, AO, CaHo, CKB, ChHa, ESB, EH, EW, EA, JG, LK, NK, and SH. AF, LL, LR, and PR provided expert intellectual input to refine and finalize trial implementation. LR also supported submissions to the Swedish Medical Products Agency and the Swedish Ethical Review Authority. HN drafted the initial manuscript, incorporating critical feedback from all co-authors. All authors have read, edited, and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are sincerely grateful to all participants and to the staff at the six psychosis outpatient clinics in Gothenburg for their essential contributions to this research. We thank the members of the Schizophrenia Association in Gothenburg for their valuable input on the intervention flowchart, brochure, and the development and revision of the worksheet prior to the start of the trial. They also reviewed the content and structure of the educational sessions for participants and their relatives.\u003c/p\u003e\n\u003cp\u003eWe would like to thank Kristina Annerbrink for her support in engaging physicians across all trial sites, and Catharina Jedenius, who served as care unit manager at PC and PM at the start of the trial, for her key role in enabling trial feasibility across the intervention clinics. We also extend our appreciation to all care unit managers\u0026mdash;Jennie Culbert, Matilda Hansson, Mickela Larsson, Maria Persson, and Marie Wennergren\u0026mdash;for their efforts in facilitating the implementation of the trial across their respective sites.\u003c/p\u003e\n\u003cp\u003eWe also acknowledge Specialist Nurse in Psychiatric Care Lisa Magnusson and Physiotherapist Martina Gustafsson for their contributions to the initial draft of the trial brochure.\u003c/p\u003e\n\u003cp\u003eWriting assistance was provided using ChatGPT and Copilot.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDruss BG, Zhao L, Von Esenwein S, Morrato EH, Marcus SC. Understanding excess mortality in persons with mental illness: 17-year follow up of a nationally representative US survey. 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Uppsala: Livsmedelsverket; 2009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePopulation statistics on 31st December. 2024 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.scb.se/en/finding-statistics/statistics-by-subject-area/population-and-living-conditions/population-composition-and-development/population-statistics/pong/tables-and-graphs/population-statistics---year/population-in-the-country-counties-and-municipalities-on-31-december-2024-and-population-change-in-2024/\u003c/span\u003e\u003cspan address=\"https://www.scb.se/en/finding-statistics/statistics-by-subject-area/population-and-living-conditions/population-composition-and-development/population-statistics/pong/tables-and-graphs/population-statistics---year/population-in-the-country-counties-and-municipalities-on-31-december-2024-and-population-change-in-2024/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e: Statistics Sweden; 2024 [updated February 21st, 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNord\u0026eacute;n T, Malm U, Norlander T. 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Diabetes. 2002;51(10):3069\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015;14(3):339\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichie S, van Stralen MM, West R. The behaviour change wheel: a new method for characterising and designing behaviour change interventions. Implement Sci. 2011;6:42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyan RM, Deci EL. Self-determination theory and the facilitation of intrinsic motivation, social development, and well-being. Am Psychol. 2000;55(1):68\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeci EL, Ryan RM. Self-determination theory: A macrotheory of human motivation, development, and health. Can Psychol. 2008;49(3):182.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFogg BJ. Tiny habits: The small changes that change everything. Harvest; 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFogg BJ, editor. A behavior model for persuasive design. Proceedings of the 4th international Conference on Persuasive Technology; 2009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGremyr A, Holmberg C, Thor J, Malm U, G\u0026auml;re BA, Andersson AC. How a point-of-care dashboard facilitates co-production of health care and health for and with individuals with psychotic disorders: a mixed-methods case study. BMC Health Serv Res. 2022;22(1):1599.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":" \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eSchedule of enrollment, interventions, and assessments\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCollected data\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eBaseline\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eEvery\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e12\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eEvery\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e24\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eEvery\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e36\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eother\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003emonths\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eother\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003emonths\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eother\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003emonths\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003emonth\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026plusmn;\u0026thinsp;60\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003emonth\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026plusmn;\u0026thinsp;60\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003emonth\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026plusmn;\u0026thinsp;60\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026plusmn;\u0026thinsp;14\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003edays\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026plusmn;\u0026thinsp;14\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003edays\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026plusmn;\u0026thinsp;14\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003edays\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003edays\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003edays\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003edays\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e8\u0026thinsp;+\u0026thinsp;9*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e15\u0026thinsp;+\u0026thinsp;16*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e22\u0026thinsp;+\u0026thinsp;23*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3\u0026ndash;7*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e10\u0026ndash;14*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e17\u0026ndash;21*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisits\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3\u0026thinsp;+\u0026thinsp;4\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5\u0026thinsp;+\u0026thinsp;6\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7\u0026thinsp;+\u0026thinsp;8\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisit 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVisit 2\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e#\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCheck for eligibility\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInformed consent\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInquire about adverse event*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSocial and background questions\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMedical anamnesis\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eQuestions about participation in educational sessions and lifestyle sessions*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLifestyle questionnaires\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Alcohol habits according to AUDIT-C\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Tobacco habits\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Dietary habits\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Physical activity\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eBlood tests\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-high-sensitivity CRP (mg/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003efP-Triacylglycerol (mmol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-HDL-cholesterol (mmol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-LDL-cholesterol (mmol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-Total cholesterol (mmol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-non-HDL-cholesterol (mmol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003efP-Glucose (mmol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eB-HbA1c (mmol/mol)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-Kreatinin (\u0026micro;mol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-ALT (\u0026micro;kat/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-AST (\u0026micro;kat/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-ALP (\u0026micro;kat/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eP-bilirubin (\u0026micro;mol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePhysical examination\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eHeight (cm)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWeight according to SECA 799 (kg)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWaist circumference (cm)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eHip circumference (cm)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eSystolic blood pressure mmHg\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDiastolic blood pressure mmHg\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePulse (bpm)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAssessment scales\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eEQ-5D-5L\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eFulfillment of criteria of metabolic syndrome*\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eSCORE2*\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eQRISK3*\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMeasurements according to TANITA body composition analyzer*\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Weight (kg)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Total body fat mass (kg)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Total body water mass (kg)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Total body muscle mass (kg)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Bone mass (kg)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026bull; Metabolic age\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e*\u003c/span\u003e Only intervention clinics.\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e# Visit 2 complements Visit 1 by ensuring completeness of the data collected during the first visit. This allows the physician to base decisions on a full assessment. Eligibility screening is always completed during Visit 1, while informed consent may be obtained at either Visit 1 or Visit 2.\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e\n\u003cp\u003eTable 2. Sample size calculation per group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003eStandard deviation (reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003eExpected mean difference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003eSignificance level (two-tailed)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003ePower (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003eExpected dropout (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003eRequired Sample Size (Intervention Group)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003eRequired Sample Size (Control Group)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eWHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003e0.08 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003e125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003e389\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003e4.5 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003e157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003e487\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eSBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003e14.4 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eDBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003e9 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003e157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003e487\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eTAG/HDL-C ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003e0.9 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eTChol/HDL-C ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003e1.1 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15.257%;\"\u003e\n \u003cp\u003eGlucose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7695%;\"\u003e\n \u003cp\u003e0.8 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9353%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.4279%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.1111%;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6036%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7745%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.12106%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Psychotic disorders, cardiometabolic risk factors, behavior change intervention, multicomponent intervention, integrated health care, pragmatic clinical trial, metabolic syndrome, cardiovascular disease prevention, quality of life, cost-effectiveness","lastPublishedDoi":"10.21203/rs.3.rs-7972355/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7972355/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCardiometabolic conditions\u0026mdash;including cardiovascular disease, type 2 diabetes, and obesity\u0026mdash;are highly prevalent among individuals with psychotic disorders. These conditions contribute substantially to reduced life expectancy, diminished quality of life, and increased societal and economic burdens. Thus, effective, individualized interventions are urgently needed. Outpatient psychiatric clinics offer an ideal setting for such efforts owing to regular patient contact and access to multidisciplinary care. We have developed a comprehensive, clinically integrated program aimed at improving cardiometabolic health, promoting healthier lifestyles, and enhancing quality of life for individuals with psychotic disorders receiving care in Gothenburg.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eLAGOM is a multicenter, naturalistic, quasi-experimental case‒control trial. A total of 644 adults with psychotic disorders will be recruited from six outpatient clinics at the Department of Psychotic Disorders, Sahlgrenska University Hospital. Two clinics will implement the LAGOM intervention, whereas four will serve as control sites delivering usual care. The intervention is embedded within routine psychiatric care and grounded in behavioral science. It includes comprehensive cardiometabolic risk assessments, two visual motivational tools (QRISK3 and a body composition analyzer), personalized follow-up plans, risk-oriented referrals to primary healthcare, and structured education for patients, relatives, and staff. The intervention is designed to be scalable, sustainable, and tailored to individual patient needs.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eIf proven superior to usual care, this pragmatic, multicomponent intervention\u0026mdash;delivered within routine psychiatric care\u0026mdash;could improve cardiometabolic health and quality of life for individuals with psychotic disorders. Embedding the intervention within existing clinical structures enhances its scalability and feasibility and, if effective, could serve as a model for wider implementation.\u003c/p\u003e\u003ch2\u003eTrial status\u003c/h2\u003e \u003cp\u003erecruitment started on 27 February 2025 and will be completed on 31 December 2026. The current clinical investigation plan version is 3.1, dated 21 October 2025.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eClinicalTrials.gov (NCT06781801; date registered: 16 January 2025).\u003c/p\u003e","manuscriptTitle":"Multicenter, cluster-based, superiority trial of a multicomponent lifestyle intervention versus usual care for reducing cardiometabolic risk in individuals with psychotic disorders over 36 months: the LAGOM protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 09:47:00","doi":"10.21203/rs.3.rs-7972355/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-28T09:02:38+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"308814419378115890196996853007406336547","date":"2026-02-17T15:43:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-16T12:55:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"74542196007145289291831893348929147926","date":"2026-02-05T13:29:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-04T19:18:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"302634672469199800897408722027766950178","date":"2026-02-02T17:55:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"235772272229449176520473371486329214838","date":"2026-01-27T08:56:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"186468506535929819911970687989841661909","date":"2026-01-21T12:55:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-16T06:25:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-30T10:19:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-30T10:17:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2025-10-28T16:42:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"801a188e-f2af-40d8-b646-2914c474ad6c","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-14T05:53:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-20 09:47:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7972355","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7972355","identity":"rs-7972355","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}