Could Chinese cardiovascular chronic conditions patients gain benefits from pharmaceutical services? A multilevel meta-analysis

Could Chinese cardiovascular chronic conditions patients gain benefits from pharmaceutical services? 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A multilevel meta-analysis Zhijie Deng , Fanglu Chen , Shunshun Peng , Lin Gui , Yangjin Huang , Jing Chen , Anhua Wei , Yufeng Ding doi: https://doi.org/10.1101/2024.07.25.24310734 Zhijie Deng 1 Department of Pharmacy, Tongji Hospital, Tongji medical College, Huazhong University of Science and Technology , Wuhan, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site Fanglu Chen 2 School of Statistics, Renmin University of China , Beijing, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shunshun Peng 1 Department of Pharmacy, Tongji Hospital, Tongji medical College, Huazhong University of Science and Technology , Wuhan, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lin Gui 1 Department of Pharmacy, Tongji Hospital, Tongji medical College, Huazhong University of Science and Technology , Wuhan, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yangjin Huang 3 School of Management, Huazhong University of Science and Technology , Wuhan, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jing Chen 1 Department of Pharmacy, Tongji Hospital, Tongji medical College, Huazhong University of Science and Technology , Wuhan, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site Anhua Wei 1 Department of Pharmacy, Tongji Hospital, Tongji medical College, Huazhong University of Science and Technology , Wuhan, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ahwei0716{at}163.com yfding463{at}163.com Yufeng Ding 1 Department of Pharmacy, Tongji Hospital, Tongji medical College, Huazhong University of Science and Technology , Wuhan, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ahwei0716{at}163.com yfding463{at}163.com Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Background The value of pharmaceutical services for Chinese patients with cardiovascular chronic conditions was not recognized. Aim To investigate the comprehensive value of pharmaceutical services in China and find factors influencing patient benefits. Design and setting This was a systematic review with multilevel meta-analysis of 183 randomized control trials focusing on the benefits of pharmaceutical services for patients with cardiovascular chronic conditions in China. Methods English databases (PubMed, EMBASE, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, WanFang database) were searched from database inception to March 27, 2023 for studies focusing on the comparation of benefits between pharmaceutical services and usual care. Results Our analysis of 187 studies involving 23,895 patients demonstrated significant benefits of pharmaceutical services, particularly in reducing readmission (OR: 0.32; 95%CI: 0.2 to 0.52; I2=50.12%), mitigating ADR (OR: 0.28; 95%CI: 0.24 to 0.33; I2=18.07%), and improving patient adherence. However, no benefit was observed in terms of mortality rate and the cost of hospitalization and medication and the risk of bias was generally existed among the included studies. Conclusions This study highlights the significant benefits of pharmaceutical services for clinical outcomes and adherence among Chinese patients with cardiovascular chronic conditions. However, the benefits in terms of economic outcomes remain unclear. The influence of population-specific factors, such as disease and age, underscores the need for context-specific and disease- tailored studies to provide precise evidence regarding the advantages of pharmaceutical services. And our findings provide some new ideas for the subsequent research and design, standard formulation and policy implementation. How this fits in Previous assessments showed clinical benefits of pharmaceutical services but were unclear about other benefits and didn’t consider patient characteristics or contexts. There is no standardized system for pharmaceutical services in China. Our meta-analysis found clear clinical benefits for patients with cardiovascular chronic conditions and showed that age negatively impacts adherence, and medication costs vary by disease type. This study is the first to analyze comprehensive benefits for Chinese patients, highlighting the importance of considering patient characteristics in pharmaceutical services. INTRODUCTION The concept of pharmaceutical care, introduced in 1990( 1 ), revolutionized the healthcare system by promoting pharmacist-led interventions in clinical practice such as medication therapy management (MTM) and medication review. These interventions have shown potential in reducing drug-related problems, lowering healthcare costs, and decreasing healthcare utilization( 2 , 3 ). However, variability in results across countries and diseases has challenged the notion of universal benefits from pharmaceutical services, highlighting the need for studies focusing on specific contexts. In the US, where pharmaceutical services originated( 4 ), their development was guaranteed by governmental support and developmental pace. While in China, though the government recognized the value of pharmaceutical services in the early 21st century and established the zero-markup drug policy to significantly altered the financial landscape by reducing hospital profits from medication sales( 5 , 6 ). Recent policies have encouraged hospitals to establish pharmacist service standards and fees, resulting in the proliferation of pharmaceutical services in most tertiary hospitals( 7 – 9 ). As pharmaceutical services in China progressively matured, research emerged demonstrating their positive impact on Chinese patients( 10 – 13 ). While research has shown their positive impact on Chinese patients, comprehensive integrative studies with high-quality evidence remain limited, hindering the full recognition and development of pharmaceutical services in China. Given the significant benefits of pharmaceutical services for patients with chronic conditions( 14 – 16 ) and the rapidly increasing number of patients with cardiovascular chronic conditions in China( 17 ), our study focused on these patients. The services aim to promote rational medication use, stabilize conditions, and provide basic healthcare( 18 , 19 ). However, evidence on the specific efficacy of these services for cardiovascular patients and the appropriate scale of service fees is lacking. Therefore, our main objective was to comprehensively analyze the efficacy of pharmaceutical services for patients with cardiovascular chronic conditions in China, provide robust evidence supporting their efficacy, and explore the relationship between economic outcomes and service fee scales. METHODS Following the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement( 20 ), this systematic review and meta-analysis was conducted after the registration in PROSPERO (Registered ID: CRD42023414180). Search strategies and selection criteria With predetermined search strategies, databases in both English (PubMed, EMBASE, the Cochrane Library) and Chinese (China National Knowledge Infrastructure (CNKI), WanFang database) were systematically retrieved from database inception to March 27, 2023. One experienced researcher refined the search terms to fit the requirements of every database (Supplement S1). The main keywords included: “Medication Therapy Management”, “Pharmaceutical Services”, “Medication Reconciliation”, “Pharmacists” and “Cardiovascular chronic conditions”. The search process was conducted by two independent researchers following the selection criteria. Studies meeting following criteria would be included: Study design should be randomized control trial (RCT) study. Participants: Patients with cardiovascular chronic conditions receiving pharmaceutical services. Intervention: Pharmaceutical services. Due to the early stage of development of pharmaceutical services in China, the definition of pharmaceutical services varied. To obtain a comprehensive analysis, the inclusion of pharmaceutical services covered several interventions, including MTM service, medication reconciliation and pharmacist-led services. Comparison: Patients in control group receiving usual care. Outcomes: Including three parts of outcomes: the clinical benefits outcome (the rate of readmission, mortality and adverse drug event (ADE), and length of stay in hospital) and economic outcome (cost of hospitalization and medication cost) and evaluation of adherence. Studies meeting following criteria were excluded: No control group in the study. Animal experiments. Protocol and feasibility studies. Study selection and data extraction Two independent researchers conducted study selection and data extraction process with predetermined eligibility criteria. A form in Excel (Microsoft Office 365 ver.2306) was developed to extract data from studies. Following information and data would be extracted: 1) basic information (study title, first author, publication year); 2) study population (age, sample size, description of participants, diseases); 3) details of interventions and comparison; 4) outcomes and 5) the length of follow-up time. The cost data from studies before 2023 would be discounted at a 5% discount rate until 2023. Any disagreement in process would be solved by consultation with a third expert. Quality assessment In accordance with the Cochrane Handbook for Systematic Reviews of Interventions (version 6.3)( 21 ), the risk of bias in RCTs was assessed using the Risk of Bias 2 tool( 22 ). And the figure of traffic light plots was illustrated by the tools of robvis( 23 ). In cases of disagreement, a consensus was reached through discussion or by consulting a third expert to solve the disagreement. Statistical analysis The continuous variables were presented as mean (± standard deviation), and categorical variables were presented by counting the number of observed events. Effect sizes were represented as odd ratios (OR) for the binary endpoints and mean differences (MD) for the continuous endpoints. Given the nested structure of our data, where multiple studies are contained within disease clusters, we performed a three-level meta-analysis to account for this hierarchy. We focused on the statistical values of the estimates (OR/MD) and their 95% confidence intervals (CI). This approach allowed us to consider studies nested within diseases. The three-level model included three variance components( 24 ): sampling variation of effect size at level 1, within-cluster variation (effect sizes from a cluster) at level 2, and between-cluster variation at level 3. This model captures both within-cluster and between- cluster heterogeneity, which we assessed using the I² statistic (% of total variance) and Cochran’s Q test. To further explore sources of heterogeneity, we conducted a moderator analysis based on the three-level meta-analytic model. Covariates included the mean age of participants, duration of follow-up, economic status of the region where pharmaceutical services were received, and the type of pharmaceutical services. For moderators with multiple strata, we conducted multiple comparisons to identify intergroup differences on a pairwise basis. Multilevel meta-analysis and moderator analysis were conducted with R version 4.3.2 using the metafor package 4.2-0 and dmetar package 0.1.0. Code of covariables Covariables included the mean age of participants in the study, the duration of follow up, the economic status of the region where pharmaceutical services are received, and the type of the pharmaceutical services. The mean age of participants was classified as less than 45 years old, 45-60 years old, 60-90 years old and unknown. The duration of follow up was classified as less than 3 months, 3-9 months, more than 9 months and unknown. The economic status was defined by human development index (HDI) 2021 in China and classified as higher or lower than the average of China( 25 ). The type of pharmaceutical services was classified as pharmacist-led pharmaceutical interventions (PI), pharmaceutical care (PC), medication therapy management (MTM) and medication reconciliation (MR). RESULTS Study selection The process of study selection was showed on PRISMA flow diagram ( Fig.1 ). Finally, a total of 187 studies met the predetermined inclusion criteria and was included for qualitative and quantitative analysis. Download figure Open in new tab Study characteristics The basic information of studies was showed in a baseline table (see Supplement S2). 23384 participants were involved in 184 studies, with 11689 in intervention group and 11695 in control group. 8 studies conducted MTM services, 85 studies conducted pharmacist-led pharmaceutical interventions (PI), 90 studies conducted pharmaceutical care (PC), and only one study carried out medication reconciliation (MR). 6 kinds of cardiovascular chronic conditions were included: 1) Diabetes Mellitus (n=88); 2) Hypertension (n=49); 3) Heart Failure (n=10); 4) Coronary Disease (n=4); 5) Myocardial Infarction (n=4); 6) Hypercholesterolemia (n=3). And there were 26 studies focusing on patients with multi-disease, like patients with hypertension and diabetes mellitus, or other kinds of disease complicating with cardiovascular chronic conditions. The location of study included 31 provinces and special administrative regions which covered almost the whole China. And the most of studies (n=124) took place in economically developed provinces of East China. Rate of readmission, mortality, adverse drug reactions (ADR), adherence rate, length of stay, hospitalization costs, medication costs, and adherence measured by the MMAS-8 were finally included in the quantitative analysis. Bias assessment The risk of bias assessment showed that approximately 85% of studies had some concerns of the bias, 8% showed high risks of bias and 7% of low risks of bias ( Fig.2 ). Traffic light plots was presented in Supplement S3. The results showed that the process of randomization in most of studies existed difficulties on generating the concealed allocation sequence. Besides, the secondary risk was from the measurement of the outcomes owing to that some studies failed to avoid the influence of intervention to assessment of the outcome. Download figure Open in new tab Outcomes with disease clusters According to the results of our multilevel meta-analysis ( Fig.3 ), patients received pharmaceutical services could significantly reduce the rate of readmission (OR: 0.32; 95%CI: 0.2 to 0.52; I 2 =50.12%), ADR (OR: 0.28; 95%CI: 0.24 to 0.33; I 2 =18.07%) and shorten the length of stay in hospital (MD: -1.34; 95%CI: -2.23 to -0.45; I 2 =47.4%), while the effect of reducing rate of mortality remained unclear (OR: 0.55; 95%CI: 0.27 to 1.12; I 2 =0%). In evaluation of adherence, our meta-analysis showed a significant result for improving both adherence rate (OR: 5.05; 95%CI: 4.35 to 5.86; I 2 =36.22%) and scores of MMAS-8 (MD: 1.24; 95%CI: 0.79 to 1.7; I 2 =97.76%). However, as for economic outcomes with high heterogeneity, pharmaceutical services were seemed having less effective than clinical outcomes. Download figure Open in new tab The results of subgroup analysis ( Fig. 4 - 6 ) showed that the disease was one of the sources of heterogeneity for rate of readmission (p=0.014), adherence of MMAS-8 (p< 0.0001), cost of hospitalization (p=0.0082) and medication cost (p<0.0001). And these results were consistent with our multilevel analysis that most of heterogeneity were in L3, which meant to heterogeneity from clusters. Download figure Open in new tab Download figure Open in new tab Download figure Open in new tab Moderator Analysis According to the results of moderator analysis, though the most of results showed that predetermined moderator variables had no effect on these outcomes ( Table 1 ), there were some results showing that the age group was one of the moderator variables for length of stay (p=0.023) and adherence evaluation with MMAS-8 (p=0.0001), HDI was for adherence evaluation with MMAS-8 (p=0.027) and the type of intervention was for medication cost (p=0.031). Additionally, for moderators that encompass multiple levels, such as the type of service, which includes options like MR, MTM, PC, and PI, we conducted multiple comparisons to determine which two specific levels significantly different from each other. Presented below are the outcomes of these comparisons, highlighting the significant differences observed. View this table: View inline View popup Table 1 Results of moderator analysis These results underscore the importance of considering multiple levels within moderator variables to understand the nuances in how different services, age groups, and other factors can influence the outcomes of interest. DISCUSSION Summary The outcomes of our meta-analysis distinctly affirm the manifold advantages associated with pharmaceutical services led by pharmacists for individuals contending with cardiovascular chronic conditions, which is consistent with extant literature. Moreover, our multilevel and moderator analyses unveil that patients with diverse cardiovascular conditions accrue comparable clinical benefits. Further, the medication cost exhibits susceptibility to variations contingent upon type of disease, while adherence rates manifest a discernible correlation with the patient’s age. These discernments underscore the imperative for future investigations to account for patient-specific characteristics, as divergent profiles may engender varying degrees of benefit. Strengths and limitations To our best knowledge, this is the first meta-analysis with multilevel model to evaluate the comprehensive value of pharmaceutical services in China. Our study confirmed this value for Chinese patients with cardiovascular chronic conditions and indicated that patients’ characteristics, such as disease and age, could significantly influence the benefits patients could gain from these services. Our study has several limitations. Firstly, despite comprehensive search strategies, the omission of studies was inevitable. Gray literature and ongoing clinical trials were not included. Secondly, due to the nascent stage of pharmaceutical services development in China, high-quality studies, particularly economic evaluations, were scarce. Many studies had issues with randomization and outcome measurement, complicating the implementation of double- blinding due to the subjective nature of the intervention. Thirdly, although we aimed to include numerous moderators to explore the relationship between benefits and population characteristics, the quality and number of studies restricted us to a limited set of moderators. Finally, while our protocol considered including multiple diseases, the study focused on patients with cardiovascular chronic conditions due to the limited availability of studies, which may affect the generalizability of our findings. Comparison with existing literature Previous studies( 2 , 3 , 26 – 28 ) had highlighted the clinical advantages of pharmaceutical services demonstrating reductions in readmission rates, improvements in overall patient health, and effective management of drug-related problems. Patients with cardiovascular chronic conditions face complex and lifelong treatment regimens, leading to challenges such as poor adherence, undertreatment, and low control rates( 29 , 30 ). A 12- month observational study showed a 32.9% reduction in readmission rates for the group receiving pharmaceutical services compared to the control group( 31 ). A systematic review confirmed the significant role of pharmaceutical care in improving health outcomes for these patients( 32 ). While the benefits of pharmaceutical services extend to various diseases, the magnitude varies with disease complexity, reinforcing the overall positive impact on patient outcomes and healthcare efficiency( 33 – 35 ). Our multilevel analysis aligns with these study findings, showing no significant differences between different cardiovascular chronic conditions, suggesting similar benefits from pharmaceutical services across this category( 19 , 36 , 37 ). This supports the idea that patients with cardiovascular conditions can be treated as a unified group for future medical insurance payment policies, similar to diagnosis-related groups (DRG)( 38 , 39 ). However, the determination of mortality rates led to less conclusive results, echoing previous research( 3 , 40 ). Future studies should consider longer follow-up periods to better understand the impact of pharmaceutical services on mortality rates. Despite the clinical benefits, translating these into clear pharmacoeconomic benefits has been challenging. High-quality studies are lacking, and previous research has produced mixed conclusions. In developed countries with established pharmaceutical services and payment systems, studies have shown pharmacoeconomic benefits. For example, a US cost-effectiveness analysis of pharmacist-led MTM for hypertension found an incremental cost-effectiveness ratio of $38,798 per QALY gained( 41 ). In contrast, in China, where pharmaceutical services and payment systems are still developing, the pharmacoeconomic benefits remain unclear. Some studies suggest cost reductions from pharmaceutical interventions, but these conclusions are often based on free services and lack adequate follow-up and a complete payment system( 42 – 44 ). The Chinese government is addressing these challenges with initiatives like Integrated Medicare Payment Methods to promote fair payment for pharmaceutical services( 45 ). In addition to clinical and economic outcomes, pharmaceutical services positively impact patient adherence, crucial for those with cardiovascular conditions requiring multiple medications and lifelong treatment. Improved adherence can lead to better disease control and subsequent clinical and economic benefits. Studies have shown that pharmaceutical interventions can increase the odds of optimal adherence by 8%, reducing readmission rates and adverse drug reactions( 46 ). Our findings, consistent with previous research( 47 – 50 ), indicate that pharmaceutical services significantly improve drug adherence and health outcomes. However, age influences these benefits, with older patients facing challenges in adhering to complex regimens, underscoring the need to consider age when implementing pharmaceutical services to ensure all age groups benefit fully( 51 , 52 ). Future high-quality studies are necessary to further understand the impact of pharmaceutical services on adherence and patient outcomes( 19 , 53 , 54 ). Recognizing the complexity of patient adherence behaviors, future high-quality studies in this domain are necessary to further understand the impact of pharmaceutical services on adherence and patient outcomes. Implications for research and practice Our investigation has yielded substantive evidence attesting to the advantageous effects of pharmaceutical services on patients grappling with cardiovascular chronic conditions in the Chinese context. These findings underscore a statistically significant enhancement in clinical outcomes attributable to these interventions. Nevertheless, a comprehensive comprehension of their ramifications on economic outcomes and patient adherence necessitates further exploration. The evidence of this study could help health authorities to construct standards and policies about Chinese pharmaceutical services model and promote the development of pharmaceutical services in China further. Data Availability All data produced in the present study are available upon reasonable request to the authors CONTRIBUTIONS Dr Wei had full access to all of the data included in this study and takes responsibility for the integrity of the data. Zhijie Deng and Fanglu Chen contributed equally as co–first authors. Anhua Wei: Conceptualization, investigation, project administration, writing – review & editing Zhijie Deng: Formal analysis, validation, writing – original draft Fanglu Chen: Methodology, software, visualization, writing – review & editing Shunshun Peng: Formal analysis, visualization Lin Gui: Data curation, software Yangjin Huang: Resources, data curation Jing Chen: Validation Yufeng Ding: Supervision, writing – review & editing Data sharing statement None reported. Declaration of interests All authors confirmed that there were no conflicts of interest to disclose. Acknowledgements None. References 1. ↵ Hepler CD , Strand LM . Opportunities and responsibilities in pharmaceutical care . Am J Hosp Pharm . 1990 ; 47 ( 3 ): 533 – 43 . OpenUrl Abstract 2. ↵ Viswanathan M , Kahwati LC , Golin CE , Blalock SJ , Coker-Schwimmer E , Posey R , et al. Medication therapy management interventions in outpatient settings: a systematic review and meta-analysis . JAMA Intern Med . 2015 ; 175 ( 1 ): 76 – 87 . OpenUrl 3. ↵ Deng ZJ , Gui L , Chen J , Peng SS , Ding YF , Wei AH . Clinical, economic and humanistic outcomes of medication therapy management services: A systematic review and meta- analysis . Front Pharmacol . 2023 ; 14 : 1143444 . 4. ↵ de Oliveira DR , Brummel AR , Miller DB . Medication Therapy Management: 10 Years of Experience in a Large Integrated Health Care System . J Manag Care Spec Pharm . 2020 ; 26 ( 9 ): 1057 – 66 . OpenUrl 5. ↵ Luan M , Shao X , Dou F . Financial conditions, health care provision, and patient outcomes: Evidence from Chinese public hospitals . Economics Letters . 2020 ; 186 : 108876 . 6. ↵ Zhang X , Lai H , Zhang L , He J , Fu B , Jin C . The impacts and unintended consequences of the nationwide pricing reform for drugs and medical services in the urban public hospitals in China . BMC Health Serv Res . 2020 ; 20 ( 1 ): 1058 . OpenUrl PubMed 7. ↵ Notice on trial implementation of pharmaceutical medical service price items 2023 [Available from: http://ylbzj.hebei.gov.cn/content/3000 . 8. Notice on trial implementation of pharmaceutical service charge policy in provincial public hospitals 2022 [Available from: http://ybj.fujian.gov.cn/zfxxgkzl/fdzdgknr/zcwj/202204/t20220414_5891649.htm . 9. ↵ Notice on the addition and revision of pharmaceutical medical service price items 2023 [Available from: http://ybj.hunan.gov.cn/ybj/first113541/firstF/f3113607/202310/t20231009_31641865.html . 10. ↵ Lu Z , Li Y , He Y , Zhai Y , Wu J , Wang J , et al. Internet-Based Medication Management Services Improve Glycated Hemoglobin Levels in Patients with Type 2 Diabetes . Telemedicine journal and e-health . 2021 ; 27 ( 6 ): 686 -93. OpenUrl 11. Wang X , Wang S , Yu X , Ma Z , Wang H , Yang J , et al. Impact of pharmacist-led medication therapy management in ambulatory elderly patients with chronic diseases . Br J Clin Pharmacol . 2021 ; 87 ( 7 ): 2937 – 44 . OpenUrl 12. Wu WC , Taveira TH , Jeffery S , Jiang L , Tokuda L , Musial J , et al. Costs and effectiveness of pharmacist-led group medical visits for type-2 diabetes: a multi-center randomized controlled trial . PloS one . 2018 ; 13 ( 4 ): e0195898 . OpenUrl CrossRef 13. ↵ Lin HW , Lin CH , Chang CK , Chou CY , Yu IW , Lin CC , et al. Economic outcomes of pharmacist-physician medication therapy management for polypharmacy elderly: a prospective, randomized, controlled trial . Journal of the Formosan Medical Association / Taiwan yi zhi . 2018 ; 117 ( 3 ): 235 -43. OpenUrl 14. ↵ Jia X , Zhou S , Luo D , Zhao X , Zhou Y , Cui YM . Effect of pharmacist-led interventions on medication adherence and inhalation technique in adult patients with asthma or COPD: A systematic review and meta-analysis . J Clin Pharm Ther . 2020 ; 45 ( 5 ): 904 – 17 . OpenUrl 15. Bennett MI , Bagnall AM , Raine G , Closs SJ , Blenkinsopp A , Dickman A , et al. Educational interventions by pharmacists to patients with chronic pain: systematic review and meta-analysis . Clin J Pain . 2011 ; 27 ( 7 ): 623 – 30 . OpenUrl CrossRef PubMed Web of Science 16. ↵ Ruiz-Ramos J , Hernández MH , Juanes-Borrego AM , Milà R , Mangues-Bafalluy MA , Mestres C . The Impact of Pharmaceutical Care in Multidisciplinary Teams on Health Outcomes: Systematic Review and Meta-Analysis . J Am Med Dir Assoc . 2021 ; 22 ( 12 ): 2518 – 26 . OpenUrl 17. ↵ NCCD . China Cardiovascular Health and Disease Report 2022 2022 [Available from: https://www.nccd.org.cn/Sites/Uploaded/File/2023/6/%E4%B8%AD%E5%9B%BD%E5%BF%83%E8%A1%80%E7%AE%A1%E5%81%A5%E5%BA%B7%E4%B8%8E%E7%96%BE%E7%97%85%E6%8A%A5%E5%91%8A2022.pdf. 18. ↵ Dunn SP , Birtcher KK , Beavers CJ , Baker WL , Brouse SD , Page RL , 2nd , et al. The role of the clinical pharmacist in the care of patients with cardiovascular disease. J Am Coll Cardiol . 2015 ; 66 ( 19 ): 2129 – 39 . OpenUrl 19. ↵ Swieczkowski D , Mogielnicki M , Merks P , Gruchala M , Jaguszewski M . Pharmaceutical services as a tool to improve outcomes in patients with cardiovascular diseases . International Journal of Cardiology . 2016 ; 222 : 238 – 41 . OpenUrl 20. ↵ Page MJ , McKenzie JE , Bossuyt PM , Boutron I , Hoffmann TC , Mulrow CD , et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews . BMJ . 2021 ; 372 : n71 . OpenUrl FREE Full Text 21. ↵ Cochrane Handbook for Systematic Reviews of Interventions 2022 [Available from: https://training.cochrane.org/handbook/current . 22. ↵ Sterne JAC , Savović J , Page MJ , Elbers RG , Blencowe NS , Boutron I , et al. RoB 2: a revised tool for assessing risk of bias in randomised trials . Bmj . 2019 ; 366 : l4898 . 23. ↵ McGuinness LA , Higgins JPT . Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments . Research Synthesis Methods . 2020 ;n/a(n/a). 24. ↵ Cheung MW . Modeling dependent effect sizes with three-level meta-analyses: a structural equation modeling approach . Psychol Methods . 2014 ; 19 ( 2 ): 211 – 29 . OpenUrl CrossRef PubMed 25. ↵ Human development index in 2021 2021 [Available from: https://globaldatalab.org/shdi/table/shdi/CHN/?levels=1+4&years=2021&interpolation=0&extrapolation=0 . 26. ↵ Ravn-Nielsen LV , Duckert ML , Lund ML , Henriksen JP , Nielsen ML , Eriksen CS , et al. Effect of an In-Hospital Multifaceted Clinical Pharmacist Intervention on the Risk of Readmission: A Randomized Clinical Trial . JAMA Intern Med . 2018 ; 178 ( 3 ): 375 – 82 . OpenUrl 27. Olesen C , Harbig P , Buus KM , Barat I , Damsgaard EM . Impact of pharmaceutical care on adherence, hospitalisations and mortality in elderly patients . Int J Clin Pharm . 2014 ; 36 ( 1 ): 163 – 71 . OpenUrl 28. ↵ Li N , Song JF , Zhang MZ , Lv XM , Hua HL , Chang YL . Impact of medication therapy management (MTM) service model on multi-morbidity (MMD) patients with hypertension: a pilot RCT . BMC Geriatr . 2023 ; 23 ( 1 ): 10 . OpenUrl 29. ↵ Hu DY , Liu LS , Yu JM , Yao CH . [National survey of blood pressure control rate in Chinese hypertensive outpatients-China STATUS] . Zhonghua Xin Xue Guan Bing Za Zhi . 2010 ; 38 ( 3 ): 230 – 8 . OpenUrl PubMed 30. ↵ Kawalec P , Holko P , Gawin M , Pilc A . Effectiveness of fixed-dose combination therapy in hypertension: systematic review and meta-analysis . Arch Med Sci . 2018 ; 14 ( 5 ): 1125 – 36 . OpenUrl 31. ↵ López Cabezas C , Falces Salvador C , Cubí Quadrada D , Arnau Bartés A , Ylla Boré M , Muro Perea N , et al. Randomized clinical trial of a postdischarge pharmaceutical care program vs. regular follow-up in patients with heart failure . Farmacia Hospitalaria . 2006 ; 30 ( 6 ): 328 – 42 . OpenUrl CrossRef PubMed 32. ↵ Babar ZU , Kousar R , Murtaza G , Azhar S , Khan SA , Curley L . Randomized controlled trials covering pharmaceutical care and medicines management: A systematic review of literature . Res Social Adm Pharm . 2018 ; 14 ( 6 ): 521 – 39 . OpenUrl 33. ↵ Choo J , Yang HM , Park S , Park M , Park YM , Lim DS . Appointment Adherence to a City- Wide Cardiovascular Disease Prevention Program: Its Predictors and Outcomes . Asia Pac J Public Health . 2021 ; 33 ( 5 ): 555 – 63 . OpenUrl 34. Rannanheimo PK , Tiittanen P , Hartikainen J , Helin-Salmivaara A , Huupponen R , Vahtera J , et al. Impact of Statin Adherence on Cardiovascular Morbidity and All-Cause Mortality in the Primary Prevention of Cardiovascular Disease: A Population-Based Cohort Study in Finland . Value Health . 2015 ; 18 ( 6 ): 896 – 905 . OpenUrl CrossRef 35. ↵ Wu H , Zhang H , Li X , Zhao Q . Effects of medication adherence on disease activity in chronic obstructive pulmonary disease: a systematic review and meta-analysis . Psychol Health Med . 2023 ; 28 ( 7 ): 1656 – 70 . OpenUrl 36. ↵ Henneh AH , Teg-Nefaah Tabong P . Community pharmacists perception and role in the prevention and management of cardiovascular disease conditions: Evidence from Ghana . Int J Health Plann Manage . 2022 ; 37 ( 5 ): 2794 – 808 . OpenUrl 37. ↵ Puspitasari HP , Aslani P , Krass I . The influence of pharmacy and pharmacist characteristics on the secondary prevention of cardiovascular disease . Int J Clin Pharm . 2015 ; 37 ( 5 ): 834 – 43 . OpenUrl 38. ↵ Yasunaga H , Ide H , Imamura T , Ohe K . Impact of the Japanese Diagnosis Procedure Combination-based Payment System on cardiovascular medicine-related costs . Int Heart J . 2005 ; 46 ( 5 ): 855 – 66 . OpenUrl CrossRef PubMed Web of Science 39. ↵ Souza J , Santos JV , Canedo VB , Betanzos A , Alves D , Freitas A . Importance of coding co-morbidities for APR-DRG assignment: Focus on cardiovascular and respiratory diseases . Health Inf Manag . 2020 ; 49 ( 1 ): 47 – 57 . OpenUrl 40. ↵ Schumacher PM , Becker N , Tsuyuki RT , Griese-Mammen N , Koshman SL , McDonald MA , et al. The evidence for pharmacist care in outpatients with heart failure: a systematic review and meta-analysis . ESC Heart Fail . 2021 ; 8 ( 5 ): 3566 – 76 . OpenUrl 41. ↵ Schultz BG , Tilton J , Jun J , Scott-Horton T , Quach D , Touchette DR . Cost-Effectiveness Analysis of a Pharmacist-Led Medication Therapy Management Program: Hypertension Management . Value in Health . 2021 ; 24 ( 4 ): 522 – 9 . OpenUrl 42. ↵ Zhang P , Lv D , Zhao J , Sun S , Li L , Liao Y . Evaluation of pharmacists’ interventions on drug-related problems and drug costs in patients with cancer pain . Int J Clin Pharm . 2021 ; 43 ( 5 ): 1274 – 82 . OpenUrl 43. Chen B , Huang JJ , Chen HF , Xu BM . Clinical pharmacy service practice in a Chinese tertiary hospital . Drug Metab Pers Ther . 2015 ; 30 ( 4 ): 215 – 30 . OpenUrl 44. ↵ Jiang SP , Zheng X , Li X , Lu XY . Effectiveness of pharmaceutical care in an intensive care unit from China. A pre- and post-intervention study . Saudi Med J . 2012 ; 33 ( 7 ): 756 – 62 . OpenUrl PubMed 45. ↵ Zhong Z , Yao Q , Chen S , Jiang J , Lin K , Yao Y , et al. China Promotes Sanming’s Model: A National Template for Integrated Medicare Payment Methods . Int J Integr Care . 2023 ; 23 ( 2 ): 15 . OpenUrl 46. ↵ Krumme AA , Glynn RJ , Schneeweiss S , Gagne JJ , Dougherty JS , Brill G , et al. Medication Synchronization Programs Improve Adherence To Cardiovascular Medications And Health Care Use . Health Aff (Millwood) . 2018 ; 37 ( 1 ): 125 – 33 . OpenUrl PubMed 47. ↵ Fritzen JS , Motter FR , Paniz VMV . Regular access and adherence to medications of the specialized component of pharmaceutical services . Rev Saude Publica . 2017 ; 51 : 109 . 48. Qi H , Zhu L , Chen L , Zhang W , Wang T , Chen H , et al. Reduced emergency room visits and improved medication adherence of an integrated oncology pharmaceutical care practice in China . J Oncol Pharm Pract . 2021 ; 27 ( 6 ): 1503 – 15 . OpenUrl 49. Morgado MP , Morgado SR , Mendes LC , Pereira LJ , Castelo-Branco M . Pharmacist interventions to enhance blood pressure control and adherence to antihypertensive therapy: Review and meta-analysis . Am J Health Syst Pharm . 2011 ; 68 ( 3 ): 241 – 53 . OpenUrl Abstract / FREE Full Text 50. ↵ Marcatto L , Boer B , Sacilotto L , Olivetti N , Darrieux FCC , Scanavacca MI , et al. Impact of adherence to warfarin therapy during 12 weeks of pharmaceutical care in patients with poor time in the therapeutic range . J Thromb Thrombolysis . 2021 ; 51 ( 4 ): 1043 – 9 . OpenUrl 51. ↵ Yeaw J , Benner JS , Walt JG , Sian S , Smith DB . Comparing adherence and persistence across 6 chronic medication classes . J Manag Care Pharm . 2009 ; 15 ( 9 ): 728 – 40 . OpenUrl CrossRef PubMed Web of Science 52. ↵ Rolnick SJ , Pawloski PA , Hedblom BD , Asche SE , Bruzek RJ . Patient characteristics associated with medication adherence . Clin Med Res . 2013 ; 11 ( 2 ): 54 – 65 . OpenUrl Abstract / FREE Full Text 53. ↵ El Hajj MS , Jaam MJ , Awaisu A . Effect of pharmacist care on medication adherence and cardiovascular outcomes among patients post-acute coronary syndrome: A systematic review . Research in Social and Administrative Pharmacy . 2018 ; 14 ( 6 ): 507 – 20 . OpenUrl 54. ↵ Dixon DL , Dunn SP , Kelly MS , McLlarky TR , Brown RE . Effectiveness of Pharmacist-Led Amiodarone Monitoring Services on Improving Adherence to Amiodarone Monitoring Recommendations: A Systematic Review . Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy . 2016 ; 36 ( 2 ): 230 – 6 . OpenUrl View the discussion thread. Back to top Previous Next Posted July 25, 2024. 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A multilevel meta-analysis Zhijie Deng , Fanglu Chen , Shunshun Peng , Lin Gui , Yangjin Huang , Jing Chen , Anhua Wei , Yufeng Ding medRxiv 2024.07.25.24310734; doi: https://doi.org/10.1101/2024.07.25.24310734 Share This Article: Copy Citation Tools Could Chinese cardiovascular chronic conditions patients gain benefits from pharmaceutical services? A multilevel meta-analysis Zhijie Deng , Fanglu Chen , Shunshun Peng , Lin Gui , Yangjin Huang , Jing Chen , Anhua Wei , Yufeng Ding medRxiv 2024.07.25.24310734; doi: https://doi.org/10.1101/2024.07.25.24310734 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Primary Care Research Subject Areas All Articles Addiction Medicine (574) Allergy and Immunology (865) Anesthesia (304) Cardiovascular Medicine (4462) Dentistry and Oral Medicine (445) Dermatology (383) Emergency Medicine (611) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1517) Epidemiology (15251) Forensic Medicine (31) Gastroenterology (1132) Genetic and Genomic Medicine (6621) Geriatric Medicine (669) Health Economics (1002) Health Informatics (4564) Health Policy (1372) Health Systems and Quality Improvement (1617) Hematology (544) HIV/AIDS (1272) Infectious Diseases (except HIV/AIDS) (15938) Intensive Care and Critical Care Medicine (1107) Medical Education (624) Medical Ethics (147) Nephrology (670) Neurology (6643) Nursing (346) Nutrition (1001) Obstetrics and Gynecology (1149) Occupational and Environmental Health (957) Oncology (3350) Ophthalmology (981) Orthopedics (369) Otolaryngology (421) Pain Medicine (436) Palliative Medicine (130) Pathology (665) Pediatrics (1698) Pharmacology and Therapeutics (694) Primary Care Research (714) Psychiatry and Clinical Psychology (5465) Public and Global Health (9259) Radiology and Imaging (2212) Rehabilitation Medicine and Physical Therapy (1372) Respiratory Medicine (1199) Rheumatology (598) Sexual and Reproductive Health (716) Sports Medicine (533) Surgery (715) Toxicology (100) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a03db8fd3efa8650',t:'MTc4MDE0MzkzOA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();