Assessment of Pharmacotherapy and Clinical Outcomes of Treatment among Tuberculosis Patients

Assessment of Pharmacotherapy and Clinical Outcomes of Treatment among Tuberculosis Patients | 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 Research Article Assessment of Pharmacotherapy and Clinical Outcomes of Treatment among Tuberculosis Patients Bheesham Kingrani, Amer Hayat Khan, Sabariah Noor Harun, Irfhan Ali Hyder Ali This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7341189/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Globally, the morbidity burden of tuberculosis and cardiovascular disease (CVD) is substantial in developing nations. A significant epidemiological and pathological co-occurrence exists between tuberculosis (TB) and CVD. A contributory relationship between tuberculosis infection and cardiovascular disease is evident. Beyond traditional risk factors such as diabetes mellitus, hypertension, and hyperlipidemia, additional risk factors, predictive indicators, and clinical markers contribute to cardiovascular disease development in tuberculosis patients. Monocytes, macrophages, lymphocytes, and cytokines, which are integral to cell-mediated immune responses against Mycobacterium tuberculosis , are also key drivers of atherosclerotic processes in the cardiovascular vasculature. Methodology : This retrospective cohort study was conducted from January 2023 to August 2023, utilizing data collected from January 2015 to December 2022. The study sought to identify risk factors and predictive indicators for the development of cardiovascular disease (CVD) among individuals with a diagnosis and screening of active tuberculosis (TB). A descriptive, retrospective research design was employed, focusing on TB patients without pre-existing CVD. A convenience sample of 402 TB patient records was included in this analysis. Results: This study's findings suggest a strong correlation between clinical markers, including high-sensitivity troponin T, C-reactive protein, electrocardiographic data, echocardiographic findings, cardiac enzymes, acute kidney injury (AKI), diabetes mellitus (DM), anaemia, and severe chest radiographic abnormalities, and the development of cardiovascular disease in tuberculosis patients. Positive values for the aforementioned clinical parameters were considered indicative of cardiovascular disease development. Conclusions: The results advance understanding of a potential correlation between Mycobacterium tuberculosis infection and the development of cardiovascular disease, examining the risk factors conducive to CVD pathogenesis, and facilitating the development of targeted interventions to improve the comprehensive care of individuals with tuberculosis. Cardiac & Cardiovascular Systems Infectious Diseases Clinical Pharmacology Development of cardiovascular disease pulmonary tuberculosis extra-pulmonary tuberculosis Mycobacterium tuberculosis cardiac enzymes C-reactive protein troponin-t (Hs) anaemia chronic kidney disease acute kidney infection hypertension diabetes mellitus Figures Figure 1 Figure 2 Introduction Mycobacterium tuberculosis , the etiological agent of tuberculosis (TB), remains a significant global public health concern. TB, a respiratory infectious disease transmitted via aerosolized respiratory droplets from infected individuals, resulted in an estimated 1.3 million fatalities in 2020, increasing to 1.4 million in 2021 despite global efforts. Diagnostic and therapeutic challenges during the COVID-19 pandemic contributed to a decline in TB control efforts, reversing previously observed progress [1]. Estimated new TB cases in 2021 reached 10.6 million, inclusive of approximately 7% with compromised immunity. Epidemiological data indicate a higher incidence of infection among male individuals compared to females [2]. In 2022, 1.3 million fatalities from TB were recorded, with 167,000 co-infected with HIV. TB ranks second as a leading cause of infectious disease mortality globally, behind COVID-19 but ahead of HIV/AIDS [3]. Data from 2023 indicate an estimated 8.2 million new cases, the highest since global surveillance began in 1995. This represents a notable increase from 7.5 million cases in 2022, making TB the leading infectious disease cause of death in 2023, thereby surpassing COVID-19 mortality. Mixed results were observed in the global fight against TB in 2023, despite a reduction in fatalities to 1.25 million from 1.32 million in 2022, while estimated incident cases rose slightly to ~10.8 million in 2023 [4]. Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), a respiratory disease transmitted by inhaling aerosolized droplets from infected individuals. Tuberculosis is a serious respiratory disease that is a serious public health problem. Effective control of the disease worldwide requires the development of effective vaccines, improved diagnostics, and new, short-term treatments [5], [6]. Increasing evidence suggests that tuberculosis (TB) disease may disrupt host metabolism and contribute to subsequent risks of chronic non-communicable diseases (NCDs) [7], [8], [9]. A large proportion of TB patients reside in low- and middle-income countries, where the risks posed by chronic NCDs, such as type 2 diabetes mellitus, acute myocardial infarction, and stroke, are substantial public health threats. [10]. Recent evidence demonstrates that Mycobacterium tuberculosis-induced inflammatory responses persist beyond treatment for active tuberculosis, resulting in chronic inflammation in individuals who have survived the infection [11], [12]. In addition, the long-term mortality of TB survivors is higher than that in the general population [13], [14]. Hyperglycemia represents a well-established risk factor for Mycobacterium tuberculosis infection [15] and suboptimal treatment outcomes [16]. Factors contributing to cardiovascular disease risk in tuberculosis may include direct effects of M. tuberculosis on the cardiac musculature and coronary vasculature, augmented immune activation resulting in elevated cytokine production, and potential cross-reactivity of antibodies targeting mycobacterial components against cardiovascular tissues [17], [18]. Studies have demonstrated a heightened susceptibility to coronary heart disease (CHD) in individuals who have survived tuberculosis (TB) infection [19]. Furthermore, accumulating evidence indicates an elevated risk of ischemic stroke, a consequence of atherosclerosis, in TB survivors, reinforcing the association between TB and CHD [20]. Recent research has revealed that individuals with either pulmonary or extrapulmonary tuberculosis exhibit an increased risk of future acute myocardial infarction and unstable angina. Remarkably, the elevated risk of cardiovascular disease (CVD) persists even several years post-initial Mycobacterium tuberculosis diagnosis. This suggests that tuberculosis may elicit both acute and chronic CVD sequelae [21]. Elevated blood pressure, diabetes mellitus, dyslipidemia, and obesity, traditional cardiovascular risk factors, are supplemented by evidence from clinical literature indicating that Mycobacterium tuberculosis (MTB) promotes atherosclerosis through its pronounced inflammatory response, thus indirectly contributing to the development and progression of cardiovascular pathologies [22], [23], [24], [25]. The pathophysiological mechanism linking MTB to atherosclerotic lesion formation and progression resides in its pro-inflammatory effect on the vascular endothelial lining [26], [27], [28]. Tuberculosis (TB) and ischemic coronary artery disease (ICAD) exhibit a heightened co-occurrence in developing nations. Several mechanistic underpinnings are posited. One proposed mechanism implicates a chronic inflammatory response, characterized by cell-mediated immune activation and the subsequent release of cytokines and chemokines, following latent infection. A second mechanism involves the initiation of an autoimmune process after chronic infection, resulting in the generation of antibodies targeting mycobacterial heat shock protein 65 (HSP65) [29]. This phenomenon elicits a cross-reactive response with human HSP65, contributing to endothelial damage and stimulating atherogenic processes. Heat shock proteins represent a homogeneous protein family, inducible in response to environmental stressors, initially identified as a heat-induced response. These proteins demonstrate high evolutionary conservation across species, and exhibit chaperone activity and a role in mediating immune responses in specific disease states. [30]. Recognizing atherosclerosis as an inflammatory process, several plasma inflammatory markers have been assessed as potential predictors of coronary event risk. These include markers of systemic inflammation, such as hepatic-derived high-sensitivity C-reactive protein (hs-CRP) and serum amyloid A; cytokines, including interleukin-6; and adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1) [31], [32], [33], [34], [35], [36], [37], [38]. A causal relationship exists between cholesterol and Mycobacterium tuberculosis (MTB), the bacterial agent requiring cholesterol for infection and survival, though infection progression correlates with the capacity of the host immune system to limit infection [39, 40]. Lipid components play a critical role in both tuberculosis development and cardiovascular disease pathogenesis, as noted by Wilburn et al. [41]. Mycobacterial cells contain diverse classes of non-structural and structural lipids, functioning as a primary energy source and contributing significantly to pathogenicity, virulence, and persistence of Mycobacterium species [42]. Cardiovascular disease encompasses a spectrum of pathologies stemming from reduced coronary blood flow. This includes life-threatening conditions such as unstable angina and myocardial infarction. Despite therapeutic advancements, these conditions remain significant contributors to morbidity and mortality. Complications of myocardial infarction can manifest as heart failure, arrhythmias, and cerebrovascular accident [43]. The impact of tuberculosis extends beyond coronary artery disease and includes other vascular diseases associated with atherosclerosis, including cerebrovascular accident. A three-year prospective cohort study of tuberculosis patients evaluated the risk of ischemic stroke; the results indicated a 50% increased risk of ischemic stroke among individuals with TB [9]. Tuberculosis (TB) infection demonstrably elevates the risk of cardiovascular disease (CVD) via mechanisms including immune system activation and inflammatory responses. However, a significant knowledge deficit remains regarding the intricate relationship between TB and CVD, especially in low- and middle-income nations such as Malaysia. Existing studies have predominantly focused on general comorbid conditions, rather than the specific interplay between TB and CVD. Clinicians frequently fail to recognize the need for targeted interventions aimed at managing CVD risk in this patient population. Further research will also improve clinical protocols and public health initiatives. Mitigation of these knowledge gaps can ultimately enhance patient outcomes and reduce morbidity and mortality linked to CVD in individuals affected by TB. Role of Tuberculosis Infection in Atherosclerosis (Inflammatory Process) Figure 1 depicts a schematic representation of the contribution of Mycobacterium tuberculosis infection to the inflammatory cascade driving atherosclerosis. Key pro-inflammatory risk factors, including oxidized low-density lipoprotein (LDL), vascular endothelial injury, and M. tuberculosis infection, are highlighted. In this model, M. tuberculosis serves as a persistent infectious stimulus that, concurrent with oxidative stress induced by oxidized LDL, primes the vascular milieu for inflammation. This initial event triggers the release of primary pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-α), which are critical signaling molecules initiating the inflammatory cascade. These cytokines subsequently induce the expression of vascular cell adhesion molecules (VCAM-1, ICAM-1, and selectins) on endothelial cells, a prerequisite for leukocyte recruitment to the vascular wall. Subsequently, interleukin-6 (IL-6) acts as a pivotal cytokine amplifier, stimulating hepatic production of acute-phase reactants including C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen. These acute-phase proteins, acting as markers of inflammation, actively participate in atherosclerotic lesion development by modulating hemostasis and vascular remodeling. Ultimately, the cumulative effect of these inflammatory events results in atherogenesis, the formation of lipid-rich plaques within arterial walls, characteristic of atherosclerosis. Study Outcomes and Impact on the Health Industry This study compiles and analyzes cardiovascular disease-associated mortality rates in a tuberculosis patient cohort. This research has the potential to significantly impact the healthcare sector by providing essential data for refining clinical protocols and public health strategies. Furthermore, insights derived from demographic analyses can inform personalized treatment regimens, enhancing healthcare effectiveness and efficiency. Ultimately, by elucidating the mortality risk associated with CVD in TB patients, this research advocates for integrated care strategies targeting both conditions concurrently, potentially reducing healthcare expenditure and improving patient outcomes in at-risk populations [45]. Methodology Study design This study used a retrospective and descriptive research design. Participants were tuberculosis (TB) patients without cardiovascular disease at the initial examination or baseline. Generally, to achieve all objectives, the study parameters of TB and CVD were correlated to find a relationship between TB and CVD and associated risk factors for the development of CVD among TB patients. Data Collection Period Retrospective data of patients with tuberculosis who were followed up at Penang General Hospital clinic were collected from January 2015 to December 2022 (01/01/2015-31/12/2022). Sampling Method Patients meeting the inclusion criteria were selected using a convenient sampling technique. Sample Size Data from 402 files of patients was extracted. The sample size was selected using the prevalence proportion formula [46]: Equation: Where n = sample size Z = statistic for a level of confidence, (Z = 1.96 for 95% CI) P = expected prevalence or proportion, (P = 50% or 0.5) E = margin of error (E = 5% or 0.05) Parameters such as the percentage score, margin of error, confidence level, and population size are essential in determining sample size. For this study, an assumed indicator percentage of 50% was used, with a 5% margin of error and a 95% confidence level. This yielded a minimum required sample size of 384. A total of 434 patient files were initially selected, but 32 files (8%) were excluded based on the exclusion and withdrawal criteria (i.e., patients whose diagnosis had changed or those who already had cardiovascular disease at baseline). Consequently, 402 patient files were included in the final analysis. Inclusion Criteria Adults ≥18 years old Patients with a confirmed diagnosis of tuberculosis (pulmonary and extrapulmonary tuberculosis) without any cardiovascular disease at baseline. Exclusion Criteria Patients with autoimmune disease Children Pregnant women Files of patients whose records were incomplete were not included in the study Files of patients whose diagnosis had changed were excluded, specifically those initially misdiagnosed with MTB but later correctly diagnosed with another condition, such as interstitial lung disease. Registered TB Cases at Penang General Hospital (Patient Case Selection Criteria) Table 1 presents the total number of registered tuberculosis (TB) cases at Penang General Hospital, Penang, Malaysia, from 2015 to 2022, along with the selection criteria for the study cohort. A convenience sampling method (random selection based on accessibility and availability) was employed due to hospital administrative restrictions imposed by the COVID-19 pandemic. Data collection was facilitated by nursing staff, owing to limitations on access to the data records. Nursing staff sorted TB case files from other respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, bronchitis, and interstitial lung disease, providing 5 to 7 randomly selected files daily. For example, in 2015, 63 of the 581 registered TB cases were included in the study (approximately 10.84%). Similarly, in 2022, 50 of the 502 registered TB cases were included (approximately 9.96%). Table 01: “Data of registered tuberculosis cases at Penang General Hospital, Malaysia” Data of the Year Total Registered Cases Selected Cases (%) 2015 581 63 (10.84) 2016 600 53 (8.83) 2017 574 39 (6.79) 2018 497 47 (9.46) 2019 623 54 (8.67) 2020 621 48 (7.73) 2021 441 48 (10.88) 2022 502 50 (9.96) Total 4439 402 Statistical Analysis Each patient's data collection form was assigned a unique serial number (patient identifier) to ensure data provenance. Responses were encoded, and the data were input into a computer and analyzed using the Statistical Package for the Social Sciences (SPSS) software, version 27.0 for Microsoft Windows operating systems. Given the data's adherence to a Gaussian distribution, parametric statistical tests were employed. A chi-squared test was used to assess the association between categorical variables (such as demographic factors including sex, race, and age) and the dependent variable (the development of cardiovascular disease). Continuous variables of interest were summarized as means or medians with standard deviations (descriptive statistics), while categorical variables (e.g., age, sex, ethnicity) were presented as proportions. Basic Criteria of Cardiovascular Disease among the Study Population Patient diagnosed with coronary heart disease, either stable coronary artery disease or acute coronary disease (NSTEMI, UA, or STEMI). Patient diagnosed with heart failure, either with preserved ejection fraction (HFpEF), defined by an LVEF ≥50%, heart failure with reduced ejection fraction (HFrEF) if the LVEF is <40%, and heart failure with mid-range ejection fraction (HFmrEF) if the LVEF is 40–49%. Patient diagnosed with arrhythmias, either supraventricular arrhythmias, ventricular arrhythmias, or Brady arrhythmias. Patient diagnosed with Stroke, whether it is Ischemic stroke, Hemorrhagic stroke, or Transient ischemic attack (Mini Stroke). Patient diagnosed with any Aortic disease, such as Aortic Aneurysm, Aortic Occlusive disease, Aortitis, or Aortic valvular disease. Patients diagnosed with Peripheral Vascular disease, which includes mainly Peripheral venous disease, Deep Vein Thrombosis, Pulmonary Embolism, Peripheral Artery Disease, Aneurysm, Chronic venous insufficiency, and Ischemic Limb disease. Cardiovascular Disease Cardiovascular diseases (CVDs) represent a spectrum of pathologies affecting the cardiovascular system. These conditions encompass hemodynamic impairments affecting the coronary, cerebral, or peripheral vasculature, frequently arising from thrombotic events or atheromatous plaque formation leading to arterial stenosis or occlusion. Four primary subtypes of CVD are distinguished: 1. Coronary heart disease 2. Stroke 3. Peripheral arterial disease 4. Aortic disease [47] Results Assessment of Pharmacotherapy and Clinical Outcomes The treatment aimed to cure the patients, to render them non -non-infectious, to reduce morbidity and mortality, and to prevent the relapse and emergence of resistant tubercle bacilli. Five drugs are generally considered essential in the treatment of tuberculosis; Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Streptomycin (S), and Ethambutol (E). The treatment regimen is divided into two phases: the intensive phase and the continuation phase. In this study, the most common treatment regimen encountered was two months of daily doses of E, H, R, and Z for the initial phase (EHRZ), followed by four months of daily doses or thrice weekly doses of R and H (4HR) for the continuation phase. Other treatment regimens were also observed for patients with problems, such as adverse drug reactions, which were grouped as miscellaneous. All the patients were supplemented with oral pyridoxine (Vitamin B6) or a combination of Vitamin B1, B6, and B12 (Tablet Neurobion) to minimize the side effects (Neurotoxicity) of isoniazid. Rifampicin was the main drug that was noted to be used throughout the full course (Intensive Phase + Maintenance Phase) of TB therapy. Streptomycin was used as a substitute for Ethambutol, where ever Ethambutol was contraindicated. Usually, fixed-dose combination therapy was observed such as Tablet Akurit-4 (Combination of Isoniazid 75mg, Rifampicin 150mg, Ethambutol 275mg, and Pyrazinamide 400mg) was prescribed for the intensive phase and Tablet Akurit-2 (Combination of Isoniazid 75mg and Rifampicin 150mg) was prescribed for continuation phase. Sometimes Tablet Akurit-3 (A combination of Isoniazid 75mg, Rifampicin 150mg, and Pyrazinamide 400mg) was observed to be prescribed in the intensive phase. Fixed-dose combination therapy was encouraged and followed to avoid prescribing errors and non-compliance to individualized drugs by patients. Fixed-dose combination therapy (FDCs) was discouraged if a patient developed any toxicity, intolerance, or contraindication to any of the components or specific drugs of therapy. The duration of treatment for TB-Meningitis was a bit longer such as 9 to 12 months (2 months intensive phase followed by 7 to 10 months continuation phase treatment). For Bone and joint TB, treatment was also a bit longer such as 9 months (2 months intensive phase followed by 7 months continuation phase). Corticosteroid therapy was seen in TB Meningitis and TB Pericarditis that included Dexamethasone injection or tablet Prednisolone. A dose of Tablet Akurit-4 (FDCs) was prescribed based on the weight range of the patient such as: 1. 30kg-37kg...........................2 Tablets daily 2. 38kg-54kg...........................3 Tablets daily 3. 55kg-70kg...........................4 Tablets daily 4. More than 70kg...................5 Tablets daily The following is the table of dosing patterns that were observed in Penang General Hospital for the anti-TB therapy of patients in this study. Table 4.19 Observed Pattern of Drug Dosing and its Types Drug Name Daily Dosing 3X a week Dosing Dose (range) in mg/kg body weight Maximum in mg Dose (range) in mg/kg body weight Maximum in mg Isoniazid (H) 5 (4-6) 300 10 (8 - 12) 900 Rifampicin (R) 10 (8-12) 600 10 (8 - 12) 600 Pyrazinamide (Z) 25 (20-30) 2000 35 (30 – 40)* 3000* Ethambutol (E) 15 (15-20) 1600 30 (25 – 35)* 2400* Streptomycin (S) 15 (12-18) 1000 15 (12 – 18)* 1500* Reported Adverse Drug Reactions (ADRs) This study identified patients experiencing adverse drug reactions (ADRs) to anti-tubercular therapy, primarily manifesting as Drug-Induced Hepatitis. For these patients, the anti-tubercular drug treatment was halted, either partially or entirely, and recovery was monitored through regular liver function tests (LFT). Upon normalization of LFT results, patients resumed treatment with the same drugs, accompanied by constant liver function monitoring. The study reported that 15% of patients encountered skin rashes and itchiness attributed to Rifampicin and Ethambutol. Patients with rashes received topical creams for relief, and Anti-TB treatment was temporarily paused. Treatment continued for patients with non-serious ADRs. Allergic reactions led to the suspension of the implicated drug, with second-line anti-tubercular drugs, such as Levofloxacin, prescribed. Other observed adverse drug reactions included blurred vision (Due to Ethambutol), thrombocytopenia (Due to Rifampicin), drug-induced liver injury (Due to Pyrazinamide), vomiting, increased ALT (Acute Transaminitis), hyperbilirubinemia, elevated ALP, and dry scaly skin with pruritus. Following were the statistics of adverse drug reactions, presented in table 4.20. Table 4.20 Statistics of Adverse Drug Reactions Adverse Drug Reaction Frequency (n) Percentage (%) Rashes and Itchiness 24 6.25 Drug-Induced Hepatitis 10 2.6 Transaminitis 32 8.33 Nausea and Vomiting 18 4.69 Blurred Vision 09 2.34 Thrombocytopenia 08 2.08 Hyperbilirubinemia 16 4.17 Drug-Resistant Tuberculosis All Mycobacterium cultures isolated from the clinical specimens of patients were sent for drug susceptibility/sensitivity testing (DST). The test was conducted to determine the susceptibility and sensitivity of the Mycobacterium to the anti-tuberculosis drugs. Sometimes GeneXpert and Line Probe Assay testing was conducted to rule out drug resistance. DST and Line Probe Assay were used to rule out resistance for all primary first-line drugs but GeneXpert was used to rule out resistance to Rifampicin only. If the Mycobacterium Tuberculosis strain is resistant to INH and RIF, it was being considered as multi-drug-resistant TB (MDR-TB). There were 14 cases of Mono-drug resistant (Resistant to either Isoniazid or Rifampicin of first-line Anti-TB approved drugs) cases, 07 Multi-drug Resistant (Resistant to two or more first-line Anti-TB drugs and at least resistant to both Isoniazid and Rifampicin) and 05 Poly-drug Resistant (Resistant to two or more first-line drugs of Anti-TB and not resistant to both Isoniazid and Rifampicin simultaneously) cases in this study. The 2 nd line anti-tubercular drug regimen was prescribed to patients with resistance to 1 st line anti-tubercular drug(s). For mono and multi-drug-resistant TB, the addition of second-line anti-TB agents such as Tablet Levofloxacin, Tablet Ethionamide, Tab. Cycloserine, Injection Kanamycin, Meropenem, and Linezolid, etc. were observed in recommended doses. Table 4.21 outlines drug-resistant tuberculosis cases that were total 26 in number as Isoniazid (1.7%), Rifampicin (1.7%), Isoniazid and Rifampicin both (MDR-1.4%), Rifampicin and Ethambutol (0.9%), Rifampicin and Streptomycin (0.2%), Isoniazid and Streptomycin (0.2%). Table 4.21 Frequency of Drug-Resistant Cases Resistant Drug Name (s) Frequency (N) of Drug-Resistant case Percentage (%) Isoniazid 07 1.7 Rifampicin 07 1.7 Isoniazid and Rifampicin 06 1.4 Isoniazid and Streptomycin 01 0.2 Rifampicin and Ethambutol 04 0.9 Rifampicin and Streptomycin 01 0.2 Total 26 6.5 Anti-Tubercular Therapeutic Outcomes Table 4.22 outlines the clinical outcomes of tuberculosis treatment. Significant findings included a cure rate of 41.5% (167 patients), a mortality rate of 15.2% (61 patients), and a treatment completion rate of 21.9% (88 patients). Notably, 5.5% of patients were lost due to follow-up, while only 0.7% experienced treatment failure. These statistics underscore the effectiveness of treatment programs, with low rates of treatment failure and loss to follow-up (Defaulter) and high rates of successful cure and treatment completion. Table 4.22 Frequency of Patients according to Clinical Outcomes of Treatment Treatment Outcome Category Frequency (N) of patient Percentage % Loss to follow-up 22 5.5 Patient Cured 167 41.5 Patient Died 61 15.2 Transferred out 60 14.9 Treatment Completed 88 21.9 Treatment failed 03 0.7 Association of Pharmacotherapy with Clinical Outcomes Table 4.23 presents the association between pharmacotherapy or treatment regimen and clinical outcomes of tuberculosis (TB) treatment across different types of TB cases. Notable findings included a higher percentage of patients cured among new TB cases (41.5%) compared to relapse cases with defaulted or completed therapy. Relapse TB cases with completed therapy also exhibited a relatively high cure rate (12 patients, 50%). Conversely, patients with multi-drug/poly-drug-resistant TB had a higher mortality rate (15.2%) and lower cure rates. The Chi-square test indicates a statistically significant association between the type of TB case and treatment outcome (χ2 = 15.826, p < 0.05), suggesting that different TB presentations respond differently to pharmacotherapy. The data suggest that patients with new TB cases have better treatment outcomes, while those with drug-resistant TB face greater challenges in treatment success. This underscores the importance of tailored treatment regimens based on the type of TB case and drug susceptibility patterns. Additionally, loss to follow-up is absent among relapse TB cases with defaulted treatment cases suggesting improved treatment adherence in this subgroup. These findings emphasize the necessity of personalized approaches to TB treatment to optimize outcomes and reduce mortality rates, especially among patients with drug-resistant TB strains. Table 4.23 Association of Pharmacotherapy with Clinical Outcomes of Treatment Type of TB case and Pharmacotherapy or Treatment Regimen Therapy Loss to follow-up Patient Cured Died Transfer Out Treatment Completed Treatment Failure Chi-Square x2 P- value New TB Case 15 118 45 50 71 02 15.826 0.920 Relapse TB case with defaulted 01 11 03 03 02 0 Relapse case with complete therapy 03 21 10 04 12 01 TB case after Treatment failed 0 01 0 0 0 0 Mono-drug Resistant 02 09 02 03 01 0 Multi-drug/Poly-drug Resistant 01 07 07 0 02 0 Treatment Outcomes of TB Patients with Comorbidity Table 4.24 explores the correlation between comorbidities and clinical outcomes among tuberculosis (TB) patients. Notably, TB patients with comorbidities such as diabetes mellitus (TB-DM) and human immunodeficiency virus (TB-HIV) showed significant associations with treatment outcomes. Specifically, TB-DM patients exhibited higher rates of treatment completion and cure compared to other groups, while TB-HIV patients had a higher mortality rate and lower treatment completion rates. The Chi-square test revealed statistically significant associations between TB-DM (χ2 = 14.720, p = 0.012) and TB-HIV (χ2 = 28.727, p = 0.001) with treatment outcomes, highlighting the importance of managing these comorbidities during TB treatment to improve patient outcomes. Conversely, TB-AKI (acute kidney injury) showed a statistically significant association with poor treatment outcomes (χ2 = 22.156, p < 0.001), indicating the need for tailored interventions for TB patients with renal complications. Table 4.24 Correlation of Comorbidities with Clinical Outcomes Type of Comorbidities Loss to follow up (n) Cured (n) Died (n) Transfer Out (n) Treatment Completed (n) Treatment Failure (n) Chi-Square value P-value TB-HTN 01 41 11 11 18 01 5.847 0.321 TB-DM 07 87 19 26 35 03 14.720 0.012 TB-HIV 04 09 16 04 09 0 28.727 0.001 TB-Dyslipidaemia 01 31 04 08 17 0 8.954 0.111 TB-AKI 0 0 04 0 0 0 22.156 <0.001 TB-CKD 0 01 03 01 04 0 6.769 0.238 TB-Anaemia 0 0 4 0 01 0 16.872 0.005 Therapy for Cardiovascular Disease During TB treatment, patients who developed cardiovascular disease were started on treatment regimens related to cardiovascular disease. Following are the medicines that were observed to treat different types of cardiovascular diseases. Table 4.25 Treatment Trend for Cardiovascular Disease Type of Drug Name of Medicine 1. Anti-Hypertensive Beta Blocker Tab. Metoprolol, Tab. Bisoprolol, Tab. Atenolol, Tab. Carvedilol ACE-Inhibitor Tab. Perindopril Angiotensin-II Receptor Antagonist Tab. Losartan, Tab. Telmisartan Calcium Channel Blocker Tab. Felodipine 2. Anti-Lipidemic HMG-CoA Reductase Inhibitor Tab. Simvastatin Advanced HMG-CoA Reductase Inhibitor Tab. Atorvastatin 3. Anti-Coagulant Anti-Platelet Clopidogrel, Cardipril, Glyprin, Aspirin 150mg, Tab. Ticlopidine Blood Thinners Tab. Warfarin 4. Diuretic Loop Diuretic Tab. Frusemide Potassium Sparing Diuretic Tab. Spironolactone Thiazide Type Diuretic Tab. Hydrochlorothiazide Table 4.25 (Continued) Type of Drug Name of Medicine 5. Blood Pumping Booster Fatty acid Oxidation Inhibitor Tab. Trimetazidine Hyperpolarization-Activated Cyclic Nucleotide Gated Channel Blocker Ivabradine 6. Inotrope Cardiotonic Glycoside Tab. Digoxin 7. Anti-Anginal Nitrates Tab. Isosorbide Dinitrate Correlation of Clinical Outcomes of TB Treatment with CVD and Without CVD Table 4.26 examines the association between clinical outcomes of tuberculosis (TB) treatment with and without cardiovascular disease (CVD) among TB patients. Significant differences were observed in various treatment outcomes between TB patients with and without CVD. Notably, TB patients with CVD had significantly lower rates of loss to follow-up compared to those without CVD (χ2 = 99.749, p < 0.001). However, they had notably higher mortality rates, with 28 deaths among TB patients with CVD compared to 34 deaths among those without CVD. Furthermore, TB patients with CVD had a substantially lower number of patients cured and completed treatment compared to those without CVD, i.e. TB Patients without CVD, successfully cured were 157 (43.49%) out of 361 patients, while TB patients with CVD, successfully cured were only 10 (24.39%) out of total 41 patients. These results make us compelled for further cardiovascular health assessment. Table 4.26 Association of Clinical Outcomes of TB Treatment with CVD and without CVD among TB Population Variable TB-Without CVD TB-With CVD Chi-Square P- value Loss to follow-up 21 01 99.749 <0.001 Patient Cured 157 10 Patient Died 34 28 Transferred Out 59 01 Completed Treatment 87 01 Treatment Failure 03 0 Total 361 41 Total 361 + 41 = 402 Discussion The widespread utilization of anti-tuberculosis drugs has led to effective tuberculosis control. Despite their efficacy, challenges such as prolonged treatment duration, the emergence of MDR strains, and adverse effects impacting therapy adherence persist. [144]. Among these adverse effects, Hepatotoxicity is a well-known complication of anti-tubercular therapy (ATT) [145]. In the present study, it was noticed that anti-TB therapy was paused until liver function tests (LFTs) normalized, after which treatment was resumed with either the same or second-line anti-tubercular drugs based on LFTs results. Noteworthy adverse effects associated with first-line anti-tuberculosis drugs included skin rashes and itchiness which is linked to Isoniazid (INH), Pyrazinamide (PZA), and Streptomycin (SM). Nausea is associated with RIP and PZA, while drug-induced hepatitis is connected to treatment with INH, Rifampicin (RIP), and PZA. Thrombocytopenia is associated with RIP, and blurring of vision is linked to Ethambutol (ETH) and SM. The present study aimed to assess pharmacotherapy and clinical outcomes of treatment among tuberculosis (TB) patients. Dosing patterns were weight-based, and corticosteroid therapy was administered for TB Meningitis and TB Pericarditis. The standard TB treatment regimen consisted of a two-month initial phase (2EHRZ) followed by a four-month continuation phase (4HR). Rifampicin was consistently used throughout the entire treatment course. Fixed dose combination therapy (FDCs) was prevalent, with Tablet Akurit-4 prescribed for the intensive phase and Tablet Akurit-2 for the continuation phase. FDCs helped prevent prescribing errors and non-compliance. The dosing pattern was weight-dependent, with specific tablet combinations based on the patient's weight. ADRs, primarily Drug-Induced Hepatitis, were identified in 15% of patients. Skin rashes and itchiness were common, attributed to Rifampicin and Ethambutol. Temporary cessation of treatment and topical creams were used for non-serious ADRs. Severe reactions led to the suspension of the implicated drug, with second-line anti-TB drugs prescribed. The statistics revealed various ADRs, with rashes and itchiness being the most frequent (6.25%). Drug susceptibility testing (DST) and additional tests like GeneXpert and Line Probe assay were conducted to identify drug-resistant strains. The study reported 14 cases of Mono-drug-resistant TB, 07 cases of multi-drug-resistant TB, and 05 cases of Poly-drug-resistant TB. Second-line anti-TB agents were prescribed for resistant cases, such as Levofloxacin, Ethionamide, Cycloserine, Kanamycin, Meropenem, and Linezolid. The frequency of drug-resistant cases was 6.8%, with Rifampicin resistance being the most common. The therapeutic outcomes varied, with a high mortality rate (59.9%). Cured patients represented 22.7%, while smaller proportions experienced loss to follow-up (2.6%), transfer out (2.9%), treatment completion (11.5%), and treatment failure (0.5%). The association between pharmacotherapy and clinical outcomes did not show statistical significance overall, but a detailed examination revealed patterns in different TB case types. The association between pharmacotherapy and clinical outcomes showed diverse patterns among different TB case types. New TB cases exhibited varied outcomes, while relapse TB cases had fewer instances of death and treatment failure. Mono and multi-drug-resistant cases demonstrated different treatment responses, emphasizing the need for personalized therapeutic approaches. In the present study, significant findings included a cure rate of 41.5% (167 patients), a mortality rate of 15.2% (61 patients), and a treatment completion rate of 21.9% (88 patients). Notably, 5.5% of patients were lost due to follow-up, while only 0.7% experienced treatment failure. These statistics underscore the effectiveness of treatment programs, with low rates of treatment failure and loss to follow-up (Defaulter) and high rates of successful cure and treatment completion. Like the Present study, A study conducted in Sudan by Monadil H Ali et al. (2019) [117] provided valuable insights into the challenges and outcomes associated with tuberculosis (TB) treatment, focusing on different aspects such as treatment success rates, pharmacotherapy, and clinical outcomes. Likewise present study, the referenced Sudanese study reports mortality rates among TB patients, although with different emphases. The study from Sudan emphasizes the overall success rate of MDR-TB treatment, which is 63.5%, and a mortality rate of 14.1%, while the current study provides a detailed breakdown of treatment outcomes, with a significant proportion (15.2%) of patients experiencing death and 41.5% success rate of treatment. The present study outlines the common treatment regimens, the use of fixed-dose combination therapy, and the dosing patterns based on patient weight. Similarly, the Sudanese study mentions the essential drugs in MDR-TB treatment, the treatment regimen phases, and the use of supplementary vitamins to mitigate side effects. Sudanese study reports an overall success rate of 63.5% in MDR-TB treatment, while the current study's clinical outcomes indicate a lower percentage (41.5%) of patients as cured. The Sudanese study specifically focuses on MDR-TB, which may have different success rates compared to the broader TB population in the present study. The present study reports 6.47% of cases with drug-resistant tuberculosis, including mono-drug, poly-drug, and multi-drug resistance. The Sudanese study does not specifically address drug resistance types among MDR-TB cases. Overall findings do not match due to a different TB population as the main subject, i.e. Sudanese study is only limited to MDR TB cases. [117]. A study conducted on “Treatment outcomes of drug-resistant tuberculosis in the Netherlands” [116] contributes valuable insights into the challenges associated with tuberculosis (TB) treatment, particularly in the context of drug-resistant TB (DR-TB). A commonality between the Netherlands study and the current study conducted in Malaysia is the emphasis on understanding treatment outcomes and risk factors associated with poor results. However, there are notable differences in the scope and methodologies of both studies. The Netherlands study highlights the importance of addressing the unique challenges posed by population migration and the complex treatment regimens for DR-TB patients. On the other hand, the current study provides a detailed analysis of anti-tuberculosis therapy, dosing patterns, adverse drug reactions, and drug-resistant TB cases, shedding light on the pharmacotherapy and clinical outcomes in a different healthcare setting. The Netherlands study identifies a low incidence of DR-TB and reports a cumulative incidence of unsuccessful treatment at 5%. In contrast, the present study reveals a higher proportion of unfavorable outcomes, with a significant percentage of patients experiencing death (15.1%). The Netherlands, being a low-incidence country, might have a more robust healthcare system and resources, contributing to comparatively better treatment outcomes. Variations in their contexts and methodologies lead to differences in observed outcomes. [116]. A study conducted by Shahzad A. et al. (2021) [120] in Pakistan reported a higher percentage of patients (35.8%) identified with drug-related problems, including untreated conditions, administration of drugs without indication, adverse drug reactions, total drug interactions, and polypharmacy issues. This contrasts with the present study, which did not explicitly report such a high incidence of drug-related problems. The Pakistan study emphasizes the role of clinical pharmacists and proper patient counseling to address these issues, suggesting a potential gap in healthcare systems. Furthermore, the current study provides a detailed breakdown of adverse drug reactions, including skin rashes, drug-induced hepatitis, transaminitis, nausea, vomiting, blurred vision, thrombocytopenia, hyperbilirubinemia, and their respective frequencies. In contrast, the Pakistan study does not provide such specific details regarding TB treatment outcomes. The present study reports a higher percentage of patient deaths (15.1%), while the Pakistan study does not provide an explicit figure for mortality. Both, Pakistan and the present study aimed to assess pharmacotherapy and clinical outcomes in TB patients and utilized retrospective data collection methods. The pharmacotherapeutic interventions in both studies involved a combination of anti-TB drugs, antibiotics, and supportive medications, showcasing a standard protocol for TB management. Moreover, both studies recognized the importance of monitoring adverse drug reactions (ADRs) and drug-resistant TB cases, indicating a comprehensive evaluation of treatment outcomes. Additionally, the present study explores the association between pharmacotherapy and clinical outcomes, demonstrating varying responses among different TB case types, such as new cases, relapse cases, and drug-resistant cases, while the Pakistan study lacks a similar in-depth analysis of the relationship between pharmacotherapy and clinical outcomes. To explain the contradictions, several factors should be considered. Firstly, differences in healthcare infrastructure, clinical practices, and patient demographics between Pakistan and Malaysia may contribute to variations in treatment outcomes. Furthermore, dissimilarities in data collection methodologies, including the definition and identification of drug-related problems, may lead to discrepancies [120]. In the present study, noteworthy findings included a higher percentage of patients cured among new TB cases (41.5%) compared to relapse cases with defaulted or completed therapy. Relapse TB cases with completed therapy also exhibited a relatively high cure rate (12 patients, 50%). Conversely, patients with multi-drug/poly-drug-resistant TB had a higher mortality rate (15.2%) and lower cure rates. The Chi-square test indicates a statistically significant association between the type of TB case and treatment outcome (χ2 = 15.826, p < 0.05), suggesting that different TB presentations respond differently to pharmacotherapy. The data suggests that patients with new TB cases have better treatment outcomes, while those with drug-resistant TB face greater challenges in treatment success. These findings emphasize the necessity of personalized approaches to TB treatment to optimize outcomes and reduce mortality rates, especially among patients with drug-resistant TB strains. Similarly, a systematic review conducted by Sileshi et al. (2021) [146] reported the impact of first-line Anti-Tubercular Drugs’ Pharmacokinetics on Treatment Outcomes. The present study shares a common ground with the referenced study in the investigation of the impact of first-line anti-tubercular drugs on treatment outcomes. Findings of this systematic review include the recognition of the importance of pharmacokinetics in influencing treatment outcomes, the utilization of first-line drugs such as isoniazid, rifampicin, pyrazinamide, and ethambutol, and the consideration of adverse drug reactions in the assessment, while the present study has no any focus upon the pharmacokinetics of first-line drugs. The findings of the systematic review identified lower plasma concentrations of anti-tubercular drugs, particularly rifampicin, isoniazid, and pyrazinamide, and associated them with poor treatment outcomes. It emphasized the importance of increasing exposure to rifampicin to improve outcomes. In contrast, the present study did not explicitly focus on drug plasma concentrations but instead highlighted the treatment regimens, drug combinations, and therapeutic outcomes. It reported a substantial proportion of patient deaths (15.1%) as the primary outcome, with notable percentages for patients cured (41.5%) and others. Further collaboration and comparative studies between different countries may provide a more comprehensive understanding of the factors influencing TB treatment outcomes [146]. Overall, discrepancies in results may stem from differences in study design, patient populations, or regional variations in risk factors. Socioeconomic factors, lifestyle patterns, and genetic predispositions may also contribute to the observed differences. Strengths and Limitations This research, employing a retrospective, descriptive cohort design with a sample size of 402 individuals diagnosed with tuberculosis, exhibits methodological strength. Comprehensive inclusion criteria, encompassing diverse demographic, lifestyle, and clinical variables, enhance study validity. This study, one of the few investigating the association between cardiovascular disease risk and tuberculosis, incorporates a broad spectrum of clinical characteristics. Limitations include the retrospective nature of data collection, precluding assessment of crucial parameters such as educational attainment, employment status, monthly income, and treatment non-adherence reasons. Dependence on patient records may limit the availability of specific variables. Furthermore, the single-center design at Penang General Hospital may restrict the generalizability of findings to wider populations. Conclusions This research investigated the principal predictors of cardiovascular disease (CVD) development, including elevated high-sensitivity troponin-T, C-reactive protein levels, ST-segment elevation, and electrocardiographic (ECG) depression. Echocardiography and cardiac enzyme assays were employed to detect CVD development. The study revealed specific associations within the cardiovascular phenotype, including elevated plasma troponin-T concentrations, ECG abnormalities, abnormal echocardiographic findings, and alterations in blood biochemical parameters, highlighting potential cardiovascular involvement. Risk factors associated with CVD development included age, body mass index, lifestyle factors (including intravenous drug use), and comorbidities (hypertension, diabetes mellitus, acute kidney injury, and anemia). Binary logistic regression analyses identified statistically significant correlations between demographic variables, lifestyle factors, comorbid conditions, and clinical characteristics with the probability of CVD among tuberculosis (TB) patients. Overall, the findings contribute valuable insight into the complex interplay between TB infection and CVD. It emphasizes the need for comprehensive assessment, management, and tailored treatment strategies for TB patients to mitigate the risk of cardiovascular complications. Furthermore, the correlation between pharmacotherapy and clinical outcomes emphasized the need for personalized treatment approaches. The association of TB case types with treatment outcomes underscored the complexity of therapeutic responses. Additionally, the correlation between comorbidities and clinical outcomes demonstrated varying associations. Treatment regimens for TB and CVD were outlined, emphasizing the individualized approach to managing both conditions simultaneously. Binary Logistic Regression analyses indicated substantial associations between the presence of CVD and clinical outcomes in TB patients, highlighting the complexity of the interplay between TB, CVD, and treatment responses. Overall, the findings contribute valuable insights into the multifaceted relationship between TB, CVD, and associated factors, emphasizing the need for integrated healthcare approaches to address the dual burden of infectious and non-communicable diseases in affected populations. This study provides evidence supporting the hypothesis that TB infection plays a significant role in the development of cardiovascular disease. It underscores the importance of comprehensive evaluation, management, and tailored treatment approaches for TB patients to mitigate the risk of cardiovascular complications. In summary, it can be concluded that there is a significant association between TB and CVD. Various factors are responsible for moving a TB patient towards cardiovascular disease. Further research is warranted to validate these associations and elucidate their clinical implications. Recommendations To prevent the development of cardiovascular disease (CVD) among tuberculosis (TB) patients, several crucial recommendations should be considered. Firstly, routine screening for latent TB infection (LTBI) in individuals with known cardiovascular risk factors can help identify and treat TB at an early stage, potentially mitigating the inflammatory processes associated with CVD. Timely initiation of anti-tubercular therapy (ATT) is vital and close monitoring for adverse drug reactions, especially hepatotoxicity, can ensure uninterrupted TB treatment, reducing the risk of cardiovascular complications. Given the intricate interplay between TB and CVD, healthcare providers should adopt an integrated approach, involving collaboration between TB and cardiovascular specialists. Managing traditional cardiovascular risk factors such as hypertension, diabetes, and dyslipidemia becomes paramount in TB patients. Lifestyle modifications, including smoking cessation and dietary interventions, should be emphasized alongside comprehensive TB care. Incorporating cardiovascular risk assessment tools into the routine evaluation and screening of TB patients can aid in stratifying individuals based on their susceptibility to CVD. A leaflet of information about the risk of CVD development and associated risk factors must be issued to patients in both Bahasa Melayu and English language versions. A minimum dose of statin and anti-coagulant (thrombolytic agent) should be established for TB patients according to the severity and stage of tuberculosis infection and traditional risk factors; especially in the case of chronic and relapse case of TB as a preventive measure for the CVD development. This strategy would be the same as a minimum dose of Pyridoxine (Vitamin B6) is administered to TB patients to nullify the side effect of neurotoxicity by Isoniazid. Future Directions Health education plays a pivotal role, empowering TB patients with knowledge about the dual burden of TB and CVD, fostering adherence to treatment regimens, and promoting a heart-healthy lifestyle. Elevated levels of cytokines in pulmonary tuberculosis (PTB) suggest the involvement of inflammation attributable to TB infection. This underscores the importance of investigating a panel of immunological markers in future research endeavours to establish a definitive connection. The Ministry of Health, Malaysia should be more alert about the defaulters of anti-TB treatment to avoid further bad consequences of drug resistance and relapse of TB; as these consequences are indirectly related to the development of cardiovascular complications among TB patients. A comprehensive prospective study encompassing a larger participant pool and an extended follow-up duration is necessary across Malaysia to elucidate the association between tuberculosis (TB) pathogenesis and the risk of cardiovascular disease (CVD). Such research endeavours will not only enhance our limited understanding but also enhance the scope of screening initiatives for concurrent TB-related ailments. Longitudinal Cohort Studies throughout the whole of Malaysia need to be conducted to understand the dynamic interplay between tuberculosis (TB) and cardiovascular disease (CVD) over time in which follow–up of TB patients with and without CVD must be monitored from diagnosis through treatment completion. Any changes in cardiovascular health markers, disease progression, and treatment outcomes must be analyzed. This approach will provide the prevalence of CVD among the TB population in the whole of Malaysia. Also, this approach will provide statistics on mortality due to cardiovascular diseases among the TB population in the whole of Malaysia. Declarations As this study was retrospective and only involved the use of existing data, it posed no harm to the patients, as confidentiality was maintained (patient names and identification were not recorded). Also, informed consent from patients was not required for this study. Ethical guidelines were followed for the study, and ethical approval was obtained from the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia, before initiation of the study (NMRR-18-95-39523 - [Research ID: 39523]). Ethical Approval As this study was a retrospective study that only involved the use of existing data, it imposed no harm on the patients as confidentiality was maintained (patient names and identification were not recorded). Informed consent from patients was not required for this study. Ethical guidelines were followed for the study, and ethical approval was obtained from the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia, before initiation of the study (NMRR-18-95-39523 - [Research ID: 39523]). Authors contributions All authors listed meet the criteria of authorship and have made a substantial, direct, and intellectual contribution to the work and approved it for publication. Conflict of interest No Research Funding Source (If any): No Acknowledgment We would like to thank the Director General of Health Malaysia for his permission to publish this article. References “TB Mortality.” Accessed: Nov. 15, 2023. [Online]. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7341189","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":498416427,"identity":"c639e7d1-4d6e-42a2-80d2-7719dabd09d1","order_by":0,"name":"Bheesham Kingrani","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-9772-013X","institution":"School of Pharmaceutical Sciences, Universiti Sains Malaysia","correspondingAuthor":true,"prefix":"","firstName":"Bheesham","middleName":"","lastName":"Kingrani","suffix":""},{"id":498416553,"identity":"a255a34b-4013-450a-a256-f1eab6e75e19","order_by":1,"name":"Amer Hayat Khan","email":"","orcid":"","institution":"School of Pharmaceutical Sciences, Universiti Sains Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Amer","middleName":"Hayat","lastName":"Khan","suffix":""},{"id":498416554,"identity":"b0585dee-cb92-48d3-bd91-58e9b23b9f6e","order_by":2,"name":"Sabariah Noor Harun","email":"","orcid":"","institution":"School of Pharmaceutical Sciences, Universiti Sains Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Sabariah","middleName":"Noor","lastName":"Harun","suffix":""},{"id":498416555,"identity":"62fb58b8-bdd1-403e-bb2e-d461b08f1486","order_by":3,"name":"Irfhan Ali Hyder Ali","email":"","orcid":"","institution":"Hospital Pulau Pinang, Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Irfhan","middleName":"Ali Hyder","lastName":"Ali","suffix":""}],"badges":[],"createdAt":"2025-08-11 00:15:08","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7341189/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7341189/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89290728,"identity":"270cfb9a-f421-4a11-bac5-e44d342818e6","added_by":"auto","created_at":"2025-08-18 12:17:16","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":423243,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRole of Tuberculosis Infection in Atherosclerosis \u003cbr\u003e\n(Inflammatory Process) [44]\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7341189/v1/81875641c9a4cef6195634c1.jpeg"},{"id":89290730,"identity":"ff474bf6-7d3e-4a50-bfd2-9092c7c7a9b2","added_by":"auto","created_at":"2025-08-18 12:17:16","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":175864,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 4.3 Bar Chart Showing Association of Type of TB case\u003cbr\u003e\n \u0026nbsp;(Pharmacotherapy) with Clinical Outcomes\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7341189/v1/23e7f94a2270623749bd3396.jpeg"},{"id":89292550,"identity":"6dbbdcd1-45fc-4546-a153-39c730bcd1af","added_by":"auto","created_at":"2025-08-18 12:41:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2149741,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7341189/v1/43616ad5-f5e2-4244-be5d-bc4a2478f760.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eAssessment of Pharmacotherapy and Clinical Outcomes of Treatment among Tuberculosis Patients\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e, the etiological agent of tuberculosis (TB), remains a significant global public health concern. TB, a respiratory infectious disease transmitted via aerosolized respiratory droplets from infected individuals, resulted in an estimated 1.3 million fatalities in 2020, increasing to 1.4 million in 2021 despite global efforts. Diagnostic and therapeutic challenges during the COVID-19 pandemic contributed to a decline in TB control efforts, reversing previously observed progress [1]. Estimated new TB cases in 2021 reached 10.6 million, inclusive of approximately 7% with compromised immunity. Epidemiological data indicate a higher incidence of infection among male individuals compared to females [2]. \u003c/p\u003e\n\u003cp\u003eIn 2022, 1.3 million fatalities from TB were recorded, with 167,000 co-infected with HIV. TB ranks second as a leading cause of infectious disease mortality globally, behind COVID-19 but ahead of HIV/AIDS [3]. Data from 2023 indicate an estimated 8.2 million new cases, the highest since global surveillance began in 1995. This represents a notable increase from 7.5 million cases in 2022, making TB the leading infectious disease cause of death in 2023, thereby surpassing COVID-19 mortality. Mixed results were observed in the global fight against TB in 2023, despite a reduction in fatalities to 1.25 million from 1.32 million in 2022, while estimated incident cases rose slightly to ~10.8 million in 2023 [4].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e is the causative agent of tuberculosis (TB), a respiratory disease transmitted by inhaling aerosolized droplets from infected individuals. Tuberculosis is a serious respiratory disease that is a serious public health problem. Effective control of the disease worldwide requires the development of effective vaccines, improved diagnostics, and new, short-term treatments [5], [6].\u003c/p\u003e\n\u003cp\u003eIncreasing evidence suggests that tuberculosis (TB) disease may disrupt host metabolism and contribute to subsequent risks of chronic non-communicable diseases (NCDs) [7], [8], [9]. A large proportion of TB patients reside in low- and middle-income countries, where the risks posed by chronic NCDs, such as type 2 diabetes mellitus, acute myocardial infarction, and stroke, are substantial public health threats. [10].\u003c/p\u003e\n\u003cp\u003eRecent evidence demonstrates that Mycobacterium tuberculosis-induced inflammatory responses persist beyond treatment for active tuberculosis, resulting in chronic inflammation in individuals who have survived the infection [11], [12]. In addition, the long-term mortality of TB survivors is higher than that in the general population [13], [14]. Hyperglycemia represents a well-established risk factor for Mycobacterium tuberculosis infection [15] and suboptimal treatment outcomes [16]. Factors contributing to cardiovascular disease risk in tuberculosis may include direct effects of M. tuberculosis on the cardiac musculature and coronary vasculature, augmented immune activation resulting in elevated cytokine production, and potential cross-reactivity of antibodies targeting mycobacterial components against cardiovascular tissues [17], [18].\u003c/p\u003e\n\u003cp\u003eStudies have demonstrated a heightened susceptibility to coronary heart disease (CHD) in individuals who have survived tuberculosis (TB) infection [19]. Furthermore, accumulating evidence indicates an elevated risk of ischemic stroke, a consequence of atherosclerosis, in TB survivors, reinforcing the association between TB and CHD [20]. Recent research has revealed that individuals with either pulmonary or extrapulmonary tuberculosis exhibit an increased risk of future acute myocardial infarction and unstable angina. Remarkably, the elevated risk of cardiovascular disease (CVD) persists even several years post-initial Mycobacterium tuberculosis diagnosis. This suggests that tuberculosis may elicit both acute and chronic CVD sequelae [21].\u003c/p\u003e\n\u003cp\u003eElevated blood pressure, diabetes mellitus, dyslipidemia, and obesity, traditional cardiovascular risk factors, are supplemented by evidence from clinical literature indicating that Mycobacterium tuberculosis (MTB) promotes atherosclerosis through its pronounced inflammatory response, thus indirectly contributing to the development and progression of cardiovascular pathologies [22], [23], [24], [25]. The pathophysiological mechanism linking MTB to atherosclerotic lesion formation and progression resides in its pro-inflammatory effect on the vascular endothelial lining [26], [27], [28].\u003c/p\u003e\n\n\u003cp\u003eTuberculosis (TB) and ischemic coronary artery disease (ICAD) exhibit a heightened co-occurrence in developing nations. Several mechanistic underpinnings are posited. One proposed mechanism implicates a chronic inflammatory response, characterized by cell-mediated immune activation and the subsequent release of cytokines and chemokines, following latent infection. A second mechanism involves the initiation of an autoimmune process after chronic infection, resulting in the generation of antibodies targeting mycobacterial heat shock protein 65 (HSP65) [29]. This phenomenon elicits a cross-reactive response with human HSP65, contributing to endothelial damage and stimulating atherogenic processes. Heat shock proteins represent a homogeneous protein family, inducible in response to environmental stressors, initially identified as a heat-induced response. These proteins demonstrate high evolutionary conservation across species, and exhibit chaperone activity and a role in mediating immune responses in specific disease states. [30].\u003c/p\u003e\n\n\u003cp\u003eRecognizing atherosclerosis as an inflammatory process, several plasma inflammatory markers have been assessed as potential predictors of coronary event risk. These include markers of systemic inflammation, such as hepatic-derived high-sensitivity C-reactive protein (hs-CRP) and serum amyloid A; cytokines, including interleukin-6; and adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1) [31], [32], [33], [34], [35], [36], [37], [38].\u003c/p\u003e\n\u003cp\u003eA causal relationship exists between cholesterol and \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e (MTB), the bacterial agent requiring cholesterol for infection and survival, though infection progression correlates with the capacity of the host immune system to limit infection [39, 40]. Lipid components play a critical role in both tuberculosis development and cardiovascular disease pathogenesis, as noted by Wilburn et al. [41]. Mycobacterial cells contain diverse classes of non-structural and structural lipids, functioning as a primary energy source and contributing significantly to pathogenicity, virulence, and persistence of \u003cem\u003eMycobacterium \u003c/em\u003especies [42].\u003c/p\u003e\n\u003cp\u003eCardiovascular disease encompasses a spectrum of pathologies stemming from reduced coronary blood flow. This includes life-threatening conditions such as unstable angina and myocardial infarction. Despite therapeutic advancements, these conditions remain significant contributors to morbidity and mortality. Complications of myocardial infarction can manifest as heart failure, arrhythmias, and cerebrovascular accident [43]. The impact of tuberculosis extends beyond coronary artery disease and includes other vascular diseases associated with atherosclerosis, including cerebrovascular accident. A three-year prospective cohort study of tuberculosis patients evaluated the risk of ischemic stroke; the results indicated a 50% increased risk of ischemic stroke among individuals with TB [9].\u003c/p\u003e\n\n\u003cp\u003eTuberculosis (TB) infection demonstrably elevates the risk of cardiovascular disease (CVD) via mechanisms including immune system activation and inflammatory responses. However, a significant knowledge deficit remains regarding the intricate relationship between TB and CVD, especially in low- and middle-income nations such as Malaysia. Existing studies have predominantly focused on general comorbid conditions, rather than the specific interplay between TB and CVD. Clinicians frequently fail to recognize the need for targeted interventions aimed at managing CVD risk in this patient population. Further research will also improve clinical protocols and public health initiatives. Mitigation of these knowledge gaps can ultimately enhance patient outcomes and reduce morbidity and mortality linked to CVD in individuals affected by TB.\u003c/p\u003e\n\n\u003ch2\u003eRole of Tuberculosis Infection in Atherosclerosis (Inflammatory Process)\u003c/h2\u003e\n\u003cp\u003eFigure 1 depicts a schematic representation of the contribution of Mycobacterium tuberculosis infection to the inflammatory cascade driving atherosclerosis. Key pro-inflammatory risk factors, including oxidized low-density lipoprotein (LDL), vascular endothelial injury, and M. tuberculosis infection, are highlighted. In this model, M. tuberculosis serves as a persistent infectious stimulus that, concurrent with oxidative stress induced by oxidized LDL, primes the vascular milieu for inflammation. This initial event triggers the release of primary pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-\u0026alpha;), which are critical signaling molecules initiating the inflammatory cascade. These cytokines subsequently induce the expression of vascular cell adhesion molecules (VCAM-1, ICAM-1, and selectins) on endothelial cells, a prerequisite for leukocyte recruitment to the vascular wall. Subsequently, interleukin-6 (IL-6) acts as a pivotal cytokine amplifier, stimulating hepatic production of acute-phase reactants including C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen. These acute-phase proteins, acting as markers of inflammation, actively participate in atherosclerotic lesion development by modulating hemostasis and vascular remodeling. Ultimately, the cumulative effect of these inflammatory events results in atherogenesis, the formation of lipid-rich plaques within arterial walls, characteristic of atherosclerosis.\u003c/p\u003e\n\n\u003ch2 id=\"_Toc182712146\"\u003eStudy Outcomes and Impact on the Health Industry\u003c/h2\u003e\n\u003cp\u003eThis study compiles and analyzes cardiovascular disease-associated mortality rates in a tuberculosis patient cohort. This research has the potential to significantly impact the healthcare sector by providing essential data for refining clinical protocols and public health strategies. Furthermore, insights derived from demographic analyses can inform personalized treatment regimens, enhancing healthcare effectiveness and efficiency. Ultimately, by elucidating the mortality risk associated with CVD in TB patients, this research advocates for integrated care strategies targeting both conditions concurrently, potentially reducing healthcare expenditure and improving patient outcomes in at-risk populations [45]. \u003c/p\u003e"},{"header":"Methodology","content":"\u003ch2\u003eStudy design \u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThis study used a retrospective and descriptive research design. Participants were tuberculosis (TB) patients without cardiovascular disease at the initial examination or baseline. Generally, to achieve all objectives, the study parameters of TB and CVD were correlated to find a relationship between TB and CVD and associated risk factors for the development of CVD among TB patients.\u003c/p\u003e\n\u003ch2 id=\"_Toc163516973\"\u003eData Collection Period\u003c/h2\u003e\n\u003cp\u003eRetrospective data of patients with tuberculosis who were followed up at Penang General Hospital clinic were collected from January 2015 to December 2022 (01/01/2015-31/12/2022).\u0026nbsp;\u003c/p\u003e\n\u003ch2 id=\"_Toc163516974\"\u003eSampling Method\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003ePatients meeting the inclusion criteria were selected using a convenient sampling technique. \u0026nbsp;\u003c/p\u003e\n\u003ch2 id=\"_Toc163516975\"\u003eSample Size\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eData from 402 files of patients was extracted. The sample size was selected using the prevalence proportion formula [46]:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEquation:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg 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width=\"298\" height=\"99\"\u003e\u003c/p\u003e\n\u003cp\u003eWhere n = sample size\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eZ\u003c/em\u003e = statistic for a level of confidence, (Z = 1.96 for 95% CI)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e = expected prevalence or proportion, (P = 50% or 0.5)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eE\u003c/em\u003e = margin of error (E = 5% or 0.05)\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" width=\"489\" height=\"384\"\u003e\u003c/p\u003e\n\u003cp\u003eParameters such as the percentage score, margin of error, confidence level, and population size are essential in determining sample size. For this study, an assumed indicator percentage of 50% was used, with a 5% margin of error and a 95% confidence level. This yielded a minimum required sample size of 384. A total of 434 patient files were initially selected, but 32 files (8%) were excluded based on the exclusion and withdrawal criteria (i.e., patients whose diagnosis had changed or those who already had cardiovascular disease at baseline). Consequently, 402 patient files were included in the final analysis.\u003c/p\u003e\n\u003ch2 id=\"_Toc163516976\"\u003e\u0026nbsp;Inclusion Criteria\u003c/h2\u003e\n\u003col\u003e\n \u003cli\u003eAdults \u0026ge;18 years old\u003c/li\u003e\n \u003cli\u003ePatients with a confirmed diagnosis of tuberculosis (pulmonary and extrapulmonary tuberculosis) without any cardiovascular disease at baseline.\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch2 id=\"_Toc163516977\"\u003eExclusion Criteria\u003c/h2\u003e\n\u003col\u003e\n \u003cli\u003ePatients with autoimmune disease\u003c/li\u003e\n \u003cli\u003eChildren\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePregnant women\u003c/li\u003e\n \u003cli\u003eFiles of patients whose records were incomplete were not included in the study\u003c/li\u003e\n \u003cli\u003eFiles of patients whose diagnosis had changed were excluded, specifically those initially misdiagnosed with MTB but later correctly diagnosed with another condition, such as interstitial lung disease.\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch2\u003eRegistered TB Cases at Penang General Hospital (Patient Case Selection Criteria)\u003c/h2\u003e\n\u003cp\u003eTable 1 presents the total number of registered tuberculosis (TB) cases at Penang General Hospital, Penang, Malaysia, from 2015 to 2022, along with the selection criteria for the study cohort. \u0026nbsp; A convenience sampling method (random selection based on accessibility and availability) was employed due to hospital administrative restrictions imposed by the COVID-19 pandemic. Data collection was facilitated by nursing staff, owing to limitations on access to the data records. \u0026nbsp;Nursing staff sorted TB case files from other respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, bronchitis, and interstitial lung disease, providing 5 to 7 randomly selected files daily. \u0026nbsp;For example, in 2015, 63 of the 581 registered TB cases were included in the study (approximately 10.84%). \u0026nbsp;Similarly, in 2022, 50 of the 502 registered TB cases were included (approximately 9.96%).\u003c/p\u003e\n\u003cp id=\"_Toc518312771\"\u003e\u003cstrong\u003eTable 01: \u0026ldquo;Data of registered tuberculosis cases at Penang General Hospital, Malaysia\u0026rdquo;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"97%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eData of the Year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Registered\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSelected Cases (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e63 (10.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e53 (8.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e39 (6.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e47 (9.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e54 (8.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e621\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e48 (7.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e441\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e48 (10.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e502\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e50 (9.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e4439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n\u003cp\u003eEach patient\u0026apos;s data collection form was assigned a unique serial number (patient identifier) to ensure data provenance. \u0026nbsp; Responses were encoded, and the data were input into a computer and analyzed using the Statistical Package for the Social Sciences (SPSS) software, version 27.0 for Microsoft Windows operating systems. \u0026nbsp;Given the data\u0026apos;s adherence to a Gaussian distribution, parametric statistical tests were employed. \u0026nbsp;A chi-squared test was used to assess the association between categorical variables (such as demographic factors including sex, race, and age) and the dependent variable (the development of cardiovascular disease). \u0026nbsp;Continuous variables of interest were summarized as means or medians with standard deviations (descriptive statistics), while categorical variables (e.g., age, sex, ethnicity) were presented as proportions.\u003c/p\u003e\n\u003ch2\u003eBasic Criteria of Cardiovascular Disease among the Study Population\u003c/h2\u003e\n\u003col style=\"list-style-type: lower-roman;\"\u003e\n \u003cli\u003ePatient diagnosed with coronary heart disease, either stable coronary artery disease or acute coronary disease (NSTEMI, UA, or STEMI).\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Patient diagnosed with heart failure, either with preserved ejection fraction (HFpEF), defined by an LVEF \u0026ge;50%, heart failure with reduced ejection fraction (HFrEF) if the LVEF is \u0026lt;40%, and heart failure with mid-range ejection fraction (HFmrEF) if the LVEF is 40\u0026ndash;49%.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Patient diagnosed with arrhythmias, either supraventricular arrhythmias, ventricular arrhythmias, or Brady arrhythmias.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePatient diagnosed with Stroke, whether it is Ischemic stroke, Hemorrhagic stroke, or Transient ischemic attack (Mini Stroke).\u003c/li\u003e\n \u003cli\u003ePatient diagnosed with any Aortic disease, such as Aortic Aneurysm, Aortic Occlusive disease, Aortitis, or\u0026nbsp;Aortic valvular disease.\u003c/li\u003e\n \u003cli\u003ePatients diagnosed with Peripheral Vascular disease, which includes mainly Peripheral venous disease, Deep Vein Thrombosis, Pulmonary Embolism, Peripheral Artery Disease, Aneurysm, Chronic venous insufficiency, and Ischemic Limb disease.\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch2 id=\"_Toc182712170\"\u003eCardiovascular Disease\u003c/h2\u003e\n\u003cp\u003eCardiovascular diseases (CVDs) represent a spectrum of pathologies affecting the cardiovascular system. \u0026nbsp; These conditions encompass hemodynamic impairments affecting the coronary, cerebral, or peripheral vasculature, frequently arising from thrombotic events or atheromatous plaque formation leading to arterial stenosis or occlusion. \u0026nbsp;Four primary subtypes of CVD are distinguished:\u003c/p\u003e\n\u003cp\u003e1. Coronary heart disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. Stroke\u003c/p\u003e\n\u003cp\u003e3. Peripheral arterial disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4. Aortic disease \u0026nbsp;[47]\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eAssessment of Pharmacotherapy and Clinical Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe treatment aimed to cure the patients, to render them non -non-infectious, to reduce morbidity and mortality, and to prevent the relapse and emergence of resistant tubercle bacilli. Five drugs are generally considered essential in the treatment of tuberculosis; Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Streptomycin (S), and Ethambutol (E). The treatment regimen is divided into two phases: the intensive phase and the continuation phase.\u003c/p\u003e\n\u003cp\u003eIn this study, the most common treatment regimen encountered was two months of daily doses of E, H, R, and Z for the initial phase (EHRZ), followed by four months of daily doses or thrice weekly doses of R and H (4HR) for the continuation phase. Other treatment regimens were also observed for patients with problems, such as adverse drug reactions, which were grouped as miscellaneous. All the patients were supplemented with oral pyridoxine (Vitamin B6) or a combination of Vitamin B1, B6, and B12 (Tablet Neurobion) to minimize the side effects (Neurotoxicity) of isoniazid. Rifampicin was the main drug that was noted to be used throughout the full course (Intensive Phase + Maintenance Phase) of TB therapy. Streptomycin was used as a substitute for Ethambutol, where ever Ethambutol was contraindicated.\u003c/p\u003e\n\u003cp\u003eUsually, fixed-dose combination therapy was observed such as Tablet Akurit-4 (Combination of Isoniazid 75mg, Rifampicin 150mg, Ethambutol 275mg, and Pyrazinamide 400mg) was prescribed for the intensive phase and Tablet Akurit-2 (Combination of Isoniazid 75mg and Rifampicin 150mg) was prescribed for continuation phase. Sometimes Tablet Akurit-3 (A combination of Isoniazid 75mg, Rifampicin 150mg, and Pyrazinamide 400mg) was observed to be prescribed in the intensive phase. Fixed-dose combination therapy was encouraged and followed to avoid prescribing errors and non-compliance to individualized drugs by patients. Fixed-dose combination therapy (FDCs) was discouraged if a patient developed any toxicity, intolerance, or contraindication to any of the components or specific drugs of therapy. The duration of treatment for TB-Meningitis was a bit longer such as 9 to 12 months (2 months intensive phase followed by 7 to 10 months continuation phase treatment). For Bone and joint TB, treatment was also a bit longer such as 9 months (2 months intensive phase followed by 7 months continuation phase). Corticosteroid therapy was seen in TB Meningitis and TB Pericarditis that included Dexamethasone injection or tablet Prednisolone. A dose of Tablet Akurit-4 (FDCs) was prescribed based on the weight range of the patient such as:\u003c/p\u003e\n\u003cp\u003e1. 30kg-37kg...........................2 Tablets daily\u003c/p\u003e\n\u003cp\u003e2. 38kg-54kg...........................3 Tablets daily\u003c/p\u003e\n\u003cp\u003e3. 55kg-70kg...........................4 Tablets daily\u003c/p\u003e\n\u003cp\u003e4. More than 70kg...................5 Tablets daily\u003c/p\u003e\n\u003cp\u003eThe following is the table of dosing patterns that were observed in Penang General Hospital for the anti-TB therapy of patients in this study.\u003c/p\u003e\n\u003cp id=\"_Toc153478442\"\u003eTable 4.19 Observed Pattern of Drug Dosing and its Types\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"94%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrug Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 35px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDaily Dosing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3X a week Dosing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDose (range) in mg/kg\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ebody weight\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaximum in mg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDose (range) in mg/kg\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ebody weight\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaximum in mg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eIsoniazid (H)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e5 (4-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e10 (8 - 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e900\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eRifampicin (R)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e10 (8-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e10 (8 - 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003ePyrazinamide (Z)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e25 (20-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e35 (30 \u0026ndash; 40)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e3000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eEthambutol (E)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e15 (15-20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e1600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e30 (25 \u0026ndash; 35)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2400*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eStreptomycin (S)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e15 (12-18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e15 (12 \u0026ndash; 18)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1500*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp id=\"_Toc182712215\"\u003e\u003cstrong\u003eReported Adverse Drug Reactions (ADRs)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study identified patients experiencing adverse drug reactions (ADRs) to anti-tubercular therapy, primarily manifesting as Drug-Induced Hepatitis. For these patients, the anti-tubercular drug treatment was halted, either partially or entirely, and recovery was monitored through regular liver function tests (LFT). Upon normalization of LFT results, patients resumed treatment with the same drugs, accompanied by constant liver function monitoring. The study reported that 15% of patients encountered skin rashes and itchiness attributed to Rifampicin and Ethambutol. Patients with rashes received topical creams for relief, and Anti-TB treatment was temporarily paused. Treatment continued for patients with non-serious ADRs. Allergic reactions led to the suspension of the implicated drug, with second-line anti-tubercular drugs, such as Levofloxacin, prescribed. Other observed adverse drug reactions included blurred vision (Due to Ethambutol), thrombocytopenia (Due to Rifampicin), drug-induced liver injury (Due to Pyrazinamide), vomiting, increased ALT (Acute Transaminitis), hyperbilirubinemia, elevated ALP, and dry scaly skin with pruritus. Following were the statistics of adverse drug reactions, presented in table 4.20.\u003c/p\u003e\n\u003cp\u003eTable 4.20 Statistics of Adverse Drug Reactions\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdverse Drug Reaction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentage (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003eRashes and Itchiness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e6.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003eDrug-Induced Hepatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003eTransaminitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e8.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003eNausea and Vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e4.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003eBlurred Vision\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e2.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003eThrombocytopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e2.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003eHyperbilirubinemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e4.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eDrug-Resistant\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTuberculosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll \u003cem\u003eMycobacterium\u0026nbsp;\u003c/em\u003ecultures isolated from the clinical specimens of patients were sent for drug susceptibility/sensitivity testing (DST). The test was conducted to determine the susceptibility and sensitivity of the \u003cem\u003eMycobacterium\u0026nbsp;\u003c/em\u003eto the anti-tuberculosis drugs. Sometimes GeneXpert and Line Probe Assay testing was conducted to rule out drug resistance. DST and Line Probe Assay were used to rule out resistance for all primary first-line drugs but GeneXpert was used to rule out resistance to Rifampicin only. If the \u003cem\u003eMycobacterium Tuberculosis\u0026nbsp;\u003c/em\u003estrain is resistant to INH and RIF, it was being considered as multi-drug-resistant TB (MDR-TB).\u003c/p\u003e\n\u003cp\u003eThere were 14 cases of Mono-drug resistant (Resistant to either Isoniazid or Rifampicin of first-line Anti-TB approved drugs) cases, 07 Multi-drug Resistant (Resistant to two or more first-line Anti-TB drugs and at least resistant to both Isoniazid and Rifampicin) and 05 Poly-drug Resistant (Resistant to two or more first-line drugs of Anti-TB and not resistant to both Isoniazid and Rifampicin simultaneously) cases in this study. The 2\u003csup\u003end\u003c/sup\u003e line anti-tubercular drug regimen was prescribed to patients with resistance to 1\u003csup\u003est\u003c/sup\u003e line anti-tubercular drug(s). For mono and multi-drug-resistant TB, the addition of second-line anti-TB agents such as Tablet Levofloxacin, Tablet Ethionamide, Tab. Cycloserine, Injection Kanamycin, Meropenem, and Linezolid, etc. were observed in recommended doses.\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc153478443\"\u003eTable 4.21 outlines drug-resistant tuberculosis cases that were total 26 in number as Isoniazid (1.7%), Rifampicin (1.7%), Isoniazid and Rifampicin both (MDR-1.4%), Rifampicin and Ethambutol (0.9%), Rifampicin and Streptomycin (0.2%), Isoniazid and Streptomycin (0.2%).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eTable 4.21 Frequency of Drug-Resistant Cases\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResistant Drug Name (s)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency (N) of Drug-Resistant case\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentage (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eIsoniazid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eRifampicin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eIsoniazid and Rifampicin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eIsoniazid and Streptomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eRifampicin and Ethambutol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eRifampicin and Streptomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 197px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 178px;\"\u003e\n \u003cp\u003e6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAnti-Tubercular Therapeutic\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4.22 outlines the clinical outcomes of tuberculosis treatment. Significant findings included a cure rate of 41.5% (167 patients), a mortality rate of 15.2% (61 patients), and a treatment completion rate of 21.9% (88 patients). Notably, 5.5% of patients were lost due to follow-up, while only 0.7% experienced treatment failure. These statistics underscore the effectiveness of treatment programs, with low rates of treatment failure and loss to follow-up (Defaulter) and high rates of successful cure and treatment completion.\u003c/p\u003e\n\u003cp\u003eTable 4.22 Frequency of Patients according to Clinical Outcomes of Treatment\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"95%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment Outcome Category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency (N) of patient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentage %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eLoss to follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003ePatient Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e41.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003ePatient Died\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e15.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eTransferred out\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eTreatment Completed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e21.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eTreatment failed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp id=\"_Toc182712218\"\u003e\u003cstrong\u003eAssociation of Pharmacotherapy with Clinical Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4.23 presents the association between pharmacotherapy or treatment regimen and clinical outcomes of tuberculosis (TB) treatment across different types of TB cases. Notable findings included a higher percentage of patients cured among new TB cases (41.5%) compared to relapse cases with defaulted or completed therapy. Relapse TB cases with completed therapy also exhibited a relatively high cure rate (12 patients, 50%). Conversely, patients with multi-drug/poly-drug-resistant TB had a higher mortality rate (15.2%) and lower cure rates. The Chi-square test indicates a statistically significant association between the type of TB case and treatment outcome (\u0026chi;2 = 15.826, p \u0026lt; 0.05), suggesting that different TB presentations respond differently to pharmacotherapy. The data suggest that patients with new TB cases have better treatment outcomes, while those with drug-resistant TB face greater challenges in treatment success. This underscores the importance of tailored treatment regimens based on the type of TB case and drug susceptibility patterns. Additionally, loss to follow-up is absent among relapse TB cases with defaulted treatment cases suggesting improved treatment adherence in this subgroup. These findings emphasize the necessity of personalized approaches to TB treatment to optimize outcomes and reduce mortality rates, especially among patients with drug-resistant TB strains.\u003c/p\u003e\n\u003cp id=\"_Toc153478445\"\u003eTable 4.23 Association of Pharmacotherapy with Clinical Outcomes of Treatment\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"94%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of TB case and Pharmacotherapy or Treatment Regimen Therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLoss to follow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient Cured\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDied\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTransfer\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Out\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCompleted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment Failure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChi-Square x2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eNew TB Case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" style=\"width: 9px;\"\u003e\n \u003cp\u003e15.826\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" style=\"width: 8px;\"\u003e\n \u003cp\u003e0.920\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eRelapse TB case with defaulted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eRelapse case with complete therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eTB case after Treatment failed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eMono-drug Resistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eMulti-drug/Poly-drug Resistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Outcomes of TB Patients with Comorbidity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4.24 explores the correlation between comorbidities and clinical outcomes among tuberculosis (TB) patients. Notably, TB patients with comorbidities such as diabetes mellitus (TB-DM) and human immunodeficiency virus (TB-HIV) showed significant associations with treatment outcomes. Specifically, TB-DM patients exhibited higher rates of treatment completion and cure compared to other groups, while TB-HIV patients had a higher mortality rate and lower treatment completion rates. The Chi-square test revealed statistically significant associations between TB-DM (\u0026chi;2 = 14.720, p = 0.012) and TB-HIV (\u0026chi;2 = 28.727, p = 0.001) with treatment outcomes, highlighting the importance of managing these comorbidities during TB treatment to improve patient outcomes. Conversely, TB-AKI (acute kidney injury) showed a statistically significant association with poor treatment outcomes (\u0026chi;2 = 22.156, p \u0026lt; 0.001), indicating the need for tailored interventions for TB patients with renal complications.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4.24 Correlation of Comorbidities with Clinical Outcomes\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"96%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of Comorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLoss to follow up\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCured\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDied\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTransfer\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOut\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment Completed\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFailure\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChi-Square value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTB-HTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e5.847\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0.321\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTB-DM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e14.720\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTB-HIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e28.727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTB-Dyslipidaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e8.954\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0.111\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTB-AKI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e22.156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTB-CKD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e6.769\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eTB-Anaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e16.872\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n\u003c/table\u003e\n\u003cp id=\"_Toc182712220\"\u003e\u003cstrong\u003eTherapy for Cardiovascular Disease\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring TB treatment, patients who developed cardiovascular disease were started on treatment regimens related to cardiovascular disease. Following are the medicines that were observed to treat different types of cardiovascular diseases.\u003c/p\u003e\n\u003cp\u003eTable 4.25 Treatment Trend for Cardiovascular Disease\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of Drug\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eName of Medicine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 511px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1. Anti-Hypertensive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eBeta Blocker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Metoprolol, Tab. Bisoprolol, Tab. Atenolol, Tab. Carvedilol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eACE-Inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Perindopril\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eAngiotensin-II Receptor Antagonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Losartan, Tab. Telmisartan\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eCalcium Channel Blocker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Felodipine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 511px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2. Anti-Lipidemic\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHMG-CoA Reductase Inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Simvastatin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eAdvanced HMG-CoA Reductase Inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Atorvastatin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 511px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3. Anti-Coagulant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eAnti-Platelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eClopidogrel, Cardipril, Glyprin, Aspirin 150mg, Tab. Ticlopidine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eBlood Thinners\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Warfarin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 511px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4. Diuretic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eLoop Diuretic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Frusemide\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003ePotassium Sparing Diuretic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Spironolactone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eThiazide Type Diuretic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 337px;\"\u003e\n \u003cp\u003eTab. Hydrochlorothiazide\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 507px;\"\u003e\n \u003cp\u003eTable 4.25 (Continued)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of Drug\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 316px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eName of Medicine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 507px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5. Blood Pumping Booster\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003eFatty acid Oxidation Inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 316px;\"\u003e\n \u003cp\u003eTab. Trimetazidine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003eHyperpolarization-Activated Cyclic Nucleotide Gated Channel Blocker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 316px;\"\u003e\n \u003cp\u003eIvabradine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 507px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6. Inotrope\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003eCardiotonic Glycoside\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 316px;\"\u003e\n \u003cp\u003eTab. Digoxin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 507px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7. Anti-Anginal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 191px;\"\u003e\n \u003cp\u003eNitrates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 316px;\"\u003e\n \u003cp\u003eTab. Isosorbide Dinitrate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp id=\"_Toc182712221\"\u003e\u003cstrong\u003eCorrelation of Clinical Outcomes of TB Treatment with CVD and Without CVD\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4.26 examines the association between clinical outcomes of tuberculosis (TB) treatment with and without cardiovascular disease (CVD) among TB patients. Significant differences were observed in various treatment outcomes between TB patients with and without CVD. Notably, TB patients with CVD had significantly lower rates of loss to follow-up compared to those without CVD (\u0026chi;2 = 99.749, p \u0026lt; 0.001). However, they had notably higher mortality rates, with 28 deaths among TB patients with CVD compared to 34 deaths among those without CVD.\u003c/p\u003e\n\u003cp\u003eFurthermore, TB patients with CVD had a substantially lower number of patients cured and completed treatment compared to those without CVD, i.e. TB Patients without CVD, successfully cured were 157 (43.49%) out of 361 patients, while TB patients with CVD, successfully cured were only 10 (24.39%) out of total 41 patients. These results make us compelled for further cardiovascular health assessment.\u003c/p\u003e\n\u003cp\u003eTable 4.26 Association of Clinical Outcomes of TB Treatment with CVD and without CVD among TB Population\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"95%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTB-Without CVD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTB-With CVD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChi-Square\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eLoss to follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" style=\"width: 11px;\"\u003e\n \u003cp\u003e99.749\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003ePatient Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003ePatient Died\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eTransferred Out\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eCompleted Treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eTreatment Failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTotal 361 + 41 = 402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe widespread utilization of anti-tuberculosis drugs has led to effective tuberculosis control. Despite their efficacy, challenges such as prolonged treatment duration, the emergence of MDR strains, and adverse effects impacting therapy adherence persist. [144]. Among these adverse effects, Hepatotoxicity is a well-known complication of anti-tubercular therapy (ATT) [145]. In the present study, it was noticed that anti-TB therapy was paused until liver function tests (LFTs) normalized, after which treatment was resumed with either the same or second-line anti-tubercular drugs based on LFTs results.\u003c/p\u003e\u003cp\u003eNoteworthy adverse effects associated with first-line anti-tuberculosis drugs included skin rashes and itchiness which is linked to Isoniazid (INH), Pyrazinamide (PZA), and Streptomycin (SM). Nausea is associated with RIP and PZA, while drug-induced hepatitis is connected to treatment with INH, Rifampicin (RIP), and PZA. Thrombocytopenia is associated with RIP, and blurring of vision is linked to Ethambutol (ETH) and SM.\u003c/p\u003e\u003cp\u003eThe present study aimed to assess pharmacotherapy and clinical outcomes of treatment among tuberculosis (TB) patients. Dosing patterns were weight-based, and corticosteroid therapy was administered for TB Meningitis and TB Pericarditis. The standard TB treatment regimen consisted of a two-month initial phase (2EHRZ) followed by a four-month continuation phase (4HR). Rifampicin was consistently used throughout the entire treatment course. Fixed dose combination therapy (FDCs) was prevalent, with Tablet Akurit-4 prescribed for the intensive phase and Tablet Akurit-2 for the continuation phase. FDCs helped prevent prescribing errors and non-compliance. The dosing pattern was weight-dependent, with specific tablet combinations based on the patient's weight. ADRs, primarily Drug-Induced Hepatitis, were identified in 15% of patients. Skin rashes and itchiness were common, attributed to Rifampicin and Ethambutol. Temporary cessation of treatment and topical creams were used for non-serious ADRs. Severe reactions led to the suspension of the implicated drug, with second-line anti-TB drugs prescribed. The statistics revealed various ADRs, with rashes and itchiness being the most frequent (6.25%). Drug susceptibility testing (DST) and additional tests like GeneXpert and Line Probe assay were conducted to identify drug-resistant strains.\u003c/p\u003e\u003cp\u003eThe study reported 14 cases of Mono-drug-resistant TB, 07 cases of multi-drug-resistant TB, and 05 cases of Poly-drug-resistant TB. Second-line anti-TB agents were prescribed for resistant cases, such as Levofloxacin, Ethionamide, Cycloserine, Kanamycin, Meropenem, and Linezolid. The frequency of drug-resistant cases was 6.8%, with Rifampicin resistance being the most common. The therapeutic outcomes varied, with a high mortality rate (59.9%). Cured patients represented 22.7%, while smaller proportions experienced loss to follow-up (2.6%), transfer out (2.9%), treatment completion (11.5%), and treatment failure (0.5%).\u003c/p\u003e\u003cp\u003eThe association between pharmacotherapy and clinical outcomes did not show statistical significance overall, but a detailed examination revealed patterns in different TB case types. The association between pharmacotherapy and clinical outcomes showed diverse patterns among different TB case types. New TB cases exhibited varied outcomes, while relapse TB cases had fewer instances of death and treatment failure. Mono and multi-drug-resistant cases demonstrated different treatment responses, emphasizing the need for personalized therapeutic approaches. In the present study, significant findings included a cure rate of 41.5% (167 patients), a mortality rate of 15.2% (61 patients), and a treatment completion rate of 21.9% (88 patients). Notably, 5.5% of patients were lost due to follow-up, while only 0.7% experienced treatment failure. These statistics underscore the effectiveness of treatment programs, with low rates of treatment failure and loss to follow-up (Defaulter) and high rates of successful cure and treatment completion.\u003c/p\u003e\u003cp\u003eLike the Present study, A study conducted in Sudan by Monadil H Ali et al. (2019) [117] provided valuable insights into the challenges and outcomes associated with tuberculosis (TB) treatment, focusing on different aspects such as treatment success rates, pharmacotherapy, and clinical outcomes. Likewise present study, the referenced Sudanese study reports mortality rates among TB patients, although with different emphases. The study from Sudan emphasizes the overall success rate of MDR-TB treatment, which is 63.5%, and a mortality rate of 14.1%, while the current study provides a detailed breakdown of treatment outcomes, with a significant proportion (15.2%) of patients experiencing death and 41.5% success rate of treatment.\u003c/p\u003e\u003cp\u003eThe present study outlines the common treatment regimens, the use of fixed-dose combination therapy, and the dosing patterns based on patient weight. Similarly, the Sudanese study mentions the essential drugs in MDR-TB treatment, the treatment regimen phases, and the use of supplementary vitamins to mitigate side effects. Sudanese study reports an overall success rate of 63.5% in MDR-TB treatment, while the current study's clinical outcomes indicate a lower percentage (41.5%) of patients as cured. The Sudanese study specifically focuses on MDR-TB, which may have different success rates compared to the broader TB population in the present study. The present study reports 6.47% of cases with drug-resistant tuberculosis, including mono-drug, poly-drug, and multi-drug resistance. The Sudanese study does not specifically address drug resistance types among MDR-TB cases. Overall findings do not match due to a different TB population as the main subject, i.e. Sudanese study is only limited to MDR TB cases. [117].\u003c/p\u003e\u003cp\u003eA study conducted on \u0026ldquo;Treatment outcomes of drug-resistant tuberculosis in the Netherlands\u0026rdquo; [116] contributes valuable insights into the challenges associated with tuberculosis (TB) treatment, particularly in the context of drug-resistant TB (DR-TB). A commonality between the Netherlands study and the current study conducted in Malaysia is the emphasis on understanding treatment outcomes and risk factors associated with poor results. However, there are notable differences in the scope and methodologies of both studies.\u003c/p\u003e\u003cp\u003eThe Netherlands study highlights the importance of addressing the unique challenges posed by population migration and the complex treatment regimens for DR-TB patients. On the other hand, the current study provides a detailed analysis of anti-tuberculosis therapy, dosing patterns, adverse drug reactions, and drug-resistant TB cases, shedding light on the pharmacotherapy and clinical outcomes in a different healthcare setting. The Netherlands study identifies a low incidence of DR-TB and reports a cumulative incidence of unsuccessful treatment at 5%. In contrast, the present study reveals a higher proportion of unfavorable outcomes, with a significant percentage of patients experiencing death (15.1%). The Netherlands, being a low-incidence country, might have a more robust healthcare system and resources, contributing to comparatively better treatment outcomes. Variations in their contexts and methodologies lead to differences in observed outcomes. [116].\u003c/p\u003e\u003cp\u003eA study conducted by Shahzad A. et al. (2021) [120] in Pakistan reported a higher percentage of patients (35.8%) identified with drug-related problems, including untreated conditions, administration of drugs without indication, adverse drug reactions, total drug interactions, and polypharmacy issues. This contrasts with the present study, which did not explicitly report such a high incidence of drug-related problems. The Pakistan study emphasizes the role of clinical pharmacists and proper patient counseling to address these issues, suggesting a potential gap in healthcare systems. Furthermore, the current study provides a detailed breakdown of adverse drug reactions, including skin rashes, drug-induced hepatitis, transaminitis, nausea, vomiting, blurred vision, thrombocytopenia, hyperbilirubinemia, and their respective frequencies. In contrast, the Pakistan study does not provide such specific details regarding TB treatment outcomes.\u003c/p\u003e\u003cp\u003eThe present study reports a higher percentage of patient deaths (15.1%), while the Pakistan study does not provide an explicit figure for mortality. Both, Pakistan and the present study aimed to assess pharmacotherapy and clinical outcomes in TB patients and utilized retrospective data collection methods. The pharmacotherapeutic interventions in both studies involved a combination of anti-TB drugs, antibiotics, and supportive medications, showcasing a standard protocol for TB management. Moreover, both studies recognized the importance of monitoring adverse drug reactions (ADRs) and drug-resistant TB cases, indicating a comprehensive evaluation of treatment outcomes. Additionally, the present study explores the association between pharmacotherapy and clinical outcomes, demonstrating varying responses among different TB case types, such as new cases, relapse cases, and drug-resistant cases, while the Pakistan study lacks a similar in-depth analysis of the relationship between pharmacotherapy and clinical outcomes. To explain the contradictions, several factors should be considered. Firstly, differences in healthcare infrastructure, clinical practices, and patient demographics between Pakistan and Malaysia may contribute to variations in treatment outcomes. Furthermore, dissimilarities in data collection methodologies, including the definition and identification of drug-related problems, may lead to discrepancies [120].\u003c/p\u003e\u003cp\u003eIn the present study, noteworthy findings included a higher percentage of patients cured among new TB cases (41.5%) compared to relapse cases with defaulted or completed therapy. Relapse TB cases with completed therapy also exhibited a relatively high cure rate (12 patients, 50%). Conversely, patients with multi-drug/poly-drug-resistant TB had a higher mortality rate (15.2%) and lower cure rates. The Chi-square test indicates a statistically significant association between the type of TB case and treatment outcome (χ2\u0026thinsp;=\u0026thinsp;15.826, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting that different TB presentations respond differently to pharmacotherapy. The data suggests that patients with new TB cases have better treatment outcomes, while those with drug-resistant TB face greater challenges in treatment success. These findings emphasize the necessity of personalized approaches to TB treatment to optimize outcomes and reduce mortality rates, especially among patients with drug-resistant TB strains.\u003c/p\u003e\u003cp\u003eSimilarly, a systematic review conducted by Sileshi et al. (2021) [146] reported the impact of first-line Anti-Tubercular Drugs\u0026rsquo; Pharmacokinetics on Treatment Outcomes. The present study shares a common ground with the referenced study in the investigation of the impact of first-line anti-tubercular drugs on treatment outcomes. Findings of this systematic review include the recognition of the importance of pharmacokinetics in influencing treatment outcomes, the utilization of first-line drugs such as isoniazid, rifampicin, pyrazinamide, and ethambutol, and the consideration of adverse drug reactions in the assessment, while the present study has no any focus upon the pharmacokinetics of first-line drugs.\u003c/p\u003e\u003cp\u003eThe findings of the systematic review identified lower plasma concentrations of anti-tubercular drugs, particularly rifampicin, isoniazid, and pyrazinamide, and associated them with poor treatment outcomes. It emphasized the importance of increasing exposure to rifampicin to improve outcomes. In contrast, the present study did not explicitly focus on drug plasma concentrations but instead highlighted the treatment regimens, drug combinations, and therapeutic outcomes. It reported a substantial proportion of patient deaths (15.1%) as the primary outcome, with notable percentages for patients cured (41.5%) and others. Further collaboration and comparative studies between different countries may provide a more comprehensive understanding of the factors influencing TB treatment outcomes [146].\u003c/p\u003e\u003cp\u003eOverall, discrepancies in results may stem from differences in study design, patient populations, or regional variations in risk factors. Socioeconomic factors, lifestyle patterns, and genetic predispositions may also contribute to the observed differences.\u003c/p\u003e\u003cdiv id=\"Sec25\" class=\"Section2\"\u003e\u003ch2\u003eStrengths and Limitations\u003c/h2\u003e\u003cp\u003eThis research, employing a retrospective, descriptive cohort design with a sample size of 402 individuals diagnosed with tuberculosis, exhibits methodological strength. Comprehensive inclusion criteria, encompassing diverse demographic, lifestyle, and clinical variables, enhance study validity. This study, one of the few investigating the association between cardiovascular disease risk and tuberculosis, incorporates a broad spectrum of clinical characteristics. Limitations include the retrospective nature of data collection, precluding assessment of crucial parameters such as educational attainment, employment status, monthly income, and treatment non-adherence reasons. Dependence on patient records may limit the availability of specific variables. Furthermore, the single-center design at Penang General Hospital may restrict the generalizability of findings to wider populations.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis research investigated the principal predictors of cardiovascular disease (CVD) development, including elevated high-sensitivity troponin-T, C-reactive protein levels, ST-segment elevation, and electrocardiographic (ECG) depression. Echocardiography and cardiac enzyme assays were employed to detect CVD development. The study revealed specific associations within the cardiovascular phenotype, including elevated plasma troponin-T concentrations, ECG abnormalities, abnormal echocardiographic findings, and alterations in blood biochemical parameters, highlighting potential cardiovascular involvement. Risk factors associated with CVD development included age, body mass index, lifestyle factors (including intravenous drug use), and comorbidities (hypertension, diabetes mellitus, acute kidney injury, and anemia). Binary logistic regression analyses identified statistically significant correlations between demographic variables, lifestyle factors, comorbid conditions, and clinical characteristics with the probability of CVD among tuberculosis (TB) patients. Overall, the findings contribute valuable insight into the complex interplay between TB infection and CVD. It emphasizes the need for comprehensive assessment, management, and tailored treatment strategies for TB patients to mitigate the risk of cardiovascular complications.\u003c/p\u003e\u003cp\u003eFurthermore, the correlation between pharmacotherapy and clinical outcomes emphasized the need for personalized treatment approaches. The association of TB case types with treatment outcomes underscored the complexity of therapeutic responses. Additionally, the correlation between comorbidities and clinical outcomes demonstrated varying associations. Treatment regimens for TB and CVD were outlined, emphasizing the individualized approach to managing both conditions simultaneously. Binary Logistic Regression analyses indicated substantial associations between the presence of CVD and clinical outcomes in TB patients, highlighting the complexity of the interplay between TB, CVD, and treatment responses.\u003c/p\u003e\u003cp\u003eOverall, the findings contribute valuable insights into the multifaceted relationship between TB, CVD, and associated factors, emphasizing the need for integrated healthcare approaches to address the dual burden of infectious and non-communicable diseases in affected populations. This study provides evidence supporting the hypothesis that TB infection plays a significant role in the development of cardiovascular disease. It underscores the importance of comprehensive evaluation, management, and tailored treatment approaches for TB patients to mitigate the risk of cardiovascular complications. In summary, it can be concluded that there is a significant association between TB and CVD. Various factors are responsible for moving a TB patient towards cardiovascular disease. Further research is warranted to validate these associations and elucidate their clinical implications.\u003c/p\u003e\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\u003ch2\u003eRecommendations\u003c/h2\u003e\u003cp\u003eTo prevent the development of cardiovascular disease (CVD) among tuberculosis (TB) patients, several crucial recommendations should be considered.\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eFirstly, routine screening for latent TB infection (LTBI) in individuals with known cardiovascular risk factors can help identify and treat TB at an early stage, potentially mitigating the inflammatory processes associated with CVD.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eTimely initiation of anti-tubercular therapy (ATT) is vital and close monitoring for adverse drug reactions, especially hepatotoxicity, can ensure uninterrupted TB treatment, reducing the risk of cardiovascular complications. Given the intricate interplay between TB and CVD, healthcare providers should adopt an integrated approach, involving collaboration between TB and cardiovascular specialists.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eManaging traditional cardiovascular risk factors such as hypertension, diabetes, and dyslipidemia becomes paramount in TB patients. Lifestyle modifications, including smoking cessation and dietary interventions, should be emphasized alongside comprehensive TB care.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eIncorporating cardiovascular risk assessment tools into the routine evaluation and screening of TB patients can aid in stratifying individuals based on their susceptibility to CVD.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eA leaflet of information about the risk of CVD development and associated risk factors must be issued to patients in both Bahasa Melayu and English language versions.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eA minimum dose of statin and anti-coagulant (thrombolytic agent) should be established for TB patients according to the severity and stage of tuberculosis infection and traditional risk factors; especially in the case of chronic and relapse case of TB as a preventive measure for the CVD development. This strategy would be the same as a minimum dose of Pyridoxine (Vitamin B6) is administered to TB patients to nullify the side effect of neurotoxicity by Isoniazid.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\u003ch2\u003eFuture Directions\u003c/h2\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eHealth education plays a pivotal role, empowering TB patients with knowledge about the dual burden of TB and CVD, fostering adherence to treatment regimens, and promoting a heart-healthy lifestyle.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eElevated levels of cytokines in pulmonary tuberculosis (PTB) suggest the involvement of inflammation attributable to TB infection. This underscores the importance of investigating a panel of immunological markers in future research endeavours to establish a definitive connection.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eThe Ministry of Health, Malaysia should be more alert about the defaulters of anti-TB treatment to avoid further bad consequences of drug resistance and relapse of TB; as these consequences are indirectly related to the development of cardiovascular complications among TB patients.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eA comprehensive prospective study encompassing a larger participant pool and an extended follow-up duration is necessary across Malaysia to elucidate the association between tuberculosis (TB) pathogenesis and the risk of cardiovascular disease (CVD). Such research endeavours will not only enhance our limited understanding but also enhance the scope of screening initiatives for concurrent TB-related ailments.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLongitudinal Cohort Studies throughout the whole of Malaysia need to be conducted to understand the dynamic interplay between tuberculosis (TB) and cardiovascular disease (CVD) over time in which follow\u0026ndash;up of TB patients with and without CVD must be monitored from diagnosis through treatment completion. Any changes in cardiovascular health markers, disease progression, and treatment outcomes must be analyzed. This approach will provide the prevalence of CVD among the TB population in the whole of Malaysia. Also, this approach will provide statistics on mortality due to cardiovascular diseases among the TB population in the whole of Malaysia.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cspan\u003eAs this study was retrospective and only involved the use of existing data, it posed no harm to the patients, as confidentiality was maintained (patient names and identification were not recorded). Also, informed consent from patients was not required for this study. Ethical guidelines were followed for the study, and ethical approval was obtained from the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia, before initiation of the study (NMRR-18-95-39523 - [Research ID: 39523]).\u003c/span\u003e\u003c/p\u003e\u003ch2\u003eEthical Approval\u003c/h2\u003e\n\u003cp\u003eAs this study was a retrospective study that only involved the use of existing data, it imposed no harm on the patients as confidentiality was maintained (patient names and identification were not recorded). Informed consent from patients was not required for this study. Ethical guidelines were followed for the study, and ethical approval was obtained from the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia, before initiation of the study (NMRR-18-95-39523 - [Research ID: 39523]).\u003c/p\u003e\n\u003ch2\u003eAuthors contributions\u003c/h2\u003e\n\u003cp\u003eAll authors listed meet the criteria of authorship and have made a substantial, direct, and intellectual contribution to the work and approved it for publication.\u003c/p\u003e\n\u003ch2\u003eConflict of interest\u003c/h2\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003ch2\u003eResearch Funding Source (If any):\u003c/h2\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003ch2\u003eAcknowledgment\u003c/h2\u003e\n\u003cp\u003eWe would like to thank the Director General of Health Malaysia for his permission to publish this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e\u0026ldquo;TB Mortality.\u0026rdquo; Accessed: Nov. 15, 2023. [Online]. 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Dis.\u003c/em\u003e, vol. 84, pp. 127\u0026ndash;130, 2019, doi: 10.1016/j.ijid.2019.05.015.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Hospital Universiti Sains Malaysia","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Development of cardiovascular disease, pulmonary tuberculosis, extra-pulmonary tuberculosis, Mycobacterium tuberculosis, cardiac enzymes, C-reactive protein, troponin-t (Hs), anaemia, chronic kidney disease, acute kidney infection, hypertension, diabetes mellitus","lastPublishedDoi":"10.21203/rs.3.rs-7341189/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7341189/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e Globally, the morbidity burden of tuberculosis and cardiovascular disease (CVD) is substantial in developing nations. A significant epidemiological and pathological co-occurrence exists between tuberculosis (TB) and CVD. A contributory relationship between tuberculosis infection and cardiovascular disease is evident. Beyond traditional risk factors such as diabetes mellitus, hypertension, and hyperlipidemia, additional risk factors, predictive indicators, and clinical markers contribute to cardiovascular disease development in tuberculosis patients. Monocytes, macrophages, lymphocytes, and cytokines, which are integral to cell-mediated immune responses against \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e, are also key drivers of atherosclerotic processes in the cardiovascular vasculature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology\u003c/strong\u003e: This retrospective cohort study was conducted from January 2023 to August 2023, utilizing data collected from January 2015 to December 2022. The study sought to identify risk factors and predictive indicators for the development of cardiovascular disease (CVD) among individuals with a diagnosis and screening of active tuberculosis (TB). A descriptive, retrospective research design was employed, focusing on TB patients without pre-existing CVD. A convenience sample of 402 TB patient records was included in this analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThis study's findings suggest a strong correlation between clinical markers, including high-sensitivity troponin T, C-reactive protein, electrocardiographic data, echocardiographic findings, cardiac enzymes, acute kidney injury (AKI), diabetes mellitus (DM), anaemia, and severe chest radiographic abnormalities, and the development of cardiovascular disease in tuberculosis patients. Positive values for the aforementioned clinical parameters were considered indicative of cardiovascular disease development.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThe results advance understanding of a potential correlation between \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003einfection and the development of cardiovascular disease, examining the risk factors conducive to CVD pathogenesis, and facilitating the development of targeted interventions to improve the comprehensive care of individuals with tuberculosis.\u003c/p\u003e","manuscriptTitle":"Assessment of Pharmacotherapy and Clinical Outcomes of Treatment among Tuberculosis Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-18 12:17:11","doi":"10.21203/rs.3.rs-7341189/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"464c6762-2c8e-4d33-a18d-036f2e435eae","owner":[],"postedDate":"August 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52935453,"name":"Cardiac \u0026 Cardiovascular Systems"},{"id":52935454,"name":"Infectious Diseases"},{"id":52935455,"name":"Clinical Pharmacology"}],"tags":[],"updatedAt":"2025-08-18T12:17:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-18 12:17:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7341189","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7341189","identity":"rs-7341189","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}