PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT): a prospective longitudinal study protocol investigating the prevalence, severity and determinants of atherosclerotic cardiovascular disease in the young adult Pakistani population.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity, mortality and health expenditures worldwide. Despite having higher ASCVD in the Pakistani population, data on subclinical coronary atherosclerosis in young Pakistanis remain scarce. The PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT) aims to assess the prevalence, severity and determinants of subclinical coronary atherosclerosis among Pakistani men (35-60 years) and women (35-65 years) free of clinically symptomatic ASCVD and will assess 5-year rates of ASCVD events. METHODS AND ANALYSIS: PAK-SEHAT is an ongoing prospective cohort study with 2000 participants from all provinces of Pakistan who will be interviewed at the baseline along with phlebotomy, measurement of carotid intima-media thickness (CIMT) and coronary CT angiography (CCTA). Phlebotomy will be repeated at 2.5 years, whereas CIMT and CCTA will be repeated at 5 years. We will report the frequency of maximal coronary stenosis ≥50% and ≥70%, number of coronary vessels with plaque and the number of coronary segments affected per participant on CCTA. We will use Cox proportional hazards regression models to evaluate the association between baseline characteristics and incident ASCVD events during follow-up. These associations will be presented as HRs with 95% CIs. ETHICS AND DISSEMINATION: The study protocol was approved by the Tabba Heart Institute Institutional Review Board (THI/IRB/FQ/22-09-2021/016). All study procedures are consistent with the principles of the Declaration of Helsinki. Findings of the study will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05156736.

Safety and efficacy of Empagliflozin in Pakistani Muslim patients with type 2 diabetes (SAFE-PAK); a randomized clinical trial.

BACKGROUND: Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitor (Empagliflozin) is an effective drug in controlling blood glucose through predominantly glycosuria. Glycosuria increases the risk of genitourinary infections in diabetes. This study was aimed to establish the safety and efficacy of Empagliflozin (Group-A) versus standard care (Group-B) in Pakistani Muslim individuals with type 2 diabetes. METHODS: A multicenter, randomized clinical trial was conducted in five cities across Pakistan from July 2019 to August 2020. Patients of both genders aged 18-75 years, body mass index (BMI) ≤ 45 kg/m2, glycosylated hemoglobin (HbA1c) 7-10% (53 mmol/mol to 86 mmol/mol) and treatment-naive to Empagliflozin were included. Treatment was given for 24 weeks, and allocation was done through randomization. RESULTS: Out of 745 screened patients, 333 met the eligibility criteria, and a total of 244 (73.3%) patients were enrolled. More hypoglycemic events were reported in the standard care group, whereas positive urine culture, fungal infection, dehydration, and hypotension occurrence were comparable between the two groups. The 6 months mean HbA1c reduction was significant in both groups; (Group-A: 0.91 ± 0.15; p < 0.001 vs. Group-B2: 0.79 ± 0.14; p < 0.001). Efficacy comparison at 6 months revealed a significant reduction in weight and systolic blood pressure (SBP) in Group A only (Group-A: 1.4 ± 0.4 kg; p < 0.002 vs. Group-B: 0.01 ± 0.5 kg; p < 1.00), (Group-A: 5.1 ± 1.7 mmHg; p < 0.012 vs. Group-B: 2.3 ± 1.7 mmHg; p < 0.526). CONCLUSIONS: Empagliflozin was a safe drug compared to standard care in Pakistani Muslim patients with diabetes. It was as effective as standard care in the clinical setting but achieved glycemic control by reducing weight and SBP in type 2 diabetes patients. TRIAL REGISTRATION: This study was registered in the NIH US National Library of Medicine clinical trials registry at Clinicaltrials.gov with the registration number: NCT04665284 on 11/12/2020.

Seroprevalence and characteristics of Coronavirus Disease (COVID-19) in workers with non-specific disease symptoms.

BACKGROUND: The population-based serosurveys are essential for estimating Coronavirus Disease-19 (COVID-19) burden and monitoring the progression of this pandemic. We aimed to assess the seroprevalence of SARS-CoV-2 antibodies and potential predictors of seropositivity in the Pakistani population. METHODOLOGY: This population-based seroprevalence study includes consenting subjects from the workplaces (factories, corporates, restaurants, media houses, schools, banks, and hospitals) located in the urban areas of Karachi, Lahore, Multan, Peshawar, and Quetta. We analyzed each subject's serum sample for SARS-CoV-2-IgM and/or IgG antibodies using UNIPER IgG/IgM Rapid COVID-19 Testing Kit. The subject's demographics, exposure history, and symptoms experienced (in last 7 days) were also obtained. The collected data was analyzed using SPSS version 22.0. RESULTS: The overall seroprevalence of SARS-CoV-2 antibodies was 16.0% (2810/17,764). The total antibody seropositivity was higher in males than females (OR 1.22, 95% CI 1.110-1.340). The symptomatic subjects had 2.18 times higher odds of IgG seropositivity while 1.2 times for IgM seropositivity than the asymptomatic subjects. The multivariable logistic regression model showed that the odds of SARS-CoV-2 total antibody seroprevalence were affected by the number of dependents (OR = 1.077; 95% CI 1.054-1.099), apparent symptomology (OR = 1.288; 95% CI 1.011-1.643), close unprotected contact with a confirmed or probable case of COVID-19 (OR 2.470; 95% CI 2.164-2.819), traveling history (last 14 days) (OR = 1.537; 95% CI 1.234-1.914) and proximity with someone who traveled (OR = 1.534; 95% CI 1.241-1.896). CONCLUSION: We found a reasonable seroprevalence of SARS-CoV-2 antibodies in the studied population. Several factors like the number of dependents, apparent symptoms, close unprotected contact with a confirmed or probable case of COVID-19, traveling history, and proximity with someone who traveled are associated with increased odds of SARS-CoV-2 antibody seropositivity.

Asymptomatic urinary tract infections and associated risk factors in Pakistani Muslim type 2 diabetic patients.

BACKGROUND: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic. METHODS: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients. RESULTS: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin. CONCLUSION: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.

New drugs and new concerns: Gaining insight through Pharmacovigilance of direct acting Anti-Viral's in chronic HCV patients.

OBJECTIVE: The study aimed to assess the safety profile of Direct Acting Anti-Viral's (DAAs) among patients with chronic Hepatitis C Virus (HCV). METHODS: This multicenter, analytical cross-sectional study was conducted in six gastroenterology and Hepatology centers including Liver Center Faisalabad, Allama Iqbal Medical Institute and Liver Center DHQ Hospital Sialkot, Isra Hospital Hyderabad, Allied Hospital Faisalabad and Rehman Medical Institute Peshawar, between May 2018 and May 2019. The data regarding patient demographics, treatment plan and the frequency of Adverse Events (AEs), and their severity was collected using a pre-designed questionnaire and analyzed through SPSS version 20.0. RESULTS: A total of 511 HCV patients were enrolled, with an overall male majority. Around 66.3% patients experienced a total of 419 AEs, out of which 61 events were suspected from DAAs while remaining 317 events were associated with Ribavirin. Pyrexia (24.6%) and fatigue (14.8%) were the most commonly reported AEs among patients receiving DAAs. Factors such as Ribavirin-based treatments and the presence of Cirrhosis were more likely to promote AEs occurrence OR [95%CI] i.e. 5.2(2.3-9.1) and 1.9(1.1-3.1) respectively (p < 0.05). CONCLUSION: It is concluded from the study results that DAAs have displayed promising outcomes due to the minimal and minor AEs reported.

Safety and Efficacy of Sofosbuvir with Ribavirin® in Hepatitis C, Genotype 3 Patients with Cirrhosis: A Real-world Experience.

Introduction Hepatitis C virus (HCV) is the leading cause of cirrhosis. The advent of Directly Acting Antivirals (DAAs) like Sofosbuvir (SOF) has dramatized the treatment and is the cornerstone for the treatment of HCV. Most trials have been conducted in HCV genotype 1 (GT-1) and data for Interferon-free regimen in genotype 3 (GT-3) is limited especially in cirrhotic patients. Aim To evaluate the safety and efficacy of SOF plus Ribavirin® (RIB) in patients with compensated and decompensated cirrhosis. Methods This was a quasi-experimental study in HCV patients with compensated and decompensated cirrhosis. Each group (compensated and decompensated) was further subdivided into the treatment-naïve and treatment-experienced groups. Efficacy was assessed by end treatment response (ETR) and sustained viral response (SVR) in the treatment-naïve and experienced groups. Adverse events were recorded on designed proforma on serial follow-up visits. Results The study consisted of 110 consecutive patients. Among 110 patients, 51 had compensated cirrhosis and 59 had decompensated cirrhosis. The mean age was 53.8 ± 11 years. Males were n=56 (50.9%) and females were n=54 (49.1%). All the patients in Child-Turcotte-Pugh class A were in the compensated group. CTP B class was found to be 10.5% and 89.5% in the compensated and decompensated groups, respectively, whereas all the patients in CTP class C were in the decompensated group. In the compensated cirrhosis group, ETR was achieved in 36 (87.8%) treatment-naïve and 8 (88.9%) experienced patients. In decompensated cirrhosis, treatment-naïve and experienced patients achieved ETR in 28 (82.4%) and 18 (85.7%) patients, respectively. Whereas in compensated cirrhosis treatment-naïve and experienced patients, SVR was achieved in 25 (83.3%) and five (71.4%), respectively. In decompensated cirrhosis, 21 (77.8%) treatment-naïve and 12 (75%) experienced patients achieved SVR. The most common adverse events experienced by the patients were fatigue followed by myalgia, nausea, and diarrhea. The new onset of complications found due to cirrhosis were ascites, followed by hepatoma, upper gastrointestinal bleed, portosystemic encephalopathy, acute on chronic liver failure, and death. Conclusion Sofosbuvir in combination with Ribavirin® is safe but suboptimal in treatment outcomes, particularly in treatment-experienced patients with decompensated cirrhosis than in treatment-naive patients with compensated cirrhosis due to HCV GT-3.

Appropriateness of Acid-suppressing Agents for Stress Ulcer Prophylaxis in Non-intensive Care Unit Setting in Saudi Arabia.

OBJECTIVE: To investigate the appropriateness of acid-suppressive therapy (AST) for stress ulcer prophylaxis (SUP) in noncritically ill hospitalized patients. MATERIALS AND METHODS: A prospective, observational study with 384 subjects was conducted between October and December 2017 in the emergency and internal medicine departments. The Herzig clinical risk scoring system and the guidelines of the American Society of Health-System Pharmacists guidelines were used to assess risk factors and determine risk scores for gastrointestinal (GI) bleeding. RESULTS: The mean age of subjects was 51.9 ± 19.4 years, and 220 (57.3%) of them were males. Among the absolute risk factors, coagulopathy was observed in 2 (0.5%) patients, mechanical ventilation in 15 (3.9%), and a history of GI bleeding in 1 (0.3%). Of 384 patients with SUP, 370 (96.4%) had a clinical risk score ≤ 9 and 14 (3.6%) had a risk score between 10 and 12 for nosocomial GI bleeding. A statistically significant relationship was found between the risk factor indication and demographics. CONCLUSION: SUP is frequently administered to noncritically ill hospitalized patients lacking risk factors for GI bleeding. Proton pump inhibitors are the overwhelming first choice of AST among prescribers. Practitioners should follow international guidelines when prescribing ASTs outside the critical-care setting.

Knowledge and Attitude of Health-Care Professionals Toward Adverse Drug Reactions Reporting at King Saud Medical City.

BACKGROUND: Health-care professionals across the globe are obligated to report adverse drug reactions (ADRs). The knowledge of ADRs and attitude of health-care professionals toward ADRs reporting is vital for patient safety. This study intends to investigate the knowledge of ADRs and attitude of health-care professionals toward ADRs reporting. MATERIALS AND METHODS: A cross-sectional study using an anonymous questionnaire was conducted over a period of 3 months (September 2016 to November 2016) at King Saud Medical City, Riyadh, Saudi Arabia. This study included 399 questionnaires submitted by health-care professionals. RESULTS: A total of 399 questionnaires were submitted by health-care professionals, of which only 14.8% knew the term "ADR" and 55.1% of the respondents reported ADRs during their practice. A total of 93.8% of the respondents agreed that ADR reporting should be made mandatory for health-care professionals, and 94.5% agreed that it improves the patient safety. CONCLUSION: The findings generally indicate that health-care professionals in a tertiary care setting have low awareness regarding the term "ADR." Lack of pharmacovigilance training, amount of workload, and legal liabilities are the main causes of underreporting. More than half of the respondents agreed that ADR reporting eventually improves patient safety.