Treating Pulmonary Arterial Hypertension With Sotatercept: A Meta-Analysis.

Pulmonary arterial hypertension (PAH) results from proliferative remodeling and narrowing of the pulmonary vasculature. Sotatercept is a first-in-class fusion protein that has recently garnered attention for showing improvements in patients with PAH. This meta-analysis of randomized controlled trials (RCTs) assesses the overall efficacy of Sotatercept in treating PAH. PubMed, Google Scholar, and Clinicaltrials.gov were searched using relevant keywords and MeSH terms. Studies were included if RCTs compared Sotatercept with placebo in patients with PAH. Our comprehensive literature search yielded 3,127 results, of which two RCTs with 429 patients were included in this meta-analysis. The patients were on background therapy for PAH. Results of the meta-analysis show that when compared with placebo, Sotatercept improved the six-minute walk distance (mean difference [MD] 34.99; 95% confidence interval [CI] 19.02-50.95; P < 0.0001), the World Health Organization (WHO) functional class (odds ratio [OR] 2.50; 95% CI 1.50-4.15; P = 0.0004), and pulmonary vascular resistance (PVR, MD -253.90; 95% CI -356.05 to -151.75; P < 0.00001). However, reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP, MD -1563.14; 95% CI -3271.93 to 145.65; P = 0.07) was not statistically significant in the Sotatercept group versus placebo. In conclusion, Sotatercept improves the six-minute walk distance, WHO functional class, and PVR in patients with PAH receiving background therapy. However, the effect on NT-proBNP levels was not statistically significant. More research is needed to assess the clinical relevance of these findings.

Clinical Efficacy and Safety of Bempedoic Acid in High Cardiovascular Risk Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Bempedoic acid (BA) is the new addition to lipid-lowering medications. This systematic review and meta-analysis of randomized controlled trials (RCTs) assess the clinical efficacy and safety of BA in high cardiovascular (CV) risk patients along with its effects on low-density lipoprotein cholesterol (LDL-C) and total cholesterol. PubMed, Google Scholar, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov were searched for RCTs comparing BA with placebo, reporting CV outcomes. Seven RCTs with a total of 17,816 patients were selected for the analysis. Results showed that BA significantly reduced the risk of MACE (RR 0.87, 95% CI 0.80-0.94; P = 0.007), nonfatal myocardial infarction (RR 0.73; 95% CI 0.62-0.85; P < 0.0001), hospitalization for unstable angina (RR 0.69; 95%CI 0.54-0.88; P = 0.003), coronary and noncoronary revascularization (RR 0.82; 95%CI 0.73-0.92; P = 0.0007) and (RR 0.41; 95%CI 0.18-0.96; P = 0.04), respectively. However, BA increased the risk of gout (RR 1.55; 95% CI 1.26-1.90; P < 0.0001), hyperuricemia (RR 1.94; 95% CI 1.73-2.18; P < 0.00001) and worsening renal function (RR 1.34; 95%CI 1.21-1.48; P < 0.00001). BA also reduced LDL-C (MD -22.38%; 95% CI -25.94 to - 18.82; P < 0.00001) and total cholesterol (MD -13.86%; 95% CI -15.82 to -11.91; P < 0.0000) compared with placebo. Bempedoic acid is an addition to the arsenal of lipid-lowering drugs used in patients that are statin intolerant or need additional lipid-lowering therapy.

Does thiamine supplementation affect heart failure? A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Heart failure is a pathophysiological condition where decreased cardiac output is observed subsequent to any structural deformity or cessation of normal function. Thiamine deficiency is one of the risk factors responsible for causing HF; other risk factors include hypertension, smoking, and obesity. OBJECTIVE: We conducted a systemic review and meta-analysis of RCTs to scrutinize whether the heart failure patients would benefit from thiamine supplementation or not when compared to placebo. METHODS: We selected only those double-arm randomized controlled trials (RCTs) which included participants presenting with symptomatic heart failure. We excluded all the articles published in languages other than English Language. Furthermore, all the studies other than RCTs were also omitted. Articles yielded from the electronic search were exported to EndNote Reference Library software to remove any duplicates. Analyses were done using the Review manager 5.4 tool. Mean values and standard deviations were retrieved for the continuous outcomes given as raw data. RESULTS: The 6 RCTs selected for the statistical analysis consisted of 298 participants (158 in the intervention group, 140 in the placebo group). The outcomes resulted to be non-significant with LVEF p-value= 0.08, NT-pro BNP p-value= 0.94, LVEDV p-value= 0.53, 6MWT p-value=0.59, mortality p-value= 0.61, hospitalization p-value= 0.53 and dyspnea p-value= 0.77. Heart rate is the only significant outcome with a p-value=0.04. CONCLUSION: To conclude, except for heart rate, thiamine supplementation had no effect on the outcomes of heart failure patients.

Relationship between the ABO blood group and Rhesus factors with COVID-19 susceptibility.

INTRODUCTION: The molecular research has raised copious hypotheses about different molecular effects on the variable expression of the current virus on the human body. The present prospective study aims to determine clinically as well as statistically, the relation between ABO blood groups and Rhesus (Rh) factor and the severity of the Covid-19 virus. RESEARCH DESIGN AND METHODS: We conducted a prospective, single-centered study at The Combined Military Hospital Lahore, Pakistan. Details of only those patients who exhibit COVID-19 symptoms were included. The odds ratios with a 95% confidence interval and the chi-square test of blood groups and Rhesus factor was also conducted individually with the severity of disease, outcomes, and respiratory symptoms. P-values less than 0.05 was considered significant. RESULTS: The chi-square test and odd ratio yielded no significant results when the covid-19 status was compared with the Rhesus factor (p-value > 0.05). However, the results were found to be significant when associations were run between Covid-19 status and all the blood groups (p-value < 0.05). CONCLUSION: According to the analytical results of the present study, protective nature of all the blood antigens (A, B, AB, none) was observed in patients presenting with Covid-19 symptoms of varying severity.

Association of Vitamin B12 deficiency with long-term PPIs use: A cohort study.

Background: Proton Pump inhibitors are widely used among the majority of the world's population as acid-suppressing medications. Proton Pump Inhibitors have been reported to cause intestinal damage and adverse gut microbiota changes affecting several mechanisms, including malabsorption, etc. Aim: In order to gain a deeper understanding, we conducted a cohort analysis to assess the prevalence & association of Vitamin B12 deficiency in patients on long-term use of PPIs. Methods: This single-center cohort study was conducted at the Department of Internal Medicine, KRL hospital in Islamabad, Pakistan from May 2021 to May 2022. Rao soft calculator with a 95% confidence interval and 5% error margin was used to find the estimated sample size. Vitamin B12 levels were analyzed using the Cobas e411 analyzer. Chi-square test, odds ratio, and t-tests were used for analysis. Results: Among the 1225 participants, more than half of the men (55.10%) had low levels of vitamin B12. Vit B12 levels were observed to be significantly lower in Omeprazole patients than in Pantoprazole patients. A vitamin B12 deficiency is 0.5 times more likely in patients taking PPIs. There is a substantial difference between the early and final levels of B12 indicated by the t-test. Conclusion: According to our findings, long-term usage of PPIs is linked to an increased risk of vitamin B12 insufficiency specifically in men falling under the ages of 18 and 40.

Samidorphan/olanzapine combination therapy for schizophrenia: Efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials.

Introduction: Schizophrenia is a complex medical illness characterized by hallucinations, delusions, and cognitive issues. Olanzapine, a second-generation antipsychotic widely prescribed for schizophrenia has proven to be efficacious, however, its use is associated with major adverse effects such as weight gain, metabolic syndrome and diabetes mellitus. Recently, FDA approved a combination dose of olanzapine and samidorphan (OLZ/SAM) to mitigate the adverse outcomes associated with olanzapine use for the treatment of Schizophrenia. Objectives: The approval of olanzapine/samidorphan combination by FDA in treatment of schizophrenia and bipolar I disorder has been a milestone. This article summarizes the clinical trials reporting the clinical efficacy and adverse effects of olanzapine/samidorphan combination along with their bias assessment. Methods: Pubmed, science direct, Ovid SP and Google Scholar were comprehensively searched for data collection. Clinical trials reporting the efficacy and adverse outcomes of the OLZ/SAM regimen were included in the review and the Cochrane risk of bias assessment tool (RoB 2.0, version 2019) was used to assess the risk of bias in each study. Results: Five trials employed the use of Positive and Negative Syndrome Scales (PANSS) and Clinical Global Impression-Severity (CGI-S) scale to assess the efficacy of OLZ/SAM. Overall, OLZ/SAM showed a significant reduction in PANSS total scores and CGI-S scores and might be a viable option for long-term treatment. The safety of combined therapy is assessed by trials considering the factors of ECG parameters, suicidal events, and movement disorders. Major adverse events included nervous system disorders, changes in blood chemistry, and metabolic or nutritional disorders, with worsening of adverse outcomes observed in a total of nineteen cases in six studies. Conclusion: The FDA-approved drug recombination of OLZ/SAM for the treatment of schizophrenia revealed efficacious outcomes and was generally well tolerated by patients partaking in various trials. The potential of samidorphan in mimicking the efficacy of olanzapine while mitigating olanzapine-induced weight gain makes it a promising regimen for improving symptoms and health outcomes in schizophrenic patients.

Safety, efficacy, and immunogenicity of COVID-19 vaccines; a systematic review.

The World Health Organization stated on 11 March 2020 that a coronavirus illness had been discovered in Wuhan, China in December 2019. Effective vaccinations are eagerly awaited as the global outbreak of COVID-19 continues. The aim is to evaluate the safety, effectiveness, and immunogenicity of Pfizer/AstraZeneca/Modera/Cansino vaccines against COVID-19. An electronic search on different databases yielded 12,907 articles. A total of 20 randomized and non-randomized, published, and ongoing trials were selected. Cochrane RoB version 2.0 was used to assess the authenticity of the studies. Of these 20 trials, three were conducted on Pfizer, three on AstraZeneca, three on Moderna, and two on the Cansino vaccine. These trials have reported promising results for the safety, efficacy, and immunogenicity of the respective vaccines. None of the trials have reported the efficacy and severe adverse outcomes for the Cansino vaccine, hindering its reliability as a safe vaccine against covid-19. Furthermore, the results of these trials have established Pfizer to be the most efficacious vaccine against covid-19, having an efficacy of 94.6%. A few severe adverse events were reported by the included trials. However, further systematic reviews are required to understand the respective vaccine profiles on Immuno-suppressive, organ transplants, and patients with other comorbidities.