The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis.

BACKGROUND: Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is uncertain. METHODS: Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials were searched for randomized control trials on the effect of blood pressure-lowering medications compared with placebo in participants with episodic migraine. Data were collected on four outcomes - monthly headache or migraine days, and monthly headache or migraine attacks, with a standardised mean difference calculated for overall. Random effect meta-analysis was performed. RESULTS: In total, 50 trials (70% of which were crossover) were included, comprising 60 comparisons. Overall mean age was 39 years, and 79% were female. Monthly headache days were fewer in all classes compared to placebo, and this was statistically significant for all but one class: alpha-blockers -0.7 (95% CI: -1.2, -0.1), angiotensin-converting enzyme inhibitors -1.3 (95% CI: -2.9, 0.2), angiotensin II receptor blockers -0.9 (-1.6, -0.1), beta-blocker -0.4 (-0.8, -0.0) and calcium channel blockers -1.8 (-3.4, -0.2). Standardised mean difference was significantly reduced for all drug classes and was separately significant for numerous specific drugs: clonidine, candesartan, atenolol, bisoprolol, metoprolol, propranolol, timolol, nicardipine and verapamil. CONCLUSION: Among people with episodic migraine, a broader number of blood pressure-lowering medication classes and drugs reduce headache frequency than those currently included in treatment guidelines.Trial Registration: The study was registered at PROSPERO (CRD42017079176).

Global prevalence and effect of comorbidities and smoking status on severity and mortality of COVID-19 in association with age and gender: a systematic review, meta-analysis and meta-regression.

A COVID-19 patient often presents with multiple comorbidities and is associated with adverse outcomes. A comprehensive assessment of the prevalence of comorbidities in patients with COVID-19 is essential. This study aimed to assess the prevalence of comorbidities, severity and mortality with regard to geographic region, age, gender and smoking status in patients with COVID-19. A systematic review and multistage meta-analyses were reported using PRISMA guidelines. PubMed/MEDLINE, SCOPUS, Google Scholar and EMBASE were searched from January 2020 to October 2022. Cross-sectional studies, cohort studies, case series studies, and case-control studies on comorbidities reporting among the COVID-19 populations that were published in English were included. The pooled prevalence of various medical conditions in COVID-19 patients was calculated based on regional population size weights. Stratified analyses were performed to understand the variations in the medical conditions based on age, gender, and geographic region. A total of 190 studies comprising 105 million COVID-19 patients were included. Statistical analyses were performed using STATA software, version 16 MP (StataCorp, College Station, TX). Meta-analysis of proportion was performed to obtain pooled values of the prevalence of medical comorbidities: hypertension (39%, 95% CI 36-42, n = 170 studies), obesity (27%, 95% CI 25-30%, n = 169 studies), diabetes (27%, 95% CI 25-30%, n = 175), and asthma (8%, 95% CI 7-9%, n = 112). Moreover, the prevalence of hospitalization was 35% (95% CI 29-41%, n = 61), intensive care admissions 17% (95% CI 14-21, n = 106), and mortality 18% (95% CI 16-21%, n = 145). The prevalence of hypertension was highest in Europe at 44% (95% CI 39-47%, n = 68), obesity and diabetes at 30% (95% CI, 26-34, n = 79) and 27% (95%CI, 24-30, n = 80) in North America, and asthma in Europe at 9% (95% CI 8-11, n = 41). Obesity was high among the ≥ 50 years (30%, n = 112) age group, diabetes among Men (26%, n = 124) and observational studies reported higher mortality than case-control studies (19% vs. 14%). Random effects meta-regression found a significant association between age and diabetes (p < 0.001), hypertension (p < 0.001), asthma (p < 0.05), ICU admission (p < 0.05) and mortality (p < 0.001). Overall, a higher global prevalence of hypertension (39%) and a lower prevalence of asthma (8%), and 18% of mortality were found in patients with COVID-19. Hence, geographical regions with respective chronic medical comorbidities should accelerate regular booster dose vaccination, preferably to those patients with chronic comorbidities, to prevent and lower the severity and mortality of COVID-19 disease with novel SARS-CoV-2 variants of concern (VOC).

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis.

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. It was approved by the United States Federal Drug Administration (US FDA) as an add-on maintenance treatment for patients with severe uncontrolled asthma in December 2021. We conducted a systematic review and meta-analysis to investigate the safety and efficacy of tezepelumab on forced expiratory volume (FEV1) (L), the rate of asthma exacerbations, health-related quality of life, fractional exhaled nitric oxide (FeNO) (ppb), and blood eosinophil count (cells/mL) in patients with severe, uncontrolled asthma. Mean changes for efficacy and proportions (safety) with their corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of six randomized controlled trials comprising 2667 patients were included, of whom 1610 were treated with tezepelumab and 1057 received placebo. The pooled analysis showed that tezepelumab treatment resulted in an improvement in FEV1 of 0.15 L (95% CI: 0.12 to 0.17), a reduction in the asthma exacerbation rate per year of 0.60 (95% CI: 0.51 to 0.70), and a reduction in FeNO of -12.41 ppb (95% CI: -14.28 to -10.53) when compared to placebo. Improvements in FEV1 and FeNO levels were maintained at 24 and 52 weeks. As for safety, patients did not experience a higher incidence of adverse drug reactions with tezepelumab (0.79 (95% CI: 0.55 to 1.12)) as compared to placebo. As for quality of life, different doses of the tezepelumab intervention group depicted non-significant improvement in the QoL, from 0.15 (95% CI: -0.09 to 0.38) for 70 mg, 0.18 (95% CI: -0.10 to 0.46) for 210 mg, 0.08 (95% CI: -0.16 to 0.32) for 280 mg as compared to the placebo. Tezepelumab significantly reduced exacerbation rates and improved FEV1 with an acceptable safety profile.

Hepatocellular Carcinoma Recurrence and Mortality Rate Post Liver Transplantation: Meta-Analysis and Systematic Review of Real-World Evidence.

BACKGROUND: liver transplantation (LT) is the best curative option for eligible patients with hepatocellular carcinoma (HCC), however recurrence remains a major concern. This meta-analysis aimed to investigate the prevalence and risk factors of HCC recurrence. METHODS: studies were selected using PubMed, Epistemonikas, and Google Scholar databases published from inception to 15 May 2022 and a meta-analysis of the proportions was conducted. Observational studies reporting the prevalence of recurrent HCC after an LT were included, with the analysis being stratified by an adherence to the Milan criteria (MC), geographical region, AFP levels, and donor type. RESULTS: out of 4081 articles, 125 were included in the study. The prevalence of recurrent HCC was 17% (CI: 15-19). Patients beyond the MC were more likely to recur than patients within the MC. Asian populations had the greatest prevalence of HCC recurrence (21%; CI: 18-24), whereas North American populations had the lowest recurrence (10%; CI: 7-12). The mortality rate after HCC recurrence was 9%; CI: 8-11. North American populations had the greatest prevalence of mortality with 11% (CI: 5-17). CONCLUSIONS: the recurrence, overall survival, and mortality rates among patients with HCC post-LT remains high, with substantial differences between regions.

Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies.

BACKGROUND AND OBJECTIVE: Saroglitazar is a newer antidiabetic agent approved to manage dyslipidemia. The objective is tevaluate the efficacy and safety profiles of saroglitazar in patients with dyslipidemia. METHODS: A systematic search was conducted using PubMed, Cochrane Library, Scopus, and Google Scholar from the inception until January 2022. Interventional studies comparing the anti-hyperlipidaemic effect and safety of saroglitazar with or without a control group(s) were included. The efficacy of saroglitazar was assessed concerning its effect on total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL)-cholesterol, triglycerides, fasting plasma glucose, and non-HDL cholesterol. The effects on serum creatinine levels, bodyweight reduction, alanine aminotransferase and aspartate aminotransferase were considered to be safety endpoint.The Cochrane risk of bias assessment tool was used to assess the methodological quality of the included studies. RESULTS: A total of six studies with 581 adults with a mean age ranging from 40.2 to 62.6 years were included in this study. A significant decrease in low-density lipoprotein cholesterol was observed with saroglitazar 4 mg therapy compared to saroglitazar 2 mg [standardized mean difference (SMD): -0.23 mg/dL, 95% CI: -0.47 to 0.00; p = 0.05; 2 studies], and control [SMD: -0.36 mg/dL, 95% CI -0.59 to -0.12; p = 0.0026; 3 studies]. Also, a significant decrease in the total cholesterol was observed with saroglitazar 4 mg therapy compared to saroglitazar 2 mg [SMD - 0.28 mg/dL, 95% CI: - 0.52 to -0.04; p < 0.01; 2 studies], and control [SMD - 0.49 mg/dL, 95% CI: - 0.72 to -0.26; p < 0.0001; 3 studies]. Saroglitazar was not associated with adverse effects such as increase in serum creatinine levels, alanine aminotransferase and aspartate aminotransferase and bodyweight reduction. CONCLUSION: Saroglitazar appeared to be an effective and safer therapeutic option for improving dyslipidemia in patients. However, comparative studies of saroglitazar with the other pharmacological agents are warranted.

Sweetened beverage consumption and risk of cardiovascular mortality: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Several studies have reported the association of sweetened beverages (SB) with cardiovascular disease. However, the relationship between SB and cardiovascular mortality has not been clearly established. This systematic review and meta-analysis investigated the association between SB consumption and cardiovascular mortality. METHODS: PubMed/MEDLINE, Web of Science, and Embase were systematically searched up to July 31, 2021, for prospective cohort studies investigating this association in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were used to assess the strength of association between SB: sugar-sweetened beverages (SSB)/artificial-sweetened beverages (ASB) exposure and cardiovascular mortality. RESULTS: A total of eight cohort studies comprising 1.2 million participants exposed to SB, reported 15,831 (1.2%) cases of cardiovascular mortality with a median follow-up of 12.2 years. Consuming at least one glass (250 ml) of SB per day (RR: 1.06; 95% CI: 1.00-1.12, P < 0.001) or ≥2 glasses per day (RR: 1.24; 95% CI: 1.16-1.31, P < 0.001) was significantly associated with increased risk of cardiovascular mortality. SSB and ASB intake of ≥2 glasses per day increased the risk of cardiovascular mortality by 21% (RR:1.21, 95% CI: 1.09-1.33, P < 0.001) and 33% (RR: 1.33, 95% CI: 1.12-1.55, P < 0.001), respectively. CONCLUSIONS: Our findings reveal that high SSB and ASB consumption are associated with an increased risk of cardiovascular mortality. Policymakers and public health practitioners should work on multisectoral strategies to reduce the consumption of sweetened beverages around the world and among all population groups.

Organic Food Consumption and Risk of Obesity: A Systematic Review and Meta-Analysis.

Recent epidemiological studies have explored the association between organic food consumption and the risk of obesity, but the results remain controversial. A systematic review and meta-analysis were conducted to determine the association between organic food consumption and the risk of obesity. Rigorous methods for a comprehensive search were employed to search for literature in PubMed/MEDLINE, Web of Science, and Embase for relevant articles published until 30 November 2021. Pooled odds ratio (OR) with 95% confidence intervals (Cis) were calculated using a DerSimonian and Laird random-effects model to understand the risk of obesity based on exposure to organic food. Four studies, comprising 104,488 healthy subjects and 39,425 adults who consumed organic food, reported 1625 incident cases of obesity. Compared with the unexposed group, organic food consumption was associated with a lower probability of obesity (OR: 0.89, 95% CI: 0.80-0.97, p < 0.001). Subgroup analysis showed that this association was higher in the cohort (OR: 0.78, 95% CI: 0.63-0.92) than cross-sectional studies (OR: 0.95, 95% CI: 0.91-1.00), respectively. Overall, organic food consumption had a modest reduction (11%) in the risk of obesity and can be an appropriate strategy to prevent obesity.

Selective serotonin reuptake inhibitor use and the risk of hepatocellular carcinoma: a systematic review and dose-response analysis of cohort studies with one million participants.

PURPOSE: Recent studies have suggested a lower risk of hepatocellular carcinoma (HCC) in patients receiving selective serotonin reuptake inhibitors (SSRIs). The current study aimed to provide an updated and comprehensive assessment of the association between SSRI use and development of HCC. METHODS: This is a systematic review and meta-analysis of all observational studies published until June 2021. We comprehensively searched PubMed/Medline, Web of Science, and Embase to identify studies comparing SSRIs use with control in relation to the risk of HCC. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between SSRI use and incident HCC risk using random-effects meta-analysis. A dose-response analysis was conducted to evaluate the HCC risk according to the defined daily dose (DDD) of SSRI use. RESULTS: Eight observational studies, comprising 1,051,096 participants and 22,316 incidences of HCC, examining the association between SSRIs use and HCC risk, were included in the systematic review (adjusted RR: 0.66; 95% CI: 0.56-0.79; P ≤ 0.001). In subgroup analysis, the magnitude of benefit associated with SSRIs was significantly higher in patients with hepatitis infection (RR: 0.70, 95% CI: 0.51-0.95) than the general population (Pheterogeneity = 0.700). The dose-response analysis indicated strong inverse association between cumulative DDD of SSRI and risk of HCC (coefficient: - 0.0030; P = 0.002; R2 = 0.78). CONCLUSIONS: The results of this review show that SSRI use was associated with a 34% lower risk of HCC, which tend to be dose dependent. Further prospective studies are warranted to confirm these observations across the spectrum of chronic liver disease and hepatitis infection.

Polypharmacy and Hyperpolypharmacy in Older Individuals with Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Polypharmacy (concomitant use of 5-9 medicines) and hyperpolypharmacy (concomitant use of over 10 medicines) were observed to be more frequent in older adults (≥65 years) and associated with adverse outcomes. Their prevalence and risk in older patients with Parkinson's disease (PD) remain unknown. We aimed to synthesize the extant evidence on the prevalence and risk of polypharmacy and hyperpolypharmacy in older adults with PD. METHODS: A systematic literature search was performed in PubMed/MEDLINE, Scopus, and Embase databases to identify pertinent studies published from 2000 to July 2021. Observational studies reporting the prevalence and association with disease of polypharmacy/hyperpolypharmacy in older adults with PD were meta-analyzed. Pooled prevalence and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: Out of the total 499 studies identified, 6 fulfilled the inclusion criteria and comprised 7,171 participants. The overall prevalence of polypharmacy and hyperpolypharmacy was 40% (95% CI: 37-44) and 18% (95% CI: 13-23), respectively. A meta-analysis of 4 studies indicated a significant association between polypharmacy (OR: 1.94, 95% CI: 1.26-2.62; p < 0.001) and PD. Hyperpolypharmacy was also strongly associated with PD (OR: 3.11, 95% CI: 2.08-4.14; p < 0.001). CONCLUSION: Polypharmacy (40%) and hyperpolypharmacy (18%) are highly prevalent and eventually increase the risk of drug-related problems in older adults with PD. Therefore, interventions that ensure rational geriatric pharmacotherapy are of critical importance for the older population with neurogenerative disorders.

Pattern, severity, and outcome of adverse drug reactions in a tertiary care hospital: an evidence from a cross-sectional study.

OBJECTIVES: Study aim to describe the spontaneous reporting of the adverse drug reactions (ADRs) among the patients admitted to medicine department of a tertiary care hospital. METHODS: A prospective observational study was conducted over a period of four months at the medicine department. On the daily basis, all the patients aged >18 years admitted to the internal medicine department were followed and analyzed for occurrence of ADRs. Naranjo scale was used to determine causal relationship between the ADRs and suspected drugs. The nature of ADRs and its severity was assessed using the Hartwig scale. RESULTS: A total of 4,530 patients were screened for the ADRs, out of which 90 ADRs were developed in the 89 patients. The overall incidence of ADRs was found to be 1.96% in the studied population. The most common ADRs encountered during the study period were type A (augmented). The least number of ADRs were observed in the age group of 31-40 years. Furthermore, the more significant number of male patients suffered from a severe type of ADRs as compared to females. Sixteen ADRs were of the mucocutaneous type of reaction followed by dizziness in 12 cases. The higher number of patients recovering from the ADRs was in the age group 41-60 years. The outcomes of ADRs were not found to be statistically significant with gender and age groups. CONCLUSIONS: There is a strong need to extend the monitoring and reporting of the ADRs to ensure the patient safety. However, the overall incidence of ADRs appeared to be less in our study, highlighting the need for strengthening reporting system of ADRs. The results indicate that elderly patients are at significant risk of developing ADRs.

Quality of systematic reviews supporting the 2017 ACC/AHA and 2018 ESC/ESH guidelines for the management of hypertension.

OBJECTIVE: To assess the methodological and reporting quality of systematic reviews (SRs) that informed recommendations in the recent American and European hypertension guidelines. DESIGN AND SETTINGS: Meta-epidemiological study. We identified SRs that were cited for class I recommendations based on Level of Evidence-A in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) and the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) hypertension guidelines. MAIN OUTCOME MEASURES: Methodological and reporting quality of the SRs was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) checklist and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, respectively. RESULTS: A total of 40 SRs was included in the analysis (28 from 2017 ACC/AHA; 22 from 2018 ESC/ESH and 10 were included in both). Based on the AMSTAR-2 assessment, only 7.5% SRs were found to be of high methodological quality, 47.5% were of moderate, each 22.5% were of low and critically low quality. Based on the PRISMA checklist assessment, a mean of 24 items (SD (2.76) were reported appropriately, and only five SRs reported all 27 items appropriately. CONCLUSION: Methodological and reporting quality of SRs were found to vary considerably. Lack of information on the funding source of included studies, use of a protocol, integration of risk of bias assessments while interpreting findings and reporting of excluded studies were major methodological deficiencies.

Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials.

Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, currently under trial to assess glycemic efficacy and safety in people with type 2 diabetes. A systematic review and meta-analysis were conducted to investigate the efficacy of tirzepatide on glycated hemoglobin (HbA1c, %), fasting serum glucose (mg/dL), and body weight (kg) in patients with uncontrolled type 2 diabetes (HbA1c > 7.0%). Mean changes for efficacy and proportions (safety) with corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of four randomized controlled trials, comprising 2783 patients of whom 69.4% (n = 1934) were treated with 5 mg (n = 646), 10 mg (n = 641), or 15 mg (n = 647) of tirzepatide, were compared to the placebo (n = 192) or the selective GLP-1 receptor agonist (n = 523). The pooled analysis showed that tirzepatide treatment resulted in a greater lowering of the HbA1c (-1.94%, 95% CI: -2.02 to -1.87), fasting serum glucose (-54.72 mg/dL, 95% CI: -62.05 to -47.39), and body weight (-8.47, 95% CI: -9.66 to -7.27). We also found that improvement in the HbA1c levels was still maintained at weeks 26 and 40 from the long-term trials. As for safety, only 3% experienced hypoglycemia, and 4% (95% CI: 2 to 6) experienced serious adverse events, while the discontinuation of therapy percentage was 7% (95% CI: 5 to 8). Tirzepatide significantly improved glycemic control and body weight and had an acceptable safety profile, indicating that it is an effective therapeutic option for glucose-lowering in patients with type 2 diabetes mellitus.

The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis.

INTRODUCTION: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. METHODS: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as 'COVID-19' OR 'SARS CoV-2' AND 'Remdesivir'. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. RESULTS: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) (n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40-0.74) p = 0.0001; I 2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38-0.84) p = 0.005; I 2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19-0.54) p = 0.0001; I 2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59-1.54) p = 0.85; I 2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59-1.11) p = 0.19; I 2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86-1.80) p = 0.25; I 2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66-1.75) p = 0.77; I 2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70-1.68) p = 0.73; I 2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80-1.08) p = 0.32; I 2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73-2.62) p = 0.32; I 2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51-2.18) p = 0.89; I 2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18-4.01) p = 0.85; I 2 = 78%]. DISCUSSION & CONCLUSION: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. PLAIN LANGUAGE SUMMARY: Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo.The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir.There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir.There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

Phosphodiesterase type 5 inhibitors use and risk of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Experimental evidence has revealed that phosphodiesterase five inhibitors (PDE5is) increase epithelial barrier function and suppress intestinal carcinogenesis. Few epidemiological studies have investigated the role of PDE5i in increasing the risk of colorectal cancer (CRC); however, these studies have proffered varying conclusions. We therefore aimed to perform a comprehensive review and meta-analysis to investigate whether PDE5i use is associated with the incidence of CRC. METHODS: Databases, namely, PubMed, Scopus, Embase, and Web of Science, were used for literature search. Observational studies (published until January 31, 2021) that assessed the association of PDE5i use with CRC incidence were considered. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the DerSimonian-Laird random-effects model. RESULTS: We identified four retrospective studies that involved 965,044 participants and 3,518 CRC cases detected during a mean follow-up of 12.7 years. Pooled results indicated a significantly reduced CRC risk among all PDE5i users (RR, 0.85; 95% CI, 0.76-0.95; P = 0.004, I2 = 63%). Moreover, continuous use of PDE5i was associated with a significantly reduced risk of CRC (RR, 0.63; 95% CI, 0.59-0.68; P < 0.001, I2 = 0.0%). However, the type of PDE5i exhibited no association with the risk of CRC (RR, 1.00; 95% CI, 0.98-1.02; I2 = 84.7%). CONCLUSION: Our findings suggest that continuous use of PDE5i was associated with a significantly reduced risk of CRC development. Future studies with a longitudinal design and adequate control of confounding factors are required to clarify whether a longer duration of PDE5i use alters the risk of CRC.

Knowledge and attitude towards HIV/AIDS in India: A systematic review and meta-analysis of 47 studies from 2010-2020.

Background: Several studies assessed the level of knowledge and general public behavior on human immunodeficiency virus/acquired immuno-deficiency syndrome (HIV/AIDS) in India. However, comprehensive scrutiny of literature is essential for any decision-making process. Our objective was to perform a systematic review and meta-analysis to examine the level of knowledge and attitude towards HIV/AIDS in India. Methods: A systematic search using Medical Subject Headings (MeSH) and free terms was conducted in PubMed/Medline, Scopus, Embase, and Google Scholar databases to investigate the level of knowledge and attitude of HIV/AIDS in India population. Cross-sectional studies published in English from January 2010 to November 2020 were included. The identified articles were screened in multiple levels of title, abstract and full-text and final studies that met the inclusion criteria were retrieved and included in the study. The methodological quality was assessed using the Joanna Briggs Institute's checklist for cross-sectional studies. Estimates with corresponding 95% confidence intervals (CIs) for each domain were pooled to examine the level of knowledge and attitude towards HIV/AIDS in India. Results: A total of 47 studies (n= 307 501) were identified, and 43 studies were included in the meta-analysis. The overall level of knowledge about HIV/AIDS was 75% (95% CI: 69-80%; I2 = 99.8%), and a higher level of knowledge was observed among female sex workers (FSWs) 89% (95% CI: 77-100%, I2 = 99.5%) than students (77%, 95% CI: 67-87%, I2 = 99.6%) and the general population (70%, 95% CI: 62-79%, I2 = 99.2%), respectively. However, HIV/AIDS attitude was suboptimal (60%, 95% CI: 51-69%, I2 = 99.2%). Students (58%, 95% CI: 38-77%, I2 = 99.7%), people living with HIV/AIDS (57%, 95% CI: 44-71%, I2 = 92.7%), the general population (71%, 95% CI: 62-80%, I2 = 94.5%), and healthcare workers (HCWs) (74%, 95% CI: 63-84%, I2 = 0.0%) had a positive attitude towards HIV/AIDS. The methodological quality of included studies was "moderate" according to Joanna Briggs Institute's checklist. Funnel plots are asymmetry and the Egger's regression test and Begg's rank test identified risk of publication bias. Conclusion: The level of knowledge was 75%, and 40% had a negative attitude. This information would help formulate appropriate policies by various departments, ministries and educational institutions to incorporate in their training, capacity building and advocacy programs. Improving the knowledge and changing the attitudes among the Indian population remains crucial for the success of India's HIV/AIDS response.

Prevalence of Polypharmacy, Hyperpolypharmacy and Potentially Inappropriate Medication Use in Older Adults in India: A Systematic Review and Meta-Analysis.

Background: Older people often receive multiple medications for chronic conditions, which often result in polypharmacy (concomitant use of 5‒9 medicines) and hyperpolypharmacy (concomitant use of ≥10 medicines). A limited number of studies have been performed to evaluate the prevalence of polypharmacy, hyperpolypharmacy, and potentially inappropriate medication (PIM) use in older people of developing countries. The present study aimed to investigate regional variations in the prevalence of polypharmacy, hyperpolypharmacy, and PIM use in older people (60 + years) in India. Methods: Studies were identified using Medline/PubMed, Scopus, and Google Scholar databases published from inception (2002) to September 31, 2020. Out of the total 1890 articles, 27 were included in the study. Results: Overall, the pooled prevalence of polypharmacy was 49% (95% confidence interval: 42-56; p < 0.01), hyperpolypharmacy was 31% (21-40; p < 0.01), and PIM use was 28% (24-32; p < 0.01) among older Indian adults. Polypharmacy was more prevalent in North-east India (65%, 50-79), whereas hyperpolypharmacy was prevalent in south India (33%, 17-48). Region-wize estimates for the pooled prevalence of PIM use in India were as follows: 23% (21-25) in East, 33% in West (24-42), 17.8% in North (11-23), and 32% (26-38) in South India. The prevalence of PIM use in adults aged ≥70°years was 35% (28-42), in those taking more medications (≥5.5/day) was 27% (22-31), and in adults using a high number of PIMs (≥3) was 29% (22-36). Subgroup analysis showed that cross-sectional studies had a higher pooled prevalence of polypharmacy 55% (44-65) than cohorts 45% (37-54). Hyperpolypharmacy in inpatient care settings was 37% (26-47), whereas PIM use was higher in private hospitals 31% (24-38) than government hospitals 25% (19-31). Conclusion: Polypharmacy and hyperpolypharmacy are widely prevalent in India. About 28% of older Indian adults are affected by PIM use. Thus, appropriate steps are needed to promote rational geriatric prescribing in India. Systematic Review Registration: https://clinicaltrials.gov, identifier [CRD42019141037].

Potentially Inappropriate Medication Use in Older Hospitalized Patients with Type 2 Diabetes: A Cross-Sectional Study.

Background: Older patients with type 2 diabetes mellitus (T2DM) are at greater risk of receiving potentially inappropriate medications (PIM) during hospitalization which may result in adverse outcomes. Aim: To evaluate the extent of PIM use in the older population with T2DM during hospitalization in a tertiary care hospital in India. Methods: A cross-sectional study was carried out from August 2019 to January 2020 in a tertiary care teaching hospital among the older population (aged ≥ 65 years) hospitalized with T2DM. Medications prescribed during hospitalization were reviewed following Beers Criteria 2019 to identify the extent of polypharmacy and PIM use. Binary logistic regression was applied to determine the factors associated with PIM use. Results: The mean age of the 150 patients hospitalized with T2DM was 68.85 ± 5.51 years, most of whom were men (54.7%). The participants had at least four comorbidities and were receiving an average of nine medications per day; the median length of hospital stay was 8 days (interquartile range (IQR): 4-19 days). Overall, three quarters (74%) of the participants had at least one PIM prescribed during their hospitalization as per Beers Criteria. Significant factors associated with the use of PIM during hospitalization are patients taking a higher number of medications (odds ratio (OR): 7.85, 95% CI 1.49-41.10), lower creatinine clearance values (OR: 12.90, 95% CI 2.81-59.28) and female patients (OR: 2.29; 95% CI: 1.05-4.97). Conclusions: PIM use is frequently observed in older T2DM patients during hospitalization. Polypharmacy, reduced renal function and female gender are associated with higher PIM use. Engaging clinical pharmacists in evaluating medication appropriateness can improve the outcomes of older patients.

Efficacy and Safety of Commonly Used Insulin Analogues in the Treatment of Diabetic Ketoacidosis: A Bayesian Indirect Treatment Comparison.

PURPOSE: Insulin analogues (IAs) are the mainstay for the management of diabetic ketoacidosis (DKA). However, the relative efficacy of newer IAs is uncertain. The aim of this study was to compare the relative efficacy and safety of IAs for the management of DKA using an indirect treatment comparison (ITC). METHODS: PubMed, EMBASE, Scopus, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing short-, rapid-, and long-acting IAs in patients with DKA. The primary outcomes of interest were time taken to normalize DKA and time taken to normalize blood glucose levels. The secondary outcomes of interest were the amount of insulin needed to normalize DKA, the length of hospital stay, and the number of hypoglycemic events in the intervention and comparator groups. Bayesian ITC was performed by using the gemtc package in the R program. Continuous outcomes are reported as mean difference (MD), and binary outcomes are reported as odds ratios (ORs), with 95% credible intervals (CrIs). The Cochrane risk of bias tool was used to assess the risk of bias in the included RCTs. FINDINGS: Ten RCTs randomizing 435 participants to treatment were included in this ITC. A total of 5 interventions (lispro, glargine with regular insulin [RI], glulisine, aspart, and regular insulin) were compared for both safety and efficacy outcomes in DKA. Glargine co-administered with regular insulin showed superiority for clinical outcomes compared with regular insulin: consuming less time (MD, -3.1 h; 95% CrI, -7.9 to 1.8), amount of insulin required (MD, -32 U; 95% CrI, 83.0 to 18.0), and the length of hospitalization (MD, -0.82 day; 95% CrI, -2.7 to 1.0) to normalize DKA. However, these results were not statistically significant. Insulin aspart had fewer reports of hypoglycemic events (OR, 1.7; 95% CrI, 0.34 to 9.3) than regular insulin. IMPLICATIONS: Newer IAs were found to be equally effective and safe as regular insulin in the treatment of DKA. Thus, administering these IAs can be considered a safe and cost-effective alternative for DKA management in non-ICU settings. Cost-effective analysis of the newer IAs is needed because these agents are expensive compared with regular insulin.