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.
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,
I
2
= 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,
I
2
= 0.0%). However, the type of PDE5i exhibited no association with the risk of CRC (RR, 1.00; 95% CI, 0.98–1.02;
I
2
= 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.
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. 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. 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. 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.
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 (
P
heterogeneity
= 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;
R
2
= 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.
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).
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.
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,
< 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.
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.
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; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 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; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 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; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%, in total AEs remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%), in mortality 10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%) and tolerability remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 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.
According to the American Geriatric Society (AGS), PIMs are medications that impose a risk of adverse effects outweighing their benefits, especially when equally effective and safer treatment ...alternatives are available 14. The prevalence of patients with PIMs varies significantly depending on the criteria used, population, healthcare setting, and country of study. ...the population presenting in memory clinics differs significantly from other healthcare settings due to the specialized focus on cognitive health, memory disorders, and the unique needs of individuals with CI and their caregivers. The multidisciplinary approach, comprehensive assessments, and tailored interventions in memory clinics make them uniquely suited to address the complexities of memory-related conditions. ...it is pertinent to explore the prevalence of PIMs, polypharmacy, and hyper-polypharmacy among older adults with dementia or CI attending memory clinics in different healthcare settings to ensure patient safety, optimization of medication management, and the enhancement of the quality of care for individuals with CIs. Most frequently prescribed PIM in older adults with dementia or CI attending memory clinics Additional outcomes Quality of life, incidence of mortality, cost of PIM, falls, hospital admission, adverse events Study design Cross-sectional studies, cohort studies, observational studies,
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