Statin Use and Risk of Prostate Cancer : A Meta-Analysis of Observational Studies

Background: Emerging evidence suggests that statins may decrease the risk of cancers. However, available evidence on prostate cancer (PCa) is conflicting. We therefore examined the association between statin use and risk of PCa by conducting a detailed meta-analysis of all observational studies published regarding this subject. Methods: Literature search in PubMed database was undertaken through February 2012 looking for observational studies evaluating the association between statin use and risk of PCa. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. Results: A total of 27 (15 cohort and 12 case-control) studies contributed to the analysis. There was heterogeneity among the studies but no publication bias. Statin use significantly reduced the risk of both total PCa by 7% (RR 0.93, 95% CI 0.87-0.99, p = 0.03) and clinically important advanced PCa by 20% (RR 0.80, 95% CI 0.70-0.90, p<0.001). Long-term statin use did not significantly affect the risk of total PCa (RR 0.94, 95% CI 0.84-1.05, p = 0.31). Stratification by study design did not substantially influence the RR. Furthermore, sensitivity analysis confirmed the stability of results. Cumulative meta-analysis showed a change in trend of reporting risk from positive to negative in statin users between 1993 and 2011. Conclusions: Our meta-analysis provides evidence supporting the hypothesis that statins reduce the risk of both total PCa and clinically important advanced PCa. Further research is needed to confirm these findings and to identify the underlying biological mechanisms.Peer reviewe

Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

Introduction: L-carnosine has been found to have multimodal activity. Aim: The aim of this review was to find out the efficacy of L-carnosine in patients with age-related diseases. Methods: Clinical studies evaluated the effect of L-carnosine on cancer, cardiovascular disease, diabetes, and neurodegenerative disorders were searched in electronic bibliographic databases. The protocol has been registered with PROSPERO (CRD42022314033). The revised Cochrane risk of bias tool for randomized trials was used to assess all of the reports for risk of bias. RevMan 5.4 was used to conduct the meta-analysis. Results: Following the screening process, 14 papers were selected for systematic review, with 9 of them being qualified for meta-analysis. Many of the included studies showed that L-carnosine has potential therapeutic activity in age related diseases. Results from the meta-analysis showed that in diabetes mellitus, HbA1c [mean difference (MD) 95% CI = –1.25 (–2.49, –0.022); p = 0.05; p = 0.001; I 2 = 85%] and fasting blood sugar (FBS) [MD 95% CI = –12.44 (–22.44, –2.44); p = 0.01; p = 0.40; I 2 = 0%] and in neurodegenerative disorder, Wechsler Memory Scale Logical Memory 2 (WMS-LM2) [MD 95% CI = 1.34 (0.83, 1.85); p < 0.00001; p = 0.43; I 2 = 0%], showed statistically significant difference, favoring the L-carnosine group over the control group. While in neurodegenerative disorder, Alzheimer ’s Disease Assessment Scale (ADAS) [MD 95% CI = 0.98 (–1.55, –0.42); p = 0.0007; p = 0.86; I 2 = 0%] and Back Depression Inventory (BDI) [MD 95% CI = –1.12 (–1.87, –0.37); p = 0.003; p = 0.73; I 2 = 0%] showed statistically significant difference, favoring the control group over L-carnosine group. Conclusions: Clinical studies were conducted to manage chemotherapy induced toxicities and there are no clinical studies available for its anti-cancer use, and the current evidence does not support its use in the treatment of cardiovascular disease

Macrolides versus placebo for chronic asthma.

BACKGROUND: Asthma is a chronic disease in which inflammation of the airways causes symptomatic wheezing, coughing and difficult breathing. Macrolides are antibiotics with antimicrobial and anti-inflammatory activities that have been explored for the long-term control of asthma symptoms. OBJECTIVES: To assess the effects of macrolides compared with placebo for managing chronic asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register up to March 2021. We also manually searched bibliographies of previously published reviews and conference proceedings and contacted study authors. We included records published in any language in the search. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) involving both children and adults with asthma treated with macrolides versus placebo for four or more weeks. Primary outcomes were exacerbation requiring hospitalisation, severe exacerbations (exacerbations requiring emergency department (ED) visits or systemic steroids, or both), symptom scales, asthma control questionnaire (ACQ, score from 0 totally controlled, to 6 severely uncontrolled), Asthma Quality of Life Questionnaire (AQLQ, with score from 1 to 7 with higher scores indicating better QoL), rescue medication puffs per day, morning and evening peak expiratory flow (PEF; litres per minutes), forced expiratory volume in one second (FEV1; litres), bronchial hyperresponsiveness, and oral corticosteroid dose. Secondary outcomes were adverse events (including mortality), withdrawal, blood eosinophils, sputum eosinophils, eosinophil cationic protein (ECP) in serum, and ECP in sputum. DATA COLLECTION AND ANALYSIS: Two review authors independently examined all records identified in the searches then reviewed the full text of all potentially relevant articles before extracting data in duplicate from all included studies. As per protocol, we used a fixed-effect model. We conducted a sensitivity analysis for analyses with high heterogeneity (I2 greater than 30%). GRADE was used to assess the certainty of the body of evidence. MAIN RESULTS: Twenty-five studies met the inclusion criteria, randomising 1973 participants to receive macrolide or placebo for at least four weeks. Most of the included studies reported data from adults (mean age 21 to 61 years) with persistent or severe asthma, while four studies included children. All participants were recruited in outpatient settings. Inclusion criteria, interventions and outcomes were highly variable. The evidence suggests macrolides probably deliver a moderately sized reduction in exacerbations requiring hospitalisations compared to placebo (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.20 to 1.12; studies = 2, participants = 529; moderate-certainty evidence). Macrolides probably reduce exacerbations requiring ED visits and/or treatment with systemic steroids (rate ratio (RaR) 0.65, 95% CI 0.53 to 0.80; studies = 4, participants = 640; moderate-certainty evidence). Macrolides may reduce symptoms (as measured on symptom scales) (standardised mean difference (SMD) -0.46, 95% CI -0.81 to -0.11; studies = 4, participants = 136 ; very low-certainty evidence). Macrolides may result in a little improvement in ACQ (SMD -0.17, 95% CI -0.31 to -0.03; studies = 5, participants = 773; low-certainty evidence). Macrolides may have little to no effect on AQLQ (mean difference (MD) 0.24, 95% CI 0.12 to 0.35; studies = 6, participants = 802; very low-certainty evidence). For both the ACQ and the AQLQ the suggested effect of macrolides versus placebo did not reach a minimal clinically important difference (MCID, 0.5 for ACQ and AQLQ) (ACQ: low-certainty evidence; AQLQ: very low-certainty evidence). Due to high heterogeneity (I2 > 30%), we conducted sensitivity analyses on the above results, which reduced the size of the suggested effects by reducing the weighting on the large, high quality studies.  Macrolides may result in a small effect compared to placebo in reducing need for rescue medication (MD -0.43 puffs/day, 95% CI -0.81 to -0.04; studies = 4, participants = 314; low-certainty evidence). Macrolides may increase FEV1, but the effect is almost certainly below a level discernible to patients (MD 0.04 L, 95% CI 0 to 0.08; studies = 10, participants = 1046; low-certainty evidence). It was not possible to pool outcomes for non-specific bronchial hyperresponsiveness or lowest tolerated oral corticosteroid dose (in people requiring oral corticosteroids at baseline). There was no evidence of a difference in severe adverse events (including mortality), although less than half of the studies reported the outcome (OR 0.80, 95% CI 0.49 to 1.31; studies = 8, participants = 854; low-certainty evidence). Reporting of specific adverse effects was too inconsistent across studies for a meaningful analysis. AUTHORS' CONCLUSIONS: Existing evidence suggests an effect of macrolides compared with placebo on the rate of exacerbations requiring hospitalisation. Macrolides probably reduce severe exacerbations (requiring ED visit and/or treatment with systemic steroids) and may reduce symptoms. However, we cannot rule out the possibility of other benefits or harms because the evidence is of very low quality due to heterogeneity among patients and interventions, imprecision and reporting biases. The results were mostly driven by a well-designed, well powered RCT, indicating that azithromycin may reduce exacerbation rate and improve symptom scores in severe asthma. The review highlights the need for researchers to report outcomes accurately and according to standard definitions. Macrolides can reduce exacerbation rate in people with severe asthma. Future trials could evaluate if this effect is sustained across all the severe asthma phenotypes, the comparison with newer biological drugs, whether effects persist or wane after treatment cessation and whether effects are associated with infection biomarkers

Knowledge, beliefs, and practice of pregnant women regarding medication use during pregnancy: a hospital-based cross-sectional study

The purpose of this study was to assess the knowledge, beliefs, and practice (KBP) of pregnant women on medication use during pregnancy, and to identify the factors influencing KBP. A cross-sectional study was conducted in the Department of Obstetrics & Gynaecology of a tertiary care hospital over a period of nine months. Pregnant women receiving at least one medication were included in the study. A 19-item questionnaire was developed, validated, and used for assessing the KBP of pregnant women. Logistic regression analysis was used to identify the factors influencing the KBP. A total of 422 pregnant women with a mean (SD) age of 24.6 (4.05) years were included in the study. Pregnant women were having less knowledge on ‘unsafe medications’ and ‘important medications’ during pregnancy, wrong belief on ‘stopping all medications during pregnancy’, and less practice of ‘asking Pharmacist how to take medications’. It was identified hat the age, education, occupation, and area of living were the factors influencing the knowledge and practice of pregnant women on medication use. This study identified the need for improvement in knowledge and practice of pregnant women who are young, having nil or low level of education, no occupation, and living in rural areas.IMPACT STATEMENT What is already known on this subject? Knowledge and beliefs on medication use play a vital role in medication adherence among pregnant women. Crisis in rural healthcare along with socio-demographic conditions and literacy status of Indian women may have contributed to the lack of understanding about use of medications during pregnancy. What the results of this study add? The knowledge of pregnant women was found to be insufficient on ‘unsafe medications’ and ‘important medications’ during pregnancy. Majority of the pregnant women believe that it is better for the foetus if they ‘stop taking all medications during pregnancy’. ‘Not asking Pharmacist how to take medications’ is one important practice in India contributes less knowledge on medication use. What the implications are of these findings for clinical practice and/or further research? There is a need for improvement in knowledge and practice of medication use among pregnant women who are young, having nil or low level of education, no occupation, and living in rural areas