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Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.
Shi, Q, Nong, K, Vandvik, PO, Guyatt, GH, Schnell, O, Rydén, L, Marx, N, Brosius, FC, Mustafa, RA, Agarwal, A, et al
BMJ (Clinical research ed.). 2023;:e074068
Abstract
OBJECTIVE To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN Systematic review and network meta-analysis. DATA SOURCES Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42022325948.
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Risk Reversal of Oral, Pharyngeal and Oesophageal Cancers after Cessation of Betel Quid Users: A Systematic Review and Meta-Analysis.
Gupta, R, Mariano, LC, Nethan, ST, Kedar, A, Sinha, DN, Warnakulasuriya, S, Monteiro, L, Sharma, S, Gupta, S, Singh, S, et al
Annals of global health. 2022;(1):5
Abstract
BACKGROUND Areca nut (AN), the principal ingredient of betel quid (BQ) has been categorized as a human carcinogen associated with various cancers of upper aerodigestive tract. However, there has been no attempt at summarizing the risk reversal of oral and other cancers after cessation of BQ with or without tobacco (BQ+T/BQ-T). OBJECTIVE To analyze the effect of cessation of betel quid without tobacco (BQ-T) and with tobacco (BQ+T) on reversal of the risk of oral, pharyngeal and oesophageal cancers. METHODS A systematic literature search was conducted for publications evaluating risk of these three cancers among current and former users of BQ-T or BQ+T. The overall as well as subgroup meta-relative risks (meta-RR) were estimated using random-effect models. RESULTS A total of 14 studies, seven each providing estimates for BQ-T and BQ+T, were identified. For BQ-T and oral cancer, a 28.9% risk reversal was observed among former users (meta-RR 5.61, 95% CI 2.24-14.04) compared to current users (meta-RR 7.89, 95% CI 3.90-15.98). A risk reversal of 48% was noted for pharyngeal cancer - former users (meta-RR 2.50, 95% CI 1.43-4.38), current users (meta-RR 4.81, 95% CI 2.05-11.30). For oesophageal cancer, no appreciable difference in risk was observed between current and former users.For BQ+T and oral cancer the overall meta-RR indicated a higher risk in former than in current users. However, sensitivity analysis including only better-quality studies showed a modestly lower cancer risk in former than in current users. Compared to current users, the risk in former users who quit less than 10 years ago (meta-RR 1.21, 95% CI 0.90-1.63) was increased, but decreased in former users who quit more than 10 years ago (meta-RR 0.72, 95% CI 0.48-1.07). CONCLUSION Our analysis highlights for the first time the potential of risk reversal for oral and pharyngeal cancers following cessation of BQ-T and for oral cancer in long-term quitters (greater than 10 years) of BQ+T. The suggestive evidence from this systematic review further supports the imperative need of a strong policy to reduce the initiation of BQ use and inclusion of interventions for BQ cessation in cancer control efforts especially in geographic regions where BQ chewing is prevalent.
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The effects of dietary nitrate supplementation on endurance exercise performance and cardiorespiratory measures in healthy adults: a systematic review and meta-analysis.
Gao, C, Gupta, S, Adli, T, Hou, W, Coolsaet, R, Hayes, A, Kim, K, Pandey, A, Gordon, J, Chahil, G, et al
Journal of the International Society of Sports Nutrition. 2021;18(1):55
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The ability to increase endurance to improve their physical fitness is of great interest to athletes. Several dietary components have been shown to increase endurance especially those which contain nitrates. It is thought that nitrates, which are found in beetroots, pomegranates, green leafy vegetables, collard greens, lettuce and spinach, aid endurance through their action on improving blood flow to the muscles, helping to improve contraction of the muscles, through increased energy production, through improved oxygen flow and through sugar and nutrient balance. However, studies in humans on the effects of nitrates on exercise endurance have been conflicting. This systematic review and meta-analysis aimed to summarise the research on the use of nitrates during exercise. The results showed that nitrate supplementation improved muscle power, time to exhaustion and distance travelled, although no difference was found to perceived exertion, time trial performance and work done. It was concluded that nitrate supplementation is of benefit to improve exercise endurance, based on very low to moderate quality evidence. This study could be used by health care professionals to recommend a nitrate rich diet and possibly a nitrate supplement to improve exercise performance.
Abstract
BACKGROUND Nitrate supplementation is thought to improve performance in endurance sports. OBJECTIVE To meta-analyze studies evaluating the effect of nitrate supplementation on endurance sports performance among adults. DATA SOURCES We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science and CINAHL without language restrictions. METHODS We included studies that: 1) compared nitrate supplementation with placebo; 2) enrolled adults engaging in an endurance-based activity; and 3) reported a performance measure or surrogate physiologic outcome. We evaluated risk of bias using the Cochrane Collaboration tool and pooled data with a random-effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate confidence in estimates. RESULTS We included 73 studies (n = 1061). Nitrate supplementation improved power output (MD 4.6 watts, P < 0.0001), time to exhaustion (MD 25.3 s, P < 0.00001), and distance travelled (MD 163.7 m, P = 0.03). We found no significant difference on perceived exertion, time trial performance and work done. Nitrate supplementation decreased VO2 (MD - 0.04 L/min, P < 0.00001) but had no significant effect on VO2max or blood lactate levels. CONCLUSION The available evidence suggests that dietary nitrate supplementation benefits performance-related outcomes for endurance sports.
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The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.
Xie, J, Liu, L, Mladkova, N, Li, Y, Ren, H, Wang, W, Cui, Z, Lin, L, Hu, X, Yu, X, et al
Nature communications. 2020;(1):1600
Abstract
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.
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Mailed Outreach Is Superior to Usual Care Alone for Colorectal Cancer Screening in the USA: A Systematic Review and Meta-analysis.
Jager, M, Demb, J, Asghar, A, Selby, K, Mello, EM, Heskett, KM, Lieberman, AJ, Geng, Z, Bharti, B, Singh, S, et al
Digestive diseases and sciences. 2019;(9):2489-2496
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Mailed outreach promoting colorectal cancer (CRC) screening with a stool blood test kit may increase participation, but magnitude and consistency of benefit of this intervention strategy is uncertain. Our aim was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing mailed outreach offering stool tests to usual care, clinic-based screening offers on CRC screening uptake in the USA. We performed a systematic literature search of five databases for RCTs of mailed outreach from January 1980 through June 2017. Primary outcome was screening completion, summarized using random-effects meta-analysis as pooled differences in proportion completing the screening and relative risk of achieving screening compared to control. Subgroup analyses by test type offered-fecal immunochemical test (FIT) or guaiac fecal occult blood test (gFOBT), the presence of telephone reminders, and the presence of predominant underserved/minority population within study were performed. Quality of evidence was evaluated using the GRADE framework. Seven RCTs which enrolled 12,501 subjects were included (n = 5703 assigned mailed outreach and n = 6798 usual care). Mailed outreach resulted in a 28% absolute (95% CI 25-30%; I2 = 47%) and a 2.8-fold relative (RR 2.65, 95% CI 2.03-3.45; I2 = 92%) increase in screening completion compared to usual care, with a number needed to invite estimated to be 3.6. Similar outcomes were observed across subgroups. Overall body of evidence was at moderate quality. Mailed outreach offering a gFOBT or FIT is associated with a large and consistent increase in CRC screening completion and should be considered for more widespread implementation for improving screening rates nationwide.
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Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.
Rai, V, Yadav, U, Kumar, P, Yadav, SK, Gupta, S
The Indian journal of medical research. 2017;(4):437-447
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BACKGROUND & OBJECTIVES Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia. METHODS PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure. RESULTS The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04). INTERPRETATION & CONCLUSIONS MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia.
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Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis.
Dulai, PS, Singh, S, Marquez, E, Khera, R, Prokop, LJ, Limburg, PJ, Gupta, S, Murad, MH
BMJ (Clinical research ed.). 2016;:i6188
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OBJECTIVE To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis. DATA SOURCES Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries. STUDY SELECTION Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events. DATA EXTRACTION Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria. RESULTS 15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated. CONCLUSIONS Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile. REGISTRATION PROSPERO (CRD42015029598).
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Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis.
Gupta, N, Gupta, S, Dama, M, David, A, Khanna, G, Khanna, A, Rajender, S
PloS one. 2011;(7):e22277
Abstract
BACKGROUND Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies. METHODOLOGY/PRINCIPAL FINDINGS We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522) and confirmed fertile (N = 315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p = 0.0025) and genotypes (CT+TT) (p = 0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility. CONCLUSIONS/SIGNIFICANCE 677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.