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Efficacy of immune checkpoint inhibitors combinations as first-line systemic treatment in patients with advanced urothelial carcinoma: A systematic review and network meta-analysis.
Monteiro, FSM, Soares, A, Mollica, V, Leite, CA, Carneiro, APCD, Rizzo, A, Bourlon, MT, Sasse, AD, Santoni, M, Gupta, S, et al
Critical reviews in oncology/hematology. 2024;:104321
Abstract
BACKGROUND Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results. METHODS Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR). RESULTS Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%). CONCLUSION This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.
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Association between calcium supplementation and gestational hypertension, and preeclampsia: A Meta-analysis of 26 randomized controlled trials.
Jaiswal, V, Joshi, A, Jha, M, Hanif, M, Arora, A, Gupta, S, Shah, M, Deb, N, Peng Ang, S, Aujla, S, et al
Current problems in cardiology. 2024;(3):102217
Abstract
BACKGROUND Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women. METHODS A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI). RESULTS A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved. CONCLUSION This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes.
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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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Sodium-glucose Cotransporter-2 Inhibitors in Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with Type 2 Diabetes Mellitus: A Meta-analysis.
Kovil, R, Chawla, M, Shah, T, Sahoo, A, Makkar, B, Kesavadev, J, Seshadri, K, Tiwaskar, M, Rajput, R, Phatak, S, et al
The Journal of the Association of Physicians of India. 2022;(8):11-12
Abstract
BACKGROUND The available evidence was systematically reviewed to evaluate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) on cardiovascular (CV) and renal outcomes in people with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors (MRF), with or without heart failure (HF), and per estimated glomerular filtration rate (eGFR) rate at baseline. METHODS We comprehensively searched three electronic databases to retrieve publications up to 30th November 2019, which were screened for inclusion. The data extracted for the outcomes according to baseline ASCVD, HF, and eGFR levels were meta-analyzed using fixed effects model. RESULTS Of the 735 screened citations, 15 primary and secondary publications from five CV or renal outcome trials were included. SGLT2is reduced the risk of CV death or hospitalization for HF (HHF), HHF alone, and composite renal-specific outcome, irrespective of ASCVD and HF at baseline. The three-point major adverse cardiovascular events (3P-MACE) risk was reduced by 14% (p<0.001) in patients with ASCVD and by 10% (p = 0.018) in those without baseline HF compared with their counterparts. SGLT2is significantly reduced the risk of MACE (18%) in patients with mild kidney dysfunction (eGFR within the range of 60-<90 mL/min/1.73 m2 and <60 mL/min/1.73 m2 ). CONCLUSION SGLT2is are effective for both secondary and primary prevention of composite CV outcomes, and secondary prevention of MACE. The upcoming evidence may strengthen the primary prevention benefits of SGLT2is.
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Efficacy and safety of low intensity vitamin K antagonists in Western and East-Asian patients with left-sided mechanical heart valves.
Pandey, AK, Xu, K, Zhang, L, Gupta, S, Eikelboom, J, Lopes, RD, Crowther, M, Belley-Côté, EP, Whitlock, RP
Journal of thrombosis and thrombolysis. 2022;(3):697-707
Abstract
The optimal INR target in patients with mechanical heart valves is unclear. Higher INR targets are often used in Western compared with East Asian countries. The objective of this systematic review and meta-analysis was to summarize the evidence for the efficacy and safety of lower versus higher INR targets in Western and East Asian left-sided mechanical heart valve patients. We searched Western databases including Cochrane CENTRAL, Medline, and Embase as well as Chinese databases including SinoMed, CNKI, and Wanfang Data in addition to grey literature for Randomized Controlled Trials (RCTs) and observational studies. We pooled risk ratios (RRs) using random-effects model. Low and high INR targets were defined by the individual studies. We identified nine RCTs, including six Western (n = 5496) and three East Asian (n = 209) trials, and 17 observational studies, including two Western (n = 3199) and 15 East Asian (n = 5485) studies. In the RCTs, lower compared with higher targets were associated with similar rates of thromboembolism (2.4 vs. 2.3%; RR: 1.14, 95% CI 0.82, 1.60, I2 = 0%) and lower rates of both total bleeding (21.9 vs. 40.9%, RR: 0.46, 95% CI 0.28, 0.78, I2 = 88%) and major bleeding. RCT data showed no statistical heterogeneity by region. These effects were consistent in the observational data. We downgraded the quality of evidence due to serious risk of bias and imprecision. In patients with left-sided contemporary mechanical heart valves, low quality evidence suggests lower INR targets are associated with similar rates of thromboembolism and moderate quality evidence suggests lower rates of bleeding.
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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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Plain language summary
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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Intravenous iron therapy for patients with preoperative iron deficiency or anaemia undergoing cardiac surgery reduces blood transfusions: a systematic review and meta-analysis.
Gupta, S, Panchal, P, Gilotra, K, Wilfred, AM, Hou, W, Siegal, D, Whitlock, RP, Belley-Cote, EP
Interactive cardiovascular and thoracic surgery. 2020;(2):141-151
Abstract
OBJECTIVES The benefits of preoperative intravenous (IV) iron treatment in cardiac surgery patients with preoperative anaemia or iron deficiency have not been well-established. We performed a systematic review and meta-analysis to determine the effects of treating preoperative anaemia or iron deficiency with IV iron in adult cardiac surgery patients. METHODS We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online and Excerpta Medica Database for randomized controlled trials (RCTs) and observational studies comparing IV iron to oral iron or no iron. We performed title and abstract, full-text screening, data extraction and risk of bias assessment independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence. RESULTS We identified 4 RCTs and 7 observational studies. Pooled data from observational studies suggested a benefit of IV iron compared to no iron on mortality [relative risk 0.39, 95% confidence interval (CI) 0.23-0.65; P < 0.001, very low quality], units transfused per patient (mean difference -1.22, 95% CI -1.85 to -0.60; P < 0.001, very low quality), renal injury (relative risk 0.50, 95% CI 0.36-0.69; P < 0.001, very low quality) and hospital length of stay (mean difference -4.24 days, 95% CI -6.86 to -1.63; P = 0.001, very low quality). Pooled data from RCTs demonstrated a reduction in the number of patients transfused with IV iron compared to oral or no iron (relative risk 0.81, 95% CI 0.70-0.94; P = 0.005, moderate quality). The pooled estimates of effect from RCTs for mortality, hospital length of stay, units transfused per patient and renal injury were consistent in direction with observational studies. CONCLUSIONS This meta-analysis suggests that IV iron improves postoperative morbidity in adult cardiac surgery patients with preoperative anaemia or iron deficiency. A large, rigorous, placebo-controlled, double-blinded, multicentre trial is needed to clarify the role of IV iron in this patient population. CLINICAL TRIAL REGISTRATION International prospective register of systematic reviews ID Number CRD42019122844.
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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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Role of Vitamin D and Its Analogues in Diabetic Nephropathy: A Meta-analysis.
Gupta, S, Goyal, P, Feinn, RS, Mattana, J
The American journal of the medical sciences. 2019;(3):223-229
Abstract
BACKGROUND Diabetic nephropathy remains one of the most common causes of chronic kidney disease in the United States and is associated with significant morbidity and mortality. Recently, there have been emerging data highlighting the role of vitamin D and its analogue in chronic kidney disease especially diabetic nephropathy independent of its effect on bone metabolism. METHODS This study aimed to evaluate effect of supplementing vitamin D and its analogues on halting or slowing progression of diabetic nephropathy. Electronic databases (PubMed, Scopus, Google scholar) were searched and randomized controlled trials (RCTs) that investigated the use of vitamin D and its analogs for diabetic nephropathy were studied. This meta-analysis of RCTs performed in accordance with Preferred Reporting Items for Systematic review and Meta-analysis statement. RESULTS This meta-analysis included 9 RCTs and suggested a favorable trend with respect to an effect of vitamin D and its analogues on albuminuria though this did not reach statistical significance (MD, -0.17; 95% CI, -0.34-0.01; P = 0.06]. Serum calcium was unaffected suggesting safe use of these agents. CONCLUSIONS Use of vitamin D and its analogues may have potential as an adjuvant therapy for reducing albuminuria and slowing progression of diabetic nephropathy but further studies are needed.