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The Effect of Liquid Meal Replacements on Cardiometabolic Risk Factors in Overweight/Obese Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Noronha, JC, Nishi, SK, Braunstein, CR, Khan, TA, Blanco Mejia, S, Kendall, CWC, Kahleová, H, Rahelić, D, Salas-Salvadó, J, Leiter, LA, et al
Diabetes care. 2019;(5):767-776
Abstract
OBJECTIVE The evidence for liquid meal replacements in diabetes has not been summarized. Our objective was to synthesize the evidence of the effect of liquid meal replacements on cardiometabolic risk factors in overweight/obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Data sources included MEDLINE, EMBASE, and the Cochrane Library through 10 December 2018. We included randomized trials of ≥2 weeks assessing the effect of liquid meal replacements in weight loss diets compared with traditional weight loss diets on cardiometabolic risk factors in overweight/obese subjects with type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS Nine trial comparisons (N = 961 [median follow-up 24 weeks]) met eligibility criteria. Mean differences were for body weight -2.37 kg (95% CI -3.30 to -1.44), BMI -0.87 kg/m2 (-1.31 to -0.42), body fat -1.66% (-2.17 to -1.15), waist circumference -2.24 cm (-3.72 to -0.77), HbA1c -0.43% (-0.66 to -0.19) (-4.7 mmol/mol [-7.2 to -2.1]), fasting glucose -0.63 mmol/L (-0.99 to -0.27), fasting insulin -11.83 pmol/L (-23.11 to -0.54), systolic blood pressure -4.97mmHg (-7.32 to -2.62), and diastolic blood pressure -1.98 mmHg (-3.05 to -0.91). There was no effect on blood lipids. The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency. CONCLUSIONS Liquid meal replacements in weight loss diets lead to modest reductions in body weight, BMI, and systolic blood pressure, and reductions of marginal clinical significance in body fat, waist circumference, HbA1c, fasting glucose, fasting insulin, and diastolic blood pressure. More high-quality trials are needed to improve the certainty in our estimates.
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2.
Acupuncture for Acute Pancreatitis: A Systematic Review and Meta-analysis.
Zhang, K, Gao, C, Li, C, Li, Y, Wang, S, Tang, Q, Zhao, C, Zhai, J
Pancreas. 2019;(9):1136-1147
Abstract
OBJECTIVE The objective of this study was to assess the efficacy and safety of acupuncture plus routine treatment (RT) for acute pancreatitis (AP). METHODS Literature searches were performed in 8 databases up to October 31, 2018. Randomized controlled trials comparing acupuncture plus RT with RT alone for AP were included. RESULTS Twelve eligible studies were included finally. The meta-analysis showed that acupuncture plus RT compared with RT alone could significantly improve the total effective rate and gastrointestinal function and reduce the Acute Physiology, Age, Chronic Health Evaluation II score, tumor necrosis factor α count, the time of resuming to diets, and the length of hospital stay. Only 3 of the studies reported adverse events or reactions. CONCLUSIONS This study suggested that acupuncture combined with RT may be effective for AP. However, more rigorously designed randomized controlled trials are warranted to confirm the current findings.
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Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants.
Yebyo, HG, Aschmann, HE, Kaufmann, M, Puhan, MA
American heart journal. 2019;:18-28
Abstract
UNLABELLED The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations. METHODS We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes. RESULTS In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile. CONCLUSIONS All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.
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Effect of preoperative bicarbonate infusion on maternal and perinatal outcomes of obstructed labour in Mbale Regional Referral Hospital: a study protocol for a randomised controlled trial.
Musaba, MW, Barageine, JK, Ndeezi, G, Wandabwa, JN, Weeks, A
BMJ open. 2019;(4):e026675
Abstract
INTRODUCTION To improve maternal and fetal outcomes among patients with obstructed labour (OL) in low-resource settings, the associated electrolyte and metabolic derangements must be adequately corrected. Oral fluid intake during labour and preoperative intravenous fluid replacement following OL corrects the associated dehydration and electrolyte changes, but it does not completely reverse the metabolic acidosis, that is, a cause of intrapartum birth asphyxia and a risk factor for primary postpartum haemorrhage due to uterine atony. Sodium bicarbonate is a safe, effective, cheap and readily available acid buffer, that is widely used by sportspeople to improve performance. It also appears to improve fetal and maternal outcomes in abnormally progressing labour. However, its effects on maternal and fetal outcomes among patients with OL is unknown. We aim at establishing the effect of a single-dose preoperative infusion of sodium bicarbonate on maternal and fetal lactate levels and clinical outcomes among patients with OL. METHODS AND ANALYSIS This will be a double blind, randomised controlled clinical phase IIb trial. We will randomise 478 patients with OL to receive either 50 mL of placebo with standard preoperative infusion of normal saline (1.5 L) or 4.2 g of sodium bicarbonate solution (50 mL of 50 mmol/L) with the preoperative infusion of normal saline (1.5 L). The primary outcome will be mean lactate levels in maternal capillary blood at 1 hour after study drug administration and in the arterial cord blood at birth. We will use the intention-to-treat analysis approach. Secondary outcomes will include safety, maternal and fetal morbidity and mortality up to 14 days postpartum. ETHICS AND DISSEMINATION Makerere University School of Medicine Research and Ethics Committee and Uganda National Council for Science and Technology have approved the protocol. Each participant will give informed consent at enrollment. TRIAL REGISTRATION NUMBER PACTR201805003364421.
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An appraisal of the SDIR as an estimate of true individual differences in training responsiveness in parallel-arm exercise randomized controlled trials.
Bonafiglia, JT, Brennan, AM, Ross, R, Gurd, BJ
Physiological reports. 2019;(14):e14163
Abstract
Calculating the standard deviation of individual responses (SDIR ) is recommended for estimating the magnitude of individual differences in training responsiveness in parallel-arm exercise randomized controlled trials (RCTs). The purpose of this review article is to discuss potential limitations of parallel-arm exercise RCTs that may confound/complicate the interpretation of the SDIR . To provide context for this discussion, we define the sources of variation that contribute to variability in the observed responses to exercise training and review the assumptions that underlie the interpretation of SDIR as a reflection of true individual differences in training responsiveness. This review also contains two novel analyses: (1) we demonstrate differences in variability in changes in diet and physical activity habits across an intervention period in both exercise and control groups, and (2) we examined participant dropout data from six RCTs and found that significantly (P < 0.001) more participants in control groups (12.8%) dropped out due to dissatisfaction with group assignment compared to exercise groups (3.4%). These novel analyses raise the possibility that the magnitude of within-subject variability may not be equal between exercise and control groups. Overall, this review highlights that potential limitations of parallel-arm exercise RCTs can violate the underlying assumptions of the SDIR and suggests that these limitations should be considered when interpreting the SDIR as an estimate of true individual differences in training responsiveness.
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Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials.
Keum, N, Lee, DH, Greenwood, DC, Manson, JE, Giovannucci, E
Annals of oncology : official journal of the European Society for Medical Oncology. 2019;(5):733-743
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Abstract
BACKGROUND Previous meta-analyses of randomized controlled trials (RCTs) of vitamin D supplementation and total cancer incidence and mortality found inconsistent results, and most included trials administered generally low doses of vitamin D (≤1100 IU/day). We updated the meta-analysis by incorporating recent RCTs that have tested higher doses of vitamin D supplements. MATERIALS AND METHODS PubMed and Embase were searched from the inception to November 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. RESULTS For total cancer incidence, 10 trials were included [6537 cases; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH) vitamin D [25(OH)D] in the intervention group]. The summary RR was 0.98 (95% CI, 0.93-1.03; P = 0.42; I2 = 0%). The results remained null across subgroups tested, including even when attained 25(OH)D levels exceeded 100 nmol/l (RR, 0.95; 95% CI, 0.83-1.09; P = 0.48; I2 = 26%). For total cancer mortality, five trials were included [1591 deaths; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH)D in the intervention group]. The summary RR was 0.87 (95% CI, 0.79-0.96; P = 0.005; I2 = 0%), which was largely attributable to interventions with daily dosing (as opposed to infrequent bolus dosing). No statistically significant heterogeneity was observed by attained levels of circulating 25(OH)D (Pheterogeneity = 0.83), with RR being 0.88 (95% CI, 0.78-0.98; P = 0.02; I2 = 0%) for ≤100 nmol/l and 0.85 (95% CI, 0.70-1.03; P = 0.11; I2 = 0%) for >100 nmol/l. CONCLUSIONS In an updated meta-analysis of RCTs, vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence.
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Very Short Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Patients With High Bleeding Risk: Insight From the STOPDAPT-2 Trial.
Watanabe, H, Domei, T, Morimoto, T, Natsuaki, M, Shiomi, H, Toyota, T, Ohya, M, Suwa, S, Takagi, K, Nanasato, M, et al
Circulation. 2019;(23):1957-1959
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Ethical Issues in Pragmatic Cluster-Randomized Trials in Dialysis Facilities.
Goldstein, CE, Weijer, C, Taljaard, M, Al-Jaishi, AA, Basile, E, Brehaut, J, Cook, CL, Grimshaw, JM, Lacson, E, Lindsay, C, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2019;(5):659-666
Abstract
A pragmatic cluster-randomized trial (CRT) is a research design that may be used to efficiently test promising interventions that directly inform dialysis care. While the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials provides general ethical guidance for CRTs, the dialysis setting raises additional considerations. In this article, we outline ethical issues raised by pragmatic CRTs in dialysis facilities. These issues may be divided into 7 key domains: justifying the use of cluster randomization, adopting randomly allocated individual-level interventions as a facility standard of care, conducting benefit-harm analyses, gatekeepers and their responsibilities, obtaining informed consent from research participants, patient notification, and including vulnerable participants. We describe existing guidelines relevant to each domain, illustrate how they were considered in the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial (a prototypical pragmatic hemodialysis CRT), and highlight remaining areas of uncertainty. The following is the first step in an interdisciplinary mixed-methods research project to guide the design and conduct of pragmatic CRTs in dialysis facilities. Subsequent work will expand on these concepts and when possible, argue for a preferred solution.
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Apixaban versus warfarin in evaluation of progression of atherosclerotic and calcified plaques (prospective randomized trial).
Win, TT, Nakanishi, R, Osawa, K, Li, D, Susaria, SS, Jayawardena, E, Hamal, S, Kim, M, Broersen, A, Kitslaar, PH, et al
American heart journal. 2019;:129-133
Abstract
Warfarin has been showed to increase vascular calcification. Apixaban, a direct factor Xa inhibitor, has no interaction with vitamin K and its effect on coronary plaques is unknown. We randomized and compared warfarin and apixaban on progression of coronary atherosclerotic plaques measured by coronary computed tomographic angiography in 66 subjects with non-valvular atrial fibrillation over the period of one-year follow up. There was significant higher total, calcified and low attenuation plaque volume in the group randomized to warfarin as compared to apixaban (all P < .05). Greater volume of total (β2 = 28.54; P = .03), low attenuation plaque (β2 = 3.58; P = .02) and calcified (β2 = 14.10; P = .005) plaque progression was observed in the VKA_group.
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Ascorbic Acid, Corticosteroids and Thiamine in Sepsis (ACTS) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomised, placebo-controlled clinical trial.
Moskowitz, A, Yankama, T, Andersen, LW, Huang, DT, Donnino, MW, Grossestreuer, AV, ,
BMJ open. 2019;(12):e034406
Abstract
INTRODUCTION Septic shock is a common and highly morbid condition. To date, there is no specific therapy proven to attenuate organ injury in septic shock. Recent studies have suggested a role for the combination of ascorbic acid, corticosteroids and thiamine, although randomised data are lacking. METHODS AND ANALYSIS The Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis trial is a multi-centre, double-blind, randomised, placebo-controlled clinical trial that aims to determine the impact of ascorbic acid, corticosteroids and thiamine versus placebo on organ injury and mortality in patients with septic shock. Patients are randomised to receive 1500 mg of ascorbic acid, 100 mg of thiamine and 50 mg of hydrocortisone parenterally versus matching placebo every 6 hours for 4 days. Clinical and laboratory data are collected at the time of study enrolment, at 24, 72 and 120 hours. The primary end-point for the trial is change in the Sequential Organ Failure Assessment score between enrolment and 72 hours. Additional key secondary outcomes include the incidence of renal failure and 30-day mortality. ETHICS AND DISSEMINATION The study was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER The trial is registered on clinicaltrials.gov (NCT03389555). It was posted on 3 January 2018.