Withdrawal reasons of randomized controlled trials on type 2 diabetes: a systematic review

PurposeType 2 diabetes mellitus (T2DM) is the subject of numerous randomized controlled trials (RCTs). The validity of RCTs may be threatened by attrition bias due to the discontinuation of the study. The aim of this systematic review is to evaluate the reasons of patient’s withdrawal from these RCTs.MethodsA systematic literature search on PubMed, Cochrane Library, Web of Science, and Scopus databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The aim was to obtain all relevant blinded RCTs published before January 2017 in which the effectiveness of synthetic drugs, vitamins/minerals were compared to that of placebo or active control in T2DM. The quality of RCTs was assessed using the Jadad score. The frequency of withdrawal reasons was presented based on treatments with placebo/active control, national/international level of the studies, and publication year. Meta-analysis was not performed due to the heterogeneity.ResultsOverall, 1368 articles comprising of 640,780 subjects were included. In the majority of the RCTs (75.0%), the intervention and the placebo arms were compared. Most of the included studies (96%) were classified in the high-quality category (Jadad score≥3). The highest proportion of reported withdrawal cases was found in international studies, national RCTs conducted in Japan, and RCTs published in 2011. The withdrawal reasons were reported for 91,669 (63.75%) of the total 143,794 participants who had withdrawn from these studies. The main reported reasons were “adverse effects” (24.04%), “withdraw consent” (16.10%), and “missing data” (11.08%). Variations in the reported withdrawal reasons were based on the country or published year. RCTs with triple blinded design as well as those in which anti-hyperlipidemia and anti-obesity medications were applied, showed significantly higher probability of reported the withdrawal.ConclusionHigh proportion of reported discontinuation in blinded RCTs on patients with T2DM was related to drug adverse effects. Overall, the total number and reason of drop out were unsatisfactory.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-020-00380-7.     

Derivation and validation of a practical Bedside Score for the diagnosis of cholecystitis

Objective

We sought to develop a practical Bedside Score for the diagnosis of cholecystitis and test its accuracy against the Tokyo Guidelines (TG13).

Isolated partial right lower lobe pulmonary venous drainage into the right atrium as a cause of pulmonary hypertension in a middle-aged woman

Partial anomalous pulmonary venous connection is a rare congenital disease characterized by drainage of one or several pulmonary veins into the systemic venous system. It is extremely rare as an isolated anomaly. We report the case of a middle-aged woman with isolated drainage of an enormously enlarged right lower pulmonary vein into the right atrium with significant left-to-right shunt, severe right ventricular enlargement, and pulmonary hypertension.     

Coal seam gas water: potential hazards and exposure pathways in Queensland

The extraction of coal seam gas (CSG) produces large volumes of potentially contaminated water. It has raised concerns about the environmental health impacts of the co-produced CSG water. In this paper, we review CSG water contaminants and their potential health effects in the context of exposure pathways in Queensland’s CSG basins. The hazardous substances associated with CSG water in Queensland include fluoride, boron, lead and benzene. The exposure pathways for CSG water are (1) water used for municipal purposes; (2) recreational water activities in rivers; (3) occupational exposures; (4) water extracted from contaminated aquifers; and (5) indirect exposure through the food chain. We recommend mapping of exposure pathways into communities in CSG regions to determine the potentially exposed populations in Queensland. Future efforts to monitor chemicals of concern and consolidate them into a central database will build the necessary capability to undertake a much needed environmental health impact assessment.     

Impact of photobiomodulation on macrophages and their polarization during diabetic wound healing: a systematic review

Lasers in Medical Science - This review aims to providing essential information and the current knowledge about the potential role of macrophages, especially their M2 subtypes in different diabetic...     

A double‐blind,randomized, controlled trial on N‐acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation

Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N‐acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double‐blind randomized placebo‐controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day ?6 to day +15. AKI was determined on the basis of the Risk–Injury–Failure–Loss–End‐stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase‐associated lipocalin (uNGAL) on days ?6, ?3, +3, +9 and +15 as the secondary outcome. Moreover, transplant‐related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non‐parametric methods including Kaplan–Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant‐related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high‐dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients. Copyright © 2014 John Wiley & Sons, Ltd.