Objectives: Randomized controlled trials evaluate diverse interventions. This can include medical interventions such as drugs or surgical procedures, or behavior change interventions (BCIs) that aim to change a habit, belief, or attitude to improve health, for example, healthy eating, psychological wellbeing. Harms are often recorded poorly or inconsistently within randomized controlled trials of BCIs. This scoping review aimed to collate and describe literature on categories, definitions, and mechanisms of harms from BCIs; methods of identifying plausible harms; and recommendations for recording harms. Study design and setting: A scoping review was conducted. Three databases (MEDLINE, PsycINFO, and CINAHL) were searched. Reference list checking and citation searching were performed. Articles were included if they discussed (1) interventions that aimed to modify behavior, (2) categories or mechanisms of harms, and (3) methods or recommendations for recording harms. All research designs were included. One reviewer reviewed titles, abstracts, and full texts; queries were checked with another reviewer. Data were extracted and synthesized descriptively by one reviewer and checked by another reviewer. A thematic map was constructed to summarize the review findings. Harms described from specific BCIs were identified, and examples were selected and summarized. Results: The review included 37 articles. Nineteen of 37 articles contributed to a thematic review. Three articles described categories of harms; categories of harm included physical, psychological, group and social interactions, cultural, equity, opportunity cost, environmental, and economic. Seven articles included mechanisms or underlying factors for harms including feelings of failure leading to shame or stigma, and group interventions enabling knowledge exchange on unhealthy behaviors. Twelve articles provided recommendations for recording harms, including taking a proportionate approach by focusing on the most plausible and important harms, collecting different perspectives on whether harms had occurred (eg, caregivers and family members), and using qualitative research methods to identify harms. One article described a three-step method to identify plausible harms from an intervention, and six articles supported aspects of the method. Eighteen of 37 articles contributed to a review which collated harms arising from specific interventions, for example, a peer support intervention in inflammatory bowel disease caused distressing conversations which might lead to anxiety and confrontation with a possible negative future. Conclusion: BCIs can cause harm. This review identified categories and proposed mechanisms of harms, as well as methods and recommendations for identifying and recording harms in BCIs for inclusion in forthcoming recommendations.

Background: Gestational weight gain (GWG) below or above the Institute of Medicine (IOM) recommendations has been associated with adverse perinatal outcomes. Few studies have examined the effect of prenatal nutrient supplementations on GWG in low- and middle-income countries (LMICs). Objectives: We aimed to investigate the effects of multiple micronutrient supplements (MMSs) and small-quantity lipid-based nutrient supplements (LNSs) on GWG in LMICs. Methods: A 2-stage meta-analysis of individual participant data was conducted to examine the effects of MMSs (45,507 women from 14 trials) and small-quantity LNSs (6237 women from 4 trials) on GWG compared with iron and folic acid supplements only. Percentage adequacy of GWG and total weight gain at delivery were calculated according to the IOM 2009 guidelines. Binary outcomes included severely inadequate (percentage adequacy 125%) GWG. Results from individual trials were pooled using fixed-effects inverse-variance models. Heterogeneity was examined using I2, stratified analysis, and meta-regression. Results: MMSs resulted in a greater percentage adequacy of GWG [weighted mean difference (WMD): 0.86%; 95% CI: 0.28%, 1.44%; P < 0.01] and higher GWG at delivery (WMD: 209 g; 95% CI: 139, 280 g; P < 0.01) than among those in the control arm. Women who received MMSs had a 2.9% reduced risk of severely inadequate GWG (RR: 0.971; 95% CI: 0.956, 0.987; P < 0.01). No association was found between small-quantity LNSs and GWG percentage adequacy (WMD: 1.51%; 95% CI: -0.38%, 3.40%; P = 0.21). Neither MMSs nor small-quantity LNSs were associated with excessive GWG. Conclusions: Maternal MMSs were associated with greater GWG percentage adequacy and total GWG at delivery than was iron and folic acid only. This finding is consistent with previous results on birth outcomes and will inform policy development and local recommendations of switching routine prenatal iron and folic acid supplements to MMSs.

Objectives: To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias.Study Design and Setting: We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias of RCTs. By extracting items and summarizing their essential content, we generated an item list. Items that two re-viewers agreed clearly did not address risk of bias were excluded. We included the remaining items in a survey in which 13 experts judged the issue each item is addressing: risk of bias, applicability, random error, reporting quality, or none of the above.Results: Seventeen eligible instruments included 127 unique items. After excluding 61 items deemed as clearly not addressing risk of bias, the item classification survey included 66 items, of which the majority of respondents deemed 20 items (30.3%) as addressing risk of bias; the majority deemed 11 (16.7%) as not addressing risk of bias; and there proved substantial disagreement for 35 (53.0%) items. Conclusion: Existing risk of bias instruments frequently include items that do not address risk of bias. For many items, experts disagree on whether or not they are addressing risk of bias.(c) 2022 Elsevier Inc. All rights reserved.

Purpose Accumulating evidence showed that probiotics therapy might be effective in treating diarrhea-predominant irritable bowel syndrome (IBS-D). This study aimed to evaluate the effectiveness and safety of probiotics therapy for the treatment of IBS-D. Methods We performed a comprehensive literature search in eight electronic databases, and gray literature from inception to August 4, 2021. Randomized controlled trials (RCTs) of probiotics therapy for the treatment of IBS-D were included and the quality was assessed using the risk of bias tool recommended by the Cochrane Handbook version 5.1.0. RevMan 5.4 software was used to perform the meta-analysis on the outcomes of IBS-D symptoms, abdominal pain, quality of life, and abdominal distension. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Results Ten RCTs evaluating 943 patients were identified. Only one study had unclear risk of bias, while nine studies had a high risk of bias. The meta-analysis results showed that, compared to the placebo, probiotics therapy significantly decreased the score of IBS-D symptoms (SMD = - 0.55, 95% CI: [- 0.83, - 0.27], P < 0.05), abdominal pain (SMD = - 0.43, 95% CI: [- 0.57, - 0.29], P < 0.05), and abdominal distension (SMD = - 0.45, 95%CI: [- 0.81, - 0.09], P < 0.05). There was no statistical difference in the quality of life. However, all the certainty of evidence was very low. Conclusion Very low certainty evidence showed that probiotics might be an effective treatment for improving the IBS-D symptoms, abdominal pain, and abdominal distension, in adult IBS-D patients. However, these conclusions should be supported by high-quality evidence.

Aim To assess the effect of lubricants on reducing perineal trauma during vaginal delivery. Methods PubMed, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, WanFang databases, and , were searched for literature up to 25 June 2021. Randomized controlled trials published in English or Chinese that compared the vaginal application of lubricant with standard care for women were included. Two reviewers independently performed study screening, data extraction, risk of bias assessment, and certainty of evidence assessment. Pooled effect sizes and corresponding 95% confidence intervals (CI) were calculated using meta-analysis. Results Nineteen trials enrolling 5445 pregnant women were included. Compared with standard care, women using lubricants had a lower incidence of perineal trauma (risk ratio [RR] 0.84, 95% CI 0.76-0.93; low certainty evidence), second-degree perineal laceration (RR 0.72, 95% CI 0.64-0.82; moderate certainty evidence) and episiotomy (RR 0.77, 95% CI 0.62-0.96; very low certainty evidence), and had a shorter duration of the second-stage labor (MD -13.72 min, 95% CI -22.68 to -4.77; very low certainty evidence). Conclusion Lubricants might reduce the incidence of perineal trauma, especially second-degree perineal laceration, and shorten the duration of the second-stage labor. More well-designed studies will continue developing high-quality evidence in this field.

Objective: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. Study design: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. Results: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled < 50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. Conclusions: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. (C) 2021 Elsevier Inc. All rights reserved.

BACKGROUND In recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial. AIM To evaluate the value of IORT for patients with rectal cancer. METHODS We searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software. RESULTS In this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000). CONCLUSION The advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.

Objectives: To assess the efficacy of electro-acupuncture (EA) relative to sham electro-acupuncture (sham EA) in treating chronic severe functional constipation (CSFC). Methods: A comprehensive search for relevant studies published between January 1, 1951 and May 14, 2020 was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Web of Science, and EMbase. Two investigators independently selected studies, extracted data, and assessed the quality of the included studies. The software Endnote X9 was used for screening articles, and the Review Manager 5.3 for analyzing data. Results: The meta-analyses involved 6 studies and 1457 individuals. The pooled results favored the EA group for the increase of complete spontaneous bowel movements (CSBMs) per week in the fourth week (MD = 0.80, P = 0.001) during treatment, and further improved in the eight weeks (MD = 1.25, P < 0.001). During the follow-up period, significant changes in CSBMs per week were seen in the experimental group (MD = 1.38, P = 0.008); the effect decreased in the twelfth week (MD = 0.87, P < 0.001). There was no significant difference in the Bristol stool scale score between the two groups in the fourth week (MD = 0.40, P = 0.08), but significant differences were observed in the eighth week (MD = 0.40, P = 0.03). A significant reduction in patient assessment of constipation quality of life (PAC-QOL) score were observed in the EA group during treatment (SMD = -0.83, P < 0.001). No serious adverse events were reported. Conclusions: EA had favorable effects on CSFC, and the longer the treatment duration was, the better was the effect, but the effect showed a certain period of validity. However, the results may be influenced by the clinical heterogeneity of acupuncture points, depth of needling, intensity, and frequency of EA.

Background: Gastric cancer (GC), particularly unresectable, metastatic, or recurrent GC, has been characterized by unfavorable prognosis. This meta-analysis of clinical randomized phase II trials was conducted to systematically evaluate the efficacy and safety of capecitabine-based versus S-1-based chemotherapy for metastatic or recurrent GC. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases to identify studies eligible for the present analysis. Data were collected from inception to June 20th, 2019. Outcomes included objective response rate (ORR); 6-, 12-, and 18-month progression-free survival (PFS); 1-, 2-, and 3-year overall survival (OS); and adverse events. A meta-analysis was conducted using a random-effects model, and a sensitivity analysis was conducted to examine whether the results of the meta-analysis were robust. Risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI) was reported as the main evaluation parameters. Results: Six eligible studies with 561 subjects were included in the present meta-analysis. There was no significant difference between S-1-based and capecitabine-based chemotherapy in ORR (RR =1.17, 95% CI: 0.95-1.44, P=0.13, I-2 =0%); 6-month (HR =0.94, 95% CI: 0.77-1.14, I-2 =0%), 12-month (HR =0.89, 95% CI: 0.61-1.31, I-2 =0%), and 18-month PFS (HR =1.02, 95% CI: 0.55-1.91, I-2 =0%); 1-year (HR =0.99, 95% CI: 0.83-1.18, I-2 =0%), 2-year (HR =0.90, 95% CI: 0.58-1.42, I-2 =0%), and 3-year OS (HR =1.08, 95% CI: 0.50-2.34, I-2 =0%). However, the capecitabine-based chemotherapy had a higher incidence in all grades of hand-foot syndrome (HFS) (RR =3.41, 95% CI: 1.98-5.90, P<0.01, I-2 =39%) and grades 3-4 neutropenia (RR =1.62, 95% CI: 1.05-2.51, P=0.03, I-2 =0%). Conclusions: In terms of efficacy, capecitabine-based chemotherapy and S-1-based chemotherapy had similar short-term outcomes. Regarding safety, we recommend S-1-based chemotherapy for patients with metastatic or recurrent GC prior to capecitabine-based treatment.

Background: Barbed suture has been widely used in some surgical fields, and it has achieved good results, but the application in total knee arthroplasty is still controversial. Objective: Literature is collected for statistical analysis so as to provide evidence for the use of barbed suture in Total knee arthroplasty. Methods: We searched PubMed, the Cochrane library and EMBASE database for randomized controlled trials (RCTs) using barbed suture and conventional suture to close incisions after primary total knee arthroplasty, and the retrieval time was from July 2019 to the establishment of the database. Literature was screened according to inclusion and exclusion criteria, quality evaluation and data extraction were conducted for the final included literature, and statistical analysis was conducted using RevMan 5.3 software. Results: A total of six RCTs (826 knees) were included in our meta-analysis. The results showed that the re-negative conversion could shorten the wound closure time (MD –4.41, 95% CI −5.11 to −3.72, P < .00001) and reduce the wound closure total cost (MD –282.61, 95% CI –445.36 to –119.85, P = .0007) and acupuncture injury (RR 0.14, 95% CI 0.03–0.78, P = .02), and did not significantly increasing the incidence of complications (RR 0.80, 95% CI 0.05–0.96, P = .38) or suture breakages (RR 4.58, 95% CI 0.16−128.29, P = .37). There were no significant differences in ROM at postoperative 6 weeks and 3 months (MD −0.74, 95% CI −4.19 to 2.71, P = .67; MD −0.30, 95% CI −2.62 to 2.02, P = .80) and no significant differences in KSS at postoperative 6 weeks (MD –0.22, 95% CI –3.10 to 2.66, P = .88). Conclusions: Our study shows that barbed suture is a fast, low-cost, safe and effective suture method in total knee arthroplasty compared with traditional suture, we also need more literature and longer follow-up to confirm this conclusion.

The study aims to evaluate the effectiveness of different durations of aerobic exercise on hypertensive patients. Four electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched from their inception until July 2018. English publications and randomized controlled trials involving aerobic exercise treatment for hypertensive population were included. Two reviewers independently extracted the data. The Cochrane's Risk of Bias tool was used to assess the quality of included studies. In this systematic review, a total of 14 articles were included, involving 860 participants. The quality of the included studies ranged from moderate to high. The results of the meta-analysis showed that compared with the control group, significant effects of aerobic exercise were observed on reducing systolic blood pressure (SBP) (mean difference [MD] = -12.26 mm Hg, 95% confidence interval [CI] = -15.17 to -9.34, P < 0.05), diastolic blood pressure (DBP; MD = -6.12 mm Hg, 95% CI = -7.76 to -4.48, P < 0.05), and heart rate (MD = -4.96 bpm, 95% CI = -6.46 to -3.43, P < 0.05). In addition, significant reductions were observed in ambulatory DBP (MD = -4.90 mm Hg, 95% CI = -8.55 to -1.25, P < 0.05) and ambulatory SBP (MD = -8.77mm Hg, 95% CI = -13.97 to -3.57, P < 0.05). Therefore, aerobic exercise might be an effective treatment for blood pressure improvement in hypertensive patients. However, the effectiveness between the duration of different treatment needs to be well-designed and rigorous studies will be required to verify the dataset.