Low Risk Of Bias Trials Research Articles

Progesterone, cerclage, pessary, or acetylsalicylic acid for prevention of preterm birth in singleton and multifetal pregnancies - A systematic review and meta-analyses.

Preterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on progesterone, cerclage, pessary, and acetylsalicylic acid (ASA) to prevent preterm birth in asymptomatic women with singleton pregnancies defined as risk of preterm birth and multifetal pregnancies. Six databases (including PubMed, Embase, Medline, the Cochrane Library) were searched up to February 2022. RCTs published in English or Scandinavian languages were included through a consensus process. Abstracts and duplicates were excluded. The trials were critically appraised by pairs of reviewers. The Cochrane risk-of-bias tool was used for risk of bias assessment. Predefined outcomes including preterm birth, perinatal/neonatal/maternal mortality and morbidity, were pooled in meta-analyses using RevMan 5.4, stratified for high and low risk of bias trials. The certainty of evidence was assessed using the GRADE approach. The systematic review followed the PRISMA guideline. The search identified 2,309 articles, of which 87 were included in the assessment: 71 original RCTs and 16 secondary publications with 23,886 women and 32,893 offspring. Conclusions were based solely on trials with low risk of bias (n = 50).Singleton pregnancies: Progesterone compared with placebo, reduced the risk of preterm birth <37 gestational weeks: 26.8% vs. 30.2% (Risk Ratio [RR] 0.82 [95% Confidence Interval [CI] 0.71 to 0.95]) (high certainty of evidence, 14 trials) thereby reducing neonatal mortality and respiratory distress syndrome. Cerclage probably reduced the risk of preterm birth <37 gestational weeks: 29.0% vs. 37.6% (RR 0.78 [95% CI 0.69 to 0.88]) (moderate certainty of evidence, four open trials). In addition, perinatal mortality may be reduced by cerclage. Pessary did not demonstrate any overall effect. ASA did not affect any outcome, but evidence was based on one underpowered study.Multifetal pregnancies: The effect of progesterone, cerclage, or pessary was minimal, if any. No study supported improved long-term outcome of the children. Progesterone and probably also cerclage have a protective effect against preterm birth in asymptomatic women with a singleton pregnancy at risk of preterm birth. Further trials of ASA are needed. Prevention of preterm birth requires screening programs to identify women at risk of preterm birth. [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021234946].

Effects of magnesium, phosphate, or zinc supplementation in intensive care unit patients-A systematic review and meta-analysis.

Low-serum levels of magnesium, phosphate, and zinc are observed in many intensive care unit (ICU) patients, but clinical equipoise exists regarding supplementation strategies. We aimed to assess the desirable and undesirable effects of supplementation with magnesium, phosphate, or zinc in adult ICU patients. We conducted a systematic review with meta-analysis of randomised clinical trials assessing the effects of supplementation with magnesium, phosphate, or zinc in adult ICU patients. Primary outcomes were mortality and duration of mechanical ventilation. We registered the protocol, followed the Preferred Reporting Items for Systematic Review and Meta-Analysis statement, used the Cochrane risk of bias 2 tool, and the grading of recommendations, assessment, development and evaluation (GRADE) approach for assessing the certainty of the evidence. We identified no low risk of bias trials. For magnesium supplementation, we included three trials (n= 235); the relative risk (RR) for mortality was 0.54, 95% confidence interval (CI) 0.30-0.96 compared to no supplementation (very low certainty of evidence). For zinc supplementation, two trials were included (n= 168); the RR for mortality was 0.73, 95% CI 0.41-1.28 compared to control. No trials assessed the effects of phosphate supplementation on mortality. For outcomes other than mortality, only zero or one trial was available. In adult ICU patients, the certainty of evidence for the effects of supplementation with magnesium, phosphate, or zinc was very low. High-quality trials are needed to assess the value of supplementation strategies in these patients.

Intimate Partner Violence and Electronic Health Interventions: Systematic Review and Meta-Analysis of Randomized Trials.

BackgroundIntimate partner violence (IPV) is a major public health concern. eHealth interventions may reduce exposure to violence and health-related consequences as the technology provides a safe and flexible space for the target population. However, the evidence is unclear.ObjectiveThe goal of the review is to examine the effect of eHealth interventions compared with standard care on reducing IPV, depression, and posttraumatic stress disorder (PTSD) among women exposed to IPV.MethodsWe searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, PsycInfo, Scopus, Global Health Library, ClinicalTrials.gov, and International Clinical Trials Registry Platform for published and unpublished trials from inception until April 2019. Trials with an eHealth intervention targeting women exposed to violence were included. We assessed risk of bias using the Cochrane Risk of Bias Tool. Trials that reported effect estimates on overall IPV; physical, sexual, and psychological violence; depression; or posttraumatic stress disorder were included in meta-analyses.ResultsA total of 14 trials were included in the review; 8 published trials, 3 unpublished trials and 3 ongoing trials. Of the 8 published trials, 2 were judged as overall low risk of bias trials. The trials reported 23 types of outcomes, and 7 of the trials had outcomes that were eligible for meta-analyses. Our pooled analyses found no effect of eHealth interventions on any of our prespecified outcomes: overall IPV (SMD –0.01; 95% CI –0.11 to 0.08; I2=0%; 5 trials, 1668 women); physical violence (SMD 0.01; 95% CI –0.22 to 0.24; I2=58%; 4 trials, 1128 women); psychological violence (SMD 0.07; 95% CI –0.12 to 0.25; I2=40%; 4 trials, 1129 women); sexual violence (MD 0.36; 95% CI –0.18 to 0.91; I2=0%; 2 trials, 1029 women); depression (SMD –0.13; 95% CI –0.37 to 0.11; I2=78%; 5 trials, 1600 women); and PTSD (MD –0.11; 95% CI –1.04 to 0.82; I2=0%; 5 trials, 1267 women).ConclusionsThere is no evidence from randomized trials of a beneficial effect of eHealth interventions on IPV. More high-quality trials are needed, and we recommend harmonizing outcome reporting in IPV trials by establishing core outcome sets.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42019130124; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130124

Systematic review and network meta-analysis: efficacy of drugs for functional dyspepsia.

Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown. To perform a systematic review with network meta-analysis to resolve this uncertainty. We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. We identified 71 eligible RCTs (19243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic=0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR=0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo. TCAs, histamine-2 receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.

Prophylactic use of acid suppressants in adult acutely ill hospitalised patients: A systematic review with meta-analysis and trial sequential analysis.

Acutely ill patients are at risk of stress-related gastrointestinal (GI) bleeding and prophylactic acid suppressants are frequently used. In this systematic review, we assessed the effects of stress ulcer prophylaxis (SUP) with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) versus placebo or no prophylaxis in acutely ill hospitalised patients. We conducted the review according to the PRISMA statement, the Cochrane Handbook and GRADE, using conventional meta-analysis and trial sequential analysis (TSA). The primary outcomes were all-cause mortality, clinically important GI bleeding and serious adverse events (SAEs). The primary analyses included overall low risk of bias trials. We included 65 comparisons from 62 trials (n=9713); 43 comparisons were from intensive care units. Only three trials (n=3596) had overall low risk of bias. We did not find an effect on all-cause mortality (RR 1.03, 95% CI 0.94 to 1.14; TSA-adjusted CI 0.90 to 1.18; high certainty). The rate of clinically important GI bleeding was lower with SUP (RR 0.62, 95% CI 0.43 to 0.89; TSA-adjusted CI 0.14 to 2.81; moderate certainty). We did not find a difference in pneumonia rates (moderate certainty). Effects on SAEs, Clostridium difficile enteritis, myocardial ischaemia and health-related quality of life (HRQoL) were inconclusive due to sparse data. Analyses of all trials regardless of risk of bias were consistent with the primary analyses. We did not observe a difference in all-cause mortality or pneumonia with SUP. The incidence of clinically important GI bleeding was reduced with SUP, whereas any effects on SAEs, myocardial ischaemia, Clostridium difficile enteritis and HRQoL were inconclusive. PROSPERO registration number CRD42017055676; published study protocol: Marker, et al 2017 in Systematic Reviews.

Intra-pleural fibrinolytic therapy versus placebo, or a different fibrinolytic agent, in the treatment of adult parapneumonic effusions and empyema.

Pleural infection, including parapneumonic effusions and thoracic empyema, may complicate lower respiratory tract infections. Standard treatment of these collections in adults involves antibiotic therapy, effective drainage of infected fluid and surgical intervention if conservative management fails. Intrapleural fibrinolytic agents such as streptokinase and alteplase have been hypothesised to improve fluid drainage in complicated parapneumonic effusions and empyema and therefore improve treatment outcomes and prevent the need for thoracic surgical intervention. Intrapleural fibrinolytic agents have been used in combination with DNase, but this is beyond the scope of this review. To assess the benefits and harms of adding intrapleural fibrinolytic therapy to standard conservative therapy (intercostal catheter drainage and antibiotic therapy) in the treatment of complicated parapneumonic effusions and empyema. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, ClinicalTrials.gov and the World Health Organization (WHO) trials portal. We contacted trial authors for further information and requested details regarding the possibility of unpublished trials. The most recent search was conducted on 28 August 2019. Parallel-group randomised controlled trials (RCTs) in adult patients with post-pneumonic empyema or complicated parapneumonic effusions (excluding tuberculous effusions) who had not had prior surgical intervention or trauma comparing an intrapleural fibrinolytic agent (streptokinase, alteplase or urokinase) versus placebo or a comparison of two fibrinolytic agents. Two review authors independently extracted data. We contacted study authors for further information. We used odds ratios (OR) for dichotomous data and reported 95% confidence intervals (CIs). We used Cochrane's standard methodological procedures of meta-analysis. We applied the GRADE approach to summarise results and to assess the overall certainty of evidence. We included in this review a total of 12 RCTs. Ten studies assessed fibrinolytic agents versus placebo (993 participants); one study compared streptokinase with urokinase (50 participants); and one compared alteplase versus urokinase (99 participants). The primary outcomes were death, requirement for surgical intervention, overall treatment failure and serious adverse effects. All studies were in the inpatient setting. Outcomes were measured at varying time points from hospital discharge to three months. Seven trials were at low or unclear risk of bias and two at high risk of bias due to inadequate randomisation and inappropriate study design respectively. We found no evidence of difference in overall mortality with fibrinolytic versus placebo (OR 1.16, 95% CI 0.71 to 1.91; 8 studies, 867 participants; I² = 0%; moderate certainty of evidence). We found evidence of a reduction in surgical intervention with fibrinolysis in the same studies (OR 0.37, 95% CI 0.21 to 0.68; 8 studies, 897 participants; I² = 51%; low certainty of evidence); and overall treatment failure (OR 0.16, 95% CI 0.05 to 0.58; 7 studies, 769 participants; I² = 88%; very low certainty of evidence, with evidence of significant heterogeneity). We found no clear evidence of an increase in adverse effects with intrapleural fibrinolysis, although this cannot be excluded (OR 1.28, 95% CI 0.36 to 4.57; low certainty of evidence). In a sensitivity analysis, the reduction in referrals for surgery and overall treatment failure with fibrinolysis disappeared when the analysis was confined to studies at low or unclear risk of bias. In a moderate-risk population (baseline 14% risk of death, 20% risk of surgery, 27% risk of treatment failure), intra-pleural fibrinolysis leads to 19 more deaths (36 fewer to 59 more), 115 fewer surgical interventions (150 fewer to 55 fewer) and 214 fewer overall treatment failures (252 fewer to 93 fewer) per 1000 people. A single study of streptokinase versus urokinase found no clear difference between the treatments for requirement for surgery (OR 1.00, 95% CI 0.13 to 7.72; 50 participants; low-certainty evidence). A single study of alteplase versus urokinase showed no clear difference in requirement for surgery (OR alteplase versus urokinase 0.46, 95% CI 0.04 to 5.24) but an increased rate of adverse effects, primarily bleeding, with alteplase (OR 5.61, 95% CI 1.16 to 27.11; 99 participants; low-certainty evidence). This translated into 154 (6 to 499 more) serious adverse events with alteplase compared with urokinase per 1000 people treated. In patients with complicated infective pleural effusion or empyema, intrapleural fibrinolytic therapy was associated with a reduction in the requirement for surgical intervention and overall treatment failure but with no evidence of change in mortality. Discordance between the negative largest trial of this therapy and other studies is of concern, however, as is an absence of significant effect when analysing low risk of bias trials only. The reasons for this difference are uncertain but may include publication bias. Intrapleural fibrinolytics may increase the rate of serious adverse events, but the evidence is insufficient to confirm or exclude this possibility.

Hemodynamic goal-directed therapy and postoperative kidney injury: an updated meta-analysis with trial sequential analysis

BackgroundPerioperative goal-directed therapy (GDT) reduces the risk of renal injury. However, several questions remain unanswered, such as target, kind of patients and surgery, and role of fluids and inotropes. We therefore update a previous analysis, including all studies published in the meanwhile, to clarify the clinical impact of this strategy on acute kidney injury.Main bodyRandomized controlled trials enrolling adult patients undergoing major surgery were considered. GDT was defined as perioperative monitoring and manipulation of hemodynamic parameters to reach normal or supranormal values by fluids alone or with inotropes. Trials comparing the effects of GDT and standard hemodynamic therapy were considered. Primary outcome was acute kidney injury, whichever definition was used. Meta-analytic techniques (analysis software RevMan, version 5.3) were used to combine studies, using random-effect odds ratios (OR) and 95% confidence intervals (CI). Trial sequential analyses were performed including all trials and considering only low risk of bias trials. Sixty-five trials with an overall sample of 9308 patients were included. OR for the development of renal injury was 0.64 (95% CI, 0.62–0.87; p = 0.0003), with no statistical heterogeneity. Trial sequential analyses and sensitivity analysis including studies with low risk of bias confirmed the main results. A significant decrease in renal injury rate was observed in studies that adopted cardiac output and oxygen delivery as hemodynamic target and that used both fluids and inotropes. The postoperative kidney injury rate was significantly lower in trials enrolling “high-risk” patients and major abdominal and orthopedic surgery.Short conclusionThe present meta-analysis suggests that targeting GDT to perioperative systemic oxygen delivery, by means of fluids and inotropes, can be the best way to improve renal perfusion and oxygenation in high-risk patients undergoing major abdominal and orthopedic surgery.

Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials.

This systematic review was designed to assess the effectiveness of oral vitamin K supplementation for increasing bone mineral density and reducing fractures in adults. MEDLINE, EMBASE, CENTRAL, CINAHL, clinicaltrials.gov, and WHO-ICTRP were searched for eligible trials. Randomised controlled trials assessing oral vitamin K supplementation that assessed bone mineral density or fractures in adult populations were included. A total of 36 studies were identified. Two independent reviewers extracted data using a piloted extraction form. For post-menopausal or osteoporotic patients, meta-analysis showed that the odds of any clinical fracture were lower for vitamin K compared to controls (OR, 0.72, 95%CI 0.55 to 0.95). Restricting the analysis to low risk of bias trials reduced the OR to 0.76 (95%CI, 0.58 to 1.01). There was no difference in vertebral fractures between the groups (OR 0.96, 95%CI 0.83 to 1.11). In the bone mineral density meta-analysis, percentage change from baseline at the lumbar spine was higher at 1 year (MD 0.93, 95%, CI - 0.02 to 1.89) and 2 years (MD 1.63%, 95%CI 0.10 to 3.16) for vitamin K compared to controls; however, removing trials at high risk of bias tended to result in smaller differences that were not statistically significant. At 6 months, it was higher in the hip (MD 0.42%, 95%CI 0.01 to 0.83) and femur (MD 0.29%, 95%CI 0.17 to 0.42). There was no significant difference at other anatomical sites. For post-menopausal or osteoporotic patients, there is no evidence that vitamin K affects bone mineral density or vertebral fractures; it may reduce clinical fractures; however, the evidence is insufficient to confirm this. There are too few trials to draw conclusions for other patient groups.

Efficacy of psychotherapy for bulimia nervosa and binge-eating disorder on self-esteem improvement: Meta-analysis.

This meta-analysis examined the effects of psychotherapy for bulimia nervosa (BN) and binge-eating disorder (BED) on self-esteem improvement. Randomized controlled trials (RCTs) of psychological treatments that assessed self-esteem change in eating disorders were included. Thirty-four RCTs were included; most sampled BED and then BN. Hedge's g effects were entered into random effects models. Psychotherapy for BN led to significantly greater post-treatment improvements in self-esteem than control conditions (g=0.45; 95% CI [0.17, 0.73]). This effect was smaller when only analysing low risk of bias trials (g=0.28; 95% CI [0.05, 0.51]). Psychotherapy for BED also led to significantly greater post-treatment improvements in self-esteem than controls (g=0.20; 95% CI [0.05, 0.35]), with some evidence that guided self-help was associated with the largest effects. This effect, however, was overestimated after adjustment for publication bias (g=0.10; 95% CI [-0.05, 0.26]). There was no evidence that cognitive-behavioural therapy was superior to non-cognitive-behavioural therapy interventions in improving self-esteem. There was no relationship between symptom improvement and self-esteem improvement in a meta-regression. Psychotherapy may lead to small improvements in self-esteem in BN and BED. Additional RCTs with follow-up assessments are required to make more definitive conclusions about the effects of psychotherapy for eating disorders on self-esteem in the long-term.

Efficacy and safety of de-escalation bone- modifying agents for cancer patients with bone metastases: a systematic review and meta-analysis.

BackgroundCompared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy.MethodsA systematic search of PubMed, EMBASE, and the Cochrane Register of Controlled Trials until November 22, 2017, was performed. Randomized controlled trials (RCTs) were included to assess skeletal-related event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12-weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses.ResultsA total of eight citations were eligible comprising 2,878 patients: zoledronate (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87–1.12; P=0.82) for SRE rates between de-escalated and standard arms was produced when seven low risk of bias trials (695 patients) were pooled, and results without statistical significance also appeared in the analysis of adverse events and bone turnover biomarkers. Due to the limited sample size and methodological differences, the data for skeletal morbidity rates (SMRs), time to first SRE, serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but systematic review still obtained similar indistinguishableness.ConclusionIn this meta-analysis of randomized clinical trials, the results “appeared” to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

The effect of exercise on cancer-related fatigue in cancer survivors: a systematic review and meta-analysis.

ObjectiveThe objective of the study was to conduct systematic review and meta-analysis to establish the effect of exercise interventions on cancer-related fatigue (CRF) in cancer survivors, compared to non-exercise intervention controls.MethodsTrials published between January 1st 2000 and August 17th 2016 were included through PubMed database search and search of references. Eligible trials compared the effect of an exercise intervention on CRF compared to non-exercise intervention controls, with CRF as primary outcome and measured by validated self-report questionnaire, in cancer survivors not receiving palliative care. We evaluated risk of bias of individual trials following Cochrane Quality criteria. We performed a random-effects meta-analysis in the low risk of bias trials with intervention type, exercise intensity, adherence, and cancer type as moderators, and also performed meta-regression analyses and a sensitivity analysis including the high risk of bias trials.ResultsOut of 274 trials, 11 met the inclusion criteria, of which six had low risk of bias. Exercise improved CRF with large effect size (Cohen’s d 0.605, 95% CI 0.235–0.975) with no significant difference between types of cancer. Aerobic exercise (Δ=1.009, CI 0.222–1.797) showed a significantly greater effect than a combination of aerobic and resistance exercises (Δ=0.341, CI 0.129–0.552). Moderator and meta-regression analyses showed high adherence yielding best improvements.ConclusionExercise has a large effect on CRF in cancer survivors. Aerobic interventions with high adherence have the best result.

Perioperative levosimendan in cardiac surgery: A systematic review with meta-analysis and trial sequential analysis.

Several studies suggested beneficial effects of perioperative levosimendan on postoperative outcome after cardiac surgery. However, three large randomized controlled trials (RCTs) have been recently published and presented neutral results. We performed a systematic review with meta-analysis and trial sequential analysis (TSA) to assess benefits and harms of perioperative levosimendan therapy in cardiac surgery. Electronic databases were searched up to September 2017 for RCTs on preoperative levosimendan versus any type of control. The Cochrane methodology was employed. We calculated odds ratio (OR) or Risk Ratio (OR) and 95% confidence interval (CI) using fixed-effects meta-analyses and we further performed TSA. We included data from 40 RCTs and 4246 patients. Pooled analysis of 5 low risk of bias trials (1910 patients) showed no association between levosimendan and mortality (OR 0.86 [95% CI, 0.62, 1.18], p=0.34, TSA inconclusive), acute kidney injury, need of renal replacement therapy, myocardial infarction, ventricular arrhythmias, and serious adverse events, but an association with higher incidence of supraventricular arrhythmias (RR 1.11 [95% CI, 1.00, 1.24], p=0.05, TSA inconclusive) and hypotension (RR 1.15 [95% CI, 1.01, 1.30], p=0.04, TSA inconclusive). Analysis including all 40 trials found that levosimendan was associated with lower postoperative mortality (OR 0.56 [95% CI, 0.44, 0.71], p<0.00001, TSA conclusive), acute kidney injury, and renal replacement therapy, and higher incidence of hypotension. There is not enough high-quality evidence to neither support nor discourage the systematic use of levosimendan in cardiac surgery.

Adhesives for bonded molar tubes during fixed brace treatment.

Orthodontic treatment involves using fixed or removable appliances (dental braces) to correct the positions of teeth. The success of a fixed appliance depends partly on the metal attachments (brackets and bands) being glued to the teeth so that they do not become detached during treatment. Brackets (metal squares) are usually attached to teeth other than molars, where bands (metal rings that go round each tooth) are more commonly used. Orthodontic tubes (stainless steel tubes that allow wires to pass through them), are typically welded to bands but they may also be glued directly (bonded) to molars. Failure of brackets, bands and bonded molar tubes slows down the progress of treatment with a fixed appliance. It can also be costly in terms of clinical time, materials and time lost from education/work for the patient. This is an update of the Cochrane review first published in 2011. A new full search was conducted on 15 February 2017 but no new studies were identified. We have only updated the search methods section in this new version. The conclusions of this Cochrane review remain the same. To evaluate the effectiveness of the adhesives used to attach bonded molar tubes, and the relative effectiveness of the adhesives used to attach bonded molar tubes versus adhesives used to attach bands, during fixed appliance treatment, in terms of: (1) how often the tubes (or bands) come off during treatment; and (2) whether they protect the bonded (or banded) teeth against decay. The following electronic databases were searched: Cochrane Oral Health's Trials Register (to 15 February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1) in the Cochrane Library (searched 15 February 2017), MEDLINE Ovid (1946 to 15 February 2017), and Embase Ovid (1980 to 15 February 2017). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials of participants with full arch fixed orthodontic appliance(s) with molar tubes, bonded to first or second permanent molars. Trials which compared any type of adhesive used to bond molar tubes (stainless steel or titanium) with any other adhesive, were included.Trials were also included where:(1) a tube was bonded to a molar tooth on one side of an arch and a band cemented to the same tooth type on the opposite side of the same arch;(2) molar tubes had been allocated to one tooth type in one patient group and molar bands to the same tooth type in another patient group. The selection of papers, decision about eligibility and data extraction were carried out independently and in duplicate without blinding to the authors, adhesives used or results obtained. All disagreements were resolved by discussion. Two trials (n = 190), at low risk of bias, were included in the review and both presented data on first time failure at the tooth level. Pooling of the data showed a statistically significant difference in favour of molar bands, with a hazard ratio of 2.92 (95% confidence intervals (CI) 1.80 to 4.72). No statistically significant heterogeneity was shown between the two studies. Data on first time failure at the patient level were also available and showed statistically different difference in favour of molar bands (risk ratio 2.30; 95% CI 1.56 to 3.41) (risk of event for molar tubes = 57%; risk of event for molar bands 25%).One trial presented data on decalcification again showing a statistically significant difference in favour of molar bands. No other adverse events identified. From the two well-designed and low risk of bias trials included in this review it was shown that the failure of molar tubes bonded with either a chemically-cured or light-cured adhesive was considerably higher than that of molar bands cemented with glass ionomer cement. One trial indicated that there was less decalcification with molar bands cemented with glass ionomer cement than with bonded molar tubes cemented with a light-cured adhesive. However, given there are limited data for this outcome, further evidence is required to draw more robust conclusions.

Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials

Objective To determine the efficacy of low intensity pulsed ultrasound (LIPUS) for healing of fracture or osteotomy.Design Systematic review and meta-analysis.Data sources Medline, Embase, CINAHL, Cochrane Central Register of Controlled...

A systematic review of pediatric clinical trials of high dose vitamin D.

Background. Due to inadequate UV exposure, intake of small quantities of vitamin D is recommended to prevent musculoskeletal disease. Both basic science and observational literature strongly suggest that higher doses may benefit specific populations and have non-musculoskeletal roles. Evaluating the evidence surrounding high dose supplementation can be challenging given a relatively large and growing body of clinical trial evidence spanning time, geography, populations and dosing regimens. Study objectives were to identify and summarize the clinical trial literature, recognize areas with high quality evidence, and develop a resource database that makes the literature more immediately accessible to end users.Methods. Medline (1946 to January 2015), Embase (1974 to January 2015), and Cochrane databases (January 2015), were searched for trials. All pediatric (0–18 years) trials administering doses higher than 400 IU (<1 year) or 600 IU (≥1 year) were included. Data was extracted independently by two of the authors. An online searchable database of trials was developed containing relevant extracted information (http://www.cheori.org/en/pedvitaminddatabaseOverview). Sensitivity and utility were assessed by comparing the trials in the database with those from systematic reviews of vitamin D supplementation including children.Results. A total of 2,579 candidate papers were identified, yielding 169 trials having one or more arms meeting eligibility criteria. The publication rate has increased significantly from 1 per year (1970–1979) to 14 per year (2010–2015). Although 84% of the total trials focused on healthy children or known high risk populations (e.g., renal, prematurity), this proportion has declined in recent years due to the rise in trials evaluating populations and outcomes not directly related to the musculoskeletal actions of vitamin D (27% in 2010s). Beyond healthy children, the only pediatric populations with more than 50 participants from low risk of bias trials evaluating a clinically relevant outcome were prematurity and respiratory illness. Finally, we created and validated the online searchable database using 13 recent systematic reviews. Of the 38 high dose trials identified by the systematic review, 36 (94.7%) could be found within the database. When compared with the search strategy reported in each systematic review, use of the database reduced the number of full papers to assess for eligibility by 85.2% (±13.4%).Conclusion. The pediatric vitamin D field is highly active, with a significant increase in trials evaluating non-classical diseases and outcomes. Despite the large overall number there are few high quality trials of sufficient size to provide answers on clinical efficacy of high-dose vitamin D. An open access online searchable data should assist end users in the rapid and comprehensive identification and evaluation of trials relevant to their population or question of interest.

Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials.

To determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trials of glucosamine's efficacy for treating pain in osteoarthritis (OA). A systematic review and stratified meta-analysis of randomized placebo-controlled trials was performed, and random-effects models were applied with inconsistency (I(2) ) and heterogeneity (tau(2) ) estimated using Review Manager and SAS, respectively. The major outcome was reduction of pain; the standardized mean difference (SMD [95% confidence interval (95% CI)]) served as effect size. The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine moderately reduced pain (SMD -0.51 [95% CI -0.72, -0.30]), although a high level of between-trial inconsistency was observed (I(2) = 88%). The single most important explanation (i.e., covariate) was brand, reducing heterogeneity by 41% (P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product resulted in significant pain reduction (SMD -1.07 [95% CI -1.47, -0.67]), although a sensitivity analysis of 3 low risk of bias trials using the Rottapharm/Madaus product showed less promising results (SMD -0.27 [95% CI -0.43, -0.12]), which is only a small effect size. Thirteen trials (1,963 patients) using non-Rottapharm/Madaus products consistently failed to show a reduction in pain (SMD -0.11 [95% CI -0.46, 0.24]). The second most important explanation was overall risk of bias (reducing heterogeneity by 32%). Most of the observed heterogeneity in glucosamine trials is explained by brand. Trials using the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine. Large inconsistency was found, however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a small effect size.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma

Hepatocellular carcinoma is the fifth most common cancer worldwide. Percutaneous interventional therapies, such as radiofrequency (thermal) ablation (RFA), have been developed for early hepatocellular carcinoma. RFA competes with other interventional techniques such as percutaneous ethanol injection, surgical resection, and liver transplantation. The potential benefits and harms of RFA compared with placebo, no intervention, chemotherapy, hepatic resection, liver transplantation, or other interventions are unclear. To assess the beneficial and harmful effects of RFA versus placebo, no intervention, or any other therapeutic approach in patients with hepatocellular carcinoma. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science to September 2012. We handsearched meeting abstracts from ASCO, ESMO, AASLD, EASL, APASL, and references of articles. We also contacted researchers in the field (last search September 2012). We considered for inclusion randomised clinical trials investigating the effects of RFA versus placebo, no intervention, or any other therapeutic approach on hepatocellular carcinoma patients regardless of blinding, language, and publication status. Two review authors independently performed the selection of trials, assessment of risk of bias, and data extraction. We contacted principal investigators for missing information. We analysed hazard ratios (HR) as relevant effect measures for overall survival, two-year survival, event-free survival, and local recurrences with 95% confidence intervals (CI). In addition, we analysed dichotomous survival outcomes using risk ratios (RR). We used trial sequential analysis to control the risk of random errors ('play of chance'). We identified no trials comparing RFA versus placebo, no intervention, or liver transplantation. We identified and included 11 randomised clinical trials with 1819 participants that included four comparisons: RFA versus hepatic resection (three trials, 578 participants); RFA versus percutaneous ethanol injection (six trials, 1088 participants) including one three-armed trial that also investigated RFA versus acetic acid injection; RFA versus microwave ablation (one trial, 72 participants); and RFA versus laser ablation (one trial, 81 participants). Ten of the eleven included trials reported on the primary outcome of this review, overall survival. Rates of major complications or procedure-related deaths were reported in 10 trials. The overall risk of bias was considered low in five trials and high in six trials. For a subgroup analysis, we included only low risk of bias trials. Regarding the comparison RFA versus hepatic resection, there was moderate-quality evidence from two low risk of bias trials that hepatic resection seems more effective than RFA regarding overall survival (HR 0.56; 95% CI 0.40 to 0.78) and two-year survival (HR 0.38; 95% CI 0.17 to 0.84). However, if we included a third trial with high risk of bias, the difference became insignificant (overall survival: HR 0.71; 95% CI 0.44 to 1.15). With regards to the outcomes event-free survival and local progression, hepatic resection also yielded better results than RFA. However, the number of complications was higher in surgically treated participants (odds ratio (OR) 8.24; 95% CI 2.12 to 31.95). RFA seemed superior to percutaneous ethanol or acetic acid injection regarding overall survival (HR 1.64; 95% CI 1.31 to 2.07). The RR for mortality was also in favour of RFA, but did not reach statistical significance (150/490 (30.6%) people in the percutaneous ethanol or acetic acid group versus 119/496 (24.0%) people in the RFA group; RR 1.76; 95% CI 0.97 to 3.22). The proportion of adverse events did not differ significantly between RFA and percutaneous ethanol or acetic acid injection (HR 0.70; 95% CI 0.33 to 1.48). Trial sequential analyses revealed that the number of participants in the included trials was insufficient and that more trials are needed to assess the effects of RFA versus other interventions. The effects of RFA versus no intervention, chemotherapeutic treatment, or liver transplantation are unknown. We found moderate-quality evidence that hepatic resection is superior to RFA regarding survival. However, RFA might be associated with fewer complications and a shorter hospital stay than hepatic resection. We found moderate-quality evidence showing that RFA seems superior to percutaneous ethanol injection regarding survival. There were too sparse data to recommend or refute ablation achieved by techniques other than RFA. More randomised clinical trials with low risk of bias and low risks of random errors assessing the effect of RFA are needed.

Interventions for the prevention of postoperative ear discharge after insertion of ventilation tubes (grommets) in children

Background Grommets are frequently inserted in children's ears for acute otitis media and otitis media with effusion. A common complication is postoperative ear discharge (otorrhoea). A wide range of treatments are used to prevent the discharge, but there is no consensus on whether or not intervention is necessary nor which is the most effective intervention. Objectives To assess the effectiveness of prophylactic interventions, both topical and systemic, in reducing the incidence of otorrhoea following the surgical insertion of grommets in children. Search methods We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 3 July 2012. Selection criteria We included randomised controlled trials (RCTs) that compared the efficacy of prophylactic interventions against placebo/control and/or with other prophylactic interventions for postoperative otorrhoea in children. Data collection and analysis Two review authors independently assessed study eligibility and risk of bias, and extracted data. The outcome data were dichotomous for all the included trials. We calculated individual and pooled risk ratios (RR) using the Mantel-Haenszel fixed-effect method. We also calculated the numbers needed to treat to benefit (NNTB). Main results We found 15 eligible RCTs (2476 children, aged from four months to 17 years). We graded seven RCTs as being at a low risk of bias (n = 926 children) and for an eighth RCT we also graded two of the arms as being at a low risk of bias. We graded the other seven trials as being at a high risk of bias. For a single application at surgery, there was evidence from two low risk of bias trials that at two weeks postoperatively the risk of otorrhoea was reduced by multiple saline washouts (from 30% to 16%; RR 0.52, 95% confidence interval (CI) 0.27 to 1.00; NNTB 7; one RCT; 140 children) and antibiotic/steroid ear drops (from 9% to 1%; RR 0.13, 95% CI 0.03 to 0.57; NNTB 13; one RCT; 322 ears). A meta-analysis of two low risk of bias trials (222 ears) failed to find an effect of a single application of antibiotic/steroid ear drops at four to six weeks postoperatively. For a prolonged application of an intervention, there was evidence from four low risk of bias trials that the risk of otorrhoea was reduced two weeks postoperatively by antibiotic ear drops (from 15% to 8%; RR 0.54, 95% CI 0.30 to 0.97; NNTB 15; one RCT; 372 children), antibiotic/steroid ear drops (from 39% to 5%; RR 0.13, 95% CI 0.05 to 0.31; NNTB 3; one RCT; 200 children), aminoglycoside/steroid ear drops (from 15% to 5%; RR 0.37, 95% CI 0.18 to 0.74; NNTB 11; one RCT; 356 children) or oral antibacterial agents/steroids (from 39% to 5%; RR 0.13, 95% CI 0.03 to 0.51; NNTB 3; one RCT; 77 children). Only one trial assessed the secondary outcome of ototoxicity, but no effect was found. There were no trials that assessed quality of life. Authors' conclusions Our review found that each of the following were effective at reducing the rate of otorrhoea up to two weeks following surgery: (1) multiple saline washouts at surgery, (2) a single application of topical antibiotic/steroid drops at surgery, (3) a prolonged application of topical drops (namely antibiotic ear drops, antibiotic/steroid eardrops or aminoglycoside/steroid ear drops) and (4) a prolonged application of oral antibacterial agents/steroids. However, the rate of otorrhoea between RCTs varied greatly and the higher the rates of otorrhoea within a RCT, the smaller the NNTB for therapy. We conclude that if a surgeon has a high rate of postoperative otorrhoea in children then either saline irrigation or antibiotic ear drops at the time of surgery would significantly reduce that rate. If topical drops are chosen, it is suggested that to reduce the cost and potential for ototoxic damage this be a single application at the time of surgery and not prolonged thereafter.