Treatments for women with gestational diabetes mellitus: an overview of Cochrane systematic reviews

Background Successful treatments for gestational diabetes mellitus (GDM) have the potential to improve health outcomes for women with GDM and their babies. Objectives To provide a comprehensive synthesis of evidence from Cochrane systematic reviews of the benefits and harms associated with interventions for treating GDM on women and their babies. Methods We searched the Cochrane Database of Systematic Reviews (5 January 2018) for reviews of treatment/management for women with GDM. Reviews of pregnant women with pre-existing diabetes were excluded. Two overview authors independently assessed reviews for inclusion, quality (AMSTAR; ROBIS), quality of evidence (GRADE), and extracted data. Main results We included 14 reviews. Of these, 10 provided relevant high-quality and low-risk of bias data (AMSTAR and ROBIS) from 128 randomised controlled trials (RCTs), 27 comparisons, 17,984 women, 16,305 babies, and 1441 children. Evidence ranged from high to very low-quality (GRADE). Only one effective intervention was found for treating women with GDM. Effective Lifestyle versus usual care Lifestyle intervention versus usual care probably reduces large-for-gestational age (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.50 to 0.71; 6 RCTs, N = 2994; GRADE moderate-quality). Promising No evidence for any outcome for any comparison could be classified to this category. Ineffective or possibly harmful Lifestyle versus usual care Lifestyle intervention versus usual care probably increases the risk of induction of labour (IOL) suggesting possible harm (average RR 1.20, 95% CI 0.99 to 1.46; 4 RCTs, N = 2699; GRADE moderate-quality). Exercise versus control Exercise intervention versus control for return to pre-pregnancy weight suggested ineffectiveness (body mass index, BMI) MD 0.11 kg/m², 95% CI -1.04 to 1.26; 3 RCTs, N = 254; GRADE moderate-quality). Insulin versus oral therapy Insulin intervention versus oral therapy probably increases the risk of IOL suggesting possible harm (RR 1.3, 95% CI 0.96 to 1.75; 3 RCTs, N = 348; GRADE moderate-quality). Probably ineffective or harmful interventions Insulin versus oral therapy For insulin compared to oral therapy there is probably an increased risk of the hypertensive disorders of pregnancy (RR 1.89, 95% CI 1.14 to 3.12; 4 RCTs, N = 1214; GRADE moderate-quality). Inconclusive Lifestyle versus usual care The evidence for childhood adiposity kg/m² (RR 0.91, 95% CI 0.75 to 1.11; 3 RCTs, N = 767; GRADE moderate-quality) and hypoglycaemia was inconclusive (average RR 0.99, 95% CI 0.65 to 1.52; 6 RCTs, N = 3000; GRADE moderate-quality). Exercise versus control The evidence for caesarean section (RR 0.86, 95% CI 0.63 to 1.16; 5 RCTs, N = 316; GRADE moderate quality) and perinatal death or serious morbidity composite was inconclusive (RR 0.56, 95% CI 0.12 to 2.61; 2 RCTs, N = 169; GRADE moderate-quality). Insulin versus oral therapy The evidence for the following outcomes was inconclusive: pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 RCTs, N = 2060), caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 RCTs, N = 1988), large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 RCTs, N = 2352), and perinatal death or serious morbidity composite (RR 1.03; 95% CI 0.84 to 1.26; 2 RCTs, N = 760). GRADE assessment was moderate-quality for these outcomes. Insulin versus diet The evidence for perinatal mortality was inconclusive (RR 0.74, 95% CI 0.41 to 1.33; 4 RCTs, N = 1137; GRADE moderate-quality). Insulin versus insulin The evidence for insulin aspart versus lispro for risk of caesarean section was inconclusive (RR 1.00, 95% CI 0.91 to 1.09; 3 RCTs, N = 410; GRADE moderate quality). No conclusions possible No conclusions were possible for: lifestyle versus usual care (perineal trauma, postnatal depression, neonatal adiposity, number of antenatal visits/admissions); diet versus control (pre-eclampsia, caesarean section); myo-inositol versus placebo (hypoglycaemia); metformin versus glibenclamide (hypertensive disorders of pregnancy, pregnancy-induced hypertension, death or serious morbidity composite, insulin versus oral therapy (development of type 2 diabetes); intensive management versus routine care (IOL, large-for-gestational age); post- versus pre-prandial glucose monitoring (large-for-gestational age). The evidence ranged from moderate-, low- and very low quality. Authors’ conclusions Currently there is insufficient high-quality evidence about the effects on health outcomes of relevance for women with GDM and their babies for many of the comparisons in this overview comparing treatment interventions for women with GDM. Lifestyle changes (including as a minimum healthy eating, physical activity and self-monitoring of blood sugar levels) was the only intervention that showed possible health improvements for women and their babies. Lifestyle interventions may result in fewer babies being large. Conversely, in terms of harms, lifestyle interventions may also increase the number of inductions. Taking insulin was also associated with an increase in hypertensive disorders, when compared to oral therapy. There was very limited information on long-term health and health services costs. Further high-quality research is needed

Are randomised controlled trials positivist? Reviewing the social science and philosophy literature to assess positivist tendencies of trials of social interventions in public health and health services

Background: We have previously proposed that trials of social interventions can be done within a ‘realist’ research paradigm. Critics have countered that such trials are irredeemably positivist and asked us to explain our philosophical position. Methods: We set out to explore what is meant by positivism and whether trials adhere to its tenets (of necessity or in practice) via a narrative literature review of social science and philosophical discussions of positivism, and of the trials literature and three case studies of trials. Results: The philosophical literature described positivism as asserting: 1) the epistemic primacy of sensory information; 2) the requirement that theoretical terms equate with empirical terms; 3) the aim of developing universal laws; and 4) the unity of method between natural and social sciences. Regarding 1), it seems that rather than embodying the epistemic primacy of sensory data, RCTs of social interventions in health embrace an anti-positivist approach aiming to test hypotheses derived deductively from prior theory. Considering 2), while some RCTs of social interventions appear to limit theorization to concepts with empirical analogues, others examine interventions underpinned by theories engaging with mechanisms and contextual contingencies not all of which can be measured. Regarding 3), while some trialists and reviewers in the health field do limit their role to estimating statistical trends as a mechanistic form of generalization, this is not an inevitable feature of RCT-based research. Trials of social interventions can instead aim to generalize at the level of theory which specifies how mechanisms are contingent on context. In terms of 4), while RCTs are used to examine biomedical as well as social interventions in health, RCTs of social interventions are often distinctive in using qualitative analyses of data on participant accounts to examine questions of meaning and agency not pursued in the natural sciences. Conclusion: We conclude that the most appropriate paradigm for RCTs of social interventions is realism not positivism

Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

<p><b>Background and Purpose:</b> The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.</p> <p><b>Methods:</b> The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P≤0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.</p> <p><b>Results:</b> The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.</p> <p><b>Conclusions:</b> The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.</p&gt

Thinking territory historically.

BACKGROUND: While the randomised controlled trial (RCT) is generally regarded as the design of choice for assessing the effects of health care, within the social sciences there is considerable debate about the relative suitability of RCTs and non-randomised studies (NRSs) for evaluating public policy interventions. // OBJECTIVES: To determine whether RCTs lead to the same effect size and variance as NRSs of similar policy interventions; and whether these findings can be explained by other factors associated with the interventions or their evaluation. // METHODS: Analyses of methodological studies, empirical reviews, and individual health and social services studies investigated the relationship between randomisation and effect size of policy interventions by: 1) Comparing controlled trials that are identical in all respects other than the use of randomisation by 'breaking' the randomisation in a trial to create non-randomised trials (re-sampling studies). 2) Comparing randomised and non-randomised arms of controlled trials mounted simultaneously in the field (replication studies). 3) Comparing similar controlled trials drawn from systematic reviews that include both randomised and non-randomised studies (structured narrative reviews and sensitivity analyses within meta-analyses). 4) Investigating associations between randomisation and effect size using a pool of more diverse RCTs and NRSs within broadly similar areas (meta-epidemiology). // RESULTS: Prior methodological reviews and meta-analyses of existing reviews comparing effects from RCTs and nRCTs suggested that effect sizes from RCTs and nRCTs may indeed differ in some circumstances and that these differences may well be associated with factors confounded with design. Re-sampling studies offer no evidence that the absence of randomisation directly influences the effect size of policy interventions in a systematic way. No consistent explanations were found for randomisation being associated with changes in effect sizes of policy interventions in field trials

Does enternal nutrition affect clinical outcome? A systematic review of the randomized trials

Background: Both parenteral nutrition (PN) and enteral nutrition (EN) are widely advocated as adjunctive care in patients with various diseases. A systematic review of 82 randomized controlled trials (RCTs) of PN published in 2001 found little, if any, effect on mortality, morbidity, or duration of hospital stay; in some situations, PN increased infectious complication rates. Objective: To assess the effect of EN or volitional nutrition support (VNS) in individual disease states from available randomized controlled trials (RCTs). Design: We conducted a systematic review. RCTs comparing EN or VNS to untreated controls, or comparing EN to PN, were identified and separated according to the underlying disease state. Meta-analysis was performed when at least 3 RCTs provided data. The evidence from the RCTs was summarized into one of five grades. A or B indicated the presence of strong or weak (low quality RCTs) evidence supporting the use of the intervention. C indicated a lack of adequate evidence to make any decision about efficacy. D indicated that limited data could not support the intervention. E indicated either that strong data found no effect, or that either strong or weak data suggested that the intervention caused harm. Patients and settings: RCTs could include either hospitalized or non-hospitalized patients. The EN or VNS had to be provided as part of a treatment plan for an underlying disease process. Interventions: The RCT had to compare recipients of either EN or VNS to controls not receiving any type of artificial nutrition or had to compare recipients of EN with recipients of PN. Outcome measures: Mortality, morbidity (disease-specific), duration of hospitalization, cost, or interventional complications. Summary of grading: A – No indication was identified. B – EN or VNS in the perioperative patient or in patients with chronic liver disease; EN in critically ill patients or low birth weight infants (trophic feeding); VNS in malnourished geriatric patients. (The low quality trials found a significant difference in survival favoring the VNS recipients in the malnourished geriatric patient trials; two high quality trials found non-significant differences that favored VNS as well.) C – EN or VNS in liver transplantation, cystic fibrosis, renal failure, pediatric conditions other than low birth weight infants, well-nourished geriatric patients, non-stroke neurologic conditions, AIDS; EN in acute pancreatitis, chronic obstructive pulmonary disease, non-malnourished geriatric patients; VNS in inflammatory bowel disease, arthritis, cardiac disease, pregnancy, allergic patients, preoperative bowel preparation D – EN or VNS in patients receiving non-surgical cancer treatment or in patients with hip fractures; EN in patients with inflammatory bowel disease; VNS in patients with chronic obstructive pulmonary disease E – EN in the first week in dysphagic, or VNS at any time in non-dysphagic, stroke patients who are not malnourished; dysphagia persisting for weeks will presumably ultimately require EN. Conclusions: There is strong evidence for not using EN in the first week in dysphagic, and not using VNS at all in non-dysphagic, stroke patients who are not malnourished. There is reasonable evidence for using VNS in malnourished geriatric patients. The recommendations to consider EN/VNS in perioperative/liver/critically ill/low birth weight patients are limited by the low quality of the RCTs. No evidence could be identified to justify the use of EN/VNS in other disease states

Digital support interventions for the self-management of low back pain: a systematic review

Background: Low back pain (LBP) is a common cause of disability and is ranked as the most burdensome health condition globally. Self-management, including components on increased knowledge, monitoring of symptoms, and physical activity, are consistently recommended in clinical guidelines as cost-effective strategies for LBP management and there is increasing interest in the potential role of digital health. Objective: The study aimed to synthesize and critically appraise published evidence concerning the use of interactive digital interventions to support self-management of LBP. The following specific questions were examined: (1) What are the key components of digital self-management interventions for LBP, including theoretical underpinnings? (2) What outcome measures have been used in randomized trials of digital self-management interventions in LBP and what effect, if any, did the intervention have on these? and (3) What specific characteristics or components, if any, of interventions appear to be associated with beneficial outcomes? Methods: Bibliographic databases searched from 2000 to March 2016 included Medline, Embase, CINAHL, PsycINFO, Cochrane Library, DoPHER and TRoPHI, Social Science Citation Index, and Science Citation Index. Reference and citation searching was also undertaken. Search strategy combined the following concepts: (1) back pain, (2) digital intervention, and (3) self-management. Only randomized controlled trial (RCT) protocols or completed RCTs involving adults with LBP published in peer-reviewed journals were included. Two reviewers independently screened titles and abstracts, full-text articles, extracted data, and assessed risk of bias using Cochrane risk of bias tool. An independent third reviewer adjudicated on disagreements. Data were synthesized narratively. Results: Of the total 7014 references identified, 11 were included, describing 9 studies: 6 completed RCTs and 3 protocols for future RCTs. The completed RCTs included a total of 2706 participants (range of 114-1343 participants per study) and varied considerably in the nature and delivery of the interventions, the duration/definition of LBP, the outcomes measured, and the effectiveness of the interventions. Participants were generally white, middle aged, and in 5 of 6 RCT reports, the majority were female and most reported educational level as time at college or higher. Only one study reported between-group differences in favor of the digital intervention. There was considerable variation in the extent of reporting the characteristics, components, and theories underpinning each intervention. None of the studies showed evidence of harm. Conclusions: The literature is extremely heterogeneous, making it difficult to understand what might work best, for whom, and in what circumstances. Participants were predominantly female, white, well educated, and middle aged, and thus the wider applicability of digital self-management interventions remains uncertain. No information on cost-effectiveness was reported. The evidence base for interactive digital interventions to support patient self-management of LBP remains weak

How should we evaluate research on counselling and the treatment of depression? A case study on how NICE’s draft 2018 guideline considered what counts as best evidence

Background: Health guidelines are developed to improve patient care by ensuring the most recent and “best available evidence” is used to guide treatment recommendations (NICE Guidance, 2017). NICE’s revised guideline development methodology acknowledges that evidence needed to answer one question (treatment efficacy) may be different from evidence needed to answer another (cost effectiveness, treatment acceptability to patients; NICE, 2014/2017). This review uses counselling in the treatment of depression as a case study, and interrogates the constructs of ‘best’ evidence and ‘best’ guideline methodologies. Method: The review comprises six sections: (1) the implications of diverse definitions of counselling in research; (2) research findings from meta-analyses and randomised controlled trials (RCTs); (3) limitations to trials-based evidence; (4) findings from large routine outcome datasets; (5) the inclusion of qualitative research that emphasises service-user voices; and (6) conclusions and recommendations. Results: Research from meta-analyses and RCTs reviewed in the draft 2018 NICE guideline is limited but positive in relation to the effectiveness of counselling in the treatment for depression. The weight of evidence suggests little, if any, advantage to CBT over counselling once bias and researcher allegiance are taken into account. A growing body of evidence from large NHS datasets also evidences that counselling is both effective and cost-effective when delivered in NHS settings. Conclusion: Recommendations in NICE’s own updated procedures suggest that sole reliance on RCTs and meta-analyses as best methodologies is no longer adequate. There is a need to include large standardised collected datasets from routine practice as well as the voice of patients via high-quality qualitative research

Cochrane acute respiratory infections group's stakeholder engagement project identified systematic review priority areas

Objective: Cochrane acute respiratory infections (ARIs) group conducts systematic reviews of the evidence for treatment and prevention of ARIs. We report the results of a prioritization project, aiming to identify highest priority systematic review topics. Study Design/Setting: The project consisted of two phases. Phase 1 analyzed the gap between existing randomized controlled trials and Cochrane systematic reviews (reported previously). Phase 2 (reported here) consisted of a two-round survey. In round 1, respondents prioritized 68 topics and suggested up to 10 additional topics; in round 2, respondents prioritized top 25 topics from round 1. Results: Respondents included clinicians, researchers, systematic reviewers, allied health, patients, and carers, from 33 different countries. In round 1, 154 respondents identified 20 priority topics, most commonly selecting topics in nonspecific ARIs, influenza, and common cold. Fifty respondents also collectively suggested 134 additional topics. In round 2, 78 respondents prioritized top 25 topics, most commonly in the areas of nonspecific ARIs, pneumonia, and influenza. Conclusion: We generated a list of priority systematic review topics to guide the Cochrane ARI group's systematic review work for the next 24 months. Stakeholder involvement enhanced the transparency of the process and will increase the usability and relevance of the group's work to stakeholders

Brief interventions to prevent sexually transmitted infections suitable for in-service use: a systematic review

Background: Sexually transmitted infections (STIs) are more common in young people and men who have sex with men (MSM) and effective in-service interventions are needed. Methods: A systematic review of randomized control trials (RCTs) of waiting-room delivered,self-delivered and brief healthcare-provider-delivered interventions designed to reduce STIs, increase use of home-based STI testing, or reduce STI-risk behaviour was conducted. Six databases were searched between January 2000 to October 2014. Results: 17,916 articles were screened. 23 RCTs of interventions for young people met our inclusion criteria. Significant STI reductions were found in four RCTs of interventions using brief one-to-one counselling (2 RCTs), video (1 RCT) and a STI home-testing kit (1 RCT). Increase in STI test uptake was found in five studies using video (1 RCT), one-to-one counselling (1 RCT), home test kit (2 RCTs) and a web-based intervention (1 RCT). Reduction in STI-risk behaviour was found in seven RCTs of interventions using digital online (web-based) and offline (computer software) (3 RCTs), printed materials (1 RCT) and video (3 RCTs). Ten RCTs of interventions for MSM met our inclusion criteria. Three tested for STI reductions but none found significant differences between intervention and control groups. Increased STI test uptake was found in two studies using brief one-to-one counselling (1 RCT) and an online web-based intervention (1 RCT. Reduction in STI-risk behaviour was found in six studies using digital online (web-based) interventions (4 RCTs) and brief one-to one counselling (2 RCTs. Conclusion: A small number of interventions which could be used, or adapted for use, in sexual health clinics were found to be effective in reducing STIs among young people and in promoting self-reported STI-risk behaviour change in MSM

Why Government Needs More Randomized Controlled Trials: Refuting The Myths

The Laura and John Arnold Foundation (LJAF) today released a policy brief focused on the value and benefits of randomized controlled trials (RCTs). Such trials are widely recognized as the gold standard in scientific research. However, some critics have claimed that they are often expensive, time-consuming, unethical, or not worth the trouble. These objections are almost always overstated or false. In this brief LJAF Vice President of Research Integrity Stuart Buck and LJAF Vice President of Public Accountability Josh McGee explain why RCTs are so valuable, why they are sometimes misunderstood, and why many common objections should be given little weight.The brief addresses seven specific myths about RCTs:RCTs are expensive and slowRCTs are often unethicalRCTs are limited to narrow contexts or questionsRCTs are a black boxRCTs are not suited to complex, fast-changing programsRCTs can still be biasedRCTs are too limitedBy clarifying the value and importance of rigorous evaluation, LJAF aims to help governments use evidence to inform policies and programs that produce meaningful improvements in people's lives