Is Unplanned PICU Readmission a Proper Quality Indicator? A Systematic Review and Meta-analysis.

CONTEXT: Unplanned PICU readmissions within 48 hours of discharge (to home or a different hospital setting) are considered a quality metric of critical care. OBJECTIVE: We sought to determine identifiable risk factors associated with early unplanned PICU readmissions. DATA SOURCES: A comprehensive search of Medline, Embase, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to July 16, 2018. STUDY SELECTION: Observational studies of early unplanned PICU readmissions (<48 hours) in children (<18 years of age) published in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently and abstracted data. A meta-analysis was performed by using the random-effects model. RESULTS: We included 11 observational studies in which 128 974 children (mean age: 5 years) were evaluated. The presence of complex chronic diseases (odds ratio 2.42; 95% confidence interval 1.06 to 5.55; I 2 79.90%) and moderate to severe disability (odds ratio 2.85; 95% confidence interval 2.40 to 3.40; I 2 11.20%) had the highest odds of early unplanned PICU readmission. Other significant risk factors included an unplanned index admission, initial admission to a general medical ward, spring season, respiratory diagnoses, and longer initial PICU stay. Readmission was less likely after trauma- and surgery-related index admissions, after direct admission from home, or during the summer season. Modifiable risk factors, such as evening or weekend discharge, revealed no statistically significant association. Included studies were retrospective, which limited our ability to account for all potential confounders and establish causality. CONCLUSIONS: Many risk factors for early unplanned PICU readmission are not modifiable, which brings into question the usefulness of this quality measure.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Medications Affecting the Biochemical Conversion to Type 2 Diabetes: A Systematic Review and Meta-Analysis.

CONTEXT: The extent to which some pharmacological interventions reduce or increase the risk of biochemical conversion to type 2 diabetes mellitus (T2DM) in at-risk individuals is unclear. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus through 24 August 2017 for randomized controlled trials evaluating the effect of drugs suspected to modify the risk of biochemical conversion to T2DM. RESULTS: We included 43 trials with 192,156 subjects (mean age, 60 years; 56% men; mean body mass index, 30.4 kg/m2). α-Glucosidase inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, metformin, orlistat, phentermine/topiramate, and pioglitazone significantly reduced the risk of biochemical conversion to T2DM, whereas statins and nateglinide increased the risk. There was insufficient direct evidence regarding the effects of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors. Most trials were brief and evaluated this outcome during treatment without a withdrawal or washout period. CONCLUSIONS: Several drugs modify the risk of biochemical conversation to T2DM, although whether this effect is persistent and clinically relevant is unclear. Future studies need to focus on cardiovascular disease prevention, mortality, and patient-important outcomes instead of biochemical conversion to T2DM.

Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit.

OBJECTIVE: We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. STUDY DESIGN AND SETTING: We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. RESULTS: We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1-13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). CONCLUSION: About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

Antifibrinolytic therapy to reduce haemoptysis from any cause.

BACKGROUND: Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious characteristics. Antifibrinolytic agents are commonly used to manage bleeding from different sources, but their usefulness in pulmonology is unclear. OBJECTIVES: To evaluate the effectiveness and safety of antifibrinolytic agents in reducing the volume and duration of haemoptysis in adult and paediatric patients. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, EMBASE and LILACS for publications that describe randomized controlled trials (RCTs) of antifibrinolytic therapy in patients presenting with haemoptysis. We also performed an independent search in MEDLINE for relevant trials not yet included in CENTRAL or DARE. Searches are up to date to the 19th September 2016. We conducted electronic and manual searches of relevant national and international journals. We reviewed the reference lists of included studies to locate relevant randomized controlled trials (RCTs). An additional search was carried out to find unpublished RCTs. SELECTION CRITERIA: We included RCTs designed to evaluate the effectiveness and safety of antifibrinolytic agents in reducing haemoptysis in adult and paediatric patients of both genders presenting with haemoptysis of any etiology and severity. The intervention of interest was the administration of antifibrinolytic agents compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: All reviewers independently assessed methodological quality and extracted data tables pre-designed for this review. MAIN RESULTS: The electronic literature search identified 1 original study that met the eligibility criteria. One unpublished study was also identified through manual searches. Therefore two randomized controlled trials met the inclusion criteria: Tscheikuna 2002 (via electronic searches) and Ruiz 1994 (via manual searches). Tscheikuna 2002, a double-blind RCT performed in Thailand, evaluated the effectiveness of tranexamic acid (TXA, an antifibrinolytic agent) administered orally in 46 hospital in- and outpatients with haemoptysis of various etiologies. Ruiz 1994, a double-blind RCT performed in Peru, evaluated the effectiveness of intravenous TXA in 24 hospitalised patients presenting with haemoptysis secondary to tuberculosis.Pooled together, results demonstrated a significant reduction in bleeding time between patients receiving TXA and patients receiving placebo with a weighted mean difference (WMD) of -19.47 (95% CI -26.90 to -12.03 hours), but with high heterogeneity (I² = 52%). TXA did not affect remission of haemoptysis evaluated at seven days after the start of treatment. Adverse effects caused by the drug's mechanism of action were not reported. There was no significant difference in the incidence of mild side effects between active and placebo groups (OR 3.13, 95% CI 0.80 to 12.24). AUTHORS' CONCLUSIONS: There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding.

A systematic review and meta-analysis of glycemic control for the prevention of diabetic foot syndrome.

OBJECTIVE: The objective of this review was to synthesize the available randomized controlled trials (RCTs) estimating the relative efficacy and safety of intensive vs less intensive glycemic control in preventing diabetic foot syndrome. METHODS: We used the umbrella design (systematic review of systematic reviews) to identify eligible RCTs. Two reviewers determined RCT eligibility and extracted descriptive, methodologic, and diabetic foot outcome data. Random-effects meta-analysis was used to pool outcome data across studies, and the I(2) statistic was used to quantify heterogeneity. RESULTS: Nine RCTs enrolling 10,897 patients with type 2 diabetes were included and deemed to be at moderate risk of bias. Compared with less intensive glycemic control, intensive control (hemoglobin A1c, 6%-7.5%) was associated with a significant decrease in risk of amputation (relative risk [RR], 0.65; 95% confidence interval [CI], 0.45-0.94; I(2) = 0%). Intensive control was significantly associated with slower decline in sensory vibration threshold (mean difference, -8.27; 95% CI, -9.75 to -6.79). There was no effect on other neuropathic changes (RR, 0.89; 95% CI, 0.75-1.05; I(2) = 32%) or ischemic changes (RR, 0.92; 95% CI, 0.67-1.26; I(2) = 0%). The quality of evidence is likely moderate. CONCLUSIONS: Compared with less intensive glycemic control therapy, intensive control may decrease the risk of amputation in patients with diabetic foot syndrome. The reported risk reduction is likely overestimated because the trials were open and the decision to proceed with amputation could be influenced by glycemic control.

A systematic review and meta-analysis of débridement methods for chronic diabetic foot ulcers.

BACKGROUND: Several methods of débridement of diabetic foot ulcers are currently used. The relative efficacy of these methods is not well established. METHODS: This systematic review and meta-analysis was conducted to find the best available evidence for the effect of débridement on diabetic foot wound outcomes. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011 for randomized controlled studies (RCTs) and observational comparative studies. RESULTS: We identified 11 RCTs and three nonrandomized studies reporting on 800 patients. The risk of bias was moderate overall. Meta-analysis of three RCTs showed that autolytic débridement significantly increased the healing rate (relative risk [RR], 1.89; 95% confidence interval [CI] 1.35-2.64). Meta-analysis of four studies (one RCT) showed that larval débridement reduced amputation (RR, 0.43; 95% CI, 0.21-0.88) but did not increase complete healing (RR, 1.27; 95% CI, 0.84-1.91). Surgical débridement was associated with shorter healing time compared with conventional wound care (one RCT). Insufficient evidence was found for comparisons between autolytic and larval débridement (one RCT), between ultrasound-guided and surgical débridement, and between hydrosurgical and surgical débridement. CONCLUSIONS: The available literature supports the efficacy of several débridement methods, including surgical, autolytic, and larval débridement. Comparative effectiveness evidence between these methods and supportive evidence for other methods is of low quality due to methodologic limitations and imprecision. Hence, the choice of débridement method at the present time should be based on the available expertise, patient preferences, the clinical context and cost.

A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers.

BACKGROUND: Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers. The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy (HBOT), arterial pump devices, and pharmacologic agents (pentoxifylline, cilostazol, and iloprost) in this setting. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest were complete wound healing and amputation. RESULTS: We identified 18 interventional studies; of which 9 were randomized, enrolling 1526 patients. The risk of bias in the included studies was moderate. In multiple randomized trials, the addition of HBOT to conventional therapy (wound care and offloading) was associated with increased healing rate (Peto odds ratio, 14.25; 95% confidence interval, 7.08-28.68) and reduced major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10-0.89), compared with conventional therapy alone. In one small trial, arterial pump devices had a favorable effect on complete healing compared with HBOT and in another small trial compared with placebo devices. Neither iloprost nor pentoxifylline had a significant effect on amputation rate compared with conventional therapy. No comparative studies were identified for cilostazol in diabetic foot ulcers. CONCLUSIONS: There is low- to moderate-quality evidence supporting the use of HBOT as an adjunctive therapy to enhance diabetic foot ulcer healing and potentially prevent amputation. However, there are only sparse data regarding the efficacy of arterial pump devices and pharmacologic interventions.

A systematic review and meta-analysis of off-loading methods for diabetic foot ulcers.

BACKGROUND: Increased plantar foot pressure is one of several key factors that lead to diabetic foot ulcers. Multiple methods have been proposed to relieve this pressure and thus enhance wound healing and potentially prevent relapse. We aimed in this systematic review to find the best available evidence for off-loading methods. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest included complete wound healing, time to complete wound healing, amputation, infection, and relapse rates. RESULTS: We identified 19 interventional studies, of which 13 were randomized controlled trials, including data from 1605 patients with diabetic foot ulcers using an off-loading method. The risk of bias in the included studies was moderate. This analysis demonstrated improved wound healing with total contact casting over removable cast walker, therapeutic shoes, and conventional therapy. There was no advantage of irremovable cast walkers over total contact casting. There was improved healing with half-shoe compared with conventional wound care. Therapeutic shoes and insoles reduced relapse rate in comparison with regular footwear. Data were sparse regarding other off-loading methods. CONCLUSIONS: Although based on low-quality evidence (ie, evidence warranting lower certainty), benefits are demonstrated for use of total contact casting and irremovable cast walkers in the treatment of diabetic foot ulcers. Reduced relapse rate is demonstrated with various therapeutic shoes and insoles in comparison with regular footwear.

Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis.

CONTEXT: Various drugs affect body weight as a side effect. OBJECTIVE: We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change. DATA SOURCES: MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials. STUDY SELECTION: We included randomized trials that compared an a priori selected list of drugs to placebo and measured weight change. DATA EXTRACTION: We extracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool. RESULTS: We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence. CONCLUSIONS: Several drugs are associated with weight change of varying magnitude. Data are provided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed.

Assessing the evidence: live attenuated influenza vaccine in children younger than 2 years. A systematic review.

BACKGROUND: Live attenuated influenza vaccine (LAIV) is effective in children but contraindicated in children <2 years of age. METHODS: We searched Medline, EMBASE, the Cochrane Library, Web of Science, Scopus, PsycInfo and CINAHL through February 2013 for existing systematic reviews, randomized controlled trials (RCTs) and observational studies (for safety). We included studies enrolling healthy children <2 years of age who received LAIV, compared with placebo or inactivated influenza vaccine (IIV). Data were extracted independently by 2 investigators. The relative risk (RR) was pooled across studies using the random effects model. RESULTS: We found 7 eligible randomized controlled trials and 2 observational studies. Randomized controlled trials included 6281 children and were at low to moderate risk of bias. LAIV reduced the incidence of influenza compared with placebo (relative risk = 0.36, 95% confidence interval: 0.23-0.58, P < 0.05) with a number needed to vaccinate of 17. LAIV increased the incidence of minor side effects (fever and rhinorrhea). LAIV had a similar effect in preventing influenza (relative risk = 0.76, 95% confidence interval: 0.45-1.30, P > 0.05) compared with inactivated influenza vaccine. There was an increase of hospitalization rate (post hoc analysis) and medical attended wheezing with LAIV. CONCLUSIONS: LAIV is highly effective in children <2 years of age compared with placebo and is as effective to inactivated influenza vaccine. The safety profile of LAIV is reasonable although evidence is sparse. LAIV may be considered as an option in this age group particularly during seasons with vaccine shortage.

Patient engagement in research: a systematic review.

BACKGROUND: A compelling ethical rationale supports patient engagement in healthcare research. It is also assumed that patient engagement will lead to research findings that are more pertinent to patients' concerns and dilemmas. However; it is unclear how to best conduct this process. In this systematic review we aimed to answer 4 key questions: what are the best ways to identify patient representatives? How to engage them in designing and conducting research? What are the observed benefits of patient engagement? What are the harms and barriers of patient engagement? METHODS: We searched MEDLINE, EMBASE, PsycInfo, Cochrane, EBSCO, CINAHL, SCOPUS, Web of Science, Business Search Premier, Academic Search Premier and Google Scholar. Included studies were published in English, of any size or design that described engaging patients or their surrogates in research design. We conducted an environmental scan of the grey literature and consulted with experts and patients. Data were analyzed using a non-quantitative, meta-narrative approach. RESULTS: We included 142 studies that described a spectrum of engagement. In general, engagement was feasible in most settings and most commonly done in the beginning of research (agenda setting and protocol development) and less commonly during the execution and translation of research. We found no comparative analytic studies to recommend a particular method. Patient engagement increased study enrollment rates and aided researchers in securing funding, designing study protocols and choosing relevant outcomes. The most commonly cited challenges were related to logistics (extra time and funding needed for engagement) and to an overarching worry of a tokenistic engagement. CONCLUSIONS: Patient engagement in healthcare research is likely feasible in many settings. However, this engagement comes at a cost and can become tokenistic. Research dedicated to identifying the best methods to achieve engagement is lacking and clearly needed.

Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review.

BACKGROUND: Poor fidelity to practice guidelines in the care of people with multiple chronic conditions (MCC) may result from patients and clinicians struggling to apply recommendations that do not consider the interplay of MCC, socio-personal context, and patient preferences. OBJECTIVE: The objective of the study was to assess the quality of guideline development and the extent to which guidelines take into account 3 important factors: the impact of MCC, patients' socio-personal contexts, and patients' personal values and preferences. RESEARCH DESIGN: We conducted a systematic search of clinical practice guidelines for patients with type 2 diabetes mellitus published between 2006 and 2012. Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, EBSCO CINAHL, and the National Guideline Clearinghouse were searched. Two reviewers working independently selected studies, extracted data, and evaluated the quality of the guidelines. RESULTS: We found 28 eligible guidelines, which, on average, had major methodological limitations (AGREE II mean score 3.8 of 7, SD=1.6). Patients or methodologists were not included in the guideline development process in 20 (71%) and 24 (86%) guidelines, respectively. There was a complete absence of incorporating the impact of MCC, socio-personal context, and patient preferences in 8 (29%), 11 (39%), and 16 (57%) of the 28 guidelines, respectively. When mentioned, MCC were considered biologically, but not as contributors of complexity or patient work or as motivation to focus on patient-centered outcomes. CONCLUSIONS: Extant clinical practice guidelines for one chronic disease sometimes consider the context of the patient with that disease, but only do so narrowly. Guideline panels must remove their contextual blinders if they want to practically guide the care of patients with MCC.

Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design.

BACKGROUND: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question. METHODS/DESIGN: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials. DISCUSSION: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

Screening for gestational diabetes: a systematic review and meta-analysis.

CONTEXT: Gestational diabetes mellitus (GDM) is defined as any degree of hyperglycemia with first recognition during pregnancy. The optimal time to screen for GDM that would maximize the yield and benefits remains unclear. OBJECTIVE: Our objective was to appraise the evidence regarding screening for GDM (accuracy, correlation with adverse outcomes, and harms). DATA SOURCES: We searched Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011. STUDY SELECTION: We included randomized controlled trials and observational studies that enrolled pregnant woman who were evaluated using different GDM screening tests. DATA EXTRACTION: Two reviewers working independently abstracted the data. RESULTS: We did not find any randomized controlled trials of GDM screening that measured feto-maternal outcomes. A 1-hour 50-g glucose challenge test with a cutoff point at 140 mg/dL was the most commonly used screening method. The results of this test were statistically associated with feto-maternal outcomes (P < .001), even though only 11% of individuals with a positive test (according to Carpenter and Coustan criteria) developed GDM. Positive Carpenter and Coustan criteria were associated with macrosomia (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.9-3.1, P < .001) and gestational hypertension (OR = 1.7, CI = 1.3-2.1, P < .001). Positive National Diabetes Data Group criteria were also associated with macrosomia (OR = 3.2, CI = 2.3-4.4, P < .001) and gestational hypertension (OR = 2.1, CI = 1.6-2.8, P < .001). CONCLUSIONS: Indirect evidence supports the use of contemporary screening tests for GDM to identify pregnancies at increased risk of adverse feto-maternal outcomes. It also suggests that use of these tests will place some women under unnecessary treatment for GDM.

Glucose targets in pregnant women with diabetes: a systematic review and meta-analysis.

BACKGROUND: Glucose-lowering treatments are used during pregnancy to reduce the risk for complications in the mother and offspring, yet treatment targets have not been established. OBJECTIVE: Our objective was to appraise and summarize the available evidence regarding the association between different blood glucose targets during pregnancy and fetal and maternal outcomes. METHODS: We searched Medline, EMBASE, Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011 for randomized trials and observational studies that enrolled women with diabetes during pregnancy and reported planned or achieved glucose targets. We used random-effects meta-regression models to estimate the odds ratio for the association of outcomes of interest and glucose targets. When possible, we adjusted for diabetes type, trimester, and diabetes treatment. RESULTS: We included 34 studies enrolling 9433 women. The studies had moderate to high risk of bias due to evidence of reporting bias and insufficient adjustment for important covariates, particularly maternal body mass index. A fasting glucose target of <90 mg/dL was the most commonly reported and the one most strongly associated with reduced risk of macrosomia (odds ratio = 0.53, 95% confidence interval = 0.31-0.90, P = .02) for women with gestational diabetes during the third trimester. For type 1 and type 2 diabetes, and for pre- and postprandial targets, data were sparse and inconclusive. CONCLUSIONS: Evidence warranting very low confidence in the estimates suggests that a fasting glucose target of <90 mg/dL is associated with a lower risk of macrosomia and other outcomes of different importance in women with gestational diabetes. Whether this target can be extrapolated to women with pregestational diabetes or whether targets above or below this threshold offer a better benefit/risk balance remains unclear.

Adverse effects of the common treatments for polycystic ovary syndrome: a systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. OBJECTIVE: We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. DATA SOURCE: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. STUDY SELECTION: We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. DATA EXTRACTION: Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. DATA SYNTHESIS: We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. CONCLUSIONS: Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.

Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. OBJECTIVE: The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. DATA SOURCES: Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). STUDY SELECTION: We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. DATA EXTRACTION: Two authors performed the data extraction independently. DATA SYNTHESIS: We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, -2.3 mg/dL; 95% confidence interval, -4.5 to -0.1, I² = 72%, P = .04) and fasting blood insulin (weighted mean difference, -2.1 µU/mL, 95% confidence interval, -3.3 to -1.0, I² = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. CONCLUSIONS: The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.