Patricia Rios

Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes

BackgroundPregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis.MethodsMEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes).ResultsAfter screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23–7.07), valproate (OR, 2.93; 95% CrI, 2.36–3.69), topiramate (OR, 1.90; 95% CrI, 1.17–2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35–2.47), phenytoin (OR, 1.67; 95% CrI, 1.30–2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10–1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72–1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43–1.16) were not.ConclusionThe newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control.Systematic Review RegistrationPROSPERO CRD42014008925

Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.

Objectives Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Design and setting Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. Participants 29 cohort studies including 5100 infants/children. Interventions Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Primary and secondary outcome measures Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. Results The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control. Conclusions Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen. Trial registration number PROSPERO database (CRD42014008925).

Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis

To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimers disease (AD).

Strategies to Prevent or Reduce Gender Bias in Peer Review of Research Grants: A Rapid Scoping Review.

Objective To review the literature on strategies implemented or identified to prevent or reduce gender bias in peer review of research grants. Methods Studies of any type of qualitative or quantitative design examining interventions to reduce or prevent gender bias during the peer review of health-related research grants were included. Electronic databases including MEDLINE, EMBASE, Education Resources Information Center (ERIC), PsycINFO, Joanna Briggs, the Cochrane Library, Evidence Based Medicine (EBM) Reviews, and the Campbell Library were searched from 2005 to April 2016. A search for grey (i.e., difficult to locate or unpublished) literature was conducted and experts in the field were consulted to identify additional potentially relevant articles. Two individuals screened titles and abstracts, full-text articles, and abstracted data with discrepancies resolved by a third person consistently. Results After screening 5524 citations and 170 full-text articles, one article evaluating gender-blinding of grant applications using an uncontrolled before-after study design was included. In this study, 891 applications for long-term fellowships in 2006 were included and 47% of the applicants were women. These were scored by 13 peer reviewers (38% were women). The intervention included eliminating references to gender from the applications, letters of recommendations, and interview reports that were sent to the committee members for evaluation. The proportion of successful applications led by women did not change with gender-blinding, although the number of successful applications that were led by men increased slightly. Conclusions There is limited research on interventions to mitigate gender bias in the peer review of grants. Only one study was identified and no difference in the proportion of women who were successful in receiving grant funding was observed. Our results suggest that interventions to prevent gender bias should be adapted and tested in the context of grant peer review to determine if they will have an impact.

Identifying older adults at risk of harm following elective surgery: a systematic review and meta-analysis

BackgroundElective surgeries can be associated with significant harm to older adults. The present study aimed to identify the prognostic factors associated with the development of postoperative complications among older adults undergoing elective surgery.MethodsMedline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. Prospective studies reporting prognostic factors associated with postoperative complications (composite outcome of medical and surgical complications), functional decline, mortality, post-hospitalization discharge destination, and prolonged hospitalization among older adults undergoing elective surgery were included. Study characteristics and prognostic factors associated with the outcomes of interest were extracted independently by two reviewers. Random effects meta-analysis models were used to derive pooled effect estimates for prognostic factors and incidences of adverse outcomes.ResultsOf the 5692 titles and abstracts that were screened for inclusion, 44 studies (12,281 patients) reported on the following adverse postoperative outcomes: postoperative complications (n =28), postoperative mortality (n = 11), length of hospitalization (n = 21), functional decline (n = 6), and destination at discharge from hospital (n = 13). The pooled incidence of postoperative complications was 25.17% (95% confidence interval (CI) 18.03–33.98%, number needed to follow = 4). The geriatric syndromes of frailty (odds ratio (OR) 2.16, 95% CI 1.29–3.62) and cognitive impairment (OR 2.01, 95% CI 1.44–2.81) were associated with developing postoperative complications; however, there was no association with traditionally assessed prognostic factors such as age (OR 1.07, 95% CI 1.00–1.14) or American Society of Anesthesiologists status (OR 2.62, 95% CI 0.78–8.79). Besides frailty, other potentially modifiable prognostic factors, including depressive symptoms (OR 1.77, 95% CI 1.22–2.56) and smoking (OR 2.43, 95% CI 1.32–4.46), were also associated with developing postoperative complications.ConclusionGeriatric syndromes are important prognostic factors for postoperative complications. We identified potentially modifiable prognostic factors (e.g., frailty, depressive symptoms, and smoking) associated with developing postoperative complications that can be targeted preoperatively to optimize care.

Prevention and management of unprofessional behaviour among adults in the workplace: A scoping review

Background Unprofessional behaviour is a challenge in academic medicine. Given that faculty are role models for trainees, it is critical to identify strategies to manage these behaviours. A scoping review was conducted to identify interventions to prevent and manage unprofessional behaviour in any workplace or professional setting. Methods A search of 14 electronic databases was conducted in March 2016, reference lists of relevant systematic reviews were scanned, and grey literature was searched to identify relevant studies. Experimental and quasi-experimental studies that reported on interventions to prevent or manage unprofessional behaviours were included. Studies that reported impact on any outcome were eligible. Two reviewers independently screened articles and completed data abstraction. Qualitative analysis of the definitions of unprofessional behaviour was conducted. Data were charted to describe the study, participant, intervention and outcome characteristics. Results 12,482 citations were retrieved; 23 studies with 11,025 participants were included. The studies were 12 uncontrolled before and after studies, 6 controlled before and after studies, 2 cluster-randomised controlled trials (RCTs), 1 RCT, 1 non-randomised controlled trial and 1 quasi-RCT. Four constructs were identified in the definitions of unprofessional behaviour: verbal and/or non-verbal acts, repeated acts, power imbalance, and unwelcome behaviour. Interventions most commonly targeted individuals (22 studies, 95.7%) rather than organisations (4 studies, 17.4%). Most studies (21 studies, 91.3%) focused on increasing awareness. The most frequently targeted behaviour change was sexual harassment (4 of 7 studies). Discussion Several interventions appear promising in addressing unprofessional behaviour. Most of the studies included single component, in-person education sessions targeting individuals and increasing awareness of unprofessional behaviour. Fewer studies targeted the institutional culture or addressed behaviour change.

Few studies exist examining methods for selecting studies, abstracting data, and appraising quality in a systematic review

OBJECTIVES The aim of the article was to identify and summarize studies assessing methodologies for study selection, data abstraction, or quality appraisal in systematic reviews. STUDY DESIGN AND SETTING A systematic review was conducted, searching MEDLINE, EMBASE, and the Cochrane Library from inception to September 1, 2016. Quality appraisal of included studies was undertaken using a modified Quality Assessment of Diagnostic Accuracy Studies 2, and key results on accuracy, reliability, efficiency of a methodology, or impact on results and conclusions were extracted. RESULTS After screening 5,600 titles and abstracts and 245 full-text articles, 37 studies were included. For screening, studies supported the involvement of two independent experienced reviewers and the use of Google Translate when screening non-English articles. For data abstraction, studies supported involvement of experienced reviewers (especially for continuous outcomes) and two independent reviewers, use of dual monitors, graphical data extraction software, and contacting authors. For quality appraisal, studies supported intensive training, piloting quality assessment tools, providing decision rules for poorly reported studies, contacting authors, and using structured tools if different study designs are included. CONCLUSION Few studies exist documenting common systematic review practices. Included studies support several systematic review practices. These results provide an updated evidence-base for current knowledge synthesis guidelines and methods requiring further research.

Correction to: Engaging policy-makers, health system managers, and policy analysts in the knowledge synthesis process: a scoping review

Following the publication of the original article [1], it was brought to our attention that the letter ‘l’ was unfortunately omitted from the word ‘health’ in the article’s title.