Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy:a systematic review and meta-analysis

Aim: To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. Method: MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure. Results: Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity. Interpretation: Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome

Nudge to Nobesity I: Minor Changes in Accessibility Decrease Food Intake

Very small but cumulated decreases in food intake may be sufficient to erase obesity over a period of years. We examine the effect of slight changes in the accessibility of different foods in a pay-by-weight-of-food salad bar in a cafeteria serving adults for the lunch period. Making a food slightly more difficult to reach (by varying its proximity by about 10 inches) or changing the serving utensil (spoon or tongs) modestly but reliably reduces intake, in the range of 8-16%. Given this effect, it is possible that making calorie-dense foods less accessible and low-calorie foods more accessible over an extended period of time would result in significant weight loss

Transparency ethics in practice: Revisiting financial conflicts of interest disclosure forms in clinical practice guidelines

Background Authors of clinical practice guidelines (CPGs) disclose financial conflicts of interest (FCOIs) to promote transparency ethics. Typically, they do so on standard declaration forms containing generic open-ended questions on FCOIs. Yet, the literature is scant on the format and effect of alternative disclosure forms. Does supplementing a standard form with subsequent detailed disclosure forms tailored to the context of the CPG improve the yield or accuracy of FCOIs declarations? Methods For an international CPG in gastroenterology on the endoscopic surveillance for colorectal neoplasia in inflammatory bowel disease, we compared the use of a standard FCOIs disclosure form with a contextual FCOIs disclosure form that detailed commercial relations related to the CPG topic. This included manufacturers of endoscopes, endoscopy equipment and accessories. Participants completed the generic form early, and the supplementary contextual form six months later. We then compared the FCOI disclosures obtained. Findings 26 participants provided FCOIs disclosures using both disclosure forms. We found discrepancies regarding (1) the disclosure of FCOIs (presence/absence), and (2) the listing of financial entities. While the number of participants who disclosed a FCOI remained the same (30.8%) using the two forms, disclosures were not from the same individuals: two additional participants disclosed a FCOI, whereas two participants withdrew previous disclosures. Among those who reported a FCOI in either form, we noted inconsistencies in disclosures for 70% of the participants. This included changes in FCOIs disclosure status or modifications of "their commercial relations". Discussion Accurate reporting of FCOIs advances the transparency and ethical integrity of CPGs. Our experience suggests that a contextual FCOIs disclosure form tailored to content of the CPG with narrow, detailed questions provides supplementary, more complete FCOIs declarations than generic forms alone. The finding raises challenges on how forms are best written and formatted, optimally timed, and more effectively processed with sensitivity to professional behaviour, so as to heighten transparency

Cost Effectiveness Analysis Evaluating Real-Time Characterization of Diminutive Colorectal Polyp Histology using Narrow Band Imaging (NBI)

Background: Endoscopists and new computer-aided programs can achieve performance benchmarks for real-time diagnosis of colorectal polyps using Narrow-Band Imaging (NBI), though do not perform as well as endoscopists with expertise in advanced imaging. Previous cost-effectiveness studies on optical diagnosis have focused on expert performance, potentially over-estimating its benefits. Aim: Determine cost-effectiveness of an NBI ‘characterize, resect and discard (CRD)’ strategy using updated assumptions based on non-expert performance. Methods: Markov model was constructed to compare cost-effectiveness of the CRD strategy, where diminutive polyps characterized as non-adenomas with high confidence are not resected and adenomas are resected and discarded, versus standard of care (SOC) in which all polyps are resected with histologic analysis. Rates related to NBI performance, missed polyps, polyp progression, malignancy, and complications, as well as quality-adjusted life years (QALYs) were derived from the literature. Costs were age and insurer-specific. Mean QALYs and costs were calculated using first order Monte Carlo simulation. Deterministic and probabilistic sensitivity analyses were conducted. Results: The mean QALY estimates were similar for the CRD (8.563, 95% CI: 8.557-8.571) and SOC strategy (8.563, 8.557-8.571), but costs were reduced ($2,693.06 vs.$2,800.27, mean incremental cost savings: $107.21/person). Accounting for colonoscopy rates, the CRD strategy would save$708 million to $1.06 billion annually. The model was sensitive to the incidence of tubular adenomas; the results were otherwise robust in all other one-way and probabilistic analyses. Conclusions: An NBI CRD strategy is cost-effective when compared to the SOC, even when employed by non-experts. The appreciated benefit is primarily due to cost savings of the CRD strategy

Nonsystem Reasons for Delay in Door-to-Balloon Time and Associated In-Hospital Mortality A Report From the National Cardiovascular Data Registry

ObjectivesThe goal of this study was to characterize nonsystem reasons for delay in door-to-balloon time (D2BT) and the impact on in-hospital mortality.BackgroundStudies have evaluated predictors of delay in D2BT, highlighting system-related issues and patient demographic characteristics. Limited data exist, however, for nonsystem reasons for delay in D2BT.MethodsWe analyzed nonsystem reasons for delay in D2BT among 82,678 ST-segment elevation myocardial infarction patients who underwent primary percutaneous coronary intervention within 24 h of symptom onset in the CathPCI Registry from January 1, 2009, to June 30, 2011.ResultsNonsystem delays occurred in 14.7% of patients (n = 12,146). Patients with nonsystem delays were more likely to be older, female, African American, and have greater comorbidities. The in-hospital mortality for patients treated without delay was 2.5% versus 15.1% for those with delay (p < 0.01). Nonsystem delay reasons included delays in providing consent (4.4%), difficult vascular access (8.4%), difficulty crossing the lesion (18.8%), “other” (31%), and cardiac arrest/intubation (37.4%). Cardiac arrest/intubation delays had the highest in-hospital mortality (29.9%) despite the shortest time delay (median D2BT: 84 min; 25th to 75th percentile: 64 to 108 min); delays in providing consent had a relatively lower in-hospital mortality rate (9.4%) despite the longest time delay (median D2BT: 100 min; 25th to 75th percentile: 80 to 131 min). Mortality for delays due to difficult vascular access, difficulty crossing a lesion, and other was also higher (8.0%, 5.6%, and 5.9%, respectively) compared with nondelayed patients (p < 0.0001). After adjustment for baseline characteristics, in-hospital mortality remained higher for patients with nonsystem delays.ConclusionsNonsystem reasons for delay in D2BT in ST-segment elevation myocardial infarction patients presenting for primary percutaneous coronary intervention are common and associated with high in-hospital mortality

Pain in Multiple System Atrophy a Systematic Review and Meta-Analysis

Background: Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. Objectives: Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: “pain,” “multiple system atrophy,” “MSA,” “olivopontocerebellar atrophy,” “OPCA,” “striatonigral degeneration,” “SND,” “Shy Drager,” and “atypical parkinsonism.”. Results: The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%–75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%–87%] vs. 45% [95% CI = 33%–57%], P = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment. Conclusions: We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA

Right-Sided Location Not Associated With Missed Colorectal Adenomas in an Individual-Level Reanalysis of Tandem Colonoscopy Studies

Background & Aims Interval cancers occur more frequently in the right colon. One reason could be that right-sided adenomas are frequently missed in colonoscopy examinations. We reanalyzed data from tandem colonoscopies to assess adenoma miss rates in relation to location and other factors. Methods We pooled data from 8 randomized tandem trials comprising 2218 patients who had diagnostic or screening colonoscopies (adenomas detected in 49.8% of patients). We performed a mixed-effects logistic regression with patients as cluster effects with different independent parameters. Factors analyzed included location (left vs right, splenic flexure as cutoff), adenoma size, form, and histologic features. Analyses were controlled for potential confounding factors such as patient sex and age, colonoscopy indication, and bowel cleanliness. Results Right-side location was not an independent risk factor for missed adenomas (odds ratio [OR] compared with the left side, 0.94; 95% CI, 0.75–1.17). However, compared with adenomas ≤5 mm, the OR for missing adenomas of 6–9 mm was 0.62 (95% CI, 0.44–0.87), and the OR for missing adenomas of ≥10 mm was 0.51 (95% CI, 0.33–0.77). Compared with pedunculated adenomas, sessile (OR, 1.82; 95% CI, 1.16–2.85) and flat adenomas (OR, 2.47; 95% CI, 1.49–4.10) were more likely to be missed. Histologic features were not significant risk factors for missed adenomas (OR for adenomas with high-grade intraepithelial neoplasia, 0.68; 95% CI, 0.34–1.37 and OR for sessile serrated adenomas, 0.87; 95% CI, 0.47–1.64 compared with low-grade adenomas). Men had a higher number of adenomas per colonoscopy (1.27; 95% CI, 1.21–1.33) than women (0.86; 95% CI, 0.80–0.93). Men were less likely to have missed adenomas than women (OR for missed adenomas in men, 0.73; 95% CI, 0.57–0.94). Conclusions In an analysis of data from 8 randomized trials, we found that right-side location of an adenoma does not increase its odds for being missed during colonoscopy but that adenoma size and histologic features do increase risk. Further studies are needed to determine why adenomas are more frequently missed during colonoscopies in women than men

Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial)

Objectives. The specific objective of the REDUCE trial was to evaluate the effect of low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Background. Unfractionated heparin and its low molecular weight fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. Methods. The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single-lesion coronary artery obstructions suitable for PTCA. Three hundred six patients received reviparin as a 7,000-U bolus before PTCA, followed by 10,500 U as an infusion over 24 h and then twice-daily 3,500-U subcutaneous application for 28 days. The 306 patients in the control group received a bolus of 10,000 U o