Trial of restarting and tolerating metformin (TreatMet).

This randomized, double-blind, placebo-controlled, n-of-1 crossover study assessed whether metformin's side effects are reproducible in patients with a history of metformin intolerance. Participants completed up to four cycles of 2 weeks of metformin exposure and 2 weeks of placebo exposure. Participants completed surveys based on the Gastrointestinal Symptom Rating Scale and the Treatment Satisfaction Questionnaire for Medication. The primary hypotheses were that treatment satisfaction would be equal for placebo and metformin and that more than 30% of the study enrollees would be able to adhere to a higher dose of metformin 6 months after participation. Thirteen patients (all women, mean age 52.4 years) enrolled, three of whom were lost to follow-up or were non-adherent to study protocol. Metformin was associated with significantly lower global treatment satisfaction scores compared with placebo (39.58 vs. 53.75, P < .05 ) but participants could not distinguish metformin from placebo and did not report higher rates of gastrointestinal side effects on metformin. Two out of 10 participants adhered to a higher dose of metformin after trial completion. Metformin appears to have barriers to use beyond its classic gastrointestinal side effects.

The impact of food order on postprandial glycaemic excursions in prediabetes.

Data suggest that nutrient order during a meal significantly impacts postprandial glucose and insulin excursions in type 2 diabetes, while its effects in prediabetes have not been reported. Fifteen participants with prediabetes consumed the same meal on 3 days in random order: carbohydrate first, followed 10 minutes later by protein and vegetables (CF); protein and vegetables first, followed 10 minutes later by carbohydrate (PVF); or vegetables first followed by protein and carbohydrate (VF). Blood was sampled for glucose and insulin measurements at 0, 30, 60, 90, 120, 150 and 180 minutes. Incremental glucose peaks were similarly attenuated by >40% in the PVF and VF meal conditions compared with CF. The incremental area under the curve for glucose was 38.8% lower following the PVF meal order, compared with CF, and postprandial insulin excursions were significantly lower in the VF meal condition compared with CF. The CF meal pattern showed marked glycaemic variability whereas glucose levels were stable in the PVF and VF meal conditions. Food order presents a novel, simple behavioural strategy to reduce glycaemic excursions in prediabetes.

A magnetic resonance imaging family study of cortical thickness in schizophrenia.

Schizophrenia is associated with abnormalities in cortical thickness, including both thicker and thinner cortices than controls. Although less reliably than in patients, non-psychotic relatives of schizophrenia patients have also demonstrated both thicker and thinner cortices than controls, suggesting an effect of familial or genetic liability. We investigated cortical thickness in 25 schizophrenia patients, 26 adult non-psychotic first-degree biological relatives, and 23 community controls using the automated program FreeSurfer. Contrary to hypotheses, we found relatives of schizophrenia patients had greater cortical thickness in all lobes compared to patients and controls; however, this finding was not as widespread when compared to controls. In contrast, schizophrenia patients only demonstrated a thinner right fusiform region than controls and relatives. Our finding of greater thickness in adult biological relatives could represent a maladaptive abnormality or alternatively, a compensatory mechanism. Previous literature suggests that the nature of abnormalities in relatives can vary by the age of relatives and change across the developmental period. Abnormalities in patients may depend on lifestyle factors and on current and previous anti-psychotic medication use. Our results speak to the need to study various populations of patients and relatives across the lifespan to better understand different developmental periods and the impact of environmental factors. © 2015 Wiley Periodicals, Inc.

Wall Thickness, Pulmonary Hypertension, and Diastolic Filling Abnormalities Predict Response to Postoperative Biventricular Pacing.

OBJECTIVE: Post-cardiopulmonary bypass biventricular pacing improves hemodynamics but without clearly defined predictors of response. Based on preclinical studies and prior observations, it was suspected that diastolic dysfunction or pulmonary hypertension is predictive of hemodynamic benefit. DESIGN: Randomized controlled study of temporary biventricular pacing after cardiopulmonary bypass. SETTING: Single-center study at university-affiliated tertiary care hospital. INTERVENTIONS: Patients who underwent bypass with preoperative ejection fraction ≤40% and QRS duration ≥100 ms or double-valve surgery were enrolled. At 3 time points between separation from bypass and postoperative day 1, pacing delays were varied to optimize hemodynamics. PARTICIPANTS: Data from 43 patients were analyzed. MEASUREMENTS AND MAIN RESULTS: Cardiac output and arterial pressure were measured under no pacing, atrial pacing, and biventricular pacing. Preoperative echocardiograms and pulmonary artery catheterizations were reviewed, and measures of both systolic and diastolic function were compared to hemodynamic response. Early after separation, improvement in cardiac output was positively correlated with pulmonary vascular resistance (R(2) = 0.97, p<0.001), ventricle wall thickness (R(2) = 0.72, p = 0.002)), and E/e', a measure of abnormal diastolic ventricular filling velocity (R(2) = 0.56, p = 0.04). Similar trends were seen with mean arterial pressure. QRS duration and ejection fraction did not correlate significantly with improvements in hemodynamics. CONCLUSIONS: There may be an effect of biventricular pacing related to amelioration of abnormal diastolic filling patterns rather than electrical resynchronization in the postoperative state.

Effects of electroconvulsive therapy on cognitive functioning in patients with depression: protocol for a systematic review and meta-analysis.

INTRODUCTION: Depression is the leading cause of disability worldwide, affecting approximately 350 million people. Evidence indicates that only 60-70% of persons with major depressive disorder who tolerate antidepressants respond to first-line drug treatment; the remainder become treatment resistant. Electroconvulsive therapy (ECT) is considered an effective therapy in persons with treatment-resistant depression. The use of ECT is controversial due to concerns about temporary cognitive impairment in the acute post-treatment period. We will conduct a meta-analysis to examine the effects of ECT on cognition in persons with depression. METHODS: This systematic review and meta-analysis has been registered with PROSPERO (registration number: CRD42014009100). We developed our methods following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We are searching MEDLINE, PsychINFO, EMBASE, CINAHL and Cochrane from the date of database inception to the end of October 2014. We are also searching the reference lists of published reviews and evidence reports for additional citations. Comparative studies (randomised controlled trials, cohort and case-control) published in English will be included in the meta-analysis. Three clinical neuropsychologists will group the cognitive tests in each included article into a set of mutually exclusive cognitive subdomains. The risk of bias of randomised controlled trials will be assessed using the Jadad scale. We will supplement the Jadad scale with additional questions based on the Cochrane risk of bias tool. The risk of bias of cohort and case-control studies will be assessed using the Newcastle-Ottawa Scale. We will employ the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the strength of evidence. STATISTICAL ANALYSIS: Separate meta-analyses will be conducted for each ECT treatment modality and cognitive subdomain using Comprehensive Meta-Analysis V.2.0.

The reporting of observational clinical functional magnetic resonance imaging studies: a systematic review.

INTRODUCTION: Complete reporting assists readers in confirming the methodological rigor and validity of findings and allows replication. The reporting quality of observational functional magnetic resonance imaging (fMRI) studies involving clinical participants is unclear. OBJECTIVES: We sought to determine the quality of reporting in observational fMRI studies involving clinical participants. METHODS: We searched OVID MEDLINE for fMRI studies in six leading journals between January 2010 and December 2011.Three independent reviewers abstracted data from articles using an 83-item checklist adapted from the guidelines proposed by Poldrack et al. (Neuroimage 2008; 40: 409-14). We calculated the percentage of articles reporting each item of the checklist and the percentage of reported items per article. RESULTS: A random sample of 100 eligible articles was included in the study. Thirty-one items were reported by fewer than 50% of the articles and 13 items were reported by fewer than 20% of the articles. The median percentage of reported items per article was 51% (ranging from 30% to 78%). Although most articles reported statistical methods for within-subject modeling (92%) and for between-subject group modeling (97%), none of the articles reported observed effect sizes for any negative finding (0%). Few articles reported justifications for fixed-effect inferences used for group modeling (3%) and temporal autocorrelations used to account for within-subject variances and correlations (18%). Other under-reported areas included whether and how the task design was optimized for efficiency (22%) and distributions of inter-trial intervals (23%). CONCLUSIONS: This study indicates that substantial improvement in the reporting of observational clinical fMRI studies is required. Poldrack et al.'s guidelines provide a means of improving overall reporting quality. Nonetheless, these guidelines are lengthy and may be at odds with strict word limits for publication; creation of a shortened-version of Poldrack's checklist that contains the most relevant items may be useful in this regard.

Changes in cortical thickness across the lifespan in major depressive disorder.

Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on age-of-onset. Our aim was to compare patients who differ in age-of-onset, while controlling for illness duration, and number of depressive episodes. By directly comparing early-(EOD) and late-onset (LOD) patients, we examined whether age-of-onset is associated with changes in the extent or spatial pattern of cortical thickness. Cross-sectional comparison of cortical thickness in EOD vs. LOD. Age-of-onset was determined based on self-report, with EOD defined as onset prior to age 25. Reduced cortical thickness in the dorsal-lateral prefrontal cortex (DLPFC), pre- and postcentral gyrus, and the lingual gyrus were found in EOD compared to healthy controls (p<0.001). In linear regression models controlling for number of episodes, illness duration, severity, and sex, differences (at p<0.001) were found between EOD and LOD in the bilateral posterior cingulate, parahippocampal gyri, right precuneus, lingual, and fusiform gyri, but not the DLPFC. EOD is associated with greater disturbances in cortical thickness than LOD, even when duration of illness and other factors are controlled. These results provide novel insights on how development of depression is differentiated by age.

Effectiveness of cognitive behavioral therapy for depression in patients receiving disability benefits: a systematic review and individual patient data meta-analysis.

OBJECTIVES: To systematically summarize the randomized trial evidence regarding the relative effectiveness of cognitive behavioural therapy (CBT) in patients with depression in receipt of disability benefits in comparison to those not receiving disability benefits. DATA SOURCES: All relevant RCTs from a database of randomized controlled and comparative studies examining the effects of psychotherapy for adult depression (http://www.evidencebasedpsychotherapies.org), electronic databases (MEDLINE, EMBASE, PSYCINFO, AMED, CINAHL and CENTRAL) to June 2011, and bibliographies of all relevant articles. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTION: Adult patients with major depression, randomly assigned to CBT versus minimal/no treatment or care-as-usual. STUDY APPRAISAL AND SYNTHESIS METHODS: Three teams of reviewers, independently and in duplicate, completed title and abstract screening, full text review and data extraction. We performed an individual patient data meta-analysis to summarize data. RESULTS: Of 92 eligible trials, 70 provided author contact information; of these 56 (80%) were successfully contacted to establish if they captured receipt of benefits as a baseline characteristic; 8 recorded benefit status, and 3 enrolled some patients in receipt of benefits, of which 2 provided individual patient data. Including both patients receiving and not receiving disability benefits, 2 trials (227 patients) suggested a possible reduction in depression with CBT, as measured by the Beck Depression Inventory, mean difference [MD] (95% confidence interval [CI]) = -2.61 (-5.28, 0.07), p = 0.06; minimally important difference of 5. The effect appeared larger, though not significantly, in those in receipt of benefits (34 patients) versus not receiving benefits (193 patients); MD (95% CI) = -4.46 (-12.21, 3.30), p = 0.26. CONCLUSIONS: Our data does not support the hypothesis that CBT has smaller effects in depressed patients receiving disability benefits versus other patients. Given that the confidence interval is wide, a decreased effect is still possible, though if the difference exists, it is likely to be small.