Cognitive Behavioural Therapy with Exposure and Response Prevention in the treatment of Obsessive-Compulsive Disorder: A systematic review and meta-analysis of randomised controlled trials

© 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Background: Cognitive behavioural therapy (CBT), incorporating exposure and response prevention (ERP) is widely recognised as the psychological treatment of choice for obsessive-compulsive disorder (OCD). Uncertainty remains however about the magnitude of the effect of CBT with ERP and the impact of moderating factors in patients with OCD. Method: This systematic review and meta-analysis assessed randomised-controlled trials of CBT with ERP in patients of all ages with OCD. The study was preregistered in PROSPERO (CRD42019122311). The primary outcome was end-of-trial OCD symptom scores. The moderating effects of patient-related and study-related factors including type of control intervention and risk of bias were examined. Additional exploratory analyses assessed the effects of treatment fidelity and impact of researcher allegiance. Results: Thirty-six studies were included, involving 2020 patients (537 children/adolescents and 1483 adults) with 1005 assigned to CBT with ERP and 1015 to control conditions. When compared against all control conditions, a large pooled effect size (ES) emerged in favour of CBT with ERP (g = 0.74: 95% CI = 0.51 to 0.97 k = 36), which appeared to diminish with increasing age. While CBT with ERP was more effective than psychological placebo (g = 1.13 95% CI 0.71 to 1.55, k = 10), it was no more effective than other active forms of psychological therapy (g = −0.05: 95% CI -0.27 to 0.16, k = 8). Similarly, whereas CBT with ERP was significantly superior when compared to all forms of pharmacological treatment (g = 0.36: 95% CI 0.7 to 0.64, k = 7), the effect became marginal when compared with adequate dosages of pharmacotherapy for OCD (g = 0.32: 95% CI -0.00 to 0.64, k = 6).A minority of studies (k = 8) were deemed to be at low risk of bias. Moreover, three quarters of studies (k = 28) demonstrated suspected researcher allegiance and these studies reported a large ES (g = 0.95: 95% CI 0.69 to 1.2), while those without suspected researcher allegiance (k = 8) indicated that CBT with ERP was not efficacious (g = 0.02: 95% CI -0.29 to 0.33). Conclusions: A large effect size was found for CBT with ERP in reducing the symptoms of OCD, but depends upon the choice of comparator control. This meta-analysis also highlights concerns about the methodological rigor and reporting of published studies of CBT with ERP in OCD. In particular, efficacy was strongly linked to researcher allegiance and this requires further future investigation.Peer reviewe

Recovery of viral RNA and infectious foot-and-mouth disease virus from positive lateral-flow devices

Foot-and-mouth disease Virus (FMDV) is an economically important, highly contagious picornavirus that affects both wild and domesticated cloven hooved animals. In developing countries, the effective laboratory diagnosis of foot-and-mouth disease (FMD) is often hindered by inadequate sample preservation due to difficulties in the transportation and storage of clinical material. These factors can compromise the ability to detect and characterise FMD virus in countries where the disease is endemic. Furthermore, the high cost of sending infectious virus material and the biosecurity risk it presents emphasises the need for a thermo-stable, non-infectious mode of transporting diagnostic samples. This paper investigates the potential of using FMDV lateral-flow devices (LFDs) for dry transportation of clinical samples for subsequent nucleic acid amplification, sequencing and recovery of infectious virus by electroporation. FMDV positive samples (epithelial suspensions and cell culture isolates) representing four FMDV serotypes were applied to antigen LFDs: after which it was possible to recover viral RNA that could be detected using real-time RT-PCR. Using this nucleic acid, it was also possible to recover VP1 sequences and also successfully utilise protocols for amplification of complete FMD virus genomes. It was not possible to recover infectious FMDV directly from the LFDs, however following electroporation into BHK-21 cells and subsequent cell passage, infectious virus could be recovered. Therefore, these results support the use of the antigen LFD for the dry, non-hazardous transportation of samples from FMD endemic countries to international reference laboratories

Commentary on the article: “Maintenance of Wellness in Patients With Obsessive-Compulsive Disorder Who Discontinue Medication After Exposure/Response Prevention Augmentation A Randomized Clinical Trial”

© 2022 The Authors. Published by Elsevier Inc. This is an open access article distributed under the Creative Commons Non Commercial-No Derivatives Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by-nc-nd/4.0/Peer reviewe

Differential effects of sertraline and cognitive behavioural therapy on behavioural inhibition in patients with obsessive compulsive disorder

© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Patients with obsessive compulsive disorder (OCD) randomised to sertraline, manualised cognitive behavioural therapy (CBT), or combination (sertraline + CBT), underwent cognitive assessment. Cognitive testing was conducted at baseline and at week 16. The stop signal reaction time task (SSRT) was used to evaluate motor impulsivity and attentional flexibility was evaluated using the intra/extra-dimensional set shifting task. Paired-samples t-tests or nonparametric variants were used to compare baseline and posttreatment scores within each treatment group. Forty-five patients were tested at baseline (sertraline n = 14; CBT n = 14; sertraline + CBT n = 17) and 23 patients at week 16 (sertraline n = 6; CBT n = 7; sertraline + CBT n = 10). The mean dosage of sertraline was numerically higher in those taking sertraline as a monotherapy (166.67 mg) compared with those taking sertraline in combination with CBT (100 mg). Analysis of pre-post treatment scores using an intent-to-treat-analysis found a significant reduction in the SSRT in those treated with sertraline, whilst there was no significant change on this task for those treated with CBT or the combination. This study found that motor inhibition improved significantly following sertraline monotherapy. Suboptimal sertraline dosing might explain the failure to detect an effect on motor inhibition in the group receiving combination of sertraline + CBT. Higher dose sertraline may have broader cognitive effects than CBT for OCD, motor impulsivity may have value as a measure of treatment outcome and, by extension, the SSRT could serve as a biomarker for personalising care.Peer reviewe

Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders: Cognitive Domains, Neural Circuitry, and Treatment.

Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder

Foot-and-Mouth Disease Virus Serotype A in Egypt

We describe the characterization of a foot-and-mouth disease (FMD) serotype A virus responsible for recent outbreaks of disease in Egypt. Phylogenetic analysis of VP1 nucleotide sequences demonstrated a close relationship to recent FMD virus isolates from East Africa, rather than to viruses currently circulating in the Middle East

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies