Cortical gyrification in women and men and the (missing) link to prenatal androgens.

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex-specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex-wise absolute mean curvature-a common estimate for cortical gyrification-in individuals with CAH (33 women and 20 men) and pair-wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH-by-sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly-the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women.

Chronic idiopathic urinary retention: Comorbidity and outcome in 102 individuals.

OBJECTIVES: Chronic Idiopathic urinary retention is poorly understood. One small study suggests higher than expected rates of functional neurological disorder and pain comorbidity which may have implications for understanding the disorder. We investigated the frequency of functional neurological disorder, chronic pain other medical and psychiatric comorbidity, triggers of urinary retention, results of urodynamic assessment, medication history, management, and outcome in patients with chronic idiopathic urinary retention. METHODS: A consecutive retrospective electronic notes analysis was undertaken of patients with chronic idiopathic urinary retention presenting to a secondary care urology clinic between Jan 2018-Jan 2021, with follow-up to their most recent urological appointment. RESULTS: 102 patients were identified (mean age of 41.9 years, 98% female). 25% had functional neurological disorder (n = 26), most commonly limb weakness (n = 19, 19%) and functional seizures (n = 16, 16%). Chronic pain (n = 58, 57%) was a common comorbidity. Surgical and medical riggers to urinary retention were found in almost half of patients (n = 49, 48%). 81% of patients underwent urodynamic assessment (n = 83). Most frequently no specific abnormality was reported (n = 30, 29%). Hypertonic urethral sphincter was the most identified urodynamic abnormality (n = 17, 17%). We noted high levels of opioid (n = 50, 49%) and benzodiazepine (n = 27, 26%) use. Urinary retention resolved in only a small number of patients (n = 6, 6%, median follow up 54 months), in three cases spontaneously. CONCLUSION: This preliminary data suggests idiopathic urinary retention is commonly comorbid with functional neurological disorder, and chronic pain, suggesting shared mechanisms.

Age of onset of obsessive-compulsive disorder differentially affects white matter microstructure.

Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.

Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

Predictors of clinical worsening during a discontinuation trial of serotonin reuptake inhibitors for obsessive compulsive disorder.

OBJECTIVE: To explore predictors and moderators of clinical worsening during a double-blind trial in which patients with obsessive-compulsive disorder (OCD) were randomized to either continue or discontinue their Serotonin Reuptake Inhibitor (SRI) medication after achieving wellness from the addition of exposure and response prevention (EX/RP) therapy. METHOD: The data came from a double-blind discontinuation trial that included N = 101 participants, 35 of whom were removed from the study due to clinical worsening. We first used LASSO logistic regression to identify which of the 34 potential baseline variables of interest (including demographics, diagnoses, other relevant clinical constructs, and specific genotypes), might moderate or predict this clinical worsening. Then logistic regression was used to examine which of these identified variables were significantly related to later clinical worsening. We verified the validity of our final prediction model using k-fold cross-validation. RESULTS: There was one significant predictor of clinical worsening: In both groups, those with more past diagnoses had a greater likelihood of clinical worsening (p = .015). There were several moderators. Rates of clinical worsening were higher in the Discontinuation group compared to the Continuation group for participants who were taking a shorter half-life SRI (p = .044), were female (p = .022), had higher baseline levels of maladaptive metacognitions (p < .001), had fewer sleep problems at baseline (p = .001), and/or had more years of education (p < .001). CONCLUSIONS: Our results identified several factors that may predict the development of clinical worsening in OCD patients discontinuing SRI medication following successful EX/RP treatment.

Selective aortic arch perfusion: a first-in-human observational cadaveric study.

BACKGROUND: Selective aortic arch perfusion (SAAP) is a novel endovascular technique that combines thoracic aortic occlusion with extracorporeal perfusion of the brain and heart. SAAP may have a role in both haemorrhagic shock and in cardiac arrest due to coronary ischaemia. Despite promising animal studies, no data is available that describes SAAP in humans. The primary aim of this study was to assess the feasibility of selective aortic arch perfusion in humans. The secondary aim of the study was to assess the feasibility of achieving direct coronary artery access via the SAAP catheter as a potential conduit for salvage percutaneous coronary intervention. METHODS: Using perfused human cadavers, a prototype SAAP catheter was inserted into the descending aorta under fluoroscopic guidance via a standard femoral percutaneous access device. The catheter balloon was inflated and the aortic arch perfused with radio-opaque contrast. The coronary arteries were cannulated through the SAAP catheter. RESULTS: The procedure was conducted four times. During the first two trials the SAAP catheter was passed rapidly and without incident to the intended descending aortic landing zone and aortic arch perfusion was successfully delivered via the device. The SAAP catheter balloon failed on the third trial. On the fourth trial the left coronary system was cannulated using a 5Fr coronary guiding catheter through the central SAAP catheter lumen. CONCLUSIONS: For the first time using a perfused cadaveric model we have demonstrated that a SAAP catheter can be easily and safely inserted and SAAP can be achieved using conventional endovascular techniques. The SAAP catheter allowed successful access to the proximal aorta and permitted retrograde perfusion of the coronary and cerebral circulation.

Out-of-hours admissions in patients treated with immune checkpoint inhibitors and their primary management with steroids.

INTRODUCTION: The incidence of immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICI) is well described. However, the impact on emergency care services is not. This study investigated the incidence of irAEs out-of-hours, and the management used to mitigate symptoms and side effects. METHODS: This retrospective cohort study reviewed all emergency presentations triaged by the acute oncology team between December 2021 and June 2022, between 5 pm and 9 am. Patients were identified from triage audit sheets and remaining data points were retrieved from electronic health records. Inclusion criteria included all adult patients admitted on an ICI at one tertiary centre. RESULTS: In 7 months, 970 patients called the acute oncology helpline 11% (n = 109) of patients were on an ICI treatment. After clinical review, 78% (n = 70) resulted in hospital admissions, with length of stay cumulating to 496 bed days. 56% (n = 39) of patients delayed reporting symptoms, ranging between 12 hours and 10 days from symptom onset to seeking support. 49% (n = 34) patients received steroids to manage suspected irAEs. Dexamethasone was the most common steroid used in 71% (n = 24) of patients, and variation was found in prescribed doses. CONCLUSIONS: These results underline the urgent need to address patient and staff education on adverse effects related to ICI. Patients require a comprehensive understanding of the symptoms and importance of prompt reporting. Staff education on recognition and treatment management is needed to reduce variation in practice. Further research is needed to identify barriers in symptom reporting and focus on realtime reporting to reduce the out-of-hours burden on services.

Diagnostic utility of 11 C-methionine PET/CT in primary hyperparathyroidism in a UK cohort: A single-centre experience and literature review.

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.

World Federation for Interventional Stroke Treatment (WIST) Multispecialty Training Guidelines for Endovascular Stroke Intervention.

INTRODUCTION: Today, endovascular treatment (EVT) is the therapy of choice for strokes due to acute large vessel occlusion, irrespective of prior thrombolysis. This necessitates fast, coordinated multi-specialty collaboration. Currently, in most countries, the number of physicians and centres with expertise in EVT is limited. Thus, only a small proportion of eligible patients receive this potentially life-saving therapy, often after significant delays. Hence, there is an unmet need to train a sufficient number of physicians and centres in acute stroke intervention in order to allow widespread and timely access to EVT. AIM: To provide multi-specialty training guidelines for competency, accreditation and certification of centres and physicians in EVT for acute large vessel occlusion strokes. MATERIAL AND METHODS: The World Federation for Interventional Stroke Treatment (WIST) consists of experts in the field of endovascular stroke treatment. This interdisciplinary working group developed competency - rather than time-based - guidelines for operator training, taking into consideration trainees' previous skillsets and experience. Existing training concepts from mostly single specialty organizations were analysed and incorporated. RESULTS: The WIST establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in EVT. WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. CONCLUSIONS: WIST multispecialty guidelines outline competency and quality standards for physicians and centres to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. SUMMARY: The World Federation for Interventional Stroke Treatment (WIST) establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in endovascular treatment (EVT). WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. WIST multispecialty guidelines outline competency and quality standards for physicians and centers to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. SIMULTANEOUS PUBLICATION: The WIST 2023 Guidelines are published simultaneously in Europe (Adv Interv Cardiol 2023).

Engaging young people and their caregivers in support services following harmful sexual behaviors: Qualitative analysis.

BACKGROUND: Harmful sexual behavior (HSB) displayed by children and young people under the age of 18 has been described as developmentally inappropriate, may be harmful towards self or others, or be abusive towards another child, young person, or adult. Early intervention and treatment completion are crucial to cease HSB, reduce impacts and address underlying issues for the child who has displayed HSB. Considerable shame attaches to seeking help for this stigmatized behavior which may result in dropout from support services. Understanding young people and caregivers' experiences of what facilitates or hinders their engagement with support services is therefore critical to preventing re-occurrence of HSB and keeping children safe. OBJECTIVE: This article draws on the first-hand experience of young people and caregivers to address the question: What have they found helpful and unhelpful when engaging with services for harmful sexual behavior? PARTICIPANTS AND SETTING: Participants were recruited from public health and youth justice services in the state of New South Wales, Australia. The 31 participants included 11 young people (aged 14 to 17) and 20 caregivers (parents, foster or kinship carers). METHODS: Qualitative data were collected through individual semi-structured interviews, following which thematic analysis was conducted. RESULTS: Data analysis identified three helpful responses: (1) non-judgmental recognition of crisis; (2) child-centred and family-focused orientation; and (3) multi-dimensional interventions. Unhelpful responses included: (1) closed doors (an inability to access a service) (2) stigmatization of HSB; and (3) reduced caregivers' autonomy. CONCLUSIONS: Greater involvement of caregivers, non-stigmatizing language and coordinated responses between generalist and specialist services are needed to facilitate service engagement.

Severe aortic stenosis management in heart valve centres compared with primary/secondary care centres.

OBJECTIVE: Current guidelines recommend use of heart valve centres (HVCs) to deliver optimal quality of care for patients with valve disease but there is no evidence to support this. The hypothesis of this study is that patient care with severe aortic stenosis (AS) will differ in HVCs compared with satellite centres. We aimed to compare the treatment of patients with AS at HVCs (tertiary care hospitals with full access to AS interventions) to satellites (hospitals without such access). METHODS: IMPULSE enhanced is a European, observational, prospective registry enrolling consecutive patients with newly diagnosed severe AS at four HVCs and 10 satellites. Clinical characteristics, interventions performed and outcomes up to 1 year by site-type were examined. RESULTS: Among 790 patients, 594 were recruited in HVCs and 196 in satellites. At baseline, patients in HVCs had more severe valve disease (higher peak aortic velocity (4.3 vs 4.1 m/s; p=0.008)) and greater comorbidity (coronary artery disease (CAD) (44% vs 27%; p<0.001) prior myocardial infarction (MI) (11% vs 5.1%; p=0.011) and chronic pulmonary disease (17% vs 8.9%; p=0.007)) than those presenting in satellites. An aortic valve replacement was performed more often by month 3 in HVCs than satellites in the overall population (52.6% of vs 31.3%; p<0.001) and in symptomatic patients (66.7% vs 43.2%, p<0.001). One-year survival rate was higher for patients in HVCs than satellites (HR2.19; 95% CI 1.28 to 3.73 total population and 2.89 (95%CI 1.64 to 5.11) for symptomatic patients. CONCLUSIONS: Our data support the implementation of referral pathways that direct patients to HVCs performing both surgery and transcatheter interventions. TRIAL REGISTRATION NUMBER: NCT03112629.

Cross-national harmonization of neurocognitive assessment across five sites in a global study.

OBJECTIVE: Cross-national work on neurocognitive testing has been characterized by inconsistent findings, suggesting the need for improved harmonization. Here, we describe a prospective harmonization approach in an ongoing global collaborative study. METHOD: Visuospatial N-Back, Tower of London (ToL), Stop Signal task (SST), Risk Aversion (RA), and Intertemporal Choice (ITC) tasks were administered to 221 individuals from Brazil, India, the Netherlands, South Africa, and the USA. Prospective harmonization methods were employed to ensure procedural similarity of task implementation and processing of derived task measures across sites. Generalized linear models tested for between-site differences controlling for sex, age, education, and socioeconomic status (SES). Associations with these covariates were also examined and tested for differences by site with site-by-covariate interactions. RESULTS: The Netherlands site performed more accurately on N-Back and ToL than the other sites, except for the USA site on the N-Back. The Netherlands and the USA sites performed faster than the other three sites during the go events in the SST. Finally, the Netherlands site also exhibited a higher tolerance for delay discounting than other sites on the ITC, and the India site showed more risk aversion than other sites on the RA task. However, effect size differences across sites on the five tasks were generally small (i.e., partial eta-squared < 0.05) after dropping the Netherlands (on ToL, N-Back, ITC, and SST tasks) and India (on the RA task). Across tasks, regardless of site, the N-Back (sex, age, education, and SES), ToL (sex, age, and SES), SST (age), and ITC (SES) showed associations with covariates. CONCLUSIONS: Four out of the five sites showed only small between-site differences for each task. Nevertheless, despite our extensive prospective harmonization steps, task score performance deviated from the other sites in the Netherlands site (on four tasks) and the India site (on one task). Because the procedural methods were standardized across sites, and our analyses were adjusted for covariates, the differences found in cognitive performance may indicate selection sampling bias due to unmeasured confounders. Future studies should follow similar cross-site prospective harmonization procedures when assessing neurocognition and consider measuring other possible confounding variables for additional statistical control. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Strengthening Schools' Responses to Students' Harmful Sexual Behaviors: A Scoping Review.

Research into harmful sexual behavior (HSB) by children and young people under the age of 18 has grown in recent years. A key concern emerging is the high prevalence of HSB in school settings. Although teachers are increasingly aware of HSB, their provision of effective responses has remained a major challenge. While progress has been made by providing teachers with best practice models and tools, little is known about what facilitates and hinders their application of these in practice. This scoping review sought to address the question: "What are the barriers and enablers for teachers in responding effectively to HSB?" Eight international databases and one search engine were employed to identify relevant academic and gray literature. The inclusion criteria comprised all study types, published in the past two decades, and focused on teachers' knowledge, experiences, and responses to HSB. Twenty-five publications met the inclusion criteria. Thematic analysis identified that minimization of HSB, harmful social norms, and inadequate support from external agencies were major barriers. These barriers could be mitigated by adopting a whole-school approach and establishing proactive partnerships with parents and external agencise, along with offering alternative pathways to safety. The findings of this review highlighted the importance of addressing the full continuum of HSB through early, secondary, or tertiary interventions, and sharpening the focus of respectful relationships education to transform gender relations in classrooms and the workplace. Further research is needed to explore schools' responses to specific populations, including those with disabilities and females.

Global multi-center and multi-modal magnetic resonance imaging study of obsessive-compulsive disorder: Harmonization and monitoring of protocols in healthy volunteers and phantoms.

OBJECTIVES: We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well-powered neuroimaging findings in neuropsychiatric research to worldwide populations. METHODS: We report on T1-weighted structural MRI, resting-state functional MRI, and multi-shell diffusion-weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans. RESULTS: Human image quality measures (IQMs) and outcome measures showed smaller within-site variation than between-site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites. CONCLUSIONS: Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre-processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Measurement fidelity of clinical assessment methods in a global study on identifying reproducible brain signatures of obsessive-compulsive disorder.

OBJECTIVE: To describe the steps of ensuring measurement fidelity of core clinical measures in a five-country study on brain signatures of obsessive-compulsive disorder (OCD). METHOD: We collected data using standardized instruments, which included the Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Dimensional YBOCS (DYBOCS), the Brown Assessment of Beliefs Scale (BABS), the 17-item Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), and the Structured Clinical Interview for DSM-5 (SCID). Steps to ensure measurement fidelity included translating instruments, developing a clinical decision manual, and continuing reliability training with 11-13 transcripts of each instrument by 13 independent evaluators across sites over 4 years. We use multigroup confirmatory factor analysis (MGCFA) to report interrater reliability (IRR) among the evaluators and factor structure for each scale in 206 participants with OCD. RESULTS: The overall IRR for most scales was high (ICC > 0.94) and remained good to excellent throughout the study. Consistent factor structures (configural invariance) were found for all instruments across the sites, while similarity in the factor loadings for the items (metric invariance) could be established only for the DYBOCS and the BABS. CONCLUSIONS: It is feasible to achieve measurement fidelity of clinical measures in multisite, multilinguistic global studies, despite the challenges inherent to such endeavors. Future studies should not only report IRR but also consider reporting methods of standardization of data collection and measurement invariance to identify factor structures of core clinical measures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Protocol for a Pragmatic Trial of Pharmacotherapy Options Following Unsatisfactory Initial Treatment in OCD (PROCEED).

Background: Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), but a large proportion of patients do not achieve remission after an adequate SSRI trial. To the best of our knowledge, there have been no well-powered randomized controlled trials (RCTs) of sequenced pharmacotherapy using pragmatic research designs. China provides a unique context for undertaking such a trial that will recruit the largest treatment-naïve participants and systematically compare the efficacy of different sequenced pharmacotherapy. Methods: A pragmatic research design will be adopted, with n = 1,600 treatment-naïve OCD patients initially treated for sertraline for 12 weeks, and with non-remitters then randomized to 5 different augmentation or switching pharmacotherapy options for another 12 weeks. The 5 arms will include: (1) treatment with higher than usual doses of sertraline, (2) switch to fluvoxamine, (3) switch to venlafaxine, (4) augmentation with memantine, and (5) augmentation with aripiprazole. Discussion: China is uniquely positioned to recruit sufficiently large sample sizes of treatment-naïve OCD patients to compare different pharmacotherapy options; data from the proposed trial promises to help inform current clinical practice guidelines by providing important information about optimal pharmacotherapy choice for those who demonstrate no response or response but no remission to first line pharmacotherapy. Trial Registration: The trail was registered on 27 August 2020 in ClinicalTrials.gov (https://register.clinicaltrials.gov/) (NCT04539951).