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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
This research aimed to explore the perspectives of primary and community care providers on the challenges that hinder the delivery and uptake of personalized type 2 diabetes (T2D) care, with a focus on the integration of mental health support and care.
Background:
The day-to-day burden and demand of self-managing T2D can negatively impact quality of life and take a toll on mental health and psychological well-being. As a result, there is a need for personalized T2D self-management education and support that integrates mental health care. Despite the need for this personalized care, existing systems remain siloed, hindering access and uptake. In response, innovative, comprehensive, and collaborative models of care have been developed to address fragmentations in care. As individuals living with T2D often receive their care in primary care settings, linking mental health care to existing teams and networks in primary care settings is required. However, there is a need to understand how best to support access, adoption, and engagement with these models in these unique contexts.
Methods:
A cross-sectional survey was distributed to primary and community providers of an Ontario-based smoking cessation network. Survey data were analyzed descriptively with free text responses thematically reported.
Findings:
Survey respondents (n = 85) represented a broad mix of health professions across primary and community care settings. Addressing challenges to the delivery and uptake of personalized T2D care requires comprehensive strategies to address patient-, practice-, and system-level challenges. Findings from this survey identify the need to tailor these models of care to individual needs, clearly addressing mental health needs, and building strong partnership as means of enhancing accessibility and sustainability of integrated care delivery in primary care settings.
Much of the existing analysis of women in O’Casey’s plays concentrates on the women in his earlier work; this chapter examines the representation of younger women in O’Casey’s later plays, revealing how O’Casey presented a strongly contemporary feminist outlook which sought to re-position his audience’s understanding of female sensibility. The chapter analyses the way in which, by questioning theatrical form and critiquing patriarchal control of women, O’Casey enabled experimentalism in dramatic form to go hand in hand with a willingness to evolve and develop a progressive expression of female sexuality.
Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease process that represents a significant health shock for thousands of patients each year. Return to work outcomes and associated factors require evaluation to counsel patients and identify domains on which to focus clinical efforts. Methods: A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines was performed using MEDLINE, EMBASE and Cochrane databases from inception to February 2024. Proportion of patients returning to work was collected from included studies. Odds ratios were pooled from studies evaluating the association between pre-rupture demographic variables, post-rupture clinical variables and return to work following aSAH. Results: Literature search yielded 3861 studies, of which 40 studies were included in the final analysis for a total of 6888 patients. On average, 55% (SD 17%) of all patients returned to work after an aSAH. Female sex (male sex OR 1.75), high grade aSAH on presentation (OR 0.30), and need for permanent CSF diversion (OR 0.50) are significantly associated with unemployment after aSAH. Conclusions: Female sex, high grade presentation, and permanent CSF diversion are associated with unemployment after aSAH. About half of all patients that experience aSAH return to work.
Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.
The concept of the protein transition represents a shift from a diet rich in animal proteins to one richer in plant-based alternatives, largely in response to environmental sustainability concerns. However, a simple swap by replacing dairy protein with plant protein will lead to lower protein quality and a lower intake of key micronutrients that sit naturally within the dairy matrix. Owing to antagonistic effects within the plant food matrix, micronutrients in plant sources exhibit lower bioavailability which is not reflected in food composition data or dietary guidelines. The dairy matrix effect includes moderation of blood lipid levels in which calcium plays a key role. Protein recommendations often take a muscle-centric approach. Hence, strategies to increase the anabolic potential of plant proteins have focused on increasing total protein intake to counter the suboptimal amino acid composition relative to dairy protein or leucine fortification. However, emerging evidence indicates a role for nutrient interactions and non-nutrient components (milk exosomes, bioactive peptides) of the dairy matrix in modulating postprandial muscle protein synthesis rates. To ensure the food system transformation is environmentally sustainable and optimal from a nutrition perspective, consideration needs to be given to complementary benefits of different food matrices and the holistic evaluation of foods in the protein transition. This narrative review critically examines the role of dairy in the protein transition, emphasising the importance of the food matrix in nutrient bioavailability and muscle health. By considering both nutritional and sustainability perspectives, we provide a holistic evaluation of dairy’s contribution within evolving dietary patterns.
Objectives/Goals: Cutaneous lupus erythematosus (CLE) is an inflammatory skin manifestation of lupus. CLE lesions are frequently colonized by Staphylococcus aureus, a microbe known to promote IFN production and inflammation. Here, we investigate whether type I IFN and inflammatory gene signatures in CLE lesions can be modulated with a topical antibiotic treatment. Methods/Study Population: SLE patients with active CLE lesions (n = 12) were recruited and randomized into a week of topical treatment with either 2% mupirocin or petroleum jelly vehicle. Paired samples were collected before and after 7 days of treatment to assess microbial lesional skin responses. Microbial samples from nares and lesional skin were used to determine baseline and posttreatment Staphylococcus abundance and microbial community profiles by 16S rRNA gene sequencing. Inflammatory responses were evaluated by bulk RNA sequencing of lesional skin biopsies. Immunophenotyping of CLE lesions was performed using CIBERSORTx to deconvolute the RNA-seq data into predicted cell populations impacted by treatment. Results/Anticipated Results: We identified 173 differentially expressed genes in CLE lesions after topical mupirocin treatment. Mupirocin treatment decreased the abundance of Staphylococcus associated with CLE lesions without altering the overall diversity of the skin microbiota relative to vehicle. Decreased lesional Staphylococcus burden correlated with decreased IFN pathway signaling and inflammatory gene expression and increased barrier dysfunction. Interestingly, mupirocin treatment lowered skin monocyte levels, and this mupirocin-associated depletion of monocytes correlated with decreased inflammatory gene expression. Discussion/Significance of Impact: Mupirocin treatment decreased lesional Staphylococcus burden and this correlated with decreased IFN signaling and inflammatory gene expression. This study suggests a topical antibiotic could be employed to decrease lupus skin inflammation and type I IFN responses by reducing Staphylococcus colonization.
Geriatric (old age) psychiatry faces growing challenges amid Europe’s ageing population. This editorial emphasises the need for specialised training, mentorship and subspecialty recognition to attract young psychiatrists. By addressing structural gaps and fostering innovation, the field offers a rewarding career in enhancing older adults’ mental healthcare and quality of life.
The marketing of unhealthy foods has been implicated in poor diet and rising levels of obesity. Rapid developments in the digital food marketing ecosystem and associated research mean that contemporary review of the evidence is warranted. This preregistered (CRD420212337091)1 systematic review and meta-analysis aimed to provide an updated synthesis of the evidence for behavioural and health impacts of food marketing on both children and adults, using the 4Ps framework (Promotion, Product, Price, Place). Ten databases were searched from 2014 to 2021 for primary data articles of quantitative or mixed design, reporting on one or more outcome of interest following food marketing exposure compared with a relevant control. Reviews, abstracts, letters/editorials and qualitative studies were excluded. Eighty-two studies were included in the narrative review and twenty-three in the meta-analyses. Study quality (RoB2/Newcastle–Ottawa scale) was mixed. Studies examined ‘promotion’ (n 55), ‘product’ (n 17), ‘price’ (n 15) and ‘place’ (n 2) (some > 1 category). There is evidence of impacts of food marketing in multiple media and settings on outcomes, including increased purchase intention, purchase requests, purchase, preference, choice, and consumption in children and adults. Meta-analysis demonstrated a significant impact of food marketing on increased choice of unhealthy foods (OR = 2·45 (95 % CI 1·41, 4·27), Z = 3·18, P = 0·002, I2 = 93·1 %) and increased food consumption (standardised mean difference = 0·311 (95 % CI 0·185, 0·437), Z = 4·83, P < 0·001, I2 = 53·0 %). Evidence gaps were identified for the impact of brand-only and outdoor streetscape food marketing, and for data on the extent to which food marketing may contribute to health inequalities which, if available, would support UK and international public health policy development.
In major depressive disorder (MDD), only ~35% achieve remission after first-line antidepressant therapy. Using UK Biobank data, we identify sociodemographic, clinical, and genetic predictors of antidepressant response through self-reported outcomes, aiming to inform personalized treatment strategies.
Methods
In UK Biobank Mental Health Questionnaire 2, participants with MDD reported whether specific antidepressants helped them. We tested whether retrospective lifetime response to four selective serotonin reuptake inhibitors (SSRIs) (N = 19,516) – citalopram (N = 8335), fluoxetine (N = 8476), paroxetine (N = 2297) and sertraline (N = 5883) – was associated with sociodemographic (e.g. age, gender) and clinical factors (e.g. episode duration). Genetic analyses evaluated the association between CYP2C19 variation and self-reported response, while polygenic score (PGS) analysis assessed whether genetic predisposition to psychiatric disorders and antidepressant response predicted self-reported SSRI outcomes.
Results
71%–77% of participants reported positive responses to SSRIs. Non-response was significantly associated with alcohol and illicit drug use (OR = 1.59, p = 2.23 × 10−20), male gender (OR = 1.25, p = 8.29 × 10−08), and lower-income (OR = 1.35, p = 4.22 × 10−07). The worst episode lasting over 2 years (OR = 1.93, p = 3.87 × 10−16) and no mood improvement from positive events (OR = 1.35, p = 2.37 × 10−07) were also associated with non-response. CYP2C19 poor metabolizers had nominally higher non-response rates (OR = 1.31, p = 1.77 × 10−02). Higher PGS for depression (OR = 1.08, p = 3.37 × 10−05) predicted negative SSRI outcomes after multiple testing corrections.
Conclusions
Self-reported antidepressant response in the UK Biobank is influenced by sociodemographic, clinical, and genetic factors, mirroring clinical response measures. While positive outcomes are more frequent than remission reported in clinical trials, these self-reports replicate known treatment associations, suggesting they capture meaningful aspects of antidepressant effectiveness from the patient’s perspective.
Diagnosis of ventilator-associated pneumonia (VAP) is challenging and relies heavily on respiratory culture results. The results of this survey underscore the potential for a diagnostic stewardship nudge limiting culture reports to “potential colonization or contamination” in those without clinical findings of VAP to decrease unnecessary antibiotic prescribing.
Antibiotic prophylaxis in children with vesicoureteral reflux (VUR) remains controversial. We reviewed patients diagnosed with VUR after an index urinary tract infection (UTI) who subsequently received antibiotic prophylaxis. Recurrent UTIs in patients with and without urologic anomalies occurred in 57% and 33%, respectively. Multidrug-resistant organisms accounted for 25% of first UTI recurrences.
A series of webinars covering widespread knowledge on paediatric cardiology and cardiac surgery topics was initiated by Association for European Paediatric and Congenital Cardiology, serving towards preparation for the Association for European Paediatric and Congenital Cardiology certification in paediatric and congenital cardiology. This study investigated the impact of webinars as educational tools for junior paediatric cardiologists in the post-COVID-19 pandemic era.
Materials and methods:
A cross-sectional survey design study using an online survey as a tool for the assessment of trainees. An open and closed-ended SurveyMonkey questionnaire was used to document the learners’ opinions on webinars. Results were reported using descriptive statistical analyses.
Results:
Twenty-seven Association for European Paediatric and Congenital Cardiology junior members participated in the online survey from twelve different countries. Most of the participants were trainees in paediatric cardiology (56%), and the remainder were junior consultants in paediatric cardiology. Approximately 70% found no difficulties in participating in the webinars. The webinars were appreciated by participants, who found the webinars interactive and highly educational with contents highly applicable to everyday clinical practice. Significant heterogeneity emerged in training programmes across Europe and worldwide in terms of programme duration, number of fellows, teaching approach, and assessments. Training opportunities such as courses, grants, and more webinars were suggested as tools to support continuous learning by the Association for European Paediatric and Congenital Cardiology.
Conclusion:
The Association for European Paediatric and Congenital Cardiology webinar series has confirmed the crucial role of online-based learning resources in the new generation of junior paediatric cardiologists. Association for European Paediatric and Congenital Cardiology webinars and the examination in paediatric cardiology may help standardise training across Europe, promoting the highest standards in patient care.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Clinical high-risk for psychosis (CHR-P) states exhibit diverse clinical presentations, prompting a shift towards broader outcome assessments beyond psychosis manifestation. To elucidate more uniform clinical profiles and their trajectories, we investigated CHR-P profiles in a community sample.
Methods
Participants (N = 829; baseline age: 16–40 years) comprised individuals from a Swiss community sample who were followed up over roughly 3 years. latent class analysis was applied to CHR-P symptom data at baseline and follow-up, and classes were examined for demographic and clinical differences, as well as stability over time.
Results
Similar three-class solutions were yielded for both time points. Class 1 was mainly characterized by subtle, subjectively experienced disturbances in mental processes, including thinking, speech and perception (basic symptoms [BSs]). Class 2 was characterized by subthreshold positive psychotic symptoms (i.e., mild delusions or hallucinations) indicative of an ultra-high risk for psychosis. Class 3, the largest group (comprising over 90% of participants), exhibited the lowest probability of experiencing any psychosis-related symptoms (CHR-P symptoms). Classes 1 and 2 included more participants with functional impairment and psychiatric morbidity. Class 3 participants had a low probability of having functional deficits or mental disorders at both time points, suggesting that Class 3 was the healthiest group and that their mental health and functioning remained stable throughout the study period. While 91% of Baseline Class 3 participants remained in their class over time, most Baseline Classes 1 (74%) and Class 2 (88%) participants moved to Follow-up Class 3.
Conclusions
Despite some temporal fluctuations, CHR-P symptoms within community samples cluster into distinct subgroups, reflecting varying levels of symptom severity and risk profiles. This clustering highlights the largely distinct nature of BSs and attenuated positive symptoms within the community. The association of Classes 1 and 2 with Axis-I disorders and functional deficits emphasizes the clinical significance of CHR-P symptoms. These findings highlight the need for personalized preventive measures targeting specific risk profiles in community-based populations.
Anhedonia characterizes major depressive episodes in bipolar depression and is associated with more severe illness/poor prognosis. These post hoc analyses assess effect of cariprazine 1.5 and 3 mg/d on anhedonia symptoms in patients with bipolar I depression.
Methods
Data were pooled from 3 randomized, double-blind, placebo-controlled bipolar I depression trials in cariprazine. Cariprazine 1.5 and 3 mg/d versus placebo were evaluated in patient subgroups stratified by median baseline MADRS anhedonia score (higher anhedonia=score ≥19; lower anhedonia=score <19). Outcomes included mean change from baseline to week 6 in MADRS total and anhedonia factor score (sum of apparent sadness, reported sadness, concentration, lassitude, and inability to feel items). The proportion of patients with week 6 anhedonia factor response (≥50% improvement from baseline) was also determined. Changes from baseline were analyzed using a mixed-effect model for repeated measures.
Results
There were 760 patients in the higher anhedonia subgroup (placebo=249, cariprazine: 1.5 mg/d=261; 3 mg/d=250) and 623 patients in the lower anhedonia subgroup (placebo=211, cariprazine: 1.5 mg/d=200; 3 mg/d=212). Mean baseline MADRS total score was higher in the higher anhedonia subgroup (total=33.6) than in the lower anhedonia subgroup (total=27.6). Change from baseline to week 6 in MADRS total score was greater for both cariprazine doses versus placebo in the higher anhedonia subgroup (least squares mean difference [LSMD] and 95% confidence interval [CI]: 1.5 mg/d=-3.01 [-4.84, -1.19], P=.0012; 3 mg/d: -3.26 [-5.12, -1.40], P=.0006); in the lower anhedonia subgroup, cariprazine 1.5 mg/d was statistically significant versus placebo (-2.61 [-4.28, -0.93], P=.0024). In the higher anhedonia subgroup at week 6, change from baseline in anhedonia factor score was significant versus placebo for both cariprazine doses (1.5 mg/d=-1.97 [-3.13, -0.81], P=.0009; 3 mg/d=-2.07 [-3.26, -0.89], P=.0006); in the lower subgroup, the difference was significant versus placebo for cariprazine 1.5 mg/d (-1.70 [-2.77, -0.62], P=.0021). After adjusting for changes in other depressive symptoms, LSMDs versus placebo in the anhedonia factor score remained significant for cariprazine 1.5 mg/d (-1.21 [-2.05, -0.36], P=.0052) and 3 mg/d (-1.00 [-1.86, -0.14], P=.0233) in the higher anhedonia subgroup, and for 1.5 mg/d (-1.06 [-1.92, -0.19], P=.0164) in the lower subgroup. In the higher anhedonia subgroup, rates of anhedonia factor response were greater versus placebo (31.7%) for cariprazine 1.5 mg/d (44.8%, P=.0028) and 3 mg/d (45.6%, P=.0019); in the lower subgroup, response rates were 39.3% for placebo, 48.0% for 1.5 mg/d, and 46.7% for 3 mg/d. Adverse events in ≥5% cariprazine and twice placebo were nausea, akathisia, restlessness, and EPS.
Importance
Those with bipolar depression and anhedonia cariprazine demonstrated a potent antidepressant and antianhedonic effect in higher/lower anhedonia subgroups.
Funding
AbbVie
This data was previously presented at the European College of Neuropsychopharmacology (ECNP) Congress; Barcelona, Spain; October 7 – 10, 2023.
The study objective was to develop and validate a clinical decision support system (CDSS) to guide clinicians through the diagnostic evaluation of hospitalized individuals with suspected pulmonary tuberculosis (TB) in low-prevalence settings.
Methods:
The “TBorNotTB” CDSS was developed using a modified Delphi method. The CDSS assigns points based on epidemiologic risk factors, TB history, symptoms, chest imaging, and sputum/bronchoscopy results. Below a set point threshold, airborne isolation precautions are automatically discontinued; otherwise, additional evaluation, including infection control review, is recommended. The model was validated through retrospective application of the CDSS to all individuals hospitalized in the Mass General Brigham system from July 2016 to December 2022 with culture-confirmed pulmonary TB (cases) and equal numbers of age and date of testing-matched controls with three negative respiratory mycobacterial cultures.
Results:
104 individuals with TB (cases) and 104 controls were identified. Prior residence in a highly endemic country, positive interferon release assay, weight loss, absence of symptom resolution with treatment for alternative diagnoses, and findings concerning for TB on chest imaging were significant predictors of TB (all P < 0.05). CDSS contents and scoring were refined based on the case–control analysis. The final CDSS demonstrated 100% sensitivity and 27% specificity for TB with an AUC of 0.87.
Conclusions:
The TBorNotTB CDSS demonstrated modest specificity and high sensitivity to detect TB even when AFB smears were negative. This CDSS, embedded into the electronic medical record system, could help reduce risks of nosocomial TB transmission, patient-time in airborne isolation, and person-time spent reviewing individuals with suspected TB.
Dual scaling (DS) is a multivariate exploratory method equivalent to correspondence analysis when analysing contingency tables. However, for the analysis of rating data, different proposals appear in the DS and correspondence analysis literature. It is shown here that a peculiarity of the DS method can be exploited to detect differences in response styles. Response styles occur when respondents use rating scales differently for reasons not related to the questions, often biasing results. A spline-based constrained version of DS is devised which can detect the presence of four prominent types of response styles, and is extended to allow for multiple response styles. An alternating nonnegative least squares algorithm is devised for estimating the parameters. The new method is appraised both by simulation studies and an empirical application.
Tape rolls are often used for multiple patients despite recommendations by manufacturers for single-patient use. We developed a survey to query Health Care Personnel about their tape use practices and beliefs and uncovered behaviors that put patients at risk for hospital-acquired infections due to tape use.