Pilot study of a culturally adapted psychoeducation (CaPE) intervention for bipolar disorder in Pakistan.

Background: Despite the use of maintenance medication, recurrence rates in bipolar affective disorder (BPAD) are high. To date, there are no clinical trials that have investigated the use of psychological interventions in bipolar disorder in Pakistan. / Aim: The purpose of the study was to assess the feasibility and acceptability of a culturally adapted bipolar psychoeducation programme (CaPE) in Pakistan. / Methods: Thirty-four euthymic bipolar I and II outpatients were randomized to either 12 weekly sessions of individual psychoeducation plus Treatment As Usual (Intervention) or Treatment As Usual (TAU) (Control). Outcomes were assessed using the Young Mania Rating Scale (YMRS), Beck Depression Inventory (BDI), EuroQoL (EQ-5D), Bipolar Knowledge and Attitudes and Questionnaire (BKAQ), and a self-reported measure of medication adherence (Morisky Medication Adherence Scale-4 items, MMAS-4). Effect sizes were derived from baseline adjusted standardized regression coefficients. / Results: Retention in the study was good, 80% of patients in the TAU follow-up assessment and 100% of patients in the CaPE group attended all 12 sessions. Patient satisfaction was higher in the CaPE group relative to control (ES = 1.41). Further, there were large effect sizes shown for CaPE versus TAU for medication adherence (MMAS-4: ES = 0.81), knowledge and attitudes towards bipolar (BKAQ: ES = 0.68), mania (YMRS: ES = 1.18), depression (BDI: ES = 1.17) and quality of life measures (EQ-5D: ES ⇒ 0.88). / Conclusions: Culturally adapted psychoeducation intervention is acceptable and feasible, and can be effective in improving mood symptoms and knowledge and attitudes to BPAD when compared with TAU. Larger scale studies are needed to confirm our findings. / Trial registration. Clinicaltrials.gov identifier NCT0221039

Categorical Dimensions of Human Odor Descriptor Space Revealed by Non-Negative Matrix Factorization

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF) – a dimensionality reduction technique – to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures

The psychometric characteristics of the revised depression attitude questionnaire (R-DAQ) in Pakistani medical practitioners: a cross-sectional study of doctors in Lahore

BACKGROUND: Depression is common mental health problem and leading contributor to the global burden of disease. The attitudes and beliefs of the public and of health professionals influence social acceptance and affect the esteem and help-seeking of people experiencing mental health problems. The attitudes of clinicians are particularly relevant to their role in accurately recognising and providing appropriate support and management of depression. This study examines the characteristics of the revised depression attitude questionnaire (R-DAQ) with doctors working in healthcare settings in Lahore, Pakistan. METHODS: A cross-sectional survey was conducted in 2015 using the revised depression attitude questionnaire (R-DAQ). A convenience sample of 700 medical practitioners based in six hospitals in Lahore was approached to participate in the survey. The R-DAQ structure was examined using Parallel Analysis from polychoric correlations. Unweighted least squares analysis (ULSA) was used for factor extraction. Model fit was estimated using goodness-of-fit indices and the root mean square of standardized residuals (RMSR), and internal consistency reliability for the overall scale and subscales was assessed using reliability estimates based on Mislevy and Bock (BILOG 3 Item analysis and test scoring with binary logistic models. Mooresville: Scientific Software, 55) and the McDonald's Omega statistic. Findings using this approach were compared with principal axis factor analysis based on Pearson correlation matrix. RESULTS: 601 (86%) of the doctors approached consented to participate in the study. Exploratory factor analysis of R-DAQ scale responses demonstrated the same 3-factor structure as in the UK development study, though analyses indicated removal of 7 of the 22 items because of weak loading or poor model fit. The 3 factor solution accounted for 49.8% of the common variance. Scale reliability and internal consistency were adequate: total scale standardised alpha was 0.694; subscale reliability for professional confidence was 0.732, therapeutic optimism/pessimism was 0.638, and generalist perspective was 0.769. CONCLUSIONS: The R-DAQ was developed with a predominantly UK-based sample of health professionals. This study indicates that this scale functions adequately and provides a valid measure of depression attitudes for medical practitioners in Pakistan, with the same factor structure as in the scale development sample. However, optimal scale function necessitated removal of several items, with a 15-item scale enabling the most parsimonious factor solution for this population

Towards Eliminating Bias in Cluster Analysis of TB Genotyped Data

The relative contributions of transmission and reactivation of latent infection to TB cases observed clinically has been reported in many situations, but always with some uncertainty. Genotyped data from TB organisms obtained from patients have been used as the basis for heuristic distinctions between circulating (clustered strains) and reactivated infections (unclustered strains). Naïve methods previously applied to the analysis of such data are known to provide biased estimates of the proportion of unclustered cases. The hypergeometric distribution, which generates probabilities of observing clusters of a given size as realized clusters of all possible sizes, is analyzed in this paper to yield a formal estimator for genotype cluster sizes. Subtle aspects of numerical stability, bias, and variance are explored. This formal estimator is seen to be stable with respect to the epidemiologically interesting properties of the cluster size distribution (the number of clusters and the number of singletons) though it does not yield satisfactory estimates of the number of clusters of larger sizes. The problem that even complete coverage of genotyping, in a practical sampling frame, will only provide a partial view of the actual transmission network remains to be explored

Association between antipsychotics and weight gain among psychiatric outpatients in Pakistan: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>It has been known for a long time that use of antipsychotics, particularly atypical antipsychotics, is associated with weight gain and increase in risk of metabolic disturbances. In this study we have tried to find out if use of antipsychotics is associated with increase in weight and body mass index (BMI) in the Pakistani population.</p> <p>Methods</p> <p>We performed a case note review of all patients who had been prescribed antipsychotic medication at the psychiatry outpatient clinic of a tertiary care university hospital in Pakistan over a 4-year period.</p> <p>Results</p> <p>A total of 50% of patients had a BMI in the overweight or higher range at baseline. Patients showed a mean weight gain of 1.88 kg from baseline in 3 months and 3.29 kg in 6 months. Both of these values were statistically significant. The increase in mean BMI from baseline was 0.74 and 1.3 in 3 months and 6 months, respectively. In patients for whom we had at least one further weight measurement after baseline, 48% (39/81) showed a clinically significant weight gain.</p> <p>Conclusion</p> <p>Pakistani patients are just as likely to put on weight during antipsychotic treatment as patients from other countries. Considering that this population already has a much higher prevalence of diabetes mellitus compared to the Western countries, the consequences of increased weight may be even more serious in terms of increased morbidity and mortality.</p

Transcriptomics and proteomics reveal distinct biology for lymph node metastases and tumour deposits in colorectal cancer

Both lymph node metastases (LNMs) and tumour deposits (TDs) are included in colorectal cancer (CRC) staging, although knowledge regarding their biological background is lacking. This study aimed to compare the biology of these prognostic features, which is essential for a better understanding of their role in CRC spread. Spatially resolved transcriptomic analysis using digital spatial profiling was performed on TDs and LNMs from 10 CRC patients using 1,388 RNA targets, for the tumour cells and tumour microenvironment. Shotgun proteomics identified 5,578 proteins in 12 different patients. Differences in RNA and protein expression were analysed, and spatial deconvolution was performed. Image-based consensus molecular subtype (imCMS) analysis was performed on all TDs and LNMs included in the study. Transcriptome and proteome profiles identified distinct clusters for TDs and LNMs in both the tumour and tumour microenvironment segment, with upregulation of matrix remodelling, cell adhesion/motility, and epithelial-mesenchymal transition (EMT) in TDs (all p < 0.05). Spatial deconvolution showed a significantly increased abundance of fibroblasts, macrophages, and regulatory T-cells (p < 0.05) in TDs. Consistent with a higher fibroblast and EMT component, imCMS classified 62% of TDs as poor prognosis subtype CMS4 compared to 36% of LNMs (p < 0.05). Compared to LNMs, TDs have a more invasive state involving a distinct tumour microenvironment and upregulation of EMT, which are reflected in a more frequent histological classification of TDs as CMS4. These results emphasise the heterogeneity of locoregional spread and the fact that TDs should merit more attention both in future research and during staging. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

<p>Abstract</p> <p>Background</p> <p>Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid) injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal). These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability.</p> <p>Methods</p> <p>In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively) or placebo (NCT#00590577). Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS) score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity) using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE) rates and relative risks (RR) with 95% confidence intervals (CI) versus placebo were determined.</p> <p>Results</p> <p>Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS) mean PANSS total score at Day 8 (p = 0.037). After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo) and Day 36 (p < 0.001). Taken together with results in the 39 mg and 234 mg Day 8 arms, these findings suggest a trend towards a dose-dependent response. During Days 1 to 7, AEs reported in ≥2% of paliperidone palmitate subjects (234 mg) and a greater proportion of paliperidone palmitate than placebo subjects were: agitation (3.2% vs. 1.3%; RR 2.52 [95% CI 0.583, 10.904]), headache (4.0% vs. 3.8%; RR 1.06 [95% CI 0.433, 2.619]), and injection site pain (6.7% vs. 3.8%; RR 1.79 [95% CI 0.764, 4.208]). Days 8 to 36 AEs meeting the same criteria in the 156 mg Day 8 arm were: anxiety (3.1% vs. 2.5%; RR 1.24 [95% CI 0.340, 4.542]), psychotic disorder (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), dizziness (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), and injection site pain (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]). Corresponding Days 8 to 36 AEs in the 39 mg Day 8 group were: agitation (4.5% vs. 4.4%; RR 1.03 [95% CI 0.371, 2.874]), anxiety (3.9% vs. 2.5%; RR 1.55 [95% CI 0.446, 5.381]), and psychotic disorder (2.6% vs. 1.3%; RR 2.07 [95% CI 0.384, 11.110]) while in the 234 mg Day 8 group it was anxiety (3.1% vs. 2.5%, RR 1.25 [95% CI 0.342, 4.570]).</p> <p>Conclusions</p> <p>Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1) compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose-dependent response. No unexpected tolerability findings were noted in the first week or month after the initiation dosing.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT#00590577">NCT#00590577</a></p

Hippocampal Volume Reduction in Congenital Central Hypoventilation Syndrome

Children with congenital central hypoventilation syndrome (CCHS), a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI) scans, with impaired responses in specific hippocampal regions, suggesting localized injury