Quantifying sustained health system benefits of primary care-based integrated disease management for COPD: a 6-year interrupted time series study.

BACKGROUND: Severe exacerbation of chronic obstructive pulmonary disease (COPD) is a trajectory-changing life event for patients and a major contributor to health system costs. This study evaluates the real-world impact of a primary care, integrated disease management (IDM) programme on acute health service utilisation (HSU) in the Canadian health system. METHODS: Interrupted time series analysis using retrospective health administrative data, comparing monthly HSU event rates 3 years prior to and 3 years following the implementation of COPD IDM. Primary outcomes were COPD-related hospitalisation and emergency department (ED) visits. Secondary outcomes included hospital bed days and all-cause HSU. RESULTS: There were 2451 participants. COPD-related and all-cause HSU rates increased in the 3 years prior to IDM implementation. With implementation, there was an immediate decrease (month 1) in COPD-related hospitalisation and ED visit rates of -4.6 (95% CI: -7.76 to -1.39) and -6.2 (95% CI: -11.88, -0.48) per 1000 participants per month, respectively, compared with the counterfactual control group. After 12 months, COPD-related hospitalisation rates decreased: -9.1 events per 1000 participants per month (95% CI: -12.72, -5.44) and ED visits -19.0 (95% CI: -25.50, -12.46). This difference nearly doubled by 36 months. All-cause HSU also demonstrated rate reductions at 12 months, hospitalisation was -10.2 events per 1000 participants per month (95% CI: -15.79, -4.44) and ED visits were -30.4 (95% CI: -41.95, -18.78). CONCLUSIONS: Implementation of COPD IDM in a primary care setting was associated with a changed trajectory of COPD-related and all-cause HSU from an increasing year-on-year trend to sustained long-term reductions. This highlights a substantial real-world opportunity that may improve health system performance and patient outcomes.

A sparse factor model for clustering high-dimensional longitudinal data.

Recent advances in engineering technologies have enabled the collection of a large number of longitudinal features. This wealth of information presents unique opportunities for researchers to investigate the complex nature of diseases and uncover underlying disease mechanisms. However, analyzing such kind of data can be difficult due to its high dimensionality, heterogeneity and computational challenges. In this article, we propose a Bayesian nonparametric mixture model for clustering high-dimensional mixed-type (eg, continuous, discrete and categorical) longitudinal features. We employ a sparse factor model on the joint distribution of random effects and the key idea is to induce clustering at the latent factor level instead of the original data to escape the curse of dimensionality. The number of clusters is estimated through a Dirichlet process prior. An efficient Gibbs sampler is developed to estimate the posterior distribution of the model parameters. Analysis of real and simulated data is presented and discussed. Our study demonstrates that the proposed model serves as a useful analytical tool for clustering high-dimensional longitudinal data.

Joint clustering multiple longitudinal features: A comparison of methods and software packages with practical guidance.

Clustering longitudinal features is a common goal in medical studies to identify distinct disease developmental trajectories. Compared to clustering a single longitudinal feature, integrating multiple longitudinal features allows additional information to be incorporated into the clustering process, which may reveal co-existing longitudinal patterns and generate deeper biological insight. Despite its increasing importance and popularity, there is limited practical guidance for implementing cluster analysis approaches for multiple longitudinal features and evaluating their comparative performance in medical datasets. In this paper, we provide an overview of several commonly used approaches to clustering multiple longitudinal features, with an emphasis on application and implementation through R software. These methods can be broadly categorized into two categories, namely model-based (including frequentist and Bayesian) approaches and algorithm-based approaches. To evaluate their performance, we compare these approaches using real-life and simulated datasets. These results provide practical guidance to applied researchers who are interested in applying these approaches for clustering multiple longitudinal features. Recommendations for applied researchers and suggestions for future research in this area are also discussed.

Lung clearance index predicts persistence of preschool wheeze.

BACKGROUND: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50->80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool-aged children with LCI and determine its utility in predicting persistent wheeze. METHODS: LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF6  multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4 symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5 years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW). RESULTS: At age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z-score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p < .01), IS (mean (SD): -0.14 (0.59), p < .01), and NCS (mean (SD): -0.08 (1.06), p < .01). LCI z-score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87). CONCLUSIONS: LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.

Bayesian consensus clustering for multivariate longitudinal data.

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.

Risk for Maternal Depressive Symptoms and Perceived Stress by Ethnicities in Canada: From Pregnancy Through the Preschool Years.

OBJECTIVE: Past cross-sectional studies have reported that mothers from ethnic minorities experience higher levels of prenatal and post-partum psychosocial distress compared with mothers from ethnic majorities. However, no studies have examined how the pattern varies longitudinally in a Canadian population of heterogeneous ethnicity. METHODS: We analyzed data from 3,138 mothers participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a longitudinal multi-center study incorporating 10 distinct waves of psychosocial data collection from pregnancy until the index child was aged 5 y. Maternal self-identified ethnicity was grouped as White Caucasian, First Nations, Black, Southeast Asian, East Asian, South Asian, Middle Eastern, Hispanic and mixed ethnicity. We performed a multi-level regression to determine whether mothers of specific minority ethnicities were more likely to experience higher levels of distress (i.e. depressive symptoms and perceived stress) compared to white Caucasian mothers. RESULTS: Mothers self-identifying as Black or First Nations had consistently higher distress scores than mothers from other ethnicities across all data collection times. After adjusting for relevant variables (history of depression, education, household income, marital status, and social support), First Nations mothers had a 20% increase in the mean scores of depressive symptoms compared to White Caucasian Mothers. CONCLUSIONS: Increased levels of perinatal and post-partum distress were seen in only some ethnic minority groups. Studies should avoid collapsing all categories into ethnic minority or majority and may need to consider how ethnicity interacts with other sociodemographic factors such as poverty.

Family functioning among adolescents with narcolepsy.

BACKGROUND: Narcolepsy is a sleep disorder with no cure with onset typically during adolescence. Caring for an adolescent with a lifelong medical condition can negatively impact family structure, cohesion, relationships, and overall functioning. The primary objective of this study was to evaluate family functioning in a cohort of adolescents with narcolepsy using the PedsQL Family Impact Module. The secondary objective was to compare family functioning in adolescents with narcolepsy to adolescents with chronic pain based on published data. METHODS: This was a cross-sectional study of adolescents (aged 10 to 18 years) with narcolepsy. The narcolepsy group was recruited from The Hospital for Sick Children in Toronto, Canada. Family functioning was assessed by the PedsQL family impact module total scores, which was completed by the patient's caregiver. The PedsQL family impact module yields a total scale which encompasses parent health-related quality of life, daily activities, family relationships, communication, and worry subscales. Lower scores suggest poorer family functioning. Secondary data analyses were used to compare participants' family functioning to a cohort of adolescents with chronic pain. RESULTS: Thirty adolescents with narcolepsy participated (mean age=13.8 ± 2.2 years, 76.7% male). Family functioning was impaired in this cohort of adolescents with narcolepsy and similar to adolescents with chronic pain (64.0 ± 19.8 versus 64.7 ± 19.5; P=0.849). CONCLUSION: Family functioning is impaired in adolescents with narcolepsy. Clinical teams should assess family functioning at routine clinic visits by asking about concerns and challenges related to caring for an adolescent with narcolepsy and providing resources and support as needed.

Ventilation inhomogeneity in infants with recurrent wheezing.

BACKGROUND: The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing. OBJECTIVE: To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls. METHODS: This is a case-control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography. RESULTS: LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (-0.11 to 0.63) vs -0.58 (-0.79 to 0.36), p<0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (>1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05). CONCLUSIONS: Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.

Diagnosing atopic dermatitis in infancy: Questionnaire reports vs criteria-based assessment.

BACKGROUND: Persisting atopic dermatitis (AD) is known to be associated with more serious allergic diseases at later ages; however, making an accurate diagnosis during infancy is challenging. We assessed the diagnostic performance of questionnaire-based AD measures with criteria-based in-person clinical assessments at age 1 year and evaluated the ability of these diagnostic methods to predict asthma, allergic rhinitis and food allergies at age 5 years. METHODS: Data relate to 3014 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study who were directly observed in a clinical assessment by an experienced healthcare professional using the UK Working Party criteria. The majority (2221; 73.7%) of these children also provided multiple other methods of AD ascertainment: a parent reporting a characteristic rash on a questionnaire, a parent reporting the diagnosis provided by an external physician and a combination of these two reports. RESULTS: Relative to the direct clinical assessment, the area under the Receiver Operating Characteristic curve for a parental report of a characteristic rash, reported physician diagnosis and a combination of both were, respectively, 0.60, 0.69 and 0.70. The strongest predictor of asthma at 5 years was AD determined by criteria-based in-person clinical assessment followed by the combination of parental and physician report. CONCLUSIONS: These findings suggest that questionnaire data cannot accurately substitute for assessment by experienced healthcare professionals using validated criteria for diagnosis of atopic dermatitis. Combining the parental report with diagnosis by a family physician might sometimes be appropriate (eg to avoid costs of a clinical assessment).

Intermittent nocturnal hypoxia and metabolic risk in obese adolescents with obstructive sleep apnea.

PURPOSE: There is conflicting data regarding the independent associations of obstructive sleep apnea (OSA) with metabolic risk in obese youth. Previous studies have not consistently addressed central adiposity, specifically elevated waist to height ratio (WHtR), which is associated with metabolic risk independent of body mass index. OBJECTIVE: The objective of this study was to determine the independent effects of the obstructive apnea-hypopnea index (OAHI) and associated indices of nocturnal hypoxia on metabolic function in obese youth after adjusting for WHtR. METHODS: Subjects had standardized anthropometric measurements. Fasting blood included insulin, glucose, glycated hemoglobin, alanine transferase, and aspartate transaminase. Insulin resistance was quantified with the homeostatic model assessment. Overnight polysomnography determined the OAHI and nocturnal oxygenation indices. RESULTS: Of the 75 recruited subjects, 23% were diagnosed with OSA. Adjusting for age, gender, and WHtR in multivariable linear regression models, a higher oxygen desaturation index was associated with a higher fasting insulin (coefficient [standard error] = 48.076 [11.255], p < 0.001), higher glycated hemoglobin (coefficient [standard error] = 0.097 [0.041], p = 0.02), higher insulin resistance (coefficient [standard error] = 1.516 [0.364], p < 0.001), elevated alanine transferase (coefficient [standard error] = 11.631 [2.770], p < 0.001), and aspartate transaminase (coefficient [standard error] = 4.880 [1.444], p = 0.001). However, there were no significant associations between OAHI, glucose metabolism, and liver enzymes. CONCLUSION: Intermittent nocturnal hypoxia rather than the OAHI was associated with metabolic risk in obese youth after adjusting for WHtR. Measures of abdominal adiposity such as WHtR should be considered in future studies that evaluate the impact of OSA on metabolic health.

Prevalence of obstructive sleep apnea among obese toddlers and preschool children.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder estimated at 1-5% in the school-aged children. With the obesity prevalence reaching staggering rates globally, OSA in obese adolescents is estimated to be 4-5-folds higher than their lean peers. There is a paucity of data regarding obesity-related OSA in children 6 years and less. This is particularly relevant as OSA is associated with neurocognitive deficits. The aim of this study is to evaluate the prevalence of OSA among obese toddlers and preschool children and further to determine what other factors may be associated with the presence of OSA. METHODS: A retrospective study involving children ≤6 years, identified from two Canadian pediatric tertiary care centers who had an in-lab polysomnography (PSG). Obesity was defined by a BMI of > 95th percentile for age and gender or a z-score of > 2. OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was greater than 2 events per hour. RESULTS: There were 60 participants included; the mean age was 4.4 years (standard deviation [SD] ± 1.7), mean BMI z-score was 3.0 (SD ± 1.2). Of these, 22/60 (36.6%) had OSA. Compared with the non-OSA group, the OSA group had a higher Epworth sleepiness score (p = 0.03) and were more likely to snore (p = 0.01). CONCLUSION: Young obese children should be assessed for OSA. A history of snoring and daytime sleepiness may be useful indicators to facilitate triage for a PSG, especially in resource-limited settings.

Breastfeeding, maternal asthma and wheezing in the first year of life: a longitudinal birth cohort study.

The impact of breastfeeding on respiratory health is uncertain, particularly when the mother has asthma. We examined the association of breastfeeding and wheezing in the first year of life.We studied 2773 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Caregivers reported on infant feeding and wheezing episodes at 3, 6 and 12 months. Breastfeeding was classified as exclusive, partial (supplemented with formula or complementary foods) or none.Overall, 21% of mothers had asthma, 46% breastfed for at least 12 months and 21% of infants experienced wheezing. Among mothers with asthma, breastfeeding was inversely associated with infant wheezing, independent of maternal smoking, education and other risk factors (adjusted rate ratio (aRR) 0.52; 95% CI 0.35-0.77 for ≥12 versus <6 months breastfeeding). Compared with no breastfeeding at 6 months, wheezing was reduced by 62% with exclusive breastfeeding (aRR 0.38; 95% CI 0.20-0.71) and by 37% with partial breastfeeding supplemented with complementary foods (aRR 0.63; 95% CI 0.43-0.93); however, breastfeeding was not significantly protective when supplemented with formula (aRR 0.89; 95% CI 0.61-1.30). Associations were not significant in the absence of maternal asthma (p-value for interaction <0.01).Breastfeeding appears to confer protection against wheezing in a dose-dependent manner among infants born to mothers with asthma.

Impact of the End PJ Paralysis interventions on patient health outcomes at the participating hospitals in Alberta, Canada.

PURPOSE: Multiple hospitals in Alberta implemented the End PJ Paralysis - a multicomponent inpatient ambulation initiative aimed at preventing the adverse physical and psychological effects patients experience due to low mobility during admission. To inform a scale-up strategy, this study assessed the impact of the initiative based on select process and outcome measures. MATERIALS AND METHODS: Clinical and administrative data were obtained from the hospital Discharge Abstract Database, Research Electronic Data Capture (Redcaps), and Reporting and Learning System for Patient Safety. The variables explored were length of stay, inpatient falls, discharge disposition, pressure injury, patient ambulation, and patient dressed rates. We then used the Interrupted Time Series design for impact analysis. RESULTS: The analysis included discharge abstracts for 32,884 patients and the results showed significant improvements in outcomes at the participating units. The length of stay and inpatient falls were reduced immediately by 1.8 days (B2=-1.80, p = 0.044, 95% CI [-3.54, -0.05]), and 2.2 events (B2=-2.22, p = 005, 95% CI [-3.75, -0.69]). The percentage of patients discharged home increased overtime (B2=.39, p=.006, 95% CI [.11, .66]). Mobilization and dressed rates also improved. CONCLUSIONS: The findings imply the interventions safely mitigated the risk of immobility-induced complications, including deconditioning and hospital-acquired disability.

Immobility during hospitalization is endemic in hospitals and, without intervention, presents a significant risk of physiological deconditioning and subsequent adverse health outcomes, such as functional decline and hospital-acquired disability.This study elevates the importance of preserving functional capacity and dignity of hospitalized patients by encouraging them to get up, dress in personal clothes, and move as much possible.Function-focused initiatives, that include intentional patient ambulation, have the potential to mitigate the risk of immobility-induced deconditioning and other adverse outcomes, such as falls and pressure injury, in older adults.In this study, we have demonstrated the End PJ Paralysis had a positive impact on patient ambulation, length of stay, inpatient falls, and discharge disposition.The study also informed a proposed transformational roadmap to strengthen rehabilitation in the provincial health system and spread the initiative to all the major hospitals to potentially benefit more patients.

Identification of obstructive sleep apnea in children with obesity: A cluster analysis approach.

BACKGROUND: Obstructive sleep apnea (OSA) is a heterogeneous disorder with a prevalence of 25%-60% in children with obesity. There is a lack of diagnostic tools to identify those at high risk for OSA. METHOD: Children with obesity, aged 8-19 years old, were enrolled into an ongoing multicenter, prospective cohort study related to OSA. We performed k-means cluster analysis to identify clinical variables which could help identify obesity related OSA. RESULTS: In this study, 118 participants were included in the analysis; 40.7% were diagnosed with OSA, 46.6% were female and the mean (SD) body mass index (BMI) and age were 39.7 (9.6) Kg/m², and 14.4 (2.6) years, respectively. The mean (SD) obstructive apnea-hypopnea index (OAHI) was 11.0 (21.1) events/h. We identified two distinct clusters based on three clustering variables (age, BMI z-score, and neck-height ratio [NHR]). The prevalence of OSA in clusters 1 and 2, were 22.4% and 58.3% (p = 0.001), respectively. Children in cluster 2, in comparison to cluster 1, had higher BMI z-score (4.7 (1.1) versus 3.2 (0.7), p < 0.001), higher NHR (0.3 (0.02) versus 0.2 (0.01), p < 0.001) and were older (15.0 (2.2) versus 13.7 (2.9) years, p = 0.09), respectively. However, there were no significant differences in sex and OSA symptoms between the clusters. The results from hierarchical clustering were similar to k-means analysis suggesting that the resulting OSA clusters were stable to different analysis approaches. INTERPRETATION: BMI, NHR, and age are easily obtained in a clinical setting and can be utilized to identify children at high risk for OSA.

Predicting long-term survival after de novo cardioverter-defibrillator implantation for primary prevention: A population based study.

Background: Implantable cardioverter-defibrillators (ICDs) reduce the risk of sudden cardiac death in patients with left ventricular dysfunction. While short-term mortality benefit of ICD insertion has been established in landmark randomized controlled trials, little is known about the long-term outcomes of patients with ICDs in clinical practice. In this paper, we describe the long-term survival of patients following de novo ICD implantation for primary prevention in clinical practice and determine the factors which help predict survival after ICD implant. Methods: Retrospective population-based study of all patients receiving a de novo ICD for primary prevention in Ontario, Canada from 2007 to 2011 using the Ontario ICD Database housed within ICES. Simple random selection was used to split the population into a derivation and internal validation cohort in a ratio of 2:1. Cox proportional hazards regression was used to determine predictors of interest and predict 10-year survival, model performance was assessed using calibration and validation. Results: In the derivation cohort (n = 3399), mean age was 65.3 years (standard deviation [SD] = 11.0), 664 patients were female (19.5 %) and 2344 patients (69.0 %) had ischemic cardiomyopathy. Ten year survival was 45.7 % (95 % confidence interval [CI] 44.0 %-47.4 %). The final prediction model included age, sex, disease factors (ischemic vs nonischemic cardiomyopathy, left ventricular ejection fraction) and patient factors (symptoms, comorbidities), and biomarkers at the time of ICD assessment. This model had good discrimination and calibration in derivation (0.79, 95 % CI 0.77, 0.81) and validation samples (0.78, 95 % CI 0.76, 0.79). Conclusions: A combination of demographic and clinical factors determined at baseline can be used to predict 10-year survival in patients with implantable cardioverter-defibrillators with good accuracy. Our findings help to identify individuals at risk of long-term mortality and may be useful in targeting future prevention strategies to enhance longevity in this high-risk population.

Clinical phenotypes of cardiogenic shock survivors: insights into late host responses and long-term outcomes.

AIMS: An elevated risk of adverse events persists for years in cardiogenic shock (CS) survivors with high mortality rate and physical/mental disability. This study aims to link clinical CS-survivor phenotypes with distinct late host-response patterns at intensive care unit (ICU) discharge and long-term outcomes using model-based clustering. METHODS AND RESULTS: In the original prospective, observational, international French and European Outcome Registry in Intensive Care Units (FROG-ICU) study, ICU patients with CS on admission were identified (N = 228). Among them, 173 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct CS-survivor phenotypes at ICU discharge using 15 readily available clinical and laboratory variables. The primary endpoint was 1 year of mortality after ICU discharge. Secondary endpoints were readmission and physical/mental disability [short form-36 questionnaire (SF-36) score] within 1 year after ICU discharge. Two distinct phenotypes at ICU discharge were identified (A and B). Patients in Phenotype B (38%) were more anaemic and had higher circulating levels of lactate, sustained kidney injury, and persistent elevation in plasma markers of inflammation, myocardial fibrosis, and endothelial dysfunction compared with Phenotype A. They had also a higher rate of non-ischaemic origin of CS and right ventricular dysfunction on admission. CS survivors in Phenotype B had higher 1 year of mortality compared with Phenotype A (P = 0.045, Kaplan-Meier analysis). When adjusted for traditional risk factors (i.e. age, severity of illness, and duration of ICU stay), Phenotype B was independently associated with 1 year of mortality [adjusted hazard ratio = 2.83 (95% confidence interval 1.21-6.60); P = 0.016]. There was a significantly lower physical quality of life in Phenotype B patients at 3 months (i.e. SF-36 physical component score). CONCLUSIONS: A phenotype with sustained inflammation, myocardial fibrosis, and endothelial dysfunction at ICU discharge was identified from readily available data and was independently associated with poor long-term outcomes in CS survivors.

Longitudinal multisite study of the chronobiological control of chronic pain: the CircaHealth CircaPain study protocol.

INTRODUCTION: One in five Canadians lives with chronic pain. Evidence shows that some individuals experience pain that fluctuates in intensity following a circadian (24-hour) rhythm. Endogenous molecular rhythms regulate the function of physiological processes that govern pain mechanisms. Addressing chronic pain rhythmicity on a molecular and biopsychosocial level can advance understanding of the disease and identify new treatment/management strategies. Our CircaHealth CircaPain study uses an online survey combined with ecological momentary assessments and biosample collection to investigate the circadian control of chronic pain and identify potential biomarkers. Our primary objective is to understand interindividual variability in pain rhythmicity, by collecting biopsychosocial measures. The secondary objective accounts for seasonal variability and the effect of latitude on rhythmicity. METHODS AND ANALYSIS: Following completion of a baseline questionnaire, participants complete a series of electronic symptom-tracking diaries to rate their pain intensity, negative affect, fatigue and stress on a 0-10 scale at 8:00, 14:00 and 20:00 daily over 10 days. These measures are repeated at 6 and 12 months postenrolment to account for potential seasonal changes. We aim to recruit ≥2500 adults with chronic pain within Canada. Infrastructure is being developed to facilitate the collection of blood samples from subgroups of participants (~800) two times per day over 24-48 hours to identify rhythmic expression of circulating genes and/or proteins. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (File No. 6038114). Participants provide informed consent to participate, and their data will not be identifiable in any publication or report. Findings will be published in a relevant scientific journal and disseminated at scientific meetings and online webinars. We maintain a website to post updated resources and engage with the community. We employ knowledge mobilisation in the form of direct data sharing with participants.

Bayesian approaches to variable selection in mixture models with application to disease clustering.

In biomedical research, cluster analysis is often performed to identify patient subgroups based on patients' characteristics or traits. In the model-based clustering for identifying patient subgroups, mixture models have played a fundamental role in modeling. While there is an increasing interest in using mixture modeling for identifying patient subgroups, little work has been done in selecting the predictors that are associated with the class assignment. In this study, we develop and compare two approaches to perform variable selection in the context of a mixture model to identify important predictors that are associated with the class assignment. These two approaches are the one-step approach and the stepwise approach. The former refers to an approach in which clustering and variable selection are performed simultaneously in one overall model, whereas the latter refers to an approach in which clustering and variable selection are performed in two sequential steps. We considered both shrinkage prior and spike-and-slab prior to select the importance of variables. Markov chain Monte Carlo algorithms are developed to estimate the posterior distribution of the model parameters. Practical applications and simulation studies are carried out to evaluate the clustering and variable selection performance of the proposed models.

Peroxiredoxin 1 transfer during mating protects eupyrene sperm against oxdative stress in Grapholita molesta.

BACKGROUND: Each Grapholita molesta female only copulates once during its lifetime and thus must maintain the viability of stored eupyrene sperm for male reproductive success. The male ejaculate comprises abundant accessory gland proteins produced by the male accessory gland (AG), and many of which are major effectors for sperm storage and maintenance. RESULTS: Here, we reported that an antioxidant protein, peroxiredoxin 1 (GmolPrx1), secreted by the male AG, is essential for protecting eupyrene sperm from oxidative stress and maintaining their quality during storage in the female bursa copulatrix (BC). Our data showed that GmolPrx1 is highly expressed in the AG of sexually mature males. The GmolPrx1 protein is localized to the cytoplasm of AG cells and delivered to the female BC during mating. Knockdown of GmolPrx1 strongly decreased the fertility of mated females. Additionally, we evaluated oxidative status in the spermatophore of females and found that the content of hydrogen peroxide increased significantly after mating with GmolPrx1 knockdown males. Finally, the quality assessment of eupyrene sperm demonstrated that the plasma membrane integrity, acrosome integrity, and DNA integrity were all severely impaired in the spermatophore of females after mating with GmolPrx1 knockdown males, which may contribute to the fertility decline in males. CONCLUSION: Our current data demonstrated that activities of eupyrene sperm stored in females can be significantly impaired by enhanced oxidative stress through knocking down of GmolPrx1 in males. Our finding thus may further lay new foundations for the control of G. molesta through suppressing their populations by manipulating male reproductive genes. © 2023 Society of Chemical Industry.

Verbal learning, working memory, and attention/vigilance may be candidate phenotypes of bipolar II depression in Chinese Han nationality.

OBJECTIVES: Bipolar II depression (BD-II) is a subtype of bipolar disorder with recurrent depressive, manic, and frequent depressive episodes as the main clinical manifestations. This study aimed to compare the cognitive function of patients with BD-II with those of healthy siblings and controls to explore the internal phenotype of BD-II in the field of cognitive function. METHODS: 66 BD-II patients, 58 healthy siblings, and 55 healthy controls were assessed with the Trail Making Test (TMT), Digit Symbol Coding Test (DSCT), Category Fluency, Hopkins Verbal Learning Test-Revised (HVLTR), Brief Visuospatial Memory Test-Revised (BVMT-R), Wechsler Memory Scale 3rd ed. Spatial Span Subtest (WMS-III SS), Neuropsychological Assessment Battery Mazes (NABM), Continuous Performance Test, and Identical Pairs (CPT-IP). RESULTS: Patients with BD-II showed cognitive deficits in visual learning, reasoning and problem solving, verbal learning, attention/vigilance, working memory, and speed of processing. Healthy siblings showed cognitive deficits in reasoning and problem solving, verbal learning, attention/vigilance, working memory, and speed of processing. Substantial differences were observed among the three groups in reasoning and problem solving. CONCLUSIONS: Verbal learning, working memory, and attention/vigilance may be potential endophenotypes that can be used to identify BD-II among Han Chinese in the early stage.