Syntrichia ruralis: emerging model moss genome reveals a conserved and previously unknown regulator of desiccation in flowering plants.

Water scarcity, resulting from climate change, poses a significant threat to ecosystems. Syntrichia ruralis, a dryland desiccation-tolerant moss, provides valuable insights into survival of water-limited conditions. We sequenced the genome of S. ruralis, conducted transcriptomic analyses, and performed comparative genomic and transcriptomic analyses with existing genomes and transcriptomes, including with the close relative S. caninervis. We took a genetic approach to characterize the role of an S. ruralis transcription factor, identified in transcriptomic analyses, in Arabidopsis thaliana. The genome was assembled into 12 chromosomes encompassing 21 169 protein-coding genes. Comparative analysis revealed copy number and transcript abundance differences in known desiccation-associated gene families, and highlighted genome-level variation among species that may reflect adaptation to different habitats. A significant number of abscisic acid (ABA)-responsive genes were found to be negatively regulated by a MYB transcription factor (MYB55) that was upstream of the S. ruralis ortholog of ABA-insensitive 3 (ABI3). We determined that this conserved MYB transcription factor, uncharacterized in Arabidopsis, acts as a negative regulator of an ABA-dependent stress response in Arabidopsis. The new genomic resources from this emerging model moss offer novel insights into how plants regulate their responses to water deprivation.

Multilayer depressive symptom networks in adults with bodily pain living in precarious housing or homelessness.

Housing insecurity is associated with co-occurring depression and pain interfering with daily activities. Network analysis of depressive symptoms along with associated risk or protective exposures may identify potential targets for intervention in patients with co-occurring bodily pain. In a community-based sample of adults (n = 408) living in precarious housing or homelessness in Vancouver, Canada, depressive symptoms were measured by the Beck Depression Inventory; bodily pain and impact were assessed with the 36-item Short Form Health Survey. Network and bootstrap permutation analyses were used to compare depressive symptoms endorsed by Low versus Moderate-to-Severe (Mod + Pain) groups. Multilayer networks estimated the effects of risk and protective factors. The overall sample was comprised of 78% men, mean age 40.7 years, with 53% opioid use disorder and 14% major depressive disorder. The Mod + Pain group was characterized by multiple types of pain, more persistent pain, more severe depressive symptoms and a higher rate of suicidal ideation. Global network connectivity did not differ between the two pain groups. Suicidal ideation was a network hub only in the Mod + Pain group, with high centrality and a direct association with exposure to lifetime trauma. Antidepressant medications had limited impact on suicidal ideation. Guilt and increased feelings of failure represented symptoms from two other communities of network nodes, and completed the shortest pathway from trauma exposure through suicidal ideation, to the non-prescribed opioid exposure node. Interventions targeting these risk factors and symptoms could affect the progression of depression among precariously housed patients.

Racial, ethnic, and socio-economic disparities in neonatal ICU admissions among neonates born with cyanotic CHD in the United States, 2009-2018.

INTRODUCTION: Disparities in CHD outcomes exist across the lifespan. However, less is known about disparities for patients with CHD admitted to neonatal ICU. We sought to identify sociodemographic disparities in neonatal ICU admissions among neonates born with cyanotic CHD. MATERIALS & METHODS: Annual natality files from the US National Center for Health Statistics for years 2009-2018 were obtained. For each neonate, we identified sex, birthweight, pre-term birth, presence of cyanotic CHD, and neonatal ICU admission at time of birth, as well as maternal age, race, ethnicity, comorbidities/risk factors, trimester at start of prenatal care, educational attainment, and two measures of socio-economic status (Special Supplemental Nutrition Program for Women, Infants, and Children [WIC] status and insurance type). Multivariable logistic regression models were fit to determine the association of maternal socio-economic status with neonatal ICU admission. A covariate for race/ethnicity was then added to each model to determine if race/ethnicity attenuate the relationship between socio-economic status and neonatal ICU admission. RESULTS: Of 22,373 neonates born with cyanotic CHD, 77.2% had a neonatal ICU admission. Receipt of WIC benefits was associated with higher odds of neonatal ICU admission (adjusted odds ratio [aOR] 1.20, 95% CI 1.1-1.29, p < 0.01). Neonates born to non-Hispanic Black mothers had increased odds of neonatal ICU admission (aOR 1.20, 95% CI 1.07-1.35, p < 0.01), whereas neonates born to Hispanic mothers were at lower odds of neonatal ICU admission (aOR 0.84, 95% CI 0.76-0.93, p < 0.01). CONCLUSION: Maternal Black race and low socio-economic status are associated with increased risk of neonatal ICU admission for neonates born with cyanotic CHD. Further work is needed to identify the underlying causes of these disparities.

Cardiac magnetic resonance predictors for successful primary biventricular repair of unbalanced complete common atrioventricular canal.

BACKGROUND: Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal. METHODS: We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve. RESULTS: We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle-right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle-right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026). CONCLUSIONS: Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle-right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.

Presence of ovarian stromal aberrations after cessation of testosterone therapy in a transgender mouse model†.

Some transmasculine individuals may be interested in pausing gender-affirming testosterone therapy and carrying a pregnancy. The ovarian impact of taking and pausing testosterone is not completely understood. The objective of this study was to utilize a mouse model mimicking transmasculine testosterone therapy to characterize the ovarian dynamics following testosterone cessation. We injected postpubertal 9-10-week-old female C57BL/6N mice once weekly with 0.9 mg of testosterone enanthate or a vehicle control for 6 weeks. All testosterone-treated mice stopped cycling and demonstrated persistent diestrus within 1 week of starting testosterone, while control mice cycled regularly. After 6 weeks of testosterone therapy, one group of testosterone-treated mice and age-matched vehicle-treated diestrus controls were sacrificed. Another group of testosterone-treated mice were maintained after stopping testosterone therapy and were sacrificed in diestrus four cycles after the resumption of cyclicity along with age-matched vehicle-treated controls. Ovarian histological analysis revealed stromal changes with clusters of large round cells in the post testosterone group as compared to both age-matched controls and mice at 6 weeks on testosterone. These clusters exhibited periodic acid-Schiff staining, which has been previously reported in multinucleated macrophages in aging mouse ovaries. Notably, many of these cells also demonstrated positive staining for macrophage markers CD68 and CD11b. Ovarian ribonucleic acid-sequencing found upregulation of immune pathways post testosterone as compared to age-matched controls and ovaries at 6 weeks on testosterone. Although functional significance remains unknown, further attention to the ovarian stroma may be relevant for transmasculine people interested in pausing testosterone to carry a pregnancy.

Improvement in Palivizumab Administration Prior to Discharge for Hospitalized Infants with Hemodynamically Significant Congenital Heart Disease: A Quality Improvement Initiative.

In this quality improvement initiative, we aimed to increase provider adherence with palivizumab administration guidelines for hospitalized infants with hemodynamically significant congenital heart disease. We included 470 infants over four respiratory syncytial virus (RSV) seasons from 11/2017 to 03/2021 (baseline season: 11/2017-03/2018). Interventions included the following: education, including palivizumab in the sign-out template, identifying a pharmacy expert, and a text alert (seasons 1 and 2: 11/2018-03/2020) that was replaced by an electronic health record (EHR) best practice alert (BPA) in season 3 (11/2020-03/2021). The text alert and BPA prompted providers to add "Need for RSV immunoprophylaxis" to the EHR problem list. The outcome metric was the percentage of eligible patients administered palivizumab prior to discharge. The process metric was the percentage of eligible patients with "Need for RSV immunoprophylaxis" on the EHR problem list. The balancing metric was the percentage of palivizumab doses administered to ineligible patients. A statistical process control P-chart was used to analyze the outcome metric. The mean percentage of eligible patients who received palivizumab prior to hospital discharge increased significantly from 70.1% (82/117) to 90.0% (86/96) in season 1 and to 97.9% (140/143) in season 3. Palivizumab guideline adherence was as high or higher for those with "Need for RSV immunoprophylaxis" on the problem list than for those without it in most time periods. The percentage of inappropriate palivizumab doses decreased from 5.7% (n = 5) at baseline to 4.4% (n = 4) in season 1 and 0.0% (n = 0) in season 3. Through this initiative, we improved adherence with palivizumab administration guidelines for eligible infants prior to hospital discharge.

Biomarkers, Socioeconomic Factors, and Right Ventricular Function After Surgical Repair for Tetralogy of Fallot.

Right ventricular (RV) dysfunction early after tetralogy of Fallot (TOF) increases post-operative morbidity. We investigated associations of circulating biomarkers and socioeconomic factors with early post-operative RV systolic function. Single-center prospective cohort study of infants undergoing TOF repair. Six serologic biomarkers of myocardial fibrosis and wall stress collected at the time of surgery were measured with immunoassay. Geocoding was performed for socioeconomic factors. Multivariate adaptive regression splines (MARS) models identified factors associated with RV function parameters: fractional area change (FAC), global longitudinal strain and strain rate, and free wall strain and strain rate. Seventy-one patients aged 3.5 months (IQR 2.4, 5.2) were included. Galectin-3 was the highest ranked predictor for FAC, global longitudinal strain, and free wall strain, and procollagen type-I carboxy-terminal propeptide (PICP) was the highest ranked predictor for global longitudinal strain rate and free wall strain rate. Several neighborhood characteristics were also highly ranked. Models adjusted R2 ranged from 0.71 to 0.85 (FAC, global longitudinal strain/strain rate), and 0.55-0.57 (RV free wall strain/strain rate). A combination of serologic biomarkers, socioeconomic, and clinical variables explain a significant proportion of the variability in RV function after TOF repair. These factors may inform pre-operative risk-stratification for these patients.

Association of race and ethnicity with resource utilisation among children with CHD: an evaluation of the National Health Interview Survey, 2010-2018.

INTRODUCTION: Racial and ethnic disparities in resource use among children with CHD remain understudied. We sought to evaluate associations between race, ethnicity, and resource utilisation in children with CHD. MATERIALS AND METHODS: Annual data from the National Health Interview Survey were collected for years 2010-2018. Children with self-reported CHD and Non-Hispanic White race, Non-Hispanic Black race, or Hispanic ethnicity were identified. Resource use in the preceding year was identified with four measures: primary place of care visited when sick, receiving well-child checkups, number of emergency department visits, and number of office visits. Cohort characteristics were compared across racial and ethnic groups using Kruskal-Wallis and Fisher's exact tests. Multivariable logistic regression was used to determine the association of race and ethnicity with likelihood of having an emergency department visit. RESULTS: We identified 209 children for the primary analysis. Non-Hispanic Black children had significantly more emergency department visits in the prior year, with 11.1% having ≥6 emergency department visits compared to 0.7% and 5.6% of Non-Hispanic White and Hispanic children. Further, 35.2% of Hispanic children primarily received care at clinics/health centres, compared to 17% of Non-Hispanic White children and 11.1% of Non-Hispanic Black children (p = 0.03). On multivariable analysis, Black race was associated with higher odds of emergency department visit compared to White race (odds ratio = 4.19, 95% confidence interval = 1.35 to 13.04, p = 0.01). CONCLUSION: In a nationally comprehensive, contemporary cohort of children with CHD, there were some significant racial and ethnic disparities in resource utilisation. Further work is needed to consider the role of socio-economics and insurance status in perpetuating these disparities.

Pre-existing anxiety and depression disorders and return to work after musculoskeletal strain or sprain: a phased-based approach.

PURPOSE: To examine the impact of pre-existing anxiety and depression disorders on return to work (RTW) using a phase-based approach. METHODS: Accepted lost-time workers' compensation claims for upper limb or spine strain or sprain from 2009 to 2013 were extracted for workers in the Canadian province of British Columbia (n = 78,186). Pre-existing anxiety and depression disorders were identified using health claims data. Probability of RTW following a first or second work lost-time episode was analyzed using Prentice, Williams and Peterson models for recurrent events (common hazards ratios (cHR)). Probability of a first lost-time recurrence was analyzed using Cox models (HR). All models included two years of follow up and were stratified by gender. RESULTS: For men, anxiety alone (cHR = 0.90, 95% CI: 0.85 to 0.94) or comorbid with depression (cHR = 0.95, 95% CI: 0.92 to 0.99) was significantly associated with a lower probability of RTW, and comorbid anxiety and depression with a higher probability of recurrence (HR = 1.29, 95% CI: 1.13 to 1.48). In women, comorbid anxiety and depression was significantly associated with a lower probability of RTW (cHR = 0.96, 95% CI: 0.93 to 0.99) and a higher probability of recurrence (HR = 1.15, 95% CI: 1.04 to 1.28); and anxiety alone with a higher probability of recurrence (HR = 1.25, 95% CI: 1.09 to 1.43). There was little evidence that depression alone was associated with RTW or recurrence. CONCLUSIONS: Workers with a pre-existing anxiety disorder may require additional supports both during lost-time and after initial RTW.

Continuation of telework in the post-pandemic era: Healthcare employees' preference and determinants.

Now in the post-pandemic era, healthcare employers and leaders must navigate decisions around use of telework arrangements made popular during the COVID-19 pandemic. Among healthcare employees who teleworked during the pandemic, this study investigates preference to continue teleworking post-pandemic and the determinants of this preference. An overwhelming majority (99%) preferred to continue teleworking to some degree and the majority (52%) preferred to telework for all work hours. Healthcare employers should consider that most employees who teleworked during the pandemic prefer to continue teleworking for most or all work hours, and that hybrid work arrangements are especially important for clinical telework employees. In addition to space and resource allocation, management considerations include supports to promote productivity, work-life balance, and effective virtual communication while teleworking to promote positive employee health, recruitment, and retention outcomes.

Dynamic networks of psychotic symptoms in adults living in precarious housing or homelessness.

BACKGROUND: People living in precarious housing or homelessness have higher than expected rates of psychotic disorders, persistent psychotic symptoms, and premature mortality. Psychotic symptoms can be modeled as a complex dynamic system, allowing assessment of roles for risk factors in symptom development, persistence, and contribution to premature mortality. METHOD: The severity of delusions, conceptual disorganization, hallucinations, suspiciousness, and unusual thought content was rated monthly over 5 years in a community sample of precariously housed/homeless adults (n = 375) in Vancouver, Canada. Multilevel vector auto-regression analysis was used to construct temporal, contemporaneous, and between-person symptom networks. Network measures were compared between participants with (n = 219) or without (n = 156) history of psychotic disorder using bootstrap and permutation analyses. Relationships between network connectivity and risk factors including homelessness, trauma, and substance dependence were estimated by multiple linear regression. The contribution of network measures to premature mortality was estimated by Cox proportional hazard models. RESULTS: Delusions and unusual thought content were central symptoms in the multilevel network. Each psychotic symptom was positively reinforcing over time, an effect most pronounced in participants with a history of psychotic disorder. Global connectivity was similar between those with and without such a history. Greater connectivity between symptoms was associated with methamphetamine dependence and past trauma exposure. Auto-regressive connectivity was associated with premature mortality in participants under age 55. CONCLUSIONS: Past and current experiences contribute to the severity and dynamic relationships between psychotic symptoms. Interrupting the self-perpetuating severity of psychotic symptoms in a vulnerable group of people could contribute to reducing premature mortality.

Delayed Opsoclonus-Myoclonus Syndrome After Ovarian Teratoma Resection.

ABSTRACT: Opsoclonus-myoclonus syndrome (OMS) is a rare syndrome characterized by opsoclonus, which is irregular, spontaneous, multivectorial saccadic eye movements, along with diffuse or focal myoclonus and sometimes ataxia. OMS is associated with paraneoplastic etiologies in 20%-40% of cases, with small-cell lung and breast cancers the most common associated primary neoplasms in adults, whereas neuroblastoma is more common in children and ovarian teratoma may occur in women younger than 30 years. Onconeural antibodies are often not identified. In existing literature, paraneoplastic OMS precedes identification of the neoplasm, and neurological recovery depends on treatment of the underlying cancer. We describe a 27-year-old woman with the delayed onset of OMS one month after resection of ovarian teratoma, likely due to immune trigger from antigen exposure at the time of resection. She was treated with intravenous methylprednisolone, immunoglobulins, and eventually rituximab with resolution of her symptoms. Identification of OMS after tumor resection and prompt immunotherapy are critical for neurologic recovery. At 30-month follow-up, this patient had not experienced recurrence of OMS.

Proteomic identification of select protein variants of the SNARE interactome associated with cognitive reserve in a large community sample.

Age-related neuropathologies progressively impair cognitive abilities by damaging synaptic function. We aimed to identify key components within the presynaptic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) machinery associated with cognitive performance and estimate their potential contribution to brain reserve in old age. We used targeted SRM proteomics to quantify amounts of 60 peptides, encoded in 30 different genes, in postmortem specimens of the prefrontal cortex from 1209 participants of two aging studies, with available antemortem cognitive evaluations and postmortem neuropathologic assessments. We found that select (but not all) proteoforms are strongly associated with cognitive function and the burden of Alzheimer's disease (AD) pathology. Specifically, greater abundance of STX1A (but not other syntaxins), SYT12, full-length SNAP25, and the GABAergic STXBP1 variant were robustly associated with better cognitive performance. By contrast, greater abundance of other presynaptic proteins (e.g., STXBP5 or tomosyn, STX7, or SYN2) showed a negative influence on cognition. Regression models adjusting for demographic and pathologic variables showed that altered levels of these protein species explained 7.7% additional between-subject variance in cognition (more than any individual age-related neuropathology in the model), suggesting that these molecules constitute key elements of brain reserve. Network analyses indicated that those peptides associated with brain reserve, and closest to the SNARE fusogenic activity, showed greater centrality measures and were better connected in the network. Validation assays confirmed the selective loss of the STX1A (but not STX1B) isoform in cognitively impaired cases. In rodent and human brains, STX1A was selectively located at glutamatergic terminals. However, in AD brains, STX1A was redistributed adjacent to neuritic pathology, and markedly expressed in astrocytes. Our study provides strong evidence, indicating that select presynaptic proteins are key in maintaining brain reserve. Compromised ability to sustain expression levels of these proteins may trigger synaptic dysfunction and concomitant cognitive impairment.

Prevalence and risk factors for anxiety and depression disorders in workers with work-related musculoskeletal strain or sprain in British Columbia, Canada: a comparison of men and women using administrative health data.

OBJECTIVE: To examine the prevalence and risk factors for medically treated anxiety and depression disorders among men and women with musculoskeletal strain or sprain work injury in British Columbia, Canada. METHODS: A retrospective population-based cohort of accepted workers' compensation lost-time claims from 2000 to 2013 was constructed using linked administrative health data. Anxiety and depression disorders were identified using diagnoses from physician, hospital and pharmaceutical records. The 1-year period prevalence was estimated for the year before and the year after injury. Sociodemographic, clinical and work-related risk factors for prevalent and new onset anxiety and depression disorders were examined using multinomial regression. RESULTS: 13.2% of men and 29.8% of women had medically treated anxiety, depression or both in the year before injury. Only a slight increase (~2%) in the prevalence of these disorders was observed in the year after injury. Somatic and mental comorbidities were both strong risk factors for pre-existing and new onset anxiety and depression for both men and women, but these relationships were stronger for men. CONCLUSION: Anxiety and depression disorders including those from prior to injury are common in workers with musculoskeletal strain or sprain and are associated with a complicated clinical profile. Gender-sensitive and sex-sensitive mental healthcare is an important consideration for work disability management.

Characterization of Bodily Pain and Use of Both Prescription and Non-Prescription Opioids in Tenants of Precarious Housing.

BACKGROUND: opioid use, which includes both prescribed and non-prescribed drugs, is relatively common amongst marginalized populations. Past research has shown that among those who use non-prescribed or diverted opioids recreationally, many were first exposed to the drug as prescribed pain medication. Objective: to better understand the relationship between pain and opioid use in tenants of precarious housing. Methods: in the present study, 440 individuals from a cohort living in homeless or precariously housed conditions in a neighborhood with high rates of poverty and drug use were interviewed for their bodily pain and opioid use. We examined the relationship between bodily pain levels, assessed using the Maudsley Addiction Profile questionnaire, and prescribed, non-prescribed and combined self-reported opioid use in the prior 28 days assessed using the Timeline Followback and Doctor-Prescribed Medication Timeline Followback questionnaires. Results: Analysis of the results indicated that sex (female), age (younger) and early exposure to opioids (≤ age 18) predicted current opioid use, but there was no association between current bodily pain levels and opioid use. Conclusions: these unexpected findings indicate the complex nature of the relationship between pain and opioid use in this population.

Engaging Community Networks to Improve Depression Services: A Cluster-Randomized Trial of a Community Engagement and Planning Intervention.

This paper explores the effects of a group-randomized controlled trial, Community Partners in Care (CPIC), on the development of interagency networks for collaborative depression care improvement between a community engagement and planning (CEP) intervention and a resources for services (RS) intervention that provided the same content solely via technical assistance to individual programs. Both interventions consisted of a diverse set of service agencies, including health, mental health, substance abuse treatment, social services, and community-trusted organizations such as churches and parks and recreation centers. Participants in the community councils for the CEP intervention reflected a range of agency leaders, staff, and other stakeholders. Network analysis of partnerships among agencies in the CEP versus RS condition, and qualitative analysis of perspectives on interagency network changes from multiple sources, suggested that agencies in the CEP intervention exhibited greater growth in partnership capacity among themselves than did RS agencies. CEP participants also viewed the coalition development intervention both as promoting collaboration in depression services and as a meaningful community capacity building activity. These descriptive results help to identify plausible mechanisms of action for the CPIC interventions and can be used to guide development of future community engagement interventions and evaluations in under-resourced communities.

Cerebral Small Vessel Disease, Risk Factors, and Cognition in Tenants of Precarious Housing.

BACKGROUND AND PURPOSE: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing. METHODS: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance. RESULTS: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3-63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05-1.15], P<0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01-1.09], P=0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07-9.16], P=0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain. CONCLUSIONS: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.

Associations of substance use, psychosis, and mortality among people living in precarious housing or homelessness: A longitudinal, community-based study in Vancouver, Canada.

BACKGROUND: The "trimorbidity" of substance use disorder and mental and physical illness is associated with living in precarious housing or homelessness. The extent to which substance use increases risk of psychosis and both contribute to mortality needs investigation in longitudinal studies. METHODS AND FINDINGS: A community-based sample of 437 adults (330 men, mean [SD] age 40.6 [11.2] years) living in Vancouver, Canada, completed baseline assessments between November 2008 and October 2015. Follow-up was monthly for a median 6.3 years (interquartile range 3.1-8.6). Use of tobacco, alcohol, cannabis, cocaine, methamphetamine, and opioids was assessed by interview and urine drug screen; severity of psychosis was also assessed. Mortality (up to November 15, 2018) was assessed from coroner's reports and hospital records. Using data from monthly visits (mean 9.8, SD 3.6) over the first year after study entry, mixed-effects logistic regression analysis examined relationships between risk factors and psychotic features. A past history of psychotic disorder was common (60.9%). Nonprescribed substance use included tobacco (89.0%), alcohol (77.5%), cocaine (73.2%), cannabis (72.8%), opioids (51.0%), and methamphetamine (46.5%). During the same year, 79.3% of participants reported psychotic features at least once. Greater risk was associated with number of days using methamphetamine (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.05-1.24, p = 0.001), alcohol (aOR 1.09, 95% CI 1.01-1.18, p = 0.04), and cannabis (aOR 1.08, 95% CI 1.02-1.14, p = 0.008), adjusted for demographic factors and history of past psychotic disorder. Greater exposure to concurrent month trauma was associated with increased odds of psychosis (adjusted model aOR 1.54, 95% CI 1.19-2.00, p = 0.001). There was no evidence for interactions or reverse associations between psychotic features and time-varying risk factors. During 2,481 total person years of observation, 79 participants died (18.1%). Causes of death were physical illness (40.5%), accidental overdose (35.4%), trauma (5.1%), suicide (1.3%), and unknown (17.7%). A multivariable Cox proportional hazard model indicated baseline alcohol dependence (adjusted hazard ratio [aHR] 1.83, 95% CI 1.09-3.07, p = 0.02), and evidence of hepatic fibrosis (aHR 1.81, 95% CI 1.08-3.03, p = 0.02) were risk factors for mortality. Among those under age 55 years, a history of a psychotic disorder was a risk factor for mortality (aHR 2.38, 95% CI 1.03-5.51, p = 0.04, adjusted for alcohol dependence at baseline, human immunodeficiency virus [HIV], and hepatic fibrosis). The primary study limitation concerns generalizability: conclusions from a community-based, diagnostically heterogeneous sample may not apply to specific diagnostic groups in a clinical setting. Because one-third of participants grew up in foster care or were adopted, useful family history information was not obtainable. CONCLUSIONS: In this study, we found methamphetamine, alcohol, and cannabis use were associated with higher risk for psychotic features, as were a past history of psychotic disorder, and experiencing traumatic events. We found that alcohol dependence, hepatic fibrosis, and, only among participants <55 years of age, history of a psychotic disorder were associated with greater risk for mortality. Modifiable risk factors in people living in precarious housing or homelessness can be a focus for interventions.

Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations.

X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor κB essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftment was documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57 months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlying mutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.

How can we help African American substance users stop smoking? client and agency perspectives.

Research is needed to better understand barriers to smoking cessation and sustained abstinence among racial/ethnic minority polydrug users. We conducted community dialogue groups involving 49 clients in substance use treatment programs with predominantly ethnic minority clientele and individual dialogues/interviews with seven program providers (stakeholders). Most clients were African American, under 40 years old, women, current smokers, and high school graduates. Smoking cessation services in these programs were considered inadequate and community programs insufficiently culturally tailored and economically and geographically inaccessible. Participants discussed individual "willpower" and choice; agency tobacco-related programs and policies; the relationships between smoking, smoking cessation, and treatment goals; and steps needed to reshape agency services and policies to provide greater support for smoking cessation in this at-risk population.