Latent human herpesvirus 6 is reactivated in CAR T cells.

Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6)1. Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4+ T cells. Using single-cell sequencing, we identify a rare population of HHV-6 'super-expressors' (about 1 in 300-10,000 cells) that possess high viral transcriptional activity, among research-grade allogeneic chimeric antigen receptor (CAR) T cells. By analysing single-cell sequencing data from patients receiving cell therapy products that are approved by the US Food and Drug Administration2 or are in clinical studies3-5, we identify the presence of HHV-6-super-expressor CAR T cells in patients in vivo. Together, the findings of our study demonstrate the utility of comprehensive genomics analyses in implicating cell therapy products as a potential source contributing to the lytic HHV-6 infection that has been reported in clinical trials1,6-8 and may influence the design and production of autologous and allogeneic cell therapies.

Reflecting on parental insights into healthy lifestyles: a qualitative study.

BACKGROUND: Children living in the most deprived regions are more than twice as likely as their affluent peers to be obese. One way we can explain the social gradient of health (determined by relative position on the scale of social disadvantage or advantage) is by identifying the barriers and drivers to health that different groups of people experience. This study explored the understanding and perceptions of (and barriers and drivers to) a healthy lifestyle to investigate how commissioned services can better support residents to enable behaviour change in an area of high social deprivation. This community engagement activity was also conducted to inform commissioning decisions in children's public health services. METHODS: We used a qualitative study design with a semi-structured interview schedule. Four focus groups (5-8 participants, n=26) were conducted in an area of high deprivation in northwest England. Parents or carers were invited to attend anonymously by the Public Health Community Engagement Officer (in June 2022). The inclusion criteria were previous attendance on a weight management programme. Data were analysed using thematic analysis. Engagement activities do not require ethics approval. All participants provided written informed consent to take part. No further information was collected about personal characteristics. FINDINGS: The study participants demonstrated an awareness and understanding of factors affecting child and family health and health behaviours: healthy eating, exercise, mental health and emotional wellbeing, family values and attitudes towards a healthy lifestyle, cooking and budgeting, wider social connections, access to open spaces, availability of local activities, costs (including hidden costs), and structural barriers. INTERPRETATION: Using the finding that participants recognise barriers and drivers to behaviour change beyond knowledge and skills, we reflect on why there was no take up for a commissioned intervention that aimed to address childhood obesity in the Lancashire area. These reflections inform arguments for an alternative model of service commission that relies less on established randomised trial evidence base and more on participatory codesign and a place-based approach (working with populations' existing knowledge and skills) and is particularly sensitive to people's own perception of the specific drivers and barriers they experience to behaviour change. Limitations include sampling from an area with low diversity and selection of participants who have previously agreed to uptake a weight management intervention. FUNDING: None.

The role of the multiple Index of deprivation in predicting mental health outcomes after the COVID-19 pandemic in adolescents: a cross-sectional study.

BACKGROUND: The number of children and young people (CYP) diagnosed with mental health problems has increased over the past decade. The COVID-19 pandemic also has accelerated this increase, raising significant concerns about adolescent emotional wellbeing. Research suggests that adolescents who live in more deprived areas are more likely to experience poor emotional wellbeing. Children in the northwest of England are among those with the poorest outcomes in the UK. We aimed to investigate the association between deprivation and mental health outcomes from 2019 to 2022. The aim was to support local authorities with targeted provision of public health services as well as predicting service need for 2022 onwards. METHODS: In this cross-sectional study, we analysed routinely collected Schools Health Needs Assessment (SHNA) data. The School Health Needs Assessment dataset contained 32 676 responses from Year 6 (ages 10-11 years) and Year 9 (ages 13-14 years) who completed the annual survey in 2019-22. The questionnaire was offered to all mainstream schools, delivered by the public health school nursing service. Index of multiple deprivation (IMD) data were provided for household postcodes. Data were analysed using IBM SPSS. Factor analysis created a composite emotional wellbeing scale (EWS) and estimates generated by school year (Years 6 and 9) and three academic years (2019-22). We calculated correlations between IMD and EWS overall and within school and academic year samples. FINDINGS: The final total sample across the three consecutive survey years and the two school years was 32 659. The sample consisted of 15 932 (49%) female students and 5066 (16%) students who registered at school as from an ethnic minority. Of the total sample, 9209 (28%) lived in a postcode in the most deprived IMD quintile in England. There was an overall decrease in EWS from Year 6 to Year 9 and from 2019 to 2022. The Year 6 students in 2022 reported mean levels of EWS equivalent to Year 9 students in 2019 indicating a shift toward poorer mental health in younger children. The correlational analyses showed no significant associations between IMD and EWS scores within the school or academic year cohorts. A follow-up analysis of children in receipt or not in receipt of free school meals also showed no significant association with EWS scores. INTERPRETATION: Findings showed that the emotional wellbeing of children and young people in the northwest of England has deteriorated since 2019, with greatest changes observed in the younger cohort of children in Year 6. This was not explained by postcode-based indices of multiple deprivation. Although it is recognised that deprivation is both a cause and a result of poor mental health, policy decisions on service provision for children and young people should not be based solely on IMD or receipt of free school meals. A rapid response is required to address the decline in emotional wellbeing currently observed in younger children of the northwest of England. FUNDING: None.

Experiences of Aging with Opioid Use Disorder and Comorbidity in Opioid Treatment Programs: A Qualitative Analysis.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder treatment and addresses the intersectional stigma this population has experienced in healthcare settings.

Variation in Receipt of Cancer Screening and Immunizations by 10-year Life Expectancy among U.S. Adults aged 65 or Older in 2019.

IMPORTANCE: The likelihood of benefit from a preventive intervention in an older adult depends on its time-to-benefit and the adult's life expectancy. For example, the time-to-benefit from cancer screening is >10 years, so adults with <10-year life expectancy are unlikely to benefit. OBJECTIVE: To examine receipt of screening for breast, prostate, or colorectal cancer and receipt of immunizations by 10-year life expectancy. DESIGN: Analysis of 2019 National Health Interview Survey. PARTICIPANTS: 8,329 non-institutionalized adults >65 years seen by a healthcare professional in the past year, representing 46.9 million US adults. MAIN MEASURES: Proportions of breast, prostate, and colorectal cancer screenings, and immunizations, were stratified by 10-year life expectancy, estimated using a validated mortality index. We used logistic regression to examine receipt of cancer screening and immunizations by life expectancy and sociodemographic factors. KEY RESULTS: Overall, 54.7% of participants were female, 41.4% were >75 years, and 76.4% were non-Hispanic White. Overall, 71.5% reported being current with colorectal cancer screening, including 61.4% of those with <10-year life expectancy. Among women, 67.0% reported a screening mammogram in the past 2 years, including 42.8% with <10-year life expectancy. Among men, 56.8% reported prostate specific antigen screening in the past two years, including 48.3% with <10-year life expectancy. Reported receipt of immunizations varied from 72.0% for influenza, 68.8% for pneumococcus, 57.7% for tetanus, and 42.6% for shingles vaccination. Lower life expectancy was associated with decreased likelihood of cancer screening and shingles vaccination but with increased likelihood of pneumococcal vaccination. CONCLUSIONS: Despite the long time-to-benefit from cancer screening, in 2019 many US adults age >65 with <10-year life expectancy reported undergoing cancer screening while many did not receive immunizations with a shorter time-to-benefit. Interventions to improve individualization of preventive care based on older adults' life expectancy may improve care of older adults.

Detection of chromosomal alteration after infusion of gene-edited allogeneic CAR T cells.

A chromosome 14 inversion was found in a patient who developed bone marrow aplasia following treatment with allogeneic chimeric antigen receptor (CAR) Tcells containing gene edits made with transcription activator-like effector nucleases (TALEN). TALEN editing sites were not involved at either breakpoint. Recombination signal sequences (RSSs) were found suggesting recombination-activating gene (RAG)-mediated activity. The inversion represented a dominant clone detected in the context of decreasing absolute CAR Tcell and overall lymphocyte counts. The inversion was not associated with clinical consequences and wasnot detected in the drug product administered to this patient or in any drug product used in this or other trials using the same manufacturing processes. Neither was the inversion detected in this patient at earlier time points or in any other patient enrolled in this or other trials treated with this or other product lots. This case illustrates that spontaneous, possibly RAG-mediated, recombination events unrelated to gene editing can occur in adoptive cell therapy studies, emphasizes the need for ruling out off-target gene editing sites, and illustrates that other processes, such as spontaneous V(D)J recombination, can lead to chromosomal alterations in infused cells independent of gene editing.

Neuroimaging-Derived Predicted Brain Age and Alcohol Use Among Community-Dwelling Older Adults.

OBJECTIVES: Observational studies have suggested that moderate alcohol use is associated with reduced risk of dementia. However, the nature of this association is not understood. We investigated whether light to moderate alcohol use may be associated with slower brain aging, among a cohort of older community-dwelling adults using a biomarker of brain age based on structural neuroimaging measures. DESIGN: Cross-sectional observational study. PARTICIPANTS: Well-characterized members of a longitudinal cohort study who underwent neuroimaging. We categorized the 163 participants (mean age 76.7 ± 7.7, 60% women) into current nondrinkers, light drinkers (1-7 drinks/week) moderate drinkers (>7-14 drinks/week), or heavier drinkers (>14 drinks/week). MEASUREMENTS: We calculated brain-predicted age using structural MRIs processed with the BrainAgeR program, and calculated the difference between brain-predicted age and chronological age (brain-predicted age difference, or brain-PAD). We used analysis of variance to determine if brain-PAD differed across alcohol groups, controlling for potential confounders. RESULTS: Brain-PAD differed across alcohol groups (F[3, 150] = 4.02; p = 0.009) with heavier drinkers showing older brain-PAD than light drinkers (by about 6 years). Brain-PAD did not differ across light, moderate, and nondrinkers. Similar results were obtained after adjusting for potentially mediating health-related measures, and after excluding individuals with a history of heavier drinking. DISCUSSION: Among this sample of healthy older adults, consumption of more than 14 drinks/week was associated with a biomarker of advanced brain aging. Light and moderate drinking was not associated with slower brain aging relative to non-drinking.

Trends in past-month cannabis use among US adults across a range of disabilities and health conditions, 2015-2019.

INTRODUCTION: While there is increasing interest in the use of cannabis to manage a range of health-related symptoms, little is known about trends in recent cannabis use with respect to various health conditions. METHODS: We examined data from a US representative sample of noninstitutionalized adults age ≥ 18 from the 2015-2019 National Survey on Drug Use and Health (N = 214,505). We estimated the pooled prevalences followed by linear time trends, overall, and by disability (i.e., difficulty hearing, seeing, thinking, walking, dressing, doing errands) and lifetime (i.e., bronchitis, cancer, diabetes, hepatitis, kidney disease) and current (i.e., asthma, depression, heart disease, hypertension) health condition status using logistic regression. Models with year-by-condition status interaction terms were used to assess differential time trends, adjusting for demographic characteristics. RESULTS: From 2015 to 2019, cannabis use increased significantly among adults with and without each disability and health condition examined. However, the increase was more rapid among those with (versus without) difficulty hearing (89.8% increase [4.9% to 9.3%] vs. 37.9% increase [8.7% to 12.0%], p = 0.015), difficulty walking (84.1% increase [6.3% to 11.6%] vs. 36.8% increase [8.7% to 11.9%], p < 0.001), 2-3 impairments (75.3% increase [9.3% to 16.3%] vs. 36.6% increase [8.2% to 11.2%], p = 0.041), and kidney disease (135.3% increase [3.4% to 8.0%] vs. 38.4% increase [8.6% to 11.9%], p = 0.045). CONCLUSION: Given the potential adverse effects of cannabis, prevention and harm reduction efforts should focus on groups at increasingly higher risk for use, including those with disabilities and kidney disease.

Cannabis use for Sleep Disturbance Among Older Patients in a Geriatrics Clinic.

Cannabis use is growing among older adults to manage medical concerns including poor sleep. In this study, we characterized how patients seen at a geriatrics clinic use cannabis to address sleep disturbance. Specifically, we conducted an anonymous survey of 568 adults, including 83 who reported cannabis use within the past 3 years, to inquire about such use. We compared cannabis use characteristics between those using it for sleep disturbance versus all other conditions. We considered a p-value <.10 to be statistically significant. Among the cannabis users in our sample, 29% reported using cannabis for sleep disturbance (N = 24). They were more likely than other users to be female (p = .07), consume cannabis more frequently (p = .01), use products containing tetrahydrocannabinol (THC) (vs. cannabidiol [CBD]-only; p < .01), and use cannabis to target more symptoms (p < .01). As cannabis use continues to grow in older populations, it is essential to delineate better how cannabis may be used safely and effectively to improve older adults' sleep health.

Race, class, caste, disability, sterilisation and hysterectomy.

This interdisciplinary historical paper focuses on the past and current state of diverse forms of surgical hysterectomy as a global phenomenon relating to population control and sterilisation. It is a paper grounded in historical inquiry but is unconventional relative to the norms of historical scholarship both in its wide geographical scope informed by the methodologies of global and intercultural history, in its critique of current clinical practices informed by recent feminist, race, biopolitical and disability studies, and by its engagement with scholarship in health sociology and medical anthropology which has focused on questions of gender and healthcare inequalities. The first part of the paper surveys existing medical, social-scientific and humanistic research on the racial, class, disability and caste inequalities which have emerged in the recent global proliferation of hysterectomy; the second part of the paper is about the diverse global rationales underlying radical gynaecological surgeries as a form of sterilisation throughout the long twentieth century. Radical gynaecological surgeries have been promoted for several different purposes throughout their history and, of course, are sometimes therapeutically necessary. However, they have often disproportionately impacted the most disadvantaged groups in several different global societies and have frequently been concentrated in populations that are already maligned on the basis of race, ethnicity, age, criminality, disability, gender deviation, lower class, caste or poverty. This heritage continues to inform current practices and contributes to ongoing global inequalities of healthcare.

Effects of switching from a metered dose inhaler to a dry powder inhaler on climate emissions and asthma control: post-hoc analysis.

OBJECTIVE: To compare the effects of switching from a pressurised metered dose inhaler (pMDI)-based to a dry powder inhaler (DPI)-based maintenance therapy versus continued usual care on greenhouse gas emissions (carbon dioxide equivalents, CO2e) and asthma control. METHODS: This post-hoc analysis was based on a subset of 2236 (53%) patients from the Salford Lung Study in Asthma who at baseline were using a pMDI-based controller therapy. During the study patients were randomised to fluticasone furoate/vilanterol (FF/VI) via the ELLIPTA DPI (switched from pMDI to DPI) (n=1081) or continued their usual care treatment (n=1155), and were managed in conditions close to everyday clinical practice. Annual CO2e (kg) was calculated for the total number of maintenance and rescue inhalers prescribed. Asthma control was assessed by the proportion of ACT responders (composite of ACT total score ≥20 and/or increase from baseline ≥3). RESULTS: The groups were well matched for demographic characteristics and baseline Asthma Control Test (ACT) total score (mean age: 49 years; mean ACT score: usual care, 16.6; FF/VI, 16.5). Annual CO2e kg per patient (maintenance plus rescue therapy) was significantly lower with FF/VI DPI treatment ('switch' group) than usual care (least squares geometric mean 108 kg (95% CI 102 to 114) vs 240 kg (95% CI 229 to 252), p<0.001). Asthma control was consistently superior over the 12 months in the FF/VI DPI group compared with usual care. CONCLUSIONS: Patients switching from a pMDI-based to a DPI-based maintenance therapy more than halved their inhaler carbon footprint without loss of asthma control. The remaining inhaler carbon footprint could be reduced through switches from pMDI to DPI rescue medications or alternative lower-carbon footprint rescue inhalers if available. Asthma control improved in both groups, with greater control demonstrated in those initiated on FF/VI DPI. TRIAL REGISTRATION NUMBER: NCT01706198.

Circumstances of Suicide Among Lesbian, Gay, Bisexual and Transgender Individuals.

INTRODUCTION: Suicide rates for sexual minorities are higher than the heterosexual population. The purpose of this study is to explore circumstances surrounding suicide completion to inform future intervention strategies for suicide among lesbian, gay, bisexual and transgender (LGBT) individuals. MATERIALS AND METHODS: We completed a retrospective analysis of data from the National Violent Death Reporting System (NVDRS) from 2013-2017. Victims identified as transgender were considered separately. We stratified analysis by identified sex of the victim for the LGB population. RESULTS: Of the 16,831 victims whose sexual orientation or transgender status was known: 3886 (23.1%) were identified as female, 12,945 (76.9%) were identified as male. 479 (2.8%) were identified as LGBT; of these, 53 (11%) were transgender. LGBT victims were younger than non-LGBT victims. Male LGB victims were more likely to have a history of prior suicide attempts, past or current mental illness diagnosis, and were less likely to use firearms than male heterosexual victims. Female LGB victims were more likely to have problems in an intimate partner relationship than heterosexual women, while LGB men were more likely to have problems in family or other relationships. Transgender victims were again more likely to have mental health problems and a history of prior attempts, but less likely to have intimate partner problems and more likely to have a history of child abuse. CONCLUSIONS: These results highlight the importance of promoting suicide interventions that recognize the complex intersection between stated gender, sex, and sexuality and the different cultural impacts these identities can have.

Identification and validation of genetic variants predictive of gait in standardbred horses.

Several horse breeds have been specifically selected for the ability to exhibit alternative patterns of locomotion, or gaits. A premature stop codon in the gene DMRT3 is permissive for "gaitedness" across breeds. However, this mutation is nearly fixed in both American Standardbred trotters and pacers, which perform a diagonal and lateral gait, respectively, during harness racing. This suggests that modifying alleles must influence the preferred gait at racing speeds in these populations. A genome-wide association analysis for the ability to pace was performed in 542 Standardbred horses (n = 176 pacers, n = 366 trotters) with genotype data imputed to ~74,000 single nucleotide polymorphisms (SNPs). Nineteen SNPs on nine chromosomes (ECA1, 2, 6, 9, 17, 19, 23, 25, 31) reached genome-wide significance (p < 1.44 x 10-6). Variant discovery in regions of interest was carried out via whole-genome sequencing. A set of 303 variants from 22 chromosomes with putative modifying effects on gait was genotyped in 659 Standardbreds (n = 231 pacers, n = 428 trotters) using a high-throughput assay. Random forest classification analysis resulted in an out-of-box error rate of 0.61%. A conditional inference tree algorithm containing seven SNPs predicted status as a pacer or trotter with 99.1% accuracy and subsequently performed with 99.4% accuracy in an independently sampled population of 166 Standardbreds (n = 83 pacers, n = 83 trotters). This highly accurate algorithm could be used by owners/trainers to identify Standardbred horses with the potential to race as pacers or as trotters, according to the genotype identified, prior to initiating training and would enable fine-tuning of breeding programs with designed matings. Additional work is needed to determine both the algorithm's utility in other gaited breeds and whether any of the predictive SNPs play a physiologically functional role in the tendency to pace or tag true functional alleles.

Alcohol use and cognitive performance: a comparison between Greece and the United States.

OBJECTIVES: To examine associations between alcohol use and cognitive performance among older adults in Greece and the United States, and assess potential differences due to differing drinking practices in the two countries. METHODS: Data came from Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) and National Alzheimer's Coordinating Center Uniform Dataset (NACC). We examined those aged 65-90 years at baseline who had no cognitive impairment and complete data for cognitive and alcohol use variables (N = 1110 from HELIAD; N = 2455 from NACC). We examined associations between current alcohol use and frequency of such use with cognitive performance on various cognitive tasks stratified by gender. RESULTS: In NACC, use of alcohol was associated with better cognitive performance. Men drinkers performed better than non-drinkers on Trail A (standardized mean 0.07 vs. -0.24, p<.001), Trail B (0.06 vs. -0.19, p=.001), and women drinkers performed better on Trail A (0.04 vs. -0.09, p=.016), Trail B (0.04 vs. -0.10, p=.005), verbal fluency (Animals: 0.05 vs. -0.13, p<.001; Vegetables: 0.04 vs. -0.09, p=.027), and MoCA (0.03 vs. -0.08, p=.039). In HELIAD, fewer differences were seen with only women drinkers exhibiting better performance than non-drinkers on the Boston Naming Task (0.11 vs. -0.05, p=.016). In general, more frequent drinkers performed better on cognitive tasks than less frequent drinkers, although this was only statistically significant in the NACC dataset. CONCLUSION: While drinking alcohol may be associated with better cognitive performance across both the US and Greece, more research is needed to assess the cultural factors that may modify this association.

Posttraumatic Stress Disorder Risk and Benzodiazepine Dependence in Older Veterans with Insomnia Symptoms.

OBJECTIVES: To measure the rate of benzodiazepine receptor agonist (BZA) dependence in older veterans with insomnia symptoms chronically using BZAs and to assess for associations between high posttraumatic stress disorder (PTSD) risk and BZA dependence. METHODS: A cross-sectional study was conducted among veterans aged 55 years and older with insomnia symptoms (current or historical) and chronic use of BZAs (≥3 months). Measurements included the Primary Care-PTSD screen (score >2 indicates high PTSD risk) and Benzodiazepine Dependence Questionnaire. Logistic regression was used to test for associations between PTSD risk and BZA dependence. RESULTS: A high PTSD risk was observed in 40% of the participants (N = 33). One-fifth (21.7%, N = 18) of participants met the criteria for benzodiazepine dependence (score ≥23 on Benzodiazepine Dependence Questionnaire). Veterans with high PTSD risk were significantly more likely to have BZA dependence (odds ratio 10.09, 95% CI [2.39, 42.54], p = .002). CONCLUSIONS: In older veterans with insomnia symptoms and chronic use of BZAs, high PTSD risk is associated with elevated risk for BZA dependence, which may make discontinuation of these medications difficult. CLINICAL IMPLICATIONS: Clinicians should consider the strong association between PTSD symptoms and benzodiazepine dependence when developing plans to taper a BZA in veterans with these symptoms.

A randomised controlled trial of the effect of a connected inhaler system on medication adherence in uncontrolled asthmatic patients.

Suboptimal adherence to maintenance therapy contributes to poor asthma control and exacerbations. This study evaluated the effect of different elements of a connected inhaler system (CIS), comprising clip-on inhaler sensors, a patient-facing app and a healthcare professional (HCP) dashboard, on adherence to asthma maintenance therapy.This was an open-label, parallel-group, 6-month, randomised controlled trial in adults with uncontrolled asthma (asthma control test (ACT) score less than 20) on fixed-dose inhaled corticosteroids/long-acting ß-agonist maintenance therapy (n=437). All subjects received fluticasone furoate/vilanterol ELLIPTA dry-powder inhalers for maintenance and salbutamol/albuterol metered-dose inhalers for rescue, with a sensor attached to each inhaler. Participants were randomised to one of five CIS study arms (allocation ratio 1:1:1:1:1) reflecting the recipient of the data feedback from the sensors, as follows: 1) maintenance use to participants and HCPs (n=87); 2) maintenance use to participants (n=88); 3) maintenance and rescue use to participants and HCPs (n=88); 4) maintenance and rescue use to participants (n=88); and 5) no feedback (control) (n=86).For the primary endpoint, observed mean±sd adherence to maintenance therapy over months 4-6 was 82.2±16.58% (n=83) in the "maintenance to participants and HCPs" arm and 70.8±27.30% (n=85) in the control arm. The adjusted least squares mean±se was 80.9±3.19% and 69.0±3.19%, respectively (study arm difference: 12.0%, 95% CI 5.2-18.8%; p<0.001). Adherence was also significantly greater in the other CIS arms versus the control arm. The mean percentage of rescue medication free days (months 4-6) was significantly greater in participants receiving data on their rescue use compared with controls. ACT scores improved in all study arms with no significant differences between groups.A CIS can improve adherence to maintenance medication and reduce rescue medication use in patients with uncontrolled asthma.

Potomac horse fever in Ontario: Clinical, geographic, and diagnostic aspects.

Clinical findings, geographic locations, laboratory diagnoses, and culture isolation of Neorickettsia spp. in Potomac horse fever (PHF) cases diagnosed in Ontario between 2015 and 2019 are described. Forty-six confirmed PHF cases occurred from late June to early September. Of 41 horses admitted to the Ontario Veterinary College, 28 (68%) survived and 13 (32%) were euthanized due to poor prognosis or financial constraints. Most cases were in southern Ontario along the Canada-USA border. Blood and fecal samples from 43 suspect PHF cases were submitted to 2 laboratories for polymerase chain reaction (PCR) testing for Neorickettsia risticii. Agreement between both laboratories for detection of N. risticii DNA was excellent for feces [κ = 0.932, 95% confidence interval (CI): 0.80 to 1], and fair for blood samples (κ = 0.494, 95% CI: 0.13 to 0.85). Neorickettia spp. were isolated from 16 of 41 (39%) blood samples. DNA analysis confirmed 14 isolates were N. risticii and 2 were N. findlayensis, a novel species of Neorickettsia recently demonstrated to cause PHF.

La fièvre équine du Potomac en Ontario : aspects cliniques, géographiques et diagnostiques. Les résultats cliniques, emplacements géographiques, diagnostics de laboratoire et isolement par culture de Neorickettsia spp. dans les cas de fièvre équine du Potomac (PHF) diagnostiqués en Ontario entre 2015 et 2019 sont décrits. Quarante-six cas confirmés de PHF sont survenus de la fin juin au début septembre. Sur 41 chevaux admis au Ontario Veterinary College, 28 (68%) ont survécu et 13 (32%) ont été euthanasiés en raison d'un mauvais pronostic ou de contraintes financières. La plupart des cas se trouvaient dans le sud de l'Ontario, le long de la frontière canado-américaine. Des échantillons de sang et de matières fécales provenant de 43 cas suspects de PHF ont été soumis à deux laboratoires pour des tests de réaction d'amplification en chaîne par la polymérase (PCR) pour Neorickettsia risticii. La concordance entre les deux laboratoires pour la détection de l'ADN de N. risticii était excellente pour les selles [κ = 0,932, intervalle de confiance (IC) à 95% : 0,80 à 1] et passable pour les échantillons sanguins (κ = 0,494, IC à 95% : 0,13 à 0,85). Neorickettia spp. ont été isolés à partir de 16 des 41 échantillons de sang (39%). L'analyse de l'ADN a confirmé que 14 isolats étaient N. risticii et deux étaient N. findlayensis, une nouvelle espèce de Neorickettsia récemment démontrée comme causant le PHF.(Traduit par Dr Serge Messier).

Descriptive network analysis of a Standardbred horse training facility contact network: Implications for disease transmission.

Infectious respiratory disease is a common cause of morbidity among racehorses. Quantification of contact patterns in training facilities could help inform disease prevention strategies. The study objectives were to: i) describe the contact network among horses, locations, and humans at a Standardbred horse training facility in Ontario; ii) describe the characteristics of highly influential individuals; and iii) investigate how management changes alter the network metrics and discuss the potential implications for disease transmission. Proximity loggers detected contacts among horses, staff, and locations (n = 144). Network metrics and node centrality measures were described for a 2-mode and horse-only contact network. The 2-mode network density was 0.16. and the median node degree was 20 [interquartile range (IQR) = 12 to 27]. Yearlings and floating staff were most influential in the network suggesting biosecurity programs should emphasize reducing contacts in these groups. Removing highly influential staff or co-housing of age groups resulted in changes to network diameter and density.

Analyse descriptive du réseau de contacts d'un centre d'entraînement de chevaux Standardbred : Implications pour la transmission de maladies. Les maladies respiratoires infectieuses sont une cause commune de morbidité parmi les chevaux de course. Une quantification des patrons de contact dans les centres d'entraînement pourrait aider à avoir des stratégies appropriées de prévention des maladies. Les objectifs de la présente étude étaient de : i) décrire le réseau des contacts entre les chevaux, les localisations et les humains à un centre d'entraînement pour chevaux Stadardbred en Ontario; ii) décrire les caractéristiques d'individus très influents; iii) examiner comment les changements de gestion altèrent le réseau des systèmes de mesure et discuter les implications potentielles pour la transmission des maladies. Des enregistreurs de proximité détectèrent les contacts parmi les chevaux, le personnel et les localisations (n = 144). Les systèmes de mesure et les mesures de centralité des noeuds furent décrits pour un réseau à 2 modes et un réseau de contact entre chevaux uniquement. La densité du réseau à 2 modes était de 0,16 et le degré médian du noeud était 20 [écart interquartile (IQR) = 12 à 27]. Les yearlings et le personnel occasionnel étaient les plus influents dans le réseau suggérant que les programmes de biosécurité devraient mettre l'emphase sur une réduction des contacts dans ces groupes. Le retrait de personnel très influent ou cohabitation de groupes d'âge a résulté en des changements dans le diamètre et la densité du réseau.(Traduit par Dr Serge Messier).

Age and Age Discordance Associations with Condomless Sex Among Men Who Have Sex with Men.

We explored the effect of older partner's age and age difference between partners on condomless sex among men who have sex with men (MSM). We analyzed dyads (n = 1720) from participants (n = 969) in the Sexual Acquisition Transmission of HIV Cooperative Agreement Program. We used modified Poisson regression to model the probability of a sexual encounter's being condomless as a function of older partner's age and age difference between partners adjusting for HIV status, substance use, race/ethnicity, and partner type. We found an interaction between older partner's age and age difference (p < 0.05). Condomless sex decreased with increasing age of the older partner when the age difference was 5-9 years (p = 0.004) or ≥10 years (p = 0.04), but not when <5 years. Condomless sex was less likely among older MSM when there was ≥5 years age difference between partners than <5 years difference. Both age and age discordance affect the likelihood of a sexual encounter between MSM being condomless.

Social networks and alcohol use among older adults: a comparison with middle-aged adults.

OBJECTIVES: This study compared the association between social networks and alcohol consumption among middle-aged (MA) and older adults (OA) to better understand the nature of the relationship between those two factors among OA and MA. METHOD: We examined Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Current drinkers aged over 50 were subdivided into two age groups: MA (50-64, n = 5214) and OA (65 and older, n = 3070). Each age group was stratified into drinking levels (low-risk vs. at-risk) based on alcohol consumption. The size and diversity of social networks were measured. Logistic regression models were used to examine age differences in the association between the social networks (size and diversity) and the probability of at-risk drinking among two age groups. RESULTS: A significant association between the social networks diversity and lower odds of at-risk drinking was found among MA and OA. However, the relationship between the diversity of social networks and the likelihood of at-risk drinking was weaker for OA than for MA. The association between social networks size and at-risk drinking was not significant among MA and OA. CONCLUSION: The current study suggests that the association between social networks diversity and alcohol use among OA differs from the association among MA, and few social networks were associated with alcohol use among OA. In the future, research should consider an in-depth exploration of the nature of social networks and alcohol consumption by using longitudinal designs and advanced methods of exploring drinking networks.