The transcription factor MEF2 directs developmental visually driven functional and structural metaplasticity.

Natural sensory input shapes both structure and function of developing neurons, but how early experience-driven morphological and physiological plasticity are interrelated remains unclear. Using rapid time-lapse two-photon calcium imaging of network activity and single-neuron growth within the unanesthetized developing brain, we demonstrate that visual stimulation induces coordinated changes to neuronal responses and dendritogenesis. Further, we identify the transcription factor MEF2A/2D as a major regulator of neuronal response to plasticity-inducing stimuli directing both structural and functional changes. Unpatterned sensory stimuli that change plasticity thresholds induce rapid degradation of MEF2A/2D through a classical apoptotic pathway requiring NMDA receptors and caspases-9 and -3/7. Knockdown of MEF2A/2D alone is sufficient to induce a metaplastic shift in threshold of both functional and morphological plasticity. These findings demonstrate how sensory experience acting through altered levels of the transcription factor MEF2 fine-tunes the plasticity thresholds of brain neurons during neural circuit formation.

Biomechanical adaptations enable phoretic mite species to occupy distinct spatial niches on host burying beetles.

Niche theory predicts that ecologically similar species coexist by minimizing interspecific competition through niche partitioning. Therefore, understanding the mechanisms of niche partitioning is essential for predicting interactions and coexistence between competing organisms. Here, we study two phoretic mite species, Poecilochirus carabi and Macrocheles nataliae that coexist on the same host burying beetle Nicrophorus vespilloides and use it to 'hitchhike' between reproductive sites. Field observations revealed clear spatial partitioning between species in distinct host body parts. Poecilochirus carabi preferred the ventral side of the thorax, whereas M. nataliae were exclusively found ventrally at the hairy base of the abdomen. Experimental manipulations of mite density showed that each species preferred these body parts, largely regardless of the density of the other mite species on the host beetle. Force measurements indicated that this spatial distribution is mediated by biomechanical adaptations, because each mite species required more force to be removed from their preferred location on the beetle. While P. carabi attached with large adhesive pads to the smooth thorax cuticle, M. nataliae gripped abdominal setae with their chelicerae. Our results show that specialist biomechanical adaptations for attachment can mediate spatial niche partitioning among species sharing the same host.

STAT5B mutations in myeloid neoplasms differ by disease subtypes but characterize a subset of chronic myeloid neoplasms with eosinophilia and/or basophilia.

STAT5B has been reported as a recurrent mutation in myeloid neoplasms (MNs) with eosinophilia, but the overall frequency and importance across a spectrum of MNs are largely unknown. We conducted a multicenter study on a series of 82 MNs with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutation in MNs was low.

Risk of interpersonal violence during and after pregnancy among people with schizophrenia: a population-based cohort study.

BACKGROUND: Schizophrenia is associated with increased risk of experiencing interpersonal violence. Little is known about risk specifically around the time of pregnancy. METHODS: This population-based cohort study included all individuals (aged 15-49 yr) listed as female on their health cards who had a singleton birth in Ontario, Canada, between 2004 and 2018. We compared those with and without schizophrenia on their risk of an emergency department (ED) visit for interpersonal violence in pregnancy or within 1 year postpartum. We adjusted relative risks (RRs) for demographics, prepregnancy history of substance use disorder and history of interpersonal violence. In a subcohort analysis, we used linked clinical registry data to evaluate interpersonal violence screening and self-reported interpersonal violence during pregnancy. RESULTS: We included 1 802 645 pregnant people, 4470 of whom had a diagnosis of schizophrenia. Overall, 137 (3.1%) of those with schizophrenia had a perinatal ED visit for interpersonal violence, compared with 7598 (0.4%) of those without schizophrenia, for an RR of 6.88 (95% confidence interval [CI] 5.66-8.37) and an adjusted RR of 3.44 (95% CI 2.86-4.15). Results were similar when calculated separately for the pregnancy (adjusted RR 3.47, 95% CI 2.68-4.51) period and the first year postpartum (adjusted RR 3.45, 95% CI 2.75-4.33). Pregnant people with schizophrenia were equally likely to be screened for interpersonal violence (74.3% v. 73.8%; adjusted RR 0.99, 95% CI 0.95-1.04), but more likely to self-report it (10.2% v. 2.4%; adjusted RR 3.38, 95% CI 2.61-4.38), compared with those without schizophrenia. Among patients who did not self-report interpersonal violence, schizophrenia was associated with an increased risk for a perinatal ED visit for interpersonal violence (4.0% v. 0.4%; adjusted RR 6.28, 95% CI 3.94-10.00). INTERPRETATION: Pregnancy and postpartum are periods of higher risk for interpersonal violence among people with schizophrenia compared with those without schizophrenia. Pregnancy is a key period for implementing violence prevention strategies in this population.

Acute presentations of eating disorders among adolescents and adults before and during the COVID-19 pandemic in Ontario, Canada.

BACKGROUND: Increased rates of pediatric eating disorders have been observed during the COVID-19 pandemic, but little is known about trends among adults. We aimed to evaluate rates of emergency department visits and hospital admissions for eating disorders among adolescents and adults during the pandemic. METHODS: We conducted a population-based, repeated cross-sectional study using linked health administrative data for Ontario residents aged 10-105 years during the prepandemic (Jan. 1, 2017, to Feb. 29, 2020) and pandemic (Mar. 1, 2020, to Aug. 31, 2022) periods. We evaluated monthly rates of emergency department visits and hospital admissions for eating disorders, stratified by age. RESULTS: Compared with expected rates derived from the prepandemic period, emergency department visits for eating disorders increased during the pandemic among adolescents aged 10-17 years (7.38 v. 3.33 per 100 000; incidence rate ratio [IRR] 2.21, 95% confidence interval [CI] 2.17-2.26), young adults aged 18-26 years (2.79 v. 2.46 per 100 000; IRR 1.13, 95% CI 1.10-1.16) and older adults aged 41-105 years (0.14 v. 0.11 per 100 000; IRR 1.15, 95% CI 1.07-1.24). Hospital admissions for eating disorders increased during the pandemic for adolescents (8.82 v. 5.74 per 100 000; IRR 1.54, 95% CI 1.54-1.54) but decreased for all adult age groups, especially older adults aged 41-105 years (0.21 v. 0.30 per 100 000; IRR 0.72, 95% CI 0.64-0.80). INTERPRETATION: Emergency department visits for eating disorders increased among adolescents, young adults and older adults during the pandemic, but hospital admissions increased only for adolescents and decreased for all adult groups. Differential rates of acute care use for eating disorders by age have important implications for allocation of inpatient mental health resources.

The relationship between rurality, travel time to care and death by suicide.

BACKGROUND: We previously found an association between rurality and death by suicide, where those living in rural areas were more likely to die by suicide. One potential reason why this relationship exists might be travel time to care. This paper examines the relationship between travel time to both psychiatric and general hospitals and suicide, and then determine whether travel time to care mediates the relationship between rurality and suicide. METHODS: This is a population-based nested case-control study. Data from 2007 to 2017 were obtained from administrative databases held at ICES, which capture all hospital and emergency department visits across Ontario. Suicides were captured using vital statistics. Travel time to care was calculated from the resident's home to the nearest hospital based on the postal codes of both locations. Rurality was measured using Metropolitan Influence Zones. RESULTS: For every hour in travel time a male resides from a general hospital, their risk of death by suicide doubles (AOR = 2.08, 95% CI = 1.61-2.69). Longer travel times to psychiatric hospitals also increases risk of suicide among males (AOR = 1.03, 95%CI = 1.02-1.05). Travel time to general hospitals is a significant mediator of the relationship between rurality and suicide among males, accounting for 6.52% of the relationship between rurality and increased risk of suicide. However, we also found that there is effect modification, where the relationship between travel time and suicide is only significant among males living in urban areas. CONCLUSIONS: Overall, these findings suggest that males who must travel longer to hospitals are at a greater risk of suicide compared to those who travel a shorter time. Furthermore, travel time to care is a mediator of the association between rurality and suicide among males.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and corresponding geographical inequalities in England: interrupted time series analysis.

BACKGROUND: There has been disruption to the detection and management of those with hypertension and atrial fibrillation (AF) during the COVID-19 pandemic. This is likely to vary geographically and could have implications for future mortality and morbidity. We aimed to estimate the change in diagnosed prevalence, treatment and prescription indicators for AF and hypertension and assess corresponding geographical inequalities. METHODS: Using the Quality and Outcomes Framework (2016/17 to 2021/22) and the English Prescribing Datasets (2018 to 2022), we described age standardised prevalence, treatment and prescription item rates for hypertension and AF by geography and over time. Using an interrupted time-series (ITS) analysis, we estimated the impact of the pandemic (from April 2020) on missed diagnoses and on the percentage change in medicines prescribed for these conditions. Finally, we described changes in treatment indicators against Public Health England 2029 cardiovascular risk targets. RESULTS: We observed 143,822 fewer (-143,822, 95%CI:-226,144, -61,500, p = 0.001) diagnoses of hypertension, 60,330 fewer (-60,330, 95%CI: -83,216, -37,444, p = 0.001) diagnoses of AF and 1.79% fewer (-1.79%, 95%CI: -2.37%, -1.22%), p < 0.0001) prescriptions for these conditions over the COVID-19 impact period. There was substantial variation across geography in England in terms of the indirect impact of the COVID-19 pandemic on the diagnosis, prescription, and treatment rates of hypertension and AF. 20% of Sub Integrated Care Boards account for approximately 62% of all missed diagnoses of hypertension. The percentage of individuals who had their hypertension controlled fell from 75.8% in 2019/20 to 64.1% in 2021/22 and the percentage of individuals with AF who were risk assessed fell from 97.2% to 90.7%. CONCLUSIONS: Hypertension and AF detection and management were disrupted during the COVID-19 pandemic. The disruption varied considerably across diseases and geography. This highlights the utility of administrative and geographically granular datasets to inform targeted efforts to mitigate the indirect impacts of the pandemic through applied secondary prevention measures.

Rurality as a Risk Factor for Attempted Suicide and Death by Suicide in Ontario, Canada.

OBJECTIVE: This study aims to examine rural and urban differences in attempted suicide and death by suicide in Ontario, Canada. METHOD: This is a population-based nested case-control study. Data were obtained from administrative databases held at ICES, which capture all hospital and emergency department visits across Ontario between 2007 and 2017. All adults living in Ontario who attempted suicide or died by suicide are included in the study, and controls were matched by sex and age. Suicides were captured using vital statistics. Suicide attempts were determined using emergency department service codes. RESULTS: Rurality is a risk factor for attempted suicide and death by suicide. Rural males are more likely to die by suicide compared with urban males (adjusted odds ratio(AOR) = 1.70, 95% confidence interval (CI), 1.49 to 1.95), and the odds of death by suicide increase with increasing levels of rurality. Rural males and females have an increased risk of attempted suicide compared with their urban counterparts (males: AOR = 1.37, 95% CI, 1.24 to 1.50) (females: AOR = 1.26, 95% CI, 1.14 to 1.39), with a pattern of increasing risk of suicide attempts with increasing rurality. Rural females are not at increased risk of suicide compared with urban females (AOR = 1.08, 95% CI, 0.80 to 1.45). Sensitivity analyses corroborated the results. CONCLUSIONS: Rural males are almost two times more likely to die by suicide compared with urban males, and both rural males and females have an elevated risk of suicide attempts compared with urban residents. Future research should examine potential mediators of the relationship between rurality and suicide.

Artificial intelligence for dermatopathology: Current trends and the road ahead.

Artificial intelligence (AI), including deep learning methods that leverage neural network-based algorithms, hold significant promise for dermatopathology and other areas of diagnostic pathology in research and clinical practice. There has been significant progress over past several years in applying AI to analyzing digital histopathology images for diagnosis. While much work in AI analysis of histopathology data remains investigational, recent regulatory agency approval in Europe and United States of AI-assisted tools for clinical use in histopathologic diagnosis of prostate and breast cancer herald broader movement of AI into the clinical diagnostic realm of anatomic pathology, including dermatopathology. However, significant challenges remain in translating AI from research into clinical practice, including algorithmic real-world performance, robustness to variation in data sets and practice settings, effective integration into clinical workflows, and cost effectiveness. This review introduces core concepts and terminology in AI, and assesses current progress and challenges in applying AI to dermatopathology.

Perinatal mental illness among women with disabilities: a population-based cohort study.

PURPOSE: To examine the risk of perinatal mental illness, including new-onset disorders and recurrent or ongoing use of mental health care, comparing women with physical, sensory, intellectual/developmental, and multiple disabilities to those without a disability. METHODS: From all women aged 15-49 years with a singleton birth in Ontario, Canada (2003-2018), those with physical (n = 144,972), sensory (n = 45,249), intellectual/developmental (n = 2,227), and ≥ 2 of these disabilities ("multiple disabilities"; n = 8,883), were compared to 1,601,363 without a disability on risk of healthcare system contact for mental illness from conception to 365 days postpartum. The cohort was stratified into: (1) no pre-pregnancy mental illness (to identify new-onset illness), (2) distal mental illness (> 2 years pre-pregnancy, to identify recurrent illness), and (3) recent mental illness (0-2 years pre-pregnancy, to identify ongoing contact). Modified Poisson regression generated relative risks (aRR), adjusted for age, parity, income quintile, and rural residence. RESULTS: About 14.7, 26.5, and 56.6% of women with no disabilities had new-onset, recurrent, and ongoing contact for mental illness, respectively, perinatally. Risks were elevated across disability groups for new-onset (physical: aRR 1.18, 95% CI 1.16-1.20; sensory: 1.11, 1.08-1.15; intellectual/developmental: 1.38, 1.17-1.62; multiple: 1.24, 1.15-1.33), recurrent (physical: 1.10, 1.08-1.12; sensory 1.06, 1.02-1.09; intellectual/developmental: 1.24, 1.11-1.37; multiple: 1.16, 1.09-1.23), and ongoing contact (physical: 1.09, 1.08-1.10; sensory: 1.08, 1.06-1.10; intellectual/developmental: 1.31, 1.26-1.37; multiple: 1.20, 1.16-1.23). CONCLUSION: The heightened use of new, recurrent, and ongoing mental health care across disability groups in the perinatal period suggests that adapted screening and intervention approaches are critical to optimize perinatal mental health in this population.

Artificial intelligence for prediction of donor liver allograft steatosis and early post-transplantation graft failure.

BACKGROUND: Donor livers undergo subjective pathologist review of steatosis before transplantation to mitigate the risk for early allograft dysfunction (EAD). We developed an objective, computer vision artificial intelligence (CVAI) platform to score donor liver steatosis and compared its capability for predicting EAD against pathologist steatosis scores. METHODS: Two pathologists scored digitized donor liver biopsy slides from 2014 to 2019. We trained four CVAI platforms with 1:99 training:prediction split. Mean intersection-over-union (IU) characterized CVAI model accuracy. We defined EAD using liver function tests within 1 week of transplantation. We calculated separate EAD logistic regression models with CVAI and pathologist steatosis and compared the models' discrimination and internal calibration. RESULTS: From 90 liver biopsies, 25,494 images trained CVAI models yielding peak mean IU = 0.80. CVAI steatosis scores were lower than pathologist scores (median 3% vs 20%, P < 0.001). Among 41 transplanted grafts, 46% developed EAD. The median CVAI steatosis score was higher for those with EAD (2.9% vs 1.9%, P = 0.02). CVAI steatosis was independently associated with EAD after adjusting for donor age, donor diabetes, and MELD score (aOR = 1.34, 95%CI = 1.03-1.75, P = 0.03). CONCLUSION: The CVAI steatosis EAD model demonstrated slightly better calibration than pathologist steatosis, meriting further investigation into which modality most accurately and reliably predicts post-transplantation outcomes.

NuSeT: A deep learning tool for reliably separating and analyzing crowded cells.

Segmenting cell nuclei within microscopy images is a ubiquitous task in biological research and clinical applications. Unfortunately, segmenting low-contrast overlapping objects that may be tightly packed is a major bottleneck in standard deep learning-based models. We report a Nuclear Segmentation Tool (NuSeT) based on deep learning that accurately segments nuclei across multiple types of fluorescence imaging data. Using a hybrid network consisting of U-Net and Region Proposal Networks (RPN), followed by a watershed step, we have achieved superior performance in detecting and delineating nuclear boundaries in 2D and 3D images of varying complexities. By using foreground normalization and additional training on synthetic images containing non-cellular artifacts, NuSeT improves nuclear detection and reduces false positives. NuSeT addresses common challenges in nuclear segmentation such as variability in nuclear signal and shape, limited training sample size, and sample preparation artifacts. Compared to other segmentation models, NuSeT consistently fares better in generating accurate segmentation masks and assigning boundaries for touching nuclei.

Accidental injury, self-injury, and assault among children of women with schizophrenia: a population-based cohort study.

OBJECTIVE: We aimed to compare the risk for injury overall and by intent (accidental injury, self-injury, and assault) among children born to women with versus without schizophrenia. METHODS: Using health administrative data from Ontario, Canada, children born from 2003 to 2017 to mothers with (n = 3769) and without (n = 1,830,054) schizophrenia diagnosed prior to their birth were compared on their risk for child injury, captured via emergency department, hospitalization, and vital statistics databases up to age 15 years. Cox proportional hazard models generated hazard ratios for time to first injury event (overall and by intent), adjusted for potential confounders (aHR). We stratified by child sex and age at follow-up: 0-1 (infancy), 2-5 (pre-school), 6-9 (primary school), and 10-15 (early adolescence) planning to collapse age categories as needed to obtain stable and reportable estimates. RESULTS: Maternal schizophrenia was associated with elevated risk for child injury overall (105.4 vs. 89.4/1000 person-years (py), aHR 1.08, 95% CI 1.03-1.14), accidental injury (104.7 vs. 88.1/1000py, 1.08, 1.03-1.14), for self-injury (0.4 vs. 0.2/1000py, 2.14 1.18-3.85), and assault (1.0 vs. 0.3/1000py, 2.29, 1.45-3.62). By child sex, point estimates were of similar magnitude and direction, though not all remained statistically significant. For accidental injury and self-injury, the risk associated with maternal schizophrenia was most elevated in 10-15-year-olds. For assault, the risk associated with maternal schizophrenia was most elevated among children in the 0-1 and 2-5-year-old age groups. CONCLUSION: The elevated risk of child injury associated with maternal schizophrenia, especially for self-injury and assault, suggests that targeted monitoring and preventive interventions are warranted.

Factors associated with higher healthcare costs in a cohort of homeless adults with a mental illness and a general cohort of adults with a history of homelessness.

BACKGROUND: Healthcare costs are disproportionately incurred by a relatively small group of people often described as high-cost users. Understanding the factors associated with high-cost use of health services among people experiencing homelessness could help guide service planning. METHODS: Survey data from a general cohort of adults with a history of homelessness and a cohort of homeless adults with mental illness were linked with administrative healthcare records in Ontario, Canada. Total costs were calculated using a validated costing algorithm and categorized based on population cut points for the top 5%, top 6-10%, top 11-50% and bottom 50% of users in Ontario. Multinomial logistic regression was used to identify the predisposing, enabling, and need factors associated with higher healthcare costs (with bottom 50% as the reference). RESULTS: Sixteen percent of the general homeless cohort and 30% percent of the cohort with a mental illness were in the top 5% of healthcare users in Ontario. Most healthcare costs for the top 5% of users were attributed to emergency department and inpatient service costs, while the costs from other strata were mostly for physician services, hospital outpatient clinics, and medications. The odds of being within the top 5% of users were higher for people who reported female gender, a regular medical doctor, past year acute service use, poor perceived general health and two or more diagnosed chronic conditions, and were lower for Black participants and other racialized groups. Older age was not consistently associated with higher cost use; the odds of being in the top 5% were highest for 35-to-49-year year age group in the cohort with a mental illness and similar for the 35-49 and ≥ 50-year age groups in the general homeless cohort. CONCLUSIONS: This study combines survey and administrative data from two cohorts of homeless adults to describe the distribution of healthcare costs and identify factors associated with higher cost use. These findings can inform the development of targeted interventions to improve healthcare delivery and support for people experiencing homelessness.

Emergence of reproducible spatiotemporal activity during motor learning.

The motor cortex is capable of reliably driving complex movements yet exhibits considerable plasticity during motor learning. These observations suggest that the fundamental relationship between motor cortex activity and movement may not be fixed but is instead shaped by learning; however, to what extent and how motor learning shapes this relationship are not fully understood. Here we addressed this issue by using in vivo two-photon calcium imaging to monitor the activity of the same population of hundreds of layer 2/3 neurons while mice learned a forelimb lever-press task over two weeks. Excitatory and inhibitory neurons were identified by transgenic labelling. Inhibitory neuron activity was relatively stable and balanced local excitatory neuron activity on a movement-by-movement basis, whereas excitatory neuron activity showed higher dynamism during the initial phase of learning. The dynamics of excitatory neurons during the initial phase involved the expansion of the movement-related population which explored various activity patterns even during similar movements. This was followed by a refinement into a smaller population exhibiting reproducible spatiotemporal sequences of activity. This pattern of activity associated with the learned movement was unique to expert animals and not observed during similar movements made during the naive phase, and the relationship between neuronal activity and individual movements became more consistent with learning. These changes in population activity coincided with a transient increase in dendritic spine turnover in these neurons. Our results indicate that a novel and reproducible activity-movement relationship develops as a result of motor learning, and we speculate that synaptic plasticity within the motor cortex underlies the emergence of reproducible spatiotemporal activity patterns for learned movements. These results underscore the profound influence of learning on the way that the cortex produces movements.

Epidemiology of Interpersonal Trauma among Women and Men Psychiatric Inpatients: A Population-Based Study.

OBJECTIVE: Small clinical samples suggest that psychiatric inpatients report a lifetime history of interpersonal trauma. Since past experiences of trauma may complicate prognosis and treatment trajectories, population-level knowledge is needed about its prevalence and correlates among inpatients. METHODS: Using health-administrative databases comprising all adult psychiatric inpatients in Ontario, Canada (2009 to 2016, n = 160,436, 49% women), we identified those who reported experiencing physical, sexual, and/or emotional trauma in their lifetime, 1 year, and 30 days preceding admission. We described the prevalence of each type of trauma, comparing women and men using modified Poisson regression, and identified individual-level characteristics associated with lifetime trauma history using multivariable logistic regression. RESULTS: 31.7% of inpatients reported experiencing trauma prior to admission. Lifetime prevalence was higher in women (39.6% vs. 24.1%; age-adjusted prevalence ratio [aPR] = 1.68; 95% CI, 1.65 to 1.71), including sexual (22.7% vs. 8.4%; aPR = 2.81; 95% CI, 2.73 to 2.89), emotional (33.3% vs. 19.4%; aPR = 1.76; 95% CI, 1.72 to 1.79), and physical trauma (24.2% vs. 14.8%; aPR = 1.68; 95% CI, 1.65 to 1.72). Factors most prominently associated with lifetime trauma were witnessing parental substance use (adjusted odds ratio [aOR] = 8.68; 95% CI, 8.39 to 8.99), female sex (aOR = 2.29; 95% CI, 2.23 to 2.35), and number of recent stressful life events (aOR = 1.62; 95% CI, 1.59 to 1.65). CONCLUSIONS: These results suggest that trauma-informed approaches are essential to consider in the design and delivery of inpatient psychiatric services for both women and men.

Impact of the diabetes Canada guideline dissemination strategy on dispensed vascular protective medications for older patients in Ontario, Canada: a linked EMR and administrative data study.

BACKGROUND: The 2013 Diabetes Canada guidelines recommended routinely using vascular protective medications for most patients with diabetes. These medications included statins and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Antiplatelet agents were only recommended for secondary prevention of cardiovascular disease. Using Electronic Medical Record (EMR) data, we previously found that guideline dissemination efforts were not associated with an increase in the rate of primary care prescriptions of these medications. However, this needs confirmation: patients can receive prescriptions from different sources including specialists and they may not always fill these prescriptions. Using both EMR and administrative health data, we examined whether guideline dissemination impacted the dispensing of vascular protective medications to patients. METHODS: The study population included patients with diabetes aged 66 or over in Ontario, Canada. We created two cohorts using two different approaches: an Electronic Medical Record (EMR) algorithm for diabetes using linked EMR-administrative data and an administrative algorithm using population level administrative data. We examined data from January 2010 to December 2016. Patients with diabetes were deemed to be likely taking a medication (or covered) during a quarter if the daily amount for a dispensed medication would last for at least 75% of days in any given quarter. An interrupted time series analysis was used to assess the proportion of patients covered by each medication class. Proton pump inhibitors (PPIs) were used as a reference. RESULTS: There was no increase in the rate of change for medication coverage following guideline release in either the EMR or the administrative diabetes cohorts. For statins, the change in trend was - 0.03, p = 0.7 (EMR) and - 0.12, p = 0.04(administrative). For ACEI/ARBs, this was 0.03, p = 0.6 (EMR) and 0, p = 1(administrative). For antiplatelets, this was 0.001, P = .97 (EMR) and - 0.03, p = 0.03 (administrative). The comparator PPI was - 0.07, p = 0.4 (EMR) and - 0.11, p = 0.002 (administrative). CONCLUSIONS: Using both EMR and administrative health data, we confirmed that the Diabetes Canada 2013 guideline dissemination strategy did not lead to an increased rate of coverage for vascular protective medications. Alternative strategies are needed to effect change in practice.

Relationship Between pH Shifts and Rate of Healing in Chronic Nonhealing Venous Stasis Lower-Extremity Wounds.

Venous stasis ulcers represent the majority of lower-extremity ulcers and place a considerable financial burden on the American health care system. Current standard of care therapies remain sub-optimal with 50% of venous stasis ulcers remaining unhealed after 4 months. Sixteen consecutive wounds were enrolled across 8 participants at a single center and underwent pH-driven therapy in addition to standard care as dictated by physicians. Following wound debridement, the pH of the wound bed was measured using pH strips. If acidic, normal saline was used to rinse the wound at every dressing change. If alkaline, nonsterile gauze was soaked in 0.25% acetic acid and applied to the wound for a minimum of 30 seconds. Participants were followed for 4 weeks with research staff observing compliance throughout. All 16 wounds had an alkaline pH at baseline, with an average pH of 8.25 ± 0.55 (range 7.5 to 9). Average area of the wound at the time of enrollment was (mean ± standard deviation) 285.48 ± 43.68 mm2, and average age of the wound was 37.5 ± 20.3 months (range 3 to 72). A simple linear regression model found a moderate relationship between pH and the rate of healing of chronic nonhealing venous stasis lower-extremity wounds (correlation coefficient  = 0.61). For every 1-unit change in pH, we can expect to see a change in wound size of 116.05 mm2. This is the first US-based, open-label, prospective study that examined the effect of pH on the rate of healing in chronic nonhealing venous stasis ulcer lowerextremity wounds.

Suicide and Self-Harm in Recent Immigrants in Ontario, Canada: A Population-Based Study.

OBJECTIVE: To estimate the rates of suicide and self-harm among recent immigrants and to determine which immigrant-specific risk factors are associated with these outcomes. METHODS: Population-based cohort study using linked health administrative data sets (2003 to 2017) in Ontario, Canada which included adults ≥18 years, living in Ontario (N = 9,055,079). The main exposure was immigrant status (long-term resident vs. recent immigrant). Immigrant-specific exposures included visa class and country of origin. Outcome measures were death by suicide or emergency department visit for self-harm. Cox proportional hazards estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: We included 590,289 recent immigrants and 8,464,790 long-term residents. Suicide rates were lower among immigrants (n = 130 suicides, 3.3/100,000) than long-term residents (n = 6,354 suicides, 11.8/100,000) with aHR 0.3, 95% CI, 0.2 to 0.3. Male-female ratios in suicide rates were attenuated in immigrants. Refugees had 2.1 (95% CI, 1.3 to 3.6; rate 6.1/100,000) and 2.8 (95% CI, 2.5 to 3.2) times the likelihood of suicide and self-harm, respectively, compared with nonrefugee immigrants. Self-harm rate was lower among immigrants (n = 2,256 events, 4.4/10,000) than long-term residents (n = 68,039 events, 9.7/10,000 person-years; aHR 0.3; 95% CI, 0.3 to 0.3). Unlike long-term residents, where low income was associated with high suicide rates, income was not associated with suicide among immigrants and there was an attenuated income gradient for self-harm. Country of origin-specific analyses showed wide ranges in suicide rates (1.4 to 9.9/100,000) and self-harm (1.8 to 14.9/10,000). CONCLUSION: Recent immigrants have lower rates of suicide and self-harm and different sociodemographic predictors compared with long-term residents. Analysis of contextual factors including immigrant class, origin, and destination should be considered for all immigrant suicide risk assessment.