Immediate and delayed risk of breast cancer associated with classic lobular carcinoma in situ and its variants.

OBJECTIVE: To determine the risk of breast cancer due to lobular carcinoma in situ (LCIS). METHODS: This retrospective IRB-approved study identified cases of LCIS after percutaneous breast biopsy from 7/2005 to 7/2022. Excluded were cases with less than 2 years of imaging surveillance or a concurrent ipsilateral breast cancer diagnosis within 6 months of the LCIS diagnosis. Final outcomes of cancer versus no cancer were determined by pathology at surgical excision or the absence of cancer on imaging surveillance. RESULTS: A total of 116 LCIS lesions were identified. The primary imaging findings targeted for percutaneous biopsy included calcifications (50.0%, 58/116), MR enhancing lesions (25.0%, 29/116), noncalcified mammographic architectural distortions (10.3%, 12/116), or masses (14.7%, 17/116). Surgical excision was performed in 49.1% (57/116) and imaging surveillance was performed in 50.9% (59/116) of LCIS cases. There were 22 cancers of which 11 cancers were discovered at immediate excision [19.3% (11/57) immediate upgrade] and 11 cancers developed later while on imaging surveillance [18.6% (11/59) delayed risk for cancer]. Among all 22 cancers, 63.6% (14/22) occurred at the site of LCIS (11 at immediate excision and 3 at surveillance) and 36.4% (8/22) occurred at a location away from the site of LCIS (6 in a different quadrant and 2 in the contralateral breast). CONCLUSION: LCIS has both an immediate risk (19.3%) and a delayed risk (18.6%) for cancer with 90.9% occurring in the ipsilateral breast (63.6% at and 27.3% away from the site of LCIS) and 9.1% occurring in the contralateral breast.

Association of virtual end-of-life care with healthcare outcomes before and during the COVID-19 pandemic: A population-based study.

The use of virtual care for people at the end-of-life significantly increased during the COVID-19 pandemic, but its association with acute healthcare use and location of death is unknown. The objective of this study was to measure the association between the use of virtual end-of-life care with acute healthcare use and an out-of-hospital death before vs. after the introduction of specialized fee codes that enabled broader delivery of virtual care during the COVID-19 pandemic. This was a population-based cohort study of 323,995 adults in their last 90 days of life between January 25, 2018 and December 31, 2021 using health administrative data in Ontario, Canada. Primary outcomes were acute healthcare use (emergency department, hospitalization) and location of death (in or out-of-hospital). Prior to March 14, 2020, 13,974 (8%) people received at least 1 virtual end-of-life care visit, which was associated with a 16% higher rate of emergency department use (adjusted Rate Ratio [aRR] 1.16, 95%CI 1.12 to 1.20), a 17% higher rate of hospitalization (aRR 1.17, 95%CI 1.15 to 1.20), and a 34% higher risk of an out-of-hospital death (aRR 1.34, 95%CI 1.31 to 1.37) compared to people who did not receive virtual end-of-life care. After March 14, 2020, 104,165 (71%) people received at least 1 virtual end-of-life care visit, which was associated with a 58% higher rate of an emergency department visit (aRR 1.58, 95%CI 1.54 to 1.62), a 45% higher rate of hospitalization (aRR 1.45, 95%CI 1.42 to 1.47), and a 65% higher risk of an out-of-hospital death (aRR 1.65, 95%CI 1.61 to 1.69) compared to people who did not receive virtual end-of-life care. The use of virtual end-of-life care was associated with higher acute healthcare use in the last 90 days of life and a higher likelihood of dying out-of-hospital, and these rates increased during the pandemic.

Effects of electroconvulsive shock on the function, circuitry, and transcriptome of dentate gyrus granule neurons.

Therapeutic use of electroconvulsive shock (ECS) is 75% effective for the remission of treatment-resistant depression. Like other more common forms of antidepressant treatment such as fluoxetine, ECS has been shown to increase neurogenesis in the hippocampal dentate gyrus of rodent models. Yet the question of how ECS-induced neurogenesis supports improvement of depressive symptoms remains unknown. Here, we show that ECS-induced neurogenesis is necessary to improve depressive-like behavior of mice exposed to chronic corticosterone (Cort). We then use slice electrophysiology to show that optogenetic stimulation of adult-born neurons produces a greater hyperpolarization in mature granule neurons after ECS vs Sham treatment. We identify that this hyperpolarization requires the activation of metabotropic glutamate receptor 2 (mGluR2). Consistent with this finding, we observe reduced expression of the immediate early gene cFos in the granule cell layer of ECS vs Sham subjects. We then show that mGluR2 knockdown specifically in ventral granule neurons blunts the antidepressant-like behavioral effects of ECS. Using single nucleus RNA sequencing, we reveal major transcriptomic shifts in granule neurons after treatment with ECS+Cort or fluoxetine+Cort vs Cort alone. We identify a population of immature cells which has greater representation in both ECS+Cort and fluoxetine+Cort treated samples vs Cort alone. We also find global differences in ECS-vs fluoxetine-induced transcriptomic shifts. Together, these findings highlight a critical role for immature granule cells and mGluR2 signaling in the antidepressant action of ECS.

Screening chest wall ultrasound in the mastectomy patient.

BACKGROUND: While there are clear guidelines regarding chest wall ultrasound in the symptomatic patient, there is conflicting evidence regarding the use of ultrasound in the screening of women post-mastectomy. OBJECTIVE: To assess the utility of screening chest wall ultrasound after mastectomy and to assess features of detected malignancies. METHODS: This IRB approved, retrospective study evaluates screening US examinations of the chest wall after mastectomy. Asymptomatic women presenting for screening chest wall ultrasound from January 2016 through May 2017 were included. Cases of known active malignancy were excluded. All patients had at least one year of clinical or imaging follow-up. 43 exams (8.5 %) were performed with a history of contralateral malignancy, 465 exams (91.3 %) were performed with a history of ipsilateral malignancy, and one exam (0.2 %) was performed in a patient with bilateral prophylactic mastectomy. RESULTS: During the 17-month period, there were 509 screening US in 389 mastectomy patients. 504 (99.0 %) exams were negative/benign. Five exams (1.0 %) were considered suspicious, with recommendation for biopsy, which was performed. Out of 509 exams, 3 (0.6 %) yielded benign results, while 2 (0.39 %) revealed recurrent malignancy, with a 95 % confidence interval (exact binomial) of 0.05 % to 1.41 % for screening ultrasound. Both patients who recurred had previously recurred, and both had initial cancer of lobular histology. CONCLUSION: Of 509 chest wall screening US exams performed in mastectomy, 2 malignancies were detected, and each patient had history of invasive lobular carcinoma and at least one prior recurrence prior to this study, suggesting benefit of screening ultrasound in these populations.

Attending physicians' annual service volume and use of virtual end-of-life care: A population-based cohort study in Ontario, Canada.

IMPORTANCE: Physicians and their practice behaviors influence access to healthcare and may represent potentially modifiable targets for practice-changing interventions. Use of virtual care at the end-of-life significantly increased during the COVID-19 pandemic, but its association with physician practice behaviors, (e.g., annual service volume) is unknown. OBJECTIVE: Measure the association of physicians' annual service volume with their use of virtual end-of-life care (EOLC) and the magnitude of physician-attributable variation in its use, before and during the pandemic. DESIGN, SETTING AND PARTICIPANTS: Population-based cohort study using administrative data of all physicians in Ontario, Canada who cared for adults in the last 90 days of life between 01/25/2018-12/31/2021. Multivariable modified Poisson regression models measured the association between attending physicians' use of virtual EOLC and their annual service volume. We calculated the variance partition coefficients for each regression and stratified by time period before and during the pandemic. EXPOSURE: Annual service volume of a person's attending physician in the preceding year. MAIN OUTCOMES AND MEASURES: Delivery of ≥1 virtual EOLC visit by a person's attending physician and the proportion of variation in its use attributable to physicians. RESULTS: Among the 35,825 unique attending physicians caring for 315,494 adults, use of virtual EOLC was associated with receiving care from a high compared to low service volume attending physician; the magnitude of this association diminished during the pandemic (adjusted RR 1.25 [95% CI 1.14, 1.37] pre-pandemic;1.10 (95% CI 1.08, 1.12) during the pandemic). Physicians accounted for 36% of the variation in virtual EOLC use pre-pandemic and 12% of this variation during the pandemic. CONCLUSIONS AND RELEVANCE: Physicians' annual service volume was associated with use of virtual EOLC and physicians accounted for a substantial proportion of the variation in its use. Physicians may be appropriate and potentially modifiable targets for interventions to modulate use of EOLC delivery.

Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Effectiveness of maternal influenza vaccination during pregnancy against laboratory-confirmed seasonal influenza among infants under 6 months of age in Ontario, Canada.

BACKGROUND: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited. METHODS: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010-2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders. RESULTS: Among 23,806 infants tested for influenza, 1,783 (7.5%) were positive and 1,708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI]: 50%-74%). VE was similar by trimester of vaccination (1st/2nd: 66%, 40%-80%; 3rd: 63%, 46%-74%), infant age at testing (0-<2 months: 63%, 46%-75%; 2-<6 months: 64%, 36%-79%), and gestational age at birth (≥37 weeks: 64%, 50%-75%; < 37 weeks: 61%, 4%-86%). VE against influenza hospitalization was 67% (95%CI: 50%-78%). CONCLUSIONS: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available.

Adult-born granule cells facilitate remapping of spatial and non-spatial representations in the dentate gyrus.

Adult-born granule cells (abGCs) have been implicated in memory discrimination through a neural computation known as pattern separation. Here, using in vivo Ca2+ imaging, we examined how chronic ablation or acute chemogenetic silencing of abGCs affects the activity of mature granule cells (mGCs). In both cases, we observed altered remapping of mGCs. Rather than broadly modulating the activity of all mGCs, abGCs promote the remapping of place cells' firing fields while increasing rate remapping of mGCs that represent sensory cues. In turn, these remapping deficits are associated with behavioral impairments in animals' ability to correctly identify new goal locations. Thus, abGCs facilitate pattern separation through the formation of non-overlapping representations for identical sensory cues encountered in different locations. In the absence of abGCs, the dentate gyrus shifts to a state that is dominated by cue information, a situation that is consistent with the overgeneralization often observed in anxiety or age-related disorders.

Self-harm among youth during the first 28 months of the COVID-19 pandemic in Ontario, Canada: a population-based study.

BACKGROUND: Youth have reported worsening mental health during the COVID-19 pandemic. We sought to evaluate rates of pediatric acute care visits for self-harm during the pandemic according to age, sex and mental health service use. METHODS: We conducted a population-based, repeated cross-sectional study using linked health administrative data sets to measure monthly rates of emergency department visits and hospital admissions for self-harm among youth aged 10-17 years between Jan. 1, 2017, and June 30, 2022, in Ontario, Canada. We modelled expected rates of acute care visits for self-harm after the pandemic onset based on prepandemic rates. We reported relative differences between observed and expected monthly rates overall and by age group (10-13 yr and 14-17 yr), sex and mental health service use (new and continuing). RESULTS: In this population of about 1.3 million children and adolescents, rates of acute care visits for self-harm during the pandemic were higher than expected for emergency department visits (0.27/1000 population v. 0.21/1000 population; adjusted rate ratio [RR] 1.29, 95% confidence interval [CI] 1.19-1.39) and hospital admissions (0.74/10 000 population v. 0.43/10 000 population, adjusted RR 1.72, 95% CI 1.46-2.03). This increase was primarily observed among females. Rates of emergency department visits and hospital admissions for self-harm were higher than expected for both those aged 10-13 years and those aged 14-17 years, as well as for both those new to the mental health system and those already engaged in care. INTERPRETATION: Rates of acute care visits for self-harm among children and adolescents were higher than expected during the first 2 and a half years of the COVID-19 pandemic, particularly among females. These findings support the need for accessible and intensive prevention efforts and mental health supports in this population.

Isolated Flat Epithelial Atypia: Upgrade Outcomes After Multidisciplinary Review-Based Management Using Excision or Imaging Surveillance.

Objective: To compare flat epithelial atypia (FEA) upgrade rates after excision versus surveillance and to identify variables associated with upgrade. Methods: This single-institution retrospective study identified isolated FEA cases determined by percutaneous biopsy from April 2005 through July 2022 with excision or ≥2 years surveillance. All cases were recommended for excision or surveillance based on multidisciplinary discussion of clinical, imaging, and pathologic variables with emphasis on sampling adequacy and significant atypia. Truth was determined by pathology at excision or the absence of cancer on surveillance. Upgrade was defined as cancer occurring ≤2 cm from the biopsy site. Demographic, imaging, and biopsy variables were compared between those that did and did not upgrade. Results: Among 112 cases of isolated FEA, imaging findings included calcifications in 81.3% (91/112), MRI lesions in 11.6% (13/112), and distortions or masses in 7.1% (8/112). Excision was recommended in 12.5% (14/112) and surveillance in 87.5% (98/112) of cases. Among those recommended for excision, 28.6% (4/14) of cases were upgraded, all to ductal carcinoma in situ. In those recommended for surveillance, 1.0% (1/98) were upgraded to invasive cancer. Overall, FEA had a 4.5% (5/112) upgrade rate, and 2.7% (3/112) also developed cancer >2 cm from the FEA. There were no significant differences in demographic, imaging, and biopsy variables between those that did and did not upgrade to cancer. Conclusion: Multidisciplinary management of isolated FEA distinguishes those at higher risk of upgrade to cancer (28.6%) in whom surgery is warranted from those at low risk of upgrade (1.0%) who can be managed non-operatively.

Identifying and Reducing Barriers to Breast Imaging.

Purpose of Review: The purpose of this review is to discuss disparities in breast health care access and outcomes related to race, gender, cultural diversity, sexual orientation, socioeconomic status, geographic location, and disability. The authors recognize the complexity of eliminating inequalities in health care but are optimistic that all patients will one day have equal access to care through dialogue, acknowledgment, recognition, and action. Recent Findings: After lung cancer, breast cancer is the second leading cause of death among American women. Mammography as a preventative screening tool has resulted in significant reductions in breast cancer mortality. Despite existing breast cancer recommendations, it has been projected that 43,250 women will die from breast cancer in 2022. Summary: Disparities in healthcare outcomes exist for many reasons including inequalities based on race, gender, cultural diversity, religion, sexual orientation, and socioeconomic status. Disparities, no matter how large or complex, are not insurmountable.

Enhanced production of difficult-to-express proteins through knocking down rnpA gene expression.

Escherichia coli has been employed as a workhorse for the efficient production of recombinant proteins. However, some proteins were found to be difficult to produce in E. coli. The stability of mRNA has been considered as one of the important factors affecting recombinant protein production. Here we report a generally applicable and simple strategy for enhancing mRNA stability, and consequently improving recombinant protein production in E. coli. RNase P, a ribozyme comprising an RNA subunit (RnpB) and a protein subunit (RnpA), is involved in tRNA maturation. Based on the finding that purified RnpA can digest rRNA and mRNA in vitro, it was reasoned that knocking down the level of RnpA might enhance recombinant protein production. For this, the synthetic small regulatory RNA-based knockdown system was applied to reduce the expression level of RnpA. The developed RnpA knockdown system allowed successful overexpression of 23 different recombinant proteins of various origins and sizes, including Cas9 protein, antibody fragment, and spider silk protein. Notably, a 284.9-kDa ultra-high molecular weight, highly repetitive glycine-rich spider silk protein, which is one of the most difficult proteins to produce, could be produced to 1.38 g L-1 , about two-fold higher than the highest value previously achieved, by a fed-batch culture of recombinant E. coli strain employing the RnpA knockdown system. The RnpA-knockdown strategy reported here will be generally useful for the production of recombinant proteins including those that have been difficult to produce.

Diagnostic ultrasound of the chest wall in the symptomatic patient after mastectomy.

BACKGROUND: Lack of standardized imaging recommendations among mastectomy patients has led to variability in how recurrences are detected. OBJECTIVE: To describe the findings and assess the diagnostic efficacy of ultrasound in the evaluation of symptomatic post-mastectomy patients. MATERIALS AND METHODS: This single institution, retrospective study included 749 consecutive diagnostic chest wall ultrasound examinations performed in mastectomy patients, from January 2016 to June 2017. Chest wall ultrasound evaluated the mastectomy bed with or without reconstruction. Electronic health records were queried for the primary breast cancer histology prior to mastectomy, clinical symptoms prompting the diagnostic ultrasound, ultrasound findings, subsequent cytology and pathology, and follow-up data. Excluded were patients with a known recurrence, asymptomatic patients, and those with <2 years of clinical or imaging follow-up. Descriptive and comparative statistical analyses were performed. RESULTS: Among the 749 ultrasounds performed, 58 malignancies were identified for a 7.7% (58/749) malignancy rate, with a median tumor size of 20 mm. Patients diagnosed with a malignancy most often presented with a palpable abnormality (79.3%, 46/58) or skin changes (13.8%, 8/58) and rarely with pain (1.7%, 1/58). Patients who underwent a biopsy yielding a benign result most often presented with a palpable abnormality (41.5%, 287/691), pain (25.6%,177/691), or postoperative swelling/suspected fluid collection (17.8%, 123/691). Diagnostic ultrasound yielded a 91.4% sensitivity (95% CI 81.0, 97.1), 96.1% specificity (95% CI 94.4, 97.4), 66.3% PPV3 (95% CI 57.4, 74.1), and 99.3% negative predictive value (95% CI 98.3, 99.7) for cancer detection. There were 5 false negative ultrasound cases after a skin punch biopsy was performed due to clinically suspicious skin changes. CONCLUSIONS: Chest wall ultrasound has a high sensitivity and negative predictive value for detection of breast cancer recurrence in symptomatic patients after mastectomy. Skin changes remain an important clinical manifestation of a cancer recurrence.

Estimating the Incidence of First RSV Hospitalization in Children Born in Ontario, Canada.

BACKGROUND: Respiratory syncytial virus (RSV) contributes significantly to morbidity in children, placing substantial burdens on health systems, thus RSV vaccine development and program implementation are a public health priority. More data on burden are needed by policymakers to identify priority populations and formulate prevention strategies as vaccines are developed and licensed. METHODS: Using health administrative data, we calculated incidence rates of RSV hospitalization in a population-based birth cohort of all children born over a six-year period (May 2009 to June 2015) in Ontario, Canada. Children were followed until their first RSV hospitalization, death, 5th birthday, or the end of the study period (June 2016). RSV hospitalizations were identified using a validated algorithm based on International Classification of Diseases, 10th Revision, and/or laboratory-confirmed outcomes. We calculated hospitalization rates by various characteristics of interest, including calendar month, age groups, sex, comorbidities, and gestational age. RESULTS: The overall RSV hospitalization rate for children <5 years was 4.2 per 1000 person-years (PY) with a wide range across age groups (from 29.6 to 0.52 per 1000 PY in children aged 1 month and 36-59 months, respectively). Rates were higher in children born at a younger gestational age (23.2 per 1000 PY for those born at <28 weeks versus 3.9 per 1000 PY born at ≥37 weeks); this increased risk persisted as age increased. While the majority of children in our study had no comorbidities, rates were higher in children with comorbidities. For all age groups, rates were highest between December and March. CONCLUSIONS: Our results confirm the high burden of RSV hospitalization and highlight young infants are at additional risk, namely premature infants. These results can inform prevention efforts.

An Open-Source Virtual Reality System for the Measurement of Spatial Learning in Head-Restrained Mice.

Head-restrained behavioral experiments in mice allow neuroscientists to observe neural circuit activity with high-resolution electrophysiological and optical imaging tools while delivering precise sensory stimuli to a behaving animal. Recently, human and rodent studies using virtual reality (VR) environments have shown VR to be an important tool for uncovering the neural mechanisms underlying spatial learning in the hippocampus and cortex, due to the extremely precise control over parameters such as spatial and contextual cues. Setting up virtual environments for rodent spatial behaviors can, however, be costly and require an extensive background in engineering and computer programming. Here, we present a simple yet powerful system based upon inexpensive, modular, open-source hardware and software that enables researchers to study spatial learning in head-restrained mice using a VR environment. This system uses coupled microcontrollers to measure locomotion and deliver behavioral stimuli while head-restrained mice run on a wheel in concert with a virtual linear track environment rendered by a graphical software package running on a single-board computer. The emphasis on distributed processing allows researchers to design flexible, modular systems to elicit and measure complex spatial behaviors in mice in order to determine the connection between neural circuit activity and spatial learning in the mammalian brain.

Evaluating the Impact of Statin Use on Influenza Vaccine Effectiveness and Influenza Infection in Older Adults.

BACKGROUND: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. METHODS: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status. RESULTS: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for ß-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated ß-blocker users. CONCLUSIONS: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.

The Association Between Opioid Prescribing and Opioid-Related Mortality Within Neighborhoods in Ontario, Canada: A Case-Control Study.

OBJECTIVE: Recent Canadian data show that the prescribing of opioids has declined while the number of opioid deaths continues to rise. This study aimed to assess the relationship between neighborhood-level opioid prescription rates and opioid-related mortality among individuals without an opioid prescription. METHOD: This was a nested case-control study using data in Ontario from 2013 to 2019. Neighborhood-level data were analyzed by using dissemination areas that consist of 400-700 people. Cases were defined as individuals who had an opioid-related death without an opioid prescription filled in the year prior. Cases and controls were matched using a disease risk score. After matching, there were 2,401 cases and 8,813 controls. The primary exposure was the total volume of opioids dispensed within the individual's dissemination area in the 90 days before the index date. Conditional logistic regression was used to examine the association between opioid prescriptions and the risk of overdose. RESULTS: There was no significant association between the total volume of opioid prescriptions dispensed in a dissemination area and opioid-related mortality. In subgroup analyses stratifying the cohort into prescription and nonprescription opioid-related mortality, the number of prescriptions dispensed was positively associated with prescription opioid-related mortality. There was also a significant inverse association between the increased total volume of opioids dispensed and nonprescription opioid mortality. CONCLUSIONS: Our results suggest that prescription opioids dispensed within a neighborhood can have both potential benefits and harms. The opioid epidemic requires a nuanced approach that ensures appropriate pain care for patients while also creating a safer environment for opioid use through harm-reduction strategies.

Health conditions and service use of autistic women and men: A retrospective population-based case-control study.

LAY ABSTRACT: This study used administrative data from Ontario, Canada to compare the health conditions and service use of autistic women and men with adults with other developmental disabilities and with adults without developmental disabilities. Autistic women and men were more likely to have physical and mental health conditions compared to adults without developmental disabilities. Rates of health conditions were similar or lower among autistic adults compared to adults with other developmental disabilities, except more autistic adults had psychiatric conditions. Autistic women and men used higher rates of psychiatric services compared to all other groups. When comparing autistic women with same aged autistic men, sex differences were found for specific physical (Crohn's disease/colitis, rheumatoid arthritis) and psychiatric conditions (psychotic disorders, non-psychotic disorders), as well differences in service use (emergency department visits, hospitalizations, family doctor and neurologist visits). These results further highlight the high health needs and service use of autistic women and men, as well as adults with other developmental disabilities. It is critical for future research to focus on mental health support for autistic adults and to better understand how to tailor supports to best serve autistic women.

Increased medical student understanding of dementia through virtual embodiment.

Given the growing prevalence of Alzheimer's disease (AD), we assessed the impact of virtually embodying someone with progressive AD. This pilot explored students' understanding of individuals' needs with dementia, as well as, the efficacy of virtual reality (VR) as a curricular tool. Second-year medical students (n = 150) completed a pre-survey, Embodied Labs, Inc. Beatriz Lab VR module, and a post-survey. Most students knew someone with dementia (72%), were a family member of someone with dementia (52%) or had worked with a patient (61%) with dementia. Using paired survey questions, students reported significant increases in understanding how their lives would be affected by dementia (71% vs. 94%) and the needs of a person with dementia (64% vs. 95%) after VR. They reported increased understanding of being a caregiver of someone with dementia (24% vs. 81%) and the impact it can have on the entire family (64% vs. 97%). Overall students agreed this simulation made them think about their approach to clinical skills (94%) and should be utilized more in the curriculum (76%). This pilot study indicated that this VR experience can be used to advance understanding of a person's experiences with dementia and that integrating VR into the medical curricula should be considered.

Nipple Discharge Imaging Evaluation with Mammography, Ultrasound, Galactography, and MRI.

RATIONALE AND OBJECTIVE: To determine the diagnostic yield of various imaging tests used to evaluate nipple discharge. MATERIALS AND METHODS: A single institution, IRB-approved, retrospective study was performed of 320 consecutive patients presenting with nipple discharge. Imaging and pathology were reviewed to determine the yield for malignancy, atypical high-risk lesions (HRLs), and intraductal papillomas (IDPs). RESULTS: Of the 320 patients, pathology or follow up confirmed 40 breast malignancies (40/320, 12.5%),14 atypical HRLs (14/320, 4.4%), 71 IDPs (71/320, 22.2%), 48 other benign pathologies (48/320,15.0%), and 147 unknown but benign cases (147/320, 45.9%). Physiologic discharge characteristics were observed in a minority of malignant cases: nonspontaneous (4/40, 10.0%); neither bloody nor clear (4/40, 10.0%); bilateral (3/40, 7.5%). Malignancy was associated with older age (p < 0.001) and bloody discharge (odds ratio 6.5, p < 0.0001). The combination of digital mammography and ultrasound had a 93% sensitivity and a 98% NPV, while contrast enhanced MRI (CE-MRI) had a 100% sensitivity and a 100% NPV for malignancy. Only three galactography examinations were performed among the malignant cohort, with minimal contribution (1 of 3) to the diagnostic evaluation. In this case, galactography findings helped determine imaging-pathology discordance, prompting a recommendation for surgical excision and subsequently a malignant diagnosis. CONCLUSION: The combination of mammography and ultrasonography detected 93% of breast malignancies associated with nipple discharge and had a 98% NPV for malignancy. The value of CE-MRI is its ability to detect the remaining malignancies, not detected on mammography or ultrasound, and its ability to obviate the need for surgical duct excision.