Exome Sequencing of a Blastomycosis Case-Control Cohort From Manitoba and Northwestern Ontario, Canada.

BACKGROUND: Blastomycosis is a pulmonary disease caused by Blastomyces spp., a group of pathogenic dimorphic fungi endemic to a number of geographic regions, specifically Manitoba and northwestern Ontario, Canada. Immunosuppression is a major risk factor affecting disease susceptibility, yet host immunity is not well understood. Genetic immunodeficiencies can also influence disease, with variants in IL6, GATA2 and VDBP shown to influence susceptibility. Additional genetic factors in disease susceptibility and severity remain undetected. Our study seeks to identify potential genetic risk factors in a blastomycosis case-control cohort from Manitoba and northwestern Ontario, Canada. METHODS: Exomes from 18 blastomycosis cases and 9 controls were sequenced, variants were identified and filtered for accuracy and quality. We performed candidate gene prioritisation and variant aggregation to identify genetic associations and explored the full exome dataset. RESULTS: Ninety-nine genetic variants in 42 candidate genes were identified in the exome dataset. No variants associated with susceptibility were identified in a single-variant analysis although two non-synonymous variants in TYK2 were enriched among cases suggesting a possible role in susceptibility. Gene-based association analysis found variants in TLR1 enriched in controls (p = 0.024) suggesting a possible protective effect. Gene cluster analysis identified genetic variants in genes of chromatin remodelling, proteasome and intraflagellar transport significantly enriched in cases (false discovery rates < 14%). CONCLUSIONS: The findings in this study show novel associations with blastomycosis susceptibility. A better understanding of host immunity and genetic predisposition to Blastomyces infection can help to inform clinical practice for improved outcomes.

Treatment reclassification in Canada from the Osteoporosis Canada 2023 clinical practice guidelines: the Manitoba BMD Registry.

Osteoporosis Canada 2023 clinical practice guidelines increase the number of individuals recommended or suggested for anti-osteoporosis pharmacotherapy by refining treatment guidance for those who fell within the 2010 guidelines' moderate-risk category. PURPOSE: In 2023, Osteoporosis Canada updated its 2010 clinical practice guidelines based upon consideration of fracture history, 10-year major osteoporotic fracture (MOF) risk, and BMD T-score in conjunction with age. The 2023 guidelines eliminated risk categories, including the moderate-risk group that did not provide clear treatment guidance. The current study was performed to appreciate the implications of the shift from 2010 risk categories to 2023 treatment guidance. METHODS: The study population consisted of 79,654 individuals age ≥ 50 years undergoing baseline DXA testing from January 1996 to March 2018. Each individual was assigned to mutually exclusive categories based on 2010 and 2023 guideline recommendations. Treatment qualification, 10-year predicted and 10-year observed MOF risk were compared. RESULTS: Treatment reclassification under the 2023 guidelines only affected 33.8% of individuals in the 2010 moderate-risk group, with 13.0% assigned to no treatment, 14.4% to suggest treatment, and 6.4% to recommend treatment. During the mean follow-up of 7.2 years, 6364 (8.0%) individuals experienced one or more incidents of MOF. The observed 10-year cumulative incidence of MOF in the study population was 10.5% versus the predicted 10.7% (observed to predicted mean calibration ratio 0.98, 95% CI 0.96-1.00). Individuals reclassified from 2010 moderate risk to 2023 recommend treatment were at greater MOF risk than those in the 2010 moderate-risk group assigned to 2023 suggest treatment or no treatment, but at lower risk than those in the 2010 high-risk group. CONCLUSIONS: Osteoporosis Canada 2023 clinical practice guidelines affect individuals within the 2010 moderate-risk category, increasing the number for whom anti-osteoporosis pharmacotherapy is recommended or suggested. Increased treatment could reduce the population burden of osteoporotic fractures, though moderate-risk individuals now qualifying for treatment have a lower predicted and observed fracture risk than high-risk individuals recommended for treatment under the 2010 guidelines.

Evaluating the impact of COVID-19 on medication adherence and health care utilization among individuals with psychotic disorders who are prescribed long-acting injectables (LAIs) or clozapine: A population-based study in Manitoba, Canada.

BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization. METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models. RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable. CONCLUSION: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.

The impact of COVID-19 public health measures on the utilization of antipsychotics in schizophrenia in Manitoba - A population-based study.

PURPOSE: During the COVID-19 pandemic, public health measures were implemented, yet it is unknown whether these measures affected medication access in those with schizophrenia (SCZ). This study aimed to assess whether the antipsychotic utilization in SCZ changed during the pandemic. METHODS: We used dispensed prescription drug data from the Canadian province of Manitoba in individuals with SCZ using linked administrative data from the Manitoba Population Research Data Repository. The quarterly incident and prevalent dispensation of antipsychotics at two periods were compared with the expected trend (April 1, 2015 to April 1, 2020 and 2021) using linear autoregression. We stratified the primary results by age and sex and examined multiple subgroups. RESULTS: There were 9045 individuals with SCZ in the first fiscal quarter of 2020. The prevalent use of the most common antipsychotics were: olanzapine (206.7/1000), risperidone (190.8/1000), quetiapine (174.4/1000), and clozapine (100.9/1000). The overall prevalent use of antipsychotics remained stable during the pandemic compared with the expected trend. A significant decrease in the incident use in April-June 2020 (estimate: -1.3, 95%CI:-2.2,-0.3) was noted compared with the expected. A significantly higher incidence of atypical antipsychotics (estimate: 1.4, 95%CI: 0.2,2.5) and risperidone separately (estimate: 1.8, 95%CI: 0.2,3.3) was noted in 2021 compared with expected. CONCLUSION: This study found a decline in the receipt of antipsychotics for people with SCZ during the initial implementation of COVID-19 public health measures, particularly on the overall incidence. Future work on investigating the impact of these trends on SCZ outcomes is needed to inform future pandemic-related policies.

Building and validating trend-based multiple sclerosis case definitions: a population-based cohort study for Manitoba, Canada.

OBJECTIVE: This study aims to (1) build and validate model-based case definitions for multiple sclerosis (MS) that use trends (ie, trend-based case definitions) and (2) to apply dynamic classification to identify the average number of data years needed for classification (ie, average trend needed). DESIGN: Retrospective cohort study design. PARTICIPANTS: 608 MS cases and 59 620 MS non-cases. SETTING: Data from 1 April 2004 to 31 March 2022 were obtained from the Manitoba Population Research Data Repository. MS case status was ascertained from homecare records and linked to health data. Trend-based case definitions were constructed using multivariate generalised linear mixed models applied to annual numbers of general and specialist physician visits, hospitalisations and MS healthcare contacts or medication dispensations. Dynamic classification, which ascertains cases and non-cases annually, was used to estimate mean classification time. Classification accuracy performance measures, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), proportion correctly classified (PCC) and F1-scores, were compared for trend-based case definitions and a deterministic case definition of 3+MS healthcare contacts or medication dispensations. RESULTS: When applied to the full study period, classification accuracy performance measure estimates for all case definitions exceeded 0.90, except sensitivity and PPV for the trend-based dynamic case definition (0.88, 0.64, respectively). PCC was high for all case definitions (0.94-0.99); F1-scores were lower for the trend-based case definitions compared with the deterministic case definition (0.74-0.93 vs 0.96). Dynamic classification identified 5 years as the average trend needed. When applied to the average trend windows, accuracy estimates for trend-based case definitions were lower than the estimates from the full study period (sensitivity: 0.77-0.89; specificity: 0.90-0.97; PPV: 0.54-0.81; NPV: 0.97-0.99; F1-score: 0.64-0.84). Accuracy estimates for the deterministic case definition remained high, except sensitivity (0.42-0.80). F1-score was variable (0.59-0.89). CONCLUSIONS: Trend-based and deterministic case definitions classifications were similar to a population-based clinician assessment reference standard for multiple measures of classification accuracy. However, accuracy estimates for both trend-based and deterministic case definitions varied as the years of data used for classification were reduced. Dynamic classification appears to be a viable option for identifying the average trend needed for trend-based case definitions.

Powassan Virus Encephalitis after Tick Bite, Manitoba, Canada.

A case of Powassan encephalitis occurred in Manitoba, Canada, after the bite of a black-legged tick. Awareness of this emerging tickborne illness is needed because the number of vector tick species is growing. No specific treatment options exist, and cases with illness and death are high. Prevention is crucial.

Birth Outcomes Among First Nations Birthing Parents Incarcerated While Pregnant: A Linked Administrative Data Study From Manitoba, Canada.

BACKGROUND: In Canada, colonial policies have resulted in health inequities between First Nations and other Canadians. These policies contribute to overrepresentation of First Nations in the criminal legal system, where incarcerated people and their infants face elevated health risks. We investigated the association between prenatal incarceration and adverse birth outcomes among First Nations and other birthing parents in Manitoba, Canada. METHODS: Using linked whole-population administrative data, we identified all live births (2004-2017) in which the birthing parent (First Nations n = 1,449; other Manitoban n = 278) was prenatally incarcerated and compared them to birthing parents who were postnatally incarcerated (First Nations n = 5,290; other Manitoban n = 790) or not incarcerated (First Nations n = 19,950; other Manitoban n = 3,203). We used generalized linear models adjusted for measured confounders with propensity score weighting to calculate risk differences and 95% confidence intervals for adverse birth outcomes among those prenatally versus postnatally incarcerated in each group. RESULTS: Low birthweight births were more likely among First Nations birthing parents who were prenatally (vs. postnatally) incarcerated (risk difference 1.59, 95% CI [.79, 2.38]) but less likely among other Manitoban birthing parents (risk difference -2.33, 95% CI [-4.50, -.16]) who were prenatally (vs. postnatally) incarcerated. Among First Nations, prenatal incarceration was also associated with large-for-gestational-age births, low Apgar scores, and no breastfeeding (vs. postnatal incarceration), as well as preterm births (vs. no incarceration). Among other Manitobans, prenatal incarceration was also associated with small-for-gestational-age births, low Apgar scores, and no breastfeeding (vs. postnatal incarceration), as well as preterm births (vs. no incarceration). CONCLUSIONS: The findings suggest that incarceration may contribute to intergenerational systems of oppression by compromising birth outcomes among First Nations and other birthing parents in Canada and underscore the need to both improve care for pregnant people who are incarcerated and invest in alternatives to incarceration.

Osteomyelitis of the Jaw: A 10-Year Retrospective Analysis at a Tertiary Health Care Centre in Canada.

BACKGROUND: Osteomyelitis (OM) of the jaw is a rare medical condition. In this review, we provide a descriptive analysis of the experience with this condition at a single tertiary health care centre in Canada over 10 years. MATERIALS AND METHODS: We conducted a retrospective chart review of adult patients aged ≥ 18 years presenting with OM of the jaw at the University of Manitoba Health Sciences Centre between January 2009 and May 2019. We included cases with consistent clinical symptoms and radiographic and/or microbiologic evidence of OM of the jaw. Excluded were cases with a previous history of head and neck cancer, radiation therapy in the head and neck regions and use of anti-resorptive medications. RESULTS: Of the 37 patients who met our criteria, the mean age was 44 years (standard deviation [SD] ± 16 years), 21 (56.8%) were male, 16 (43.2%) were diagnosed with acute OM and 21 (57.8%) with chronic OM. Underlying comorbidities, such as diabetes mellitus and chronic kidney diseases, were reported in 6 (16.2%) and 3 patients (8.1%), respectively. Traumatic injuries to the facial skeleton were the most common predisposing factor (11 patients [29.7%]). The most commonly isolated infective organisms were viridans group streptococci (VGS; 75.8%), followed by Prevotella spp. (45.4%). Results showed a higher level of resistance to penicillin of the isolated organisms in chronic OM compared with acute OM. CONCLUSIONS: This description of acute and chronic forms of OM of the jaw will enable clinicians to better understand OM patient profiles, leading to early diagnosis, improved patient care and better outcomes.

Examining the Association Between the COVID-19 Pandemic and the Rate of Diagnostic Tests for Breast, Cervical, and Colorectal Cancer in Manitoba, Canada.

Background: Strategies to minimize the impact of the COVID-19 pandemic led to a reduction in diagnostic testing. It is important to assess the magnitude and duration of this impact to plan ongoing care and avoid long-lasting impacts of the pandemic. Objective: We examined the association between the COVID-19 pandemic and the rate of diagnostic tests for breast, cervical, and colorectal cancer in Manitoba, Canada. Design and Participants: A population-based, cross-sectional study design with an interrupted time series analysis was used that included diagnostic tests from January 1, 2015 until August 31, 2022. Setting: Manitoba, Canada. Main Outcomes: Outcomes included mammogram, breast ultrasound, colposcopy, and colonoscopy rates per 100,000. Cumulative and percent cumulative differences between the fitted and counterfactual number of tests were estimated. Mean, median, and 90th percentile number of days from referral to colonoscopy date by referral type (elective, semiurgent, urgent) were determined. Results: In April 2020, following the declaration of the COVID-19 public health emergency, bilateral mammograms decreased by 77%, unilateral mammograms by 70%, breast ultrasounds by 53%, colposcopies by 63%, and colonoscopies by 75%. In Winnipeg (the largest urban center in the province), elective and semiurgent colonoscopies decreased by 76% and 39%, respectively. There was no decrease in urgent colonoscopies. As of August 2022, there were an estimated 7270 (10.7%) fewer bilateral mammograms, 2722 (14.8%) fewer breast ultrasounds, 836 (3.3%) fewer colposcopies, and 11 600 (13.8%) fewer colonoscopies than expected in the absence of COVID-19. As of December 2022, in Winnipeg, there were an estimated 6030 (23.9%) fewer elective colonoscopies, 313 (2.6%) fewer semiurgent colonoscopies, and 438 (27.3%) more urgent colonoscopies. Conclusions: In Manitoba, the COVID-19 pandemic was associated with sizable decreases in diagnostic tests for breast, colorectal, and cervical cancer. Two and a half years later, there remained large cumulative deficits in bilateral mammograms, breast ultrasounds, and colonoscopies.

Clinical Outcomes in T4 and/or N2 Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: A Retrospective Study.

INTRODUCTION: Total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features. METHODOLOGY: In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with chemoradiotherapy followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019. RESULTS: The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (P = .001) and in the N2 sub-cohort (P = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR. CONCLUSIONS: Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.

Introduction of an order set after hip fracture improves osteoporosis medication initiation and persistence: a population-based before-after analysis.

We found that a standardized order set after hip fracture increased initiation of anti-osteoporosis medication and increased persistence at 1 year, but did not reduce secondary fractures. BACKGROUND: A treatment gap exists after osteoporosis-related fractures. Introducing standardized care can improve treatment. We evaluated the impact of a hip fracture order set (OS) on anti-osteoporosis medication (AOM) initiation, persistence, and secondary fracture prevention. METHODS: In 2015, one hospital in Manitoba, Canada, introduced a hip fracture OS including recommendations for the initiation of AOM (OS group). A control group was identified from the other hospitals in the same region. A retrospective cohort study was conducted using linked administrative health data. All individuals 50 + years with surgical treatment for low-energy hip fracture between 2010 and 2019 were included and followed for AOM initiation, medication persistence at 1 year, and secondary fractures. Between-group differences for each year were assessed using chi-square tests. Logistic regression models tested the impact of socio-demographic and clinical factors on initiation, persistence of AOM. Cox regression tested the risk of secondary fracture. RESULTS: No baseline differences between OS group (813 patients) and control group (2150 patients) were observed in demographics, socioeconomic factors, or comorbidities. An increase in post-fracture AOM initiation was seen with OS introduction (OS group year before 16.7% versus year after 48.6%, p < 0.001). No change was seen in the control group. Persistence on AOM also increased (OS group year before 17.7% versus year after 28.4%, p < 0.001). No difference in secondary fractures was observed (OS group 19.8% versus control group 18.8%, p = 0.38). CONCLUSION: Introduction of a hip fracture OS significantly increased AOM initiation and persistence at 1-year post-fracture. There was no significant difference in secondary fractures.

Burden of recreational water illness due to exposure to cyanobacteria and their toxins in freshwater beaches in Canada: protocol of a prospective cohort study.

INTRODUCTION: Cyanobacterial blooms are increasingly common in freshwater sources used for swimming and other recreational water contact activities in Canada. Many species of cyanobacteria can produce toxins that affect human and animal health, but there are limited data on the risk of illness associated with water contact at impacted beaches. METHODS AND ANALYSIS: This study will investigate the incidence of recreational water illness due to exposure to cyanobacterial blooms and their toxins in four targeted and popular freshwater beaches in Ontario, Manitoba and Nova Scotia, Canada. A prospective cohort design and One Health approach will be used. On-site recruitment of recreational water users will be conducted at two beaches per year during the summers of 2024 and 2025. The population of interest includes recreational water users of any age and their pet dogs. After enrolment, an in-person survey will determine beach exposures and confounding factors, and a 3-day follow-up survey will ascertain any acute illness outcomes experienced by participants or their dogs. The target sample size is 2500 recreational water users. Water samples will be taken each recruitment day and analysed for cyanobacterial indicators (pigments), cell counts and toxin levels. Bayesian regression analysis will be conducted to estimate the association with water contact, cyanobacterial levels and risks of different acute illness outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Toronto Metropolitan University Research Ethics Board (REB 2023-461). Study results will be published in a peer-reviewed journal and as infographics on a project website.

Body Louse Pathogen Surveillance among Persons Experiencing Homelessness, Canada, 2020-2021.

We analyzed body lice collected from persons experiencing homelessness in Winnipeg, Manitoba, Canada, during 2020-2021 to confirm vector species and ecotype and to identify louseborne pathogens. Of 556 lice analyzed from 7 persons, 17 louse pools (218 lice) from 1 person were positive for the louseborne bacterium Bartonella quintana.

A case for implementing an HSV1/2, VZV, and syphilis lesion panel in Manitoba, Canada.

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.IMPORTANCESyphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis.

The Gigii-Bapiimin Study: resilience and the impacts of COVID-19 on health and wellbeing of Indigenous people living with HIV in Manitoba and Saskatchewan.

The Gigii-Bapiimin study explored the impacts of the COVID-19 pandemic on the health and wellbeing of First Nations, Inuit, and Métis people living with HIV in Manitoba and Saskatchewan, two provinces in Canada with alarmingly high rates of HIV infections. Participants (n = 28 in Manitoba and n = 23 in Saskatchewan) were recruited using various methods, including flyers, community organizations, peers, and social media. The qualitative interviews focused on the pandemic's impact on health, access to services, and ceremonies. The data were analyzed using inductive thematic analysis. The study identified three key themes: (a) resilience and coping; (b) negative impacts on health and substance use; (c) decreased access to health services, HIV care and harm reduction. The participants shared their experiences of social isolation and the loss of community support, which had deleterious effects on their mental health and substance use. The impacts on access to HIV care were exacerbated by poverty, homelessness, and distress over inadvertent disclosure of HIV status. Participants mitigated these impacts by relying on Indigenous knowledges, ceremonies, and resilience within their communities. Service providers must address the impacts of the COVID-19 pandemic on Indigenous people living with HIV and their access to HIV services and ceremonies.

Risks of congenital malformations and neonatal intensive care unit admissions with gabapentin use in pregnancy: A cohort study and scoping review with meta-analysis.

BACKGROUND: The increasing and prevalent use of gabapentin among pregnant people highlights the necessity to assess its neonatal safety. OBJECTIVES: This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence. METHODS: We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results. RESULTS: Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95% confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99, 95% CI 1.70, 2.32). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I2 = 0%). CONCLUSIONS: Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.

Effect of abdominal tissue thickness on trabecular bone score and fracture risk in adults with diabetes: the Manitoba BMD registry.

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher bone mineral density. However, measures of trabecular microarchitecture from high-resolution peripheral computed tomography are not lower in type 2 diabetes. We hypothesized that confounding effects of abdominal tissue thickness may explain this discrepancy, since central obesity is a risk factor for diabetes and also artifactually lowers TBS. This hypothesis was tested in individuals aged 40 years and older from a large DXA registry, stratified by sex and diabetes status. When DXA-measured abdominal tissue thickness was not included as a covariate, men without diabetes had lower TBS than women without diabetes (mean difference -0.074, P < .001). TBS was lower in women with versus without diabetes (mean difference -0.037, P < .001), and men with versus without diabetes (mean difference -0.007, P = .042). When adjusted for tissue thickness these findings reversed, TBS became greater in men versus women without diabetes (mean difference +0.053, P < .001), in women with versus without diabetes (mean difference +0.008, P < .001), and in men with versus without diabetes (mean difference +0.014, P < .001). During mean 8.7 years observation, incident major osteoporotic fractures were seen in 7048 (9.6%). Adjusted for multiple covariates except tissue thickness, TBS predicted fracture in all subgroups with no significant diabetes interaction. When further adjusted for tissue thickness, HR per SD lower TBS remained significant and even increased slightly. In conclusion, TBS predicts fractures independent of other clinical risk factors in both women and men, with and without diabetes. Excess abdominal tissue thickness in men and individuals with type 2 diabetes may artifactually lower TBS using the current algorithm, which reverses after accounting for tissue thickness. This supports ongoing efforts to update the TBS algorithm to directly account for the effects of abdominal tissue thickness for improved fracture risk prediction.

Individuals with type 2 diabetes are at increased fracture risk despite having higher bone mineral density (BMD). Previous studies suggest that trabecular bone score (TBS), a measure of bone derived from spine DXA images that can be used to assess fracture risk in addition to BMD, may be lower in individuals with type 2 diabetes. However, TBS is artificially lowered by greater abdominal obesity. We showed that abdominal obesity explained the lower TBS measurements that were seen in individuals with type 2 diabetes. However, even when we considered the effect of abdominal obesity, TBS was still able to predict major fractures in both women and men, with and without diabetes.

The Intergenerational Transfer of Mental Disorders: A Population-Based Multigenerational Linkage Study: Le transfert intergénérationnel des troubles mentaux : une étude sur les liens multigénérationnels basée sur la population.

OBJECTIVES: The aetiology of mental disorders involves genetic and environmental factors, both reflected in family health history. We examined the intergenerational transmission of multiple mental disorders from parents and grandparents using population-based, objectively measured family histories. METHODS: This population-based retrospective cohort study used administrative healthcare databases in Manitoba, Canada and included adults living in Manitoba from 1977 to 2020 with linkages to at least one parent and one grandparent. Index date was when individuals turned 18 or 1 April 1977, whichever occurred later. Mental disorder diagnoses (mood and anxiety, substance use and psychotic disorders) were identified in individuals, parents and grandparents from hospitalization and outpatient records. Cox proportional hazards regression models included sociodemographic characteristics, individual's comorbidity and mental disorder history in a grandparent, mother and father. RESULTS: Of 109,359 individuals with no mental disorder prior to index date, 47.1% were female, 36.3% had a mental disorder during follow-up, and 90.9% had a parent or grandparent with a history of a mental disorder prior to the index date. Both paternal and maternal history of a mental disorder increased the risk of the disorder in individuals. Psychotic disorders had the strongest association with parental history and were mostly influenced by paternal (hazards ratio [HR] 3.73, 95% confidence interval [CI] 2.99 to 4.64) compared to maternal history (HR 2.23, 95% CI, 1.89 to 2.64). Grandparent history was independently associated with the risk of all mental disorders but had the strongest influence on substance use disorders (HR 1.42, 95% CI, 1.34 to 1.50). CONCLUSIONS: Parental history of mental disorders was associated with an increased risk of all mental disorders. Grandparent history of mental disorders was associated with a small risk increase of the disorders above and beyond parental history influence. This three-generation study further highlights the need for family-based interventional programs in families affected by mental disorders. PLAIN LANGUAGE SUMMARY TITLE: The Intergenerational Transfer of Mental Illnesses.

ObjectivesBoth genetics and environmental factors, such as poverty, maltreatment and parental education, have a role in the development of mental illnesses. Some genetic and environmental risk factors for mental illnesses are shared within families. We conducted a large study to test the extent to which mental illnesses are passed down through generations.MethodsThis study used healthcare data from Manitoba, Canada captured during the delivery of healthcare services for administrative purposes. These data included all adults from 1977 to 2020 who had at least one parent and one grandparent with linked data. Mental illnesses were diagnosed in individuals, parents and grandparents by doctors during hospitalizations or physician visits. The illnesses included mood and anxiety, substance use, and psychotic illnesses. We estimated the likelihood of developing a mental illness when parents and/or grandparents had a mental illness as well.ResultsThe study included 109,359 individuals; a third developed a mental illness during the study period. The majority had a history of a mental illness in a parent or grandparent. We found that a history of mental illness in a mother and father increased the chance of developing the illness. Psychotic illnesses had the strongest relation with parental history. In particular, having a father with a psychotic illness increased the chance of developing the illness by four times. The likelihood of developing a mental illness was higher if a grandparent had a mental illness, above and beyond parental history influence, particularly for substance use disorders.ConclusionsHaving a parent or grandparent with a mental illness increases an individual's chance of developing a mental illness. Family-based intervention programs are needed to support families affected by mental illnesses in coping with their heavy burden.

Fracture Risk Associated with Different Numbers and Combinations of Lumbar Vertebrae: The Manitoba BMD Registry.

Bone mineral density (BMD) is widely used for assessment of fracture risk. For the lumbar spine, BMD is typically measured from L1-L4 as it provides the largest area for assessment with the best measurement precision. Structural artifact often confounds spine BMD in clinical practice, and the International Society for Clinical Densitometry (ISCD) recommends removing vertebrae with artifact when reporting spine BMD. In its most recent position statements, the ISCD recommended against the use of a single vertebra when reporting spine BMD but stated that further studies should be done. The current analysis was performed to compare the performance of BMD from different numbers and combination of vertebral levels on fracture prediction in a large clinical registry of DXA tests for the Province of Manitoba, Canada. The study population comprised 39,727 individuals aged 40 years and older (mean age 62.7 years, 91.0 % female) with baseline DXA after excluding those with evidence of structural artifact. Mean follow-up for ascertaining fracture outcomes was 8.7 years. Area under the curve (AUC) for incident fracture risk stratification was statistically significant regardless of the BMD measurement site or fracture outcome. AUC differences with the various numbers and combinations of vertebral levels including a single vertebral body were small (less than or equal to 0.01). More substantial AUC differences were seen for femoral neck and total hip BMD versus L1-L4 BMD, approaching 0.1 for hip fracture stratification. In summary, we found that using combinations of fewer than 4 vertebrae including individual lumbar vertebrae predicted incident fractures. Importantly, differences between these different combinations were small when compared with L1-L4. Spine BMD was a better predictor of incident spine fracture compared to the hip, whereas the hip was better for hip fracture and overall fracture prediction.

Gastroschisis and septo-optic-pituitary dysplasia: Is there an association?

AIM: There are several case reports describing patients with both optic nerve hypoplasia/septo-optic-pituitary dysplasia (ONH/SOD) and gastroschisis (GS). Our aim was to investigate whether ONH/SOD is associated with GS. METHODS: A retrospective population-based study was undertaken using the Population Research Data Repository at the Manitoba Center for Health Policy in Manitoba, Canada to investigate if any patient with ONH/SOD also had GS. In addition, Winnipeg's Surgical Database of Outcomes and Management (WiSDOM), a hospital-based paediatric surgical database, was searched to ascertain if any of the patients with GS also have ONH/SOD. RESULTS: Cases were 124 patients with ONH/SOD diagnosed during 1990-2019. None had GS. The surgical database had 188 patients from Manitoba with GS during 1991-2019. None had ONH/SOD. CONCLUSION: There does not appear to be an association between ONH/SOD and GS in our cohorts of patients with these two disorders.