Linkage of whole genome sequencing and administrative health data in autism: A proof of concept study.

Whether genetic testing in autism can help understand longitudinal health outcomes and health service needs is unclear. The objective of this study was to determine whether carrying an autism-associated rare genetic variant is associated with differences in health system utilization by autistic children and youth. This retrospective cohort study examined 415 autistic children/youth who underwent genome sequencing and data collection through a translational neuroscience program (Province of Ontario Neurodevelopmental Disorders Network). Participant data were linked to provincial health administrative databases to identify historical health service utilization, health care costs, and complex chronic medical conditions during a 3-year period. Health administrative data were compared between participants with and without a rare genetic variant in at least 1 of 74 genes associated with autism. Participants with a rare variant impacting an autism-associated gene (n = 83, 20%) were less likely to have received psychiatric care (at least one psychiatrist visit: 19.3% vs. 34.3%, p = 0.01; outpatient mental health visit: 66% vs. 77%, p = 0.04). Health care costs were similar between groups (median: $5589 vs. $4938, p = 0.4) and genetic status was not associated with odds of being a high-cost participant (top 20%) in this cohort. There were no differences in the proportion with complex chronic medical conditions between those with and without an autism-associated genetic variant. Our study highlights the feasibility and potential value of genomic and health system data linkage to understand health service needs, disparities, and health trajectories in individuals with neurodevelopmental conditions.

Validation of the International Breast Cancer Intervention Study (IBIS) model in the High Risk Ontario Breast Screening Program: A retrospective cohort study.

PURPOSE: Women with a remaining lifetime risk of breast cancer of ≥25%, estimated using the International Breast Cancer Intervention Study (IBIS) model, were eligible for the High Risk Ontario Breast Screening Program. This study examined the performance of IBIS 10-year risk estimates in the program. METHODS: This retrospective study included 7487 women aged 30 to 69 years referred to the High Risk Ontario Breast Screening Program between July 1, 2011, and December 31, 2016, with follow-up until December 31, 2018. Model calibration and discrimination were assessed. Analyses were conducted overall and stratified by age (< or ≥50 years). Different 10-year risk thresholds were compared with the current eligibility criteria. RESULTS: Overall, IBIS overestimated the risk of breast cancer with an expected vs observed case ratio of 1.17 (95% CI = 1.04-1.35). Overestimation was highest in women aged 50 to 69 years (expected vs observed case ratio = 1.29, 95% CI = 1.03-1.69) and for those in the top quartile of risk. Overall discrimination was fair with a concordance statistic of 0.66 (95% CI = 0.63-0.70). Furthermore, when using different 10-year risk eligibility thresholds, most cases would have been missed in the 30 to 49 age group using the 8% 10-year risk threshold, whereas relatively few women aged 50 to 69 would have been ineligible at any of the thresholds examined. CONCLUSION: We found that IBIS overestimated the risk of breast cancer in this screening cohort but had adequate discrimination. Age-specific risk thresholds should be considered to optimize the program eligibility criteria.

Screening behaviours, demographics, and stage at diagnosis in the publicly funded Ontario Breast Screening Program.

PURPOSE: The Ontario Breast Screening Program (OBSP) offers free screening mammograms every 2 years, to women aged 50-74. Study objectives were to determine demographic characteristics associated with the adherence to OBSP and if women screened in the OBSP have a lower stage at diagnosis than non-screened eligible women. METHODS: We used the Ontario cancer registry (OCR) to identify 48,927 women, aged 51-74 years, diagnosed with breast cancer between 2010 and 2017. These women were assigned as having undergone adherent screening (N = 26,108), non-adherent screening (N = 6546) or not-screened (N = 16,273) in the OBSP. We used multinomial logistic regression to investigate the demographic characteristics associated with screening behaviour, as well as the association between screening status and stage at diagnosis. RESULTS: Among women with breast cancer, those living in rural areas (versus the largest urban areas) had a lower odds of not being screened (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.68, 0.78). Women in low-income (versus high-income) communities were more likely not to be screened (OR 1.42, 95% CI 1.33, 1.51). When stratified, the association between income and screening status only held in urban areas. Non-screened women were more likely to be diagnosed with stage II (OR 1.91, 95% CI 1.82, 2.01), III (OR 2.96, 95% CI 2.76, 3.17), or IV (OR 8.96, 95% CI 7.94, 10.12) disease compared to stage I and were less likely to be diagnosed with ductal carcinoma in situ (DCIS) (OR 0.91, 95% CI 0.84-0.98). CONCLUSIONS: This study suggests that targeting OBSP recruitment efforts to lower income urban communities could increase screening rates. OBSP adherent women were more likely to be diagnosed with earlier stage disease, supporting the value of this initiative and those like it.

Maternal acetaminophen use and cognitive development at 4 years: the Ontario Birth Study.

BACKGROUND: Studies have suggested a link between prenatal maternal acetaminophen use and adverse developmental outcomes in children. However, there exists a knowledge gap regarding overall cognitive development and use of acetaminophen, especially concerning the timing of use in pregnancy. This study aimed to characterize the relationship between maternal acetaminophen use and cognitive development at 4 years. METHODS: This analysis included data collected throughout pregnancy and delivery from women in the Ontario Birth Study prospective cohort from 2013 to 2019 and from the NIH Toolbox Early Childhood Cognition battery administered to 4-year-old children between 2018 and 2021 (n = 436). The exposure was maternal acetaminophen use and the primary outcome was a cognition composite score. The relationship between exposure and outcome was determined using Poisson regression with a robust error variance. RESULTS: We did not observe any association between maternal acetaminophen intake any time before or during pregnancy and low cognition composite score of offspring. The IRR of suboptimal overall cognition was 1.38 (0.78-2.45), 1.22 (0.67-2.22), 0.80 (0.44-1.47), and 1.56 (0.74-3.29) for maternal use of acetaminophen before, in early, late, or overall pregnancy, respectively. CONCLUSION: Current data do not provide evidence to support a relationship of maternal acetaminophen use during pregnancy with adverse cognitive effects at 4 years. IMPACT: Acetaminophen use during pregnancy may influence the risk of child neurocognitive disorders, but there is conflicting evidence of its relationship to sub-clinical measures of cognitive development such as executive function. The study design allowed us to examine the role of timing of acetaminophen use in its relationship with cognitive development, based on a validated and standardized tablet-administered instrument for children, instead of a teacher or parent report. We did not observe a clear relationship between maternal acetaminophen use at different timepoints during pregnancy and child cognitive development.

The impact of chronic comorbidities at the time of breast cancer diagnosis on quality of life, and emotional health following treatment in Canada.

INTRODUCTION: Advances in breast cancer screening and treatment have led to an increasing number of breast cancer survivors. The objective of this study was to determine the impact of comorbidities on self-reported quality of life (QOL) and emotional health following a breast cancer diagnosis and treatment. METHODS: Women with a personal history of breast cancer (N = 3,372) were identified from the cross-sectional Canadian Partnership Against Cancer (CPAC) Experiences of Cancer Patients in Transitions Survey. Multinomial (nominal) logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the relationship between burden of comorbidities and overall QOL and emotional health (very poor/poor, fair, good, very good). RESULTS: Of the 3,372 participants, 57% reported at least one chronic condition at the time of breast cancer diagnosis. As the number of chronic conditions at diagnosis increased, the odds of reporting worse quality of life and emotional health following treatment also increased. Specifically, compared to women reporting very good QOL, for each additional chronic condition, women reported significantly higher odds of reporting good (OR = 1.22, 95% CI: 1.12, 1.32), fair (OR = 1.76, 95% CI: 1.58, 1.96), or poor/very poor (OR = 2.31, 95% CI: 1.86, 2.88) QOL. Similarly, for each additional comorbidity, women reported significantly higher odds of reporting good (OR = 1.17, 95% CI: 1.07, 1.28), fair (OR = 1.63, 95% CI: 1.46, 1.82), or poor/very poor (OR = 2.17, 95% CI: 1.81, 2.60) emotional health, relative to very good emotional health. CONCLUSION: Breast cancer survivors coping with a high comorbidity burden experience worse overall QOL and emotional health following treatment. This highlights the importance of integrating information on comorbidities into survivorship care to improve the experience and overall outcomes of patients with complex needs.

The association of estimated cardiorespiratory fitness with COVID-19 incidence and mortality: A cohort study.

BACKGROUND: It has been suggested that cardiorespiratory fitness (CRF) may be used to identify those at greatest risk for severe COVID-19 illness. However, no study to date has examined the association between CRF and COVID-19. The objectives of this study were to determine whether CRF is independently associated with testing positive with or dying from COVID-19. METHODS: This is a prospective cohort study of 2,690 adults from the UK Biobank Study that were followed from March 16th, 2020 to July 26th, 2020. Participants who were tested for COVID-19 and had undergone CRF assessment were examined. CRF was estimated (eCRF) and categorized as low (<20th percentile), moderate (20th to 80th percentile) and high (≥80th percentile) within sex and ten-year age groups (e.g. 50-60 years). Participants were classified as having COVID-19 if they tested positive (primarily PCR tests) at an in-patient or out-patient setting as of July 26, 2020. Participants were classified as having died from COVID-19 if the primary or underlying cause of death was listed ICD-10 codes U071 or U072 by June 30th, 2020. Adjusted risk ratios (aRR) and 95% confidence intervals (CI) were estimated and a forward model building approach used to identify covariates. FINDINGS: There was no significant association between eCRF and testing positive for COVID-19. Conversely, individuals with moderate (aRR = 0.43, 95% CI: 0.25, 0.75) and high fitness (aRR = 0.37, 95% CI: 0.16, 0.85) had a significantly lower risk of dying from COVID-19 than those with low fitness. CONCLUSIONS: While eCRF was not significantly associated with testing positive for COVID-19, we observed a significant dose-response between having higher eCRF and a decreased risk of dying from COVID-19. This suggests that prior gains in CRF could be protective against dying from COVID-19 should someone develop the virus.

Assessing the validity of administrative health data for the identification of children and youth with autism spectrum disorder in Ontario.

Population-level identification of children and youth with ASD is essential for surveillance and planning for required services. The objective of this study was to develop and validate an algorithm for the identification of children and youth with ASD using administrative health data. In this retrospective validation study, we linked an electronic medical record (EMR)-based reference standard, consisting 10,000 individuals aged 1-24 years, including 112 confirmed ASD cases to Ontario administrative health data, for the testing of multiple case-finding algorithms. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and corresponding 95% confidence intervals (CI) were calculated for each algorithm. The optimal algorithm was validated in three external cohorts representing family practice, education, and specialized clinical settings. The optimal algorithm included an ASD diagnostic code for a single hospital discharge or emergency department visit or outpatient surgery, or three ASD physician billing codes in 3 years. This algorithm's sensitivity was 50.0% (95%CI 40.7-88.7%), specificity 99.6% (99.4-99.7), PPV 56.6% (46.8-66.3), and NPV 99.4% (99.3-99.6). The results of this study illustrate limitations and need for cautious interpretation when using administrative health data alone for the identification of children and youth with ASD. LAY SUMMARY: We tested algorithms (set of rules) to identify young people with ASD using routinely collected administrative health data. Even the best algorithm misses more than half of those in Ontario with ASD. To understand this better, we tested how well the algorithm worked in different settings (family practice, education, and specialized clinics). The identification of individuals with ASD at a population level is essential for planning for support services and the allocation of resources. Autism Res 2021, 14: 1037-1045. © 2021 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

Measures of Adiposity and Risk of Testing Positive for SARS-CoV-2 in the UK Biobank Study.

Objective: To assess if body mass index (BMI) and high waist circumference (HWC) are associated with testing positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: 9,386 UK Biobank study participants tested for SARS-CoV-2 from March 16th 2020 to June 29th 2020 were analyzed. A forward model building approach was used to estimate adjusted risk ratios (RR) and 95% confidence intervals (95% CI). Analyses were stratified by age due to a significant first-order interaction between age and HWC. Results: Approximately 17% (n = 1,577) of participants tested positive for SARS-CoV-2. BMI category had a linear association with testing positive for SARS-CoV-2 among participants <65 years (RR = 1.09, 95% CI 1.02-1.17). For participants ≥65 years, only obesity class II (RR = 1.38, 95% CI 1.10-1.74) had a significantly greater risk of testing positive for SARS-CoV-2 than those who were underweight/normal weight. While HWC was not associated with testing positive for SARS-CoV-2 in those <65 years, having an HWC was associated with an increased risk of testing positive for SARS-CoV-2 in participants ≥65 years (RR = 1.12, 95% CI 1.00-1.27). Conclusion: The associations of BMI and HWC with testing positive for SARS-CoV-2 differed by age. Notably, HWC was associated with testing positive in those ≥65 years, but not those who were younger, independent of BMI. This suggests that measures of adiposity in addition to BMI may be used to identify older individuals at greater risk of testing positive for SARS-CoV-2.

Identifying Children and Youth With Autism Spectrum Disorder in Electronic Medical Records: Examining Health System Utilization and Comorbidities.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder requiring significant health and educational resources for affected individuals. A reference standard for ASD was generated from an existing population-based cohort of 10,000 children and youth aged 1-24 years who were randomly selected for chart abstraction from 29,256 patients from 119 family physicians. We developed and validated an algorithm to identify children and youth with ASD within an electronic medical record system (N = 80,237, aged 1-24 years) in order to examine the prevalence of comorbidities and quantify health system utilization within the cohort. We identified 1,062 children and youth with ASD representing a prevalence of 1.32%. Compared to individuals without ASD, those with ASD had a higher prevalence of asthma, were more likely to visit a specialist, undergo surgery, and be hospitalized for psychiatric reasons. Children and youth with ASD in Ontario have complex health system needs, illustrated through a significant burden of comorbidities and increased health system utilization. LAY SUMMARY: Our paper generates population-based estimates of health system use by children and youth with ASD, who have a higher burden of comorbidities than the general population. We developed a case-finding algorithm and applied it in electronic medical records to create a cohort of children and youth with ASD, thereby generating an important resource to further study the health care needs of individuals with ASD.

Association between maternal acetaminophen use and adverse birth outcomes in a pregnancy and birth cohort.

INTRODUCTION: Acetaminophen is the only analgesic recommended for use during pregnancy. This use has recently been linked to childhood developmental disorders, a finding that requires further investigation. Adverse birth outcomes-preterm birth, low birthweight, and small for gestational age-are associated with increased risk of developmental disorders and can serve as intermediate outcomes when examining the impact of maternal acetaminophen use. METHODS: Clinical and lifestyle-factor data were gathered from 1200 women within the Ontario Birth Study who delivered between January 2013 and June 2017. Poisson regression with robust error variance was used to estimate the relationship between acetaminophen use before and during pregnancy and low birthweight, preterm birth, and small for gestational age. RESULTS: Offspring of mothers who used acetaminophen before pregnancy had a higher risk of low birthweight and small for gestational age. Acetaminophen use

"You've got to look after yourself, to be able to look after them" a qualitative study of the unmet needs of caregivers of community based primary health care patients.

BACKGROUND: There is growing reliance on unpaid caregivers to provide support to people with care needs. Integrated care approaches that aim to coordinate primary care with community care known as community based primary health care (CBPHC) has been a key policy initiative across health systems; however most attention has been paid to the needs of patients and not caregivers. The objective of this paper was to explore the unmet needs of caregivers of older adults with complex care needs receiving CBPHC. METHODS: This qualitative descriptive study entailed one-to-one interviews with 80 caregivers from Canada and New Zealand where roles, experiences and needs were explored. Interview text related to unmet need was reviewed inductively and core themes identified. RESULTS: Three themes were identified across CBPHC sites: unrecognized role; lack of personal resources; and no breaks even when services are in place. CONCLUSIONS: To support caregivers, models of care such as CBPHC need to look beyond the patient to meaningfully engage caregivers, address their needs and recognize the insight they hold. This knowledge needs to be valued as a key source of evidence to inform developments in health and social care.

How Can We Keep Immigrant Travelers Healthy? Health Challenges Experienced by Canadian South Asian Travelers Visiting Friends and Relatives.

Immigrant travelers who visit friends and relatives (VFR travelers) experience substantially higher rates of travel-related infections than other travelers, in part due to low uptake of pretravel health advice. While barriers to accessing advice have been identified, better characterization is needed to inform targeted interventions. We sought to understand how South Asian VFR travelers perceived and responded to travel-related health risks by conducting group interviews with 32 adult travelers from an ethnoculturally diverse Canadian region. Travelers positioned themselves as knowledgeable of key health risks, despite not seeking pretravel health advice. Their responses to risks were pragmatic and rooted in experience, but often constrained by competing concerns, including rushed travel, familial obligations, cost, and a desire to preserve authentic experiences. Moving beyond risk awareness to reinforcing the value of medical advice and intervention, in a manner that is sensitive to these unique concerns, is needed when delivering tailored health promotion messages to VFR travelers.