Ethnic differences in the association between age at diagnosis of diabetes and the risk of cardiovascular complications: a population-based cohort study.

BACKGROUND: We examined ethnic differences in the association between age at diagnosis of diabetes and the risk of cardiovascular complications. METHODS: We conducted a population-based cohort study in Ontario, Canada among individuals with diabetes and matched individuals without diabetes (2002-18). We fit Cox proportional hazards models to determine the associations of age at diagnosis and ethnicity (Chinese, South Asian, general population) with cardiovascular complications. We tested for an interaction between age at diagnosis and ethnicity. RESULTS: There were 453,433 individuals with diabetes (49.7% women) and 453,433 matches. There was a significant interaction between age at diagnosis and ethnicity (P < 0.0001). Young-onset diabetes (age at diagnosis < 40) was associated with higher cardiovascular risk [hazard ratios: Chinese 4.25 (3.05-5.91), South Asian: 3.82 (3.19-4.57), General: 3.46 (3.26-3.66)] than usual-onset diabetes [age at diagnosis ≥ 40 years; Chinese: 2.22 (2.04-2.66), South Asian: 2.43 (2.22-2.66), General: 1.83 (1.81-1.86)] versus ethnicity-matched individuals. Among those with young-onset diabetes, Chinese ethnicity was associated with lower overall cardiovascular [0.44 (0.32-0.61)] but similar stroke risks versus the general population; while South Asian ethnicity was associated with lower overall cardiovascular [0.75 (0.64-0.89)] but similar coronary artery disease risks versus the general population. In usual-onset diabetes, Chinese ethnicity was associated with lower cardiovascular risk [0.44 (0.42-0.46)], while South Asian ethnicity was associated with lower cardiovascular [0.90 (0.86-0.95)] and higher coronary artery disease [1.08 (1.01-1.15)] risks versus the general population. CONCLUSIONS: There are important ethnic differences in the association between age at diagnosis and risk of cardiovascular complications.

A comparison of family physician and dermatologist topical corticosteroid prescriptions: A population-based cross-sectional study.

BACKGROUND: Topical corticosteroids (TCS) are commonly prescribed to treat inflammatory skin diseases, and appropriate prescription is necessary for treatment success. OBJECTIVE: To quantify differences between TCS prescribed by dermatologists at consultation and family physicians for patients treated for any skin condition. METHODS: Using administrative health data in Ontario, we included all Ontario Drug Benefit recipients who filled at least one TCS prescription from a dermatologist at consultation and a family physician in the year prior between January 2014 and December 2019. We estimated mean differences and 95% confidence intervals in amount (in grams) and potency between the index dermatologist prescription and the highest and most recent family physician prescription amounts and potencies in the preceding year using linear mixed-effect models. RESULTS: A total of 69,335 persons were included. The mean dermatologist amount was 34% larger than the highest amount and 54% larger than the most recent amount prescribed by family physicians. There were small but statistically significant differences in potency using established 7-category and 4-category potency classification systems. CONCLUSIONS: Compared to family physicians, dermatologists prescribed substantially larger amounts and similarly potent TCS at consultation. Further research is needed to determine the effect of these differences on clinical outcomes.

Sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors and the risk of heart failure: A nationwide cohort study of older adults with diabetes mellitus.

AIMS: To analyse the rate of heart failure hospitalization for older adults prescribed a sodium-glucose co-transporter-2 (SGLT2) inhibitor. MATERIALS AND METHODS: The study cohort included adults aged 66 years and older diagnosed with diabetes mellitus in Ontario, Canada, between July 2015 and March 2019, who received either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor. The primary outcome was a composite of heart failure hospitalization and all-cause mortality. Secondary outcomes included diabetic ketoacidosis and hypoglycaemia. RESULTS: A total of 29 916 adults prescribed an SGLT2 inhibitor were compared with 29 916 adults prescribed a DPP-4 inhibitor. The mean age was 72 years, 60% were men, the baseline glycated haemoglobin concentration was 8.2% and the baseline creatinine was 89 µmol/L. The incidence rate of the primary outcome was 19/1000 person-years for adults prescribed an SGLT2 inhibitor compared to 38/1000 person-years in those prescribed a DPP-4 inhibitor. This resulted in a hazard ratio (HR) of 0.49 (95% confidence interval [CI] 0.45, 0.54) and a rate difference (RD) of 19 fewer events per 1000 person-years (RD -19 [95% CI -22, -17]). Patients prescribed an SGLT2 inhibitor also had a lower rate of hypoglycaemia (HR 0.61 [95% CI 0.46, 0.81); RD -1.6 [95% CI -2.4, -0.8]), but a higher rate of diabetic ketoacidosis (HR 1.84 [95% CI 1.26, 2.70]; RD 1.0 [95% CI 0.4, 1.6]). CONCLUSIONS: Older adults prescribed an SGLT2 inhibitor had a lower rate of heart failure hospitalization or death, and a lower rate of hypoglycaemia, but an increased rate of diabetic ketoacidosis compared to older adults prescribed a DPP-4 inhibitor.

Traumatic brain injury as an independent risk factor for problem gambling: a matched case-control study.

PURPOSE: To assess whether traumatic brain injury (TBI) increases the risks of subsequent problem gambling. METHODS: We conducted a matched case-control analysis of adults in Ontario, Canada. The study included those who self-reported their gambling activities in the Canadian Community Health Survey 2007-2008. Using Problem Gambling Severity Index, we defined cases as those who were problem gamblers and controls who were recreational gamblers. Cases were matched to controls 1:2 using propensity scores based on demographics, prior mental health, and self-reported behaviours. The main predictor was prior TBI defined as requiring emergency care and identified using ICD-10 codes from administrative health databases. We estimated the likelihood of prior TBI in problem gamblers compared to controls using conditional logistic regression. RESULTS: Of 30,652 survey participants, 16,002 (53%) reported gambling activity of whom 14,910 (49%) were recreational gamblers and 4% (n = 1092) were problem gamblers. A total of 1469 respondents (5%) had a prior TBI. Propensity score matching yielded 2038 matched pairs with 1019 cases matched to 2037 controls. Case-control analysis showed a significant association between prior TBI and subsequent problem gambling (odds ratio 1.27, 95% confidence interval 1.07-1.51, P = 0.007). The increased risk was mostly apparent in men aged 35 to 64 years who reported alcohol use or smoking. The relative risk of problem gambling in those with two or more TBIs equated to an odds ratio of 2.04 (95% confidence interval 1.05-3.99). CONCLUSIONS: We found that a prior TBI was associated with an increased subsequent risk of problem gambling. Our findings support more awareness, screening, and treating problem gambling risks among TBI patients.

Risk of suicide after a concussion.

BACKGROUND: Head injuries have been associated with subsequent suicide among military personnel, but outcomes after a concussion in the community are uncertain. We assessed the long-term risk of suicide after concussions occurring on weekends or weekdays in the community. METHODS: We performed a longitudinal cohort analysis of adults with diagnosis of a concussion in Ontario, Canada, from Apr. 1, 1992, to Mar. 31, 2012 (a 20-yr period), excluding severe cases that resulted in hospital admission. The primary outcome was the long-term risk of suicide after a weekend or weekday concussion. RESULTS: We identified 235,110 patients with a concussion. Their mean age was 41 years, 52% were men, and most (86%) lived in an urban location. A total of 667 subsequent suicides occurred over a median follow-up of 9.3 years, equivalent to 31 deaths per 100,000 patients annually or 3 times the population norm. Weekend concussions were associated with a one-third further increased risk of suicide compared with weekday concussions (relative risk 1.36, 95% confidence interval 1.14-1.64). The increased risk applied regardless of patients' demographic characteristics, was independent of past psychiatric conditions, became accentuated with time and exceeded the risk among military personnel. Half of these patients had visited a physician in the last week of life. INTERPRETATION: Adults with a diagnosis of concussion had an increased long-term risk of suicide, particularly after concussions on weekends. Greater attention to the long-term care of patients after a concussion in the community might save lives because deaths from suicide can be prevented.

Weight loss surgery and subsequent emergency care use: a population-based cohort study.

STUDY OBJECTIVE: This study assessed long-term emergency care utilization after weight loss surgery. METHODS: We conducted a self-matched longitudinal cohort analysis of weight loss surgery patients in Ontario operated between April 1, 2006, and March 31, 2011. Using population-wide registries, we compared emergency visits in the 3-year interval after surgery to the 3 years before surgery using incidence rate ratios with 95% confidence intervals. The study excluded patients with repeat surgeries, and the analysis excluded visits in the immediate perioperative interval (ie, 3 months before and after surgery). RESULTS: A total of 8815 patients were identified of whom most were women (81%), living in an urban area (84%), and treated with gastric bypass (99%). Approximately half (53%) were aged 25 to 45 years. Approximately half of the patients 4364 (49%) had at least 1 emergency in both preoperative and postoperative intervals, 1417 (16%) in the preoperative interval only and 1661 (19%) in the postoperative interval only. Total emergencies significantly increased from 852 per 1000 patient-years to 1000 per 1000 patient-years, equal to an incidence rate ratio of 1.17 (95% confidence interval, 1.13-1.21; P<.001). Compared to baseline, emergencies from gastrointestinal, genitourinary, substance misuse, trauma, and miscellaneous complaints increased significantly after surgery. Conversely, emergencies due to cardiovascular, ear, respiratory, and dermatology complaints decreased significantly after surgery. Ambulance use, triage urgency, and hospitalizations were significantly higher for emergencies after surgery. CONCLUSION: Persistent and resource-intensive emergency care utilization after weight loss surgery underscores the need of long-term patient support.

Physicians' warnings for unfit drivers and the risk of trauma from road crashes.

BACKGROUND: Physicians' warnings to patients who are potentially unfit to drive are a medical intervention intended to prevent trauma from motor vehicle crashes. We assessed the association between medical warnings and the risk of subsequent road crashes. METHODS: We identified consecutive patients who received a medical warning in Ontario, Canada, between April 1, 2006, and December 31, 2009, from a physician who judged them to be potentially unfit to drive. We excluded patients who were younger than 18 years of age, who were not residents of Ontario, or who lacked valid health-card numbers under universal health insurance. We analyzed emergency department visits for road crashes during a baseline interval before the warning and a subsequent interval after the warning. RESULTS: A total of 100,075 patients received a medical warning from a total of 6098 physicians. During the 3-year baseline interval, there were 1430 road crashes in which the patient was a driver and presented to the emergency department, as compared with 273 road crashes during the 1-year subsequent interval, representing a reduction of approximately 45% in the annual rate of crashes per 1000 patients after the warning (4.76 vs. 2.73, P<0.001). The lower rate was observed across patients with diverse characteristics. No significant change was observed in subsequent crashes in which patients were pedestrians or passengers. Medical warnings were associated with an increase in subsequent emergency department visits for depression and a decrease in return visits to the responsible physician. CONCLUSIONS: Physicians' warnings to patients who are potentially unfit to drive may contribute to a decrease in subsequent trauma from road crashes, yet they may also exacerbate mood disorders and compromise the doctor-patient relationship. (Funded by the Canada Research Chairs program and others.).

Pregnancy and the risk of a traffic crash.

INTRODUCTION: Pregnancy causes diverse physiologic and lifestyle changes that may contribute to increased driving and driving error. We compared the risk of a serious motor vehicle crash during the second trimester to the baseline risk before pregnancy. METHODS: We conducted a population-based self-matched longitudinal cohort analysis of women who gave birth in Ontario between April 1, 2006, and March 31, 2011. We excluded women less than age 18 years, those living outside Ontario, those who lacked a valid health card identifier under universal insurance, and those under the care of a midwife. The primary outcome was a motor vehicle crash resulting in a visit to an emergency department. RESULTS: A total of 507,262 women gave birth during the study period. These women accounted for 6922 motor vehicle crashes as drivers during the 3-year baseline interval (177 per mo) and 757 motor vehicle crashes as drivers during the second trimester (252 per mo), equivalent to a 42% relative increase (95% confidence interval 32%-53%; p<0.001). The increased risk extended to diverse populations, varied obstetrical cases and different crash characteristics. The increased risk was largest in the early second trimester and compensated for by the third trimester. No similar increase was observed in crashes as passengers or pedestrians, cases of intentional injury or inadvertent falls, or self-reported risky behaviours. INTERPRETATION: Pregnancy is associated with a substantial risk of a serious motor vehicle crash during the second trimester. This risk merits attention for prenatal care.

Association Between Age at Diagnosis of Type 2 Diabetes and Hospitalization for Heart Failure: A Population-Based Study.

BACKGROUND: The relation between age at diagnosis of type 2 diabetes (T2D) and hospitalization for heart failure (HHF) is unclear. We assessed the association between age at diagnosis of T2D and HHF. METHODS AND RESULTS: We conducted a population-based cohort study using administrative health databases from the Canadian province of Ontario, including participants without prior heart failure. We identified people with new-onset T2D between April 1, 2005 and March 31, 2015, and matched each person with 3 diabetes-free adults, according to birth year and sex. We estimated adjusted hazard ratios (HRs) and rate ratios (RRs) for the association between age at T2D diagnosis and incident HHF, which was assessed until March 31, 2020. Among 743 053 individuals with T2D and 2 199 539 matched individuals without T2D, 126 241 incident HHF events occurred over 8.9 years. T2D was associated with a greater adjusted hazard of HHF at younger ages (eg, HR at age 30 years: 6.94 [95% CI, 6.54-7.36]) than at older ages (eg, HR at age 60 years: 2.50 [95% CI, 2.45-2.56]) relative to matched individuals. Additional adjustment for mediators (hypertension, coronary artery disease, and chronic kidney disease) marginally attenuated this relationship. Age at T2D diagnosis was associated with a greater number of HHF events relative to matched individuals at younger ages (eg, RR at age 30 years: 6.39 [95% CI, 5.76-7.08]) than at older ages (eg, RR at age 60 years: 2.65 [95% CI, 2.54-2.76]). CONCLUSIONS: Younger age at T2D diagnosis is associated with a disproportionately elevated HHF risk relative to age-matched individuals without T2D.

Risk Prediction Scores for Type 2 Diabetes Microvascular and Cardiovascular Complications Derived and Validated With Real-world Data From 2 Provinces: The DIabeteS COmplications (DISCO) Risk Scores.

OBJECTIVES: Existing tools to predict the risk of complications among people with type 2 diabetes poorly discriminate high- from low-risk patients. Our aim in this study was to develop risk prediction scores for major type 2 diabetes complications using real-world clinical care data, and to externally validate these risk scores in a different jurisdiction. METHODS: Using health-care administrative data and electronic medical records data, risk scores were derived using data from 25,088 people with type 2 diabetes from the Canadian province of Ontario, followed between 2002 and 2017. Scores were developed for major clinically important microvascular events (treatment for retinopathy, foot ulcer, incident end-stage renal disease), cardiovascular disease events (acute myocardial infarction, heart failure, stroke, amputation), and mortality (cardiovascular, noncardiovascular, all-cause). They were then externally validated using the independent data of 11,416 people with type 2 diabetes from the province of Manitoba. RESULTS: The 10 derived risk scores had moderate to excellent discrimination in the independent validation cohort, ranging from 0.705 to 0.977. Their calibration to predict 5-year risk was excellent across most levels of predicted risk, albeit with some displaying underestimation at the highest levels of predicted risk. CONCLUSIONS: The DIabeteS COmplications (DISCO) risk scores for major type 2 diabetes complications were derived and externally validated using contemporary real-world clinical data. As a result, they may be more accurate than other risk prediction scores derived using randomized trial data. The use of more accurate risk scores in clinical practice will help improve personalization of clinical care for patients with type 2 diabetes.

Can we select individuals with low risk ductal carcinoma in situ (DCIS)? A population-based outcomes analysis.

Ductal carcinoma in situ (DCIS), a non-invasive breast cancer, is usually treated by breast-conserving surgery (BCS). Randomized trials prove that the addition of radiotherapy (XRT) leads to lower rates of recurrence. Despite the evidence, half of women do not receive XRT after BCS. It is unknown how well clinicians identify women with low risk DCIS for treatment by BCS alone or to what extent women with DCIS develop recurrent cancer due to the omission of radiotherapy. We report the outcomes of a population of women with DCIS treated with BCS, alone or with radiotherapy, and evaluate the effectiveness of each therapeutic approach. All women diagnosed with DCIS and treated with BCS, alone or with radiotherapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were validated by chart review. Survival analyses were used to study the development of local recurrence (LR) in relation to patient and tumor characteristics and the use of radiotherapy. The cohort included 3,762 women treated with breast-conserving therapy; 1,895 of whom (50 %) also received radiation. At 10 years median follow-up, LR developed in 233 (12 %) women who received radiotherapy and in 363 (19 %) of women who did not (p < 0.0001). The 10-year actuarial LR rate for women who did and did not receive radiotherapy was 12.7 and 20.0 % (p < 0.0001). Differences were significant for both for invasive LR (7.0 vs. 10.0 %, p < 0.0001) and for DCIS recurrence (6.1 vs. 10.8 %, p < 0.0001). We estimate that 22 % of recurrences diagnosed in Ontario women treated for DCIS between 1994 and 2003 would have been prevented if all patients had received radiotherapy. The omission of radiotherapy after BCS for DCIS resulted in substantive recurrences that might have been avoided with treatment. Additional markers are needed to identify a low risk group in whom radiation can be safely omitted.

COVID Vaccine Hesitancy and Risk of a Traffic Crash.

BACKGROUND: Coronavirus disease (COVID) vaccine hesitancy is a reflection of psychology that might also contribute to traffic safety. We tested whether COVID vaccination was associated with the risks of a traffic crash. METHODS: We conducted a population-based longitudinal cohort analysis of adults and determined COVID vaccination status through linkages to individual electronic medical records. Traffic crashes requiring emergency medical care were subsequently identified by multicenter outcome ascertainment of all hospitals in the region over a 1-month follow-up interval (178 separate centers). RESULTS: A total of 11,270,763 individuals were included, of whom 16% had not received a COVID vaccine and 84% had received a COVID vaccine. The cohort accounted for 6682 traffic crashes during follow-up. Unvaccinated individuals accounted for 1682 traffic crashes (25%), equal to a 72% increased relative risk compared with those vaccinated (95% confidence interval, 63-82; P < 0.001). The increased traffic risks among unvaccinated individuals extended to diverse subgroups, was similar to the relative risk associated with sleep apnea, and was equal to a 48% increase after adjustment for age, sex, home location, socioeconomic status, and medical diagnoses (95% confidence interval, 40-57; P < 0.001). The increased risks extended across the spectrum of crash severity, appeared similar for Pfizer, Moderna, or other vaccines, and were validated in supplementary analyses of crossover cases, propensity scores, and additional controls. CONCLUSIONS: These data suggest that COVID vaccine hesitancy is associated with significant increased risks of a traffic crash. An awareness of these risks might help to encourage more COVID vaccination.

Costs for Long-Term Health Care After a Police Shooting in Ontario, Canada.

Importance: Police shootings can cause serious acute injury, and knowledge of subsequent health outcomes may inform interventions to improve care. Objective: To analyze long-term health care costs among survivors of police shootings compared with those surviving nonfirearm police enforcement injuries using a retrospective design. Design, Setting, and Participants: This population-based cohort analysis identified adults (age ≥16 years) who were injured by police and required emergency medical care between April 1, 2002, and March 31, 2022, in Ontario, Canada. Exposure: Police shootings compared with other mechanisms of injury involving police. Main Outcomes and Measures: Long-term health care costs determined using a validated costing algorithm. Secondary outcomes included short-term mortality, acute care treatments, and rates of subsequent disability. Results: Over the study, 13 545 adults were injured from police enforcement (mean [SD] age, 35 [12] years; 11 637 males [86%]). A total of 13 520 individuals survived acute injury, and 8755 had long-term financial data available (88 surviving firearm injury, 8667 surviving nonfirearm injury). Patients surviving firearm injury had 3 times greater health care costs per year (CAD$16 223 vs CAD$5412; mean increase, CAD$9967; 95% CI, 6697-13 237; US $11 982 vs US $3997; mean increase, US $7361; 95% CI, 4946-9776; P < .001). Greater costs after a firearm injury were not explained by baseline costs and primarily reflected increased psychiatric care. Other characteristics associated with increased long-term health care costs included prior mental illness and a substance use diagnosis. Conclusions and Relevance: In this longitudinal cohort study of long-term health care costs, patients surviving a police shooting had substantial health care costs compared with those injured from other forms of police enforcement. Costs primarily reflected psychiatric care and suggest the need to prioritize early recognition and prevention.

The impact of routine Edmonton symptom assessment system use on receiving palliative care services: results of a population-based retrospective-matched cohort analysis.

BACKGROUND: In 2007, Cancer Care Ontario began standardised symptom assessment as part of routine care using the Edmonton Symptom Assessment System (ESAS). AIM: The purpose of this study was to evaluate the impact of ESAS on receipt of palliative care when compared with a matched group of unexposed patients. DESIGN: A retrospective-matched cohort study examined the impact of ESAS screening on initiation of palliative care services provided by physicians or homecare nurses. The study included adult patients diagnosed with cancer between 2007 and 2015. Exposure was defined as completing ≥1 ESAS during the study period. Using 4 hard and 14 propensity score-matched variables, patients with cancer exposed to ESAS were matched 1:1 to those who were not. Matched patients were followed from first ESAS until initiation of palliative care, death or end of study. RESULTS: The final cohort consisted of 204 688 matched patients with no prior palliative care consult. The pairs were well matched. The cumulative incidence of receiving palliative care within the first 5 years was higher among those exposed to ESAS compared with those who were not (27.9% (95% CI: 27.5% to 28.2%) versus 27.9% (95% CI: 27.5% to 28.2%)), when death is considered as a competing event. In the adjusted cause-specific Cox proportional hazards model, ESAS assessment was associated with a 6% increase in palliative care services (HR: 1.06, 95% CI: 1.04 to 1.08). CONCLUSION: We have demonstrated that patients exposed to ESAS were more likely to receive palliative care services compared with patients who were not exposed. This observation provides real-world data of the impact of routine assessment with a patient-reported outcome.

A Population-Based Analysis of Long-Term Costs and Adverse Events after Pneumatic Retinopexy and Pars Plana Vitrectomy.

PURPOSE: To comprehensively examine the cost effectiveness, reattachment rate, and complications of pneumatic retinopexy (PnR) compared with pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) within a universal health care system. DESIGN: Population-based, multicenter, consecutive, retrospective longitudinal cohort analysis. SUBJECTS: We identified consecutive adults aged ≥ 50 years requiring surgery for primary RRD over a 20-year interval between April 1, 2002, and March 31, 2022. Initial surgery was considered the index date for analyses. INTERVENTION: Pneumatic retinopexy was compared with PPV in all analyses. MAIN OUTCOME MEASURES: The primary analysis investigated the mean annualized health care costs comparing PnR to PPV over the 2 years after initial surgery. Secondary analyses examined the primary reattachment rate and complications. RESULTS: In total, 25 665 eligible patients were identified, with 8794 undergoing PnR and 16 871 undergoing PPV. The mean patient age was 65 years and 39% were women. The mean annualized cost after PnR was $8924 and $11 937 after PPV (mean difference, $3013; 95% confidence interval, $2533-$3493; P < 0.001). The primary reattachment rate at 90 days after PnR was 83% and after PPV was 93% (P < 0.001). The risk of cataract or glaucoma surgery was lower after PnR, and the frequency of ophthalmology clinic visits, intravitreal injections, and anxiety was higher after PnR. Hospitalizations and long-term disability were less frequent after PnR. CONCLUSIONS: Pneumatic retinopexy, when compared with PPV, was associated with lower long-term health care costs. Pneumatic retinopexy appeared to be effective, safe, and inexpensive, thus offering a viable option for improving access to RRD repair in appropriately selected cases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The impact of the COVID-19 pandemic on blood culture practices and bloodstream infections.

IMPORTANCE: Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures.

Association of Different Prescribing Patterns for Oral Corticosteroids With Fracture Preventive Care Among Older Adults in the UK and Ontario.

Importance: Identifying and mitigating modifiable gaps in fracture preventive care for people with relapsing-remitting conditions such as eczema, asthma, and chronic obstructive pulmonary disease who are prescribed high cumulative oral corticosteroid doses may decrease fracture-associated morbidity and mortality. Objective: To estimate the association between different oral corticosteroid prescribing patterns and appropriate fracture preventive care, including treatment with fracture preventive care medications, among older adults with high cumulative oral corticosteroid exposure. Design, Setting, and Participants: This cohort study included 65 195 participants with UK electronic medical record data from the Clinical Practice Research Datalink (January 2, 1998, to January 31, 2020) and 28 674 participants with Ontario, Canada, health administrative data from ICES (April 1, 2002, to September 30, 2020). Participants were adults 66 years or older with eczema, asthma, or chronic obstructive pulmonary disease receiving prescriptions for oral corticosteroids with cumulative prednisolone equivalent doses of 450 mg or higher within 6 months. Data were analyzed October 22, 2020, to September 6, 2022. Exposures: Participants with prescriptions crossing the 450-mg cumulative oral corticosteroid threshold in less than 90 days were classified as having high-intensity prescriptions, and participants crossing the threshold in 90 days or more as having low-intensity prescriptions. Multiple alternative exposure definitions were used in sensitivity analyses. Main Outcomes and Measures: The primary outcome was prescribed fracture preventive care. A secondary outcome was major osteoporotic fracture. Individuals were followed up from the date they crossed the cumulative oral corticosteroid threshold until their outcome or the end of follow-up (up to 1 year after index date). Rates were calculated for fracture preventive care and fractures, and hazard ratios (HRs) were estimated from Cox proportional hazards regression models comparing high- vs low-intensity oral corticosteroid prescriptions. Results: In both the UK cohort of 65 195 participants (mean [IQR] age, 75 [71-81] years; 32 981 [50.6%] male) and the Ontario cohort of 28 674 participants (mean [IQR] age, 73 [69-79] years; 17 071 [59.5%] male), individuals with high-intensity oral corticosteroid prescriptions had substantially higher rates of fracture preventive care than individuals with low-intensity prescriptions (UK: 134 vs 57 per 1000 person-years; crude HR, 2.34; 95% CI, 2.19-2.51, and Ontario: 73 vs 48 per 1000 person-years; crude HR, 1.49; 95% CI, 1.29-1.72). People with high- and low-intensity oral corticosteroid prescriptions had similar rates of major osteoporotic fractures (UK: crude rates, 14 vs 13 per 1000 person-years; crude HR, 1.07; 95% CI, 0.98-1.15 and Ontario: crude rates, 20 vs 23 per 1000 person-years; crude HR, 0.87; 95% CI, 0.79-0.96). Results from sensitivity analyses suggested that reaching a high cumulative oral corticosteroid dose within a shorter time, with fewer prescriptions, or with fewer or shorter gaps between prescriptions, increased fracture preventive care prescribing. Conclusions: The results of this cohort study suggest that older adults prescribed high cumulative oral corticosteroids across multiple prescriptions, or with many or long gaps between prescriptions, may be missing opportunities for fracture preventive care.

Testing for a Sweet Spot in Randomized Trials.

INTRODUCTION: Randomized trials recruit diverse patients, including some individuals who may be unresponsive to the treatment. Here we follow up on prior conceptual advances and introduce a specific method that does not rely on stratification analysis and that tests whether patients in the intermediate range of disease severity experience more relative benefit than patients at the extremes of disease severity (sweet spot). METHODS: We contrast linear models to sigmoidal models when describing associations between disease severity and accumulating treatment benefit. The Gompertz curve is highlighted as a specific sigmoidal curve along with the Akaike information criterion (AIC) as a measure of goodness of fit. This approach is then applied to a matched analysis of a published landmark randomized trial evaluating whether implantable defibrillators reduce overall mortality in cardiac patients (n = 2,521). RESULTS: The linear model suggested a significant survival advantage across the spectrum of increasing disease severity (ß = 0.0847, P < 0.001, AIC = 2,491). Similarly, the sigmoidal model suggested a significant survival advantage across the spectrum of disease severity (α = 93, ß = 4.939, γ = 0.00316, P < 0.001 for all, AIC = 1,660). The discrepancy between the 2 models indicated worse goodness of fit with a linear model compared to a sigmoidal model (AIC: 2,491 v. 1,660, P < 0.001), thereby suggesting a sweet spot in the midrange of disease severity. Model cross-validation using computational statistics also confirmed the superior goodness of fit of the sigmoidal curve with a concentration of survival benefits for patients in the midrange of disease severity. CONCLUSION: Systematic methods are available beyond simple stratification for identifying a sweet spot according to disease severity. The approach can assess whether some patients experience more relative benefit than other patients in a randomized trial.[Box: see text].

Prenatal electrocardiogram testing and postpartum depression: A population-based cohort study.

Background: Cardiovascular symptoms in pregnancy may be a clue to psychological distress. We examined whether electrocardiogram testing in pregnant women is associated with an increased risk of subsequent postpartum depression. Methods: We conducted a population-based cohort study of pregnant women who delivered in Ontario, Canada comparing women who received a prenatal ECG to women who did not. Results: In total, 3,238,218 women gave birth during the 25-year study period of whom 157,352 (5%) received an electrocardiogram during prenatal care. Receiving an electrocardiogram test was associated with a one-third relative increase in the odds of postpartum depression (odds ratio 1.34; 95% confidence interval 1.29-1.39, p < 0.001). Conclusion: The association between prenatal electrocardiogram testing and postpartum depression suggests a possible link of organic disease with mental illness, and emphasizes that cardiovascular symptoms may be a clinical clue to the presence of an underlying mood disorder.

Serious Adverse Events of Oral and Topical Carbonic Anhydrase Inhibitors.

IMPORTANCE: Some ophthalmologists may be reluctant to prescribe oral carbonic anhydrase inhibitors, given the potential for life-threatening systemic adverse reactions. OBJECTIVE: To conduct a population-based analysis of the safety of oral or topical carbonic anhydrase inhibitors in clinical care. DESIGN, SETTING, AND PARTICIPANTS: This matched longitudinal cohort study took place in Ontario, Canada. Consecutive patients older than 65 years who were prescribed an oral or topical carbonic anhydrase inhibitor in Ontario, Canada, between January 1, 1995, and January 1, 2020, were identified. Patients were matched 1-to-1 based on age, sex, and diabetes status. Time zero was defined as the date of the first identified prescription for the medication, and the primary analysis focused on the first 120 days of follow-up. MAIN OUTCOMES AND MEASURES: The primary end point was a severe complicated adverse event of either Stevens-Johnson syndrome, toxic epidermal necrolysis, or aplastic anemia. RESULTS: Overall, 128 942 matched patients initiated an oral or topical carbonic anhydrase inhibitor during the 25-year study period. The mean (SD) age was 75 (6.6) years, 71 958 (55.8%) were women, and 25 058 (19.4%) had a diagnosis of diabetes. The oral and topical carbonic anhydrase inhibitor groups had similar baseline demographics. Patients prescribed an oral carbonic anhydrase inhibitor had an absolute risk of a severe complicated adverse event of 2.90 per 1000 patients, whereas patients prescribed a topical carbonic anhydrase inhibitor had an absolute risk of 2.08 per 1000 patients. This difference was equivalent to a risk ratio of 1.40, with a number needed to harm of 1 in 1220 patients (95% CI, 1.12-1.74; P = .003). This generally low risk was replicated in multivariable regression controlling for confounding factors. Additional risk factors for a severe complicated adverse event included patients with more comorbidities and those with more frequent clinic contacts. CONCLUSIONS AND RELEVANCE: The risk of a serious adverse reaction following prescription of an oral or topical carbonic anhydrase inhibitor was low and similar between agents. Given the low risk of severe adverse reactions, this population-level analysis supports reconsidering the reluctance toward prescribing an oral carbonic anhydrase inhibitor.