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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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].

Association of socioeconomic status with medical assistance in dying: a case-control analysis.

OBJECTIVES: Economic constraints are a common explanation of why patients with low socioeconomic status tend to experience less access to medical care. We tested whether the decreased care extends to medical assistance in dying in a healthcare system with no direct economic constraints. DESIGN: Population-based case-control study of adults who died. SETTING: Ontario, Canada, between 1 June 2016 and 1 June 2019. PATIENTS: Patients receiving palliative care under universal insurance with no user fees. EXPOSURE: Patient's socioeconomic status identified using standardised quintiles. MAIN OUTCOME MEASURE: Whether the patient received medical assistance in dying. RESULTS: A total of 50 096 palliative care patients died, of whom 920 received medical assistance in dying (cases) and 49 176 did not receive medical assistance in dying (controls). Medical assistance in dying was less frequent for patients with low socioeconomic status (166 of 11 008=1.5%) than for patients with high socioeconomic status (227 of 9277=2.4%). This equalled a 39% decreased odds of receiving medical assistance in dying associated with low socioeconomic status (OR=0.61, 95% CI 0.50 to 0.75, p<0.001). The relative decrease was evident across diverse patient groups and after adjusting for age, sex, home location, malignancy diagnosis, healthcare utilisation and overall frailty. The findings also replicated in a subgroup analysis that matched patients on responsible physician, a sensitivity analysis based on a different socioeconomic measure of low-income status and a confirmation study using a randomised survey design. CONCLUSIONS: Patients with low socioeconomic status are less likely to receive medical assistance in dying under universal health insurance. An awareness of this imbalance may help in understanding patient decisions in less extreme clinical settings.

Hand hygiene sprayed into eye.

Hand hygiene is a practical, affordable, acceptable, reliable, and effective strategy to mitigate nosocomial infection risks in hospitals. Here we provide an image of clinical medicine that documents a potential error related to hand sanitizer dispenser malfunction. An awareness of this adverse event can lead to immediate modifiable changes in healthcare settings to reduce the risks of nosocomial infections.

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.

Risks of Serious Injury with Testosterone Treatment.

BACKGROUND: Injury causes significant morbidity and mortality that is sometimes attributed to testosterone and violence. We hypothesized that prescribed testosterone might be associated with the subsequent risk of serious injury. METHODS: We conducted a self-matched individual-patient exposure-crossover analysis comparing injury risks before and after initiation of testosterone. We selected adults treated with testosterone in Ontario, Canada, from October 1, 2012, to October 1, 2017 (enrollment) and continued until October 1, 2018 (follow-up). The primary outcome was defined as an acute traumatic event that required emergency medical care. RESULTS: A total of 64,386 patients were treated with testosterone of whom 89% were men with a median age of 52 years. We identified 34,439 serious injuries during the baseline interval before starting testosterone (584 per month) and 7349 serious injuries during the subsequent interval after starting testosterone (565 per month). Rates of injuries were substantially above the population norm in both intervals with no significant increased risk after starting testosterone (relative risk = 1.00; 95% confidence interval: 0.96-1.04, P = 0.850). The unchanged risk extended to diverse patients, was observed for different formulations and applied to all injury mechanisms. In contrast, testosterone treatment was associated with a 48% increased risk of a thromboembolic event (relative risk = 1.48; 95% confidence interval: 1.25-1.74, P < 0.001). CONCLUSIONS: Testosterone treatment was associated with a substantial baseline risk of serious injury that did not increase further after starting therapy. Physicians prescribing testosterone could consider basic safety reminders to mitigate injury risks.