Preterm birth and the future risk of orthopedic fracture.

BACKGROUND: Preterm birth occurs during a critical period of bone mineralization. We assessed whether preterm birth increases the risk of childhood fracture. METHODS: We analyzed a cohort of 788,903 infants born between 2006 and 2016 in Quebec, Canada. The exposure was preterm birth (<37 weeks). The outcome was any future hospitalization for fracture before 2018. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of prematurity with fractures in adjusted Cox regression models. We determined if the risk of facture varied by the child's age. RESULTS: The incidence of fracture hospitalizations was higher in preterm children than in term children (17.9 vs. 15.3 per 10,000 person-years). Compared with term, preterm children had 1.27 times the risk of femur fracture hospitalization (95% CI 1.01-1.60) and 2.27 times the risk of assault-related fractures (95% CI 1.37-3.76). Preterm children had 2.20 times the risk of femur fracture between 6 and 17 months of age (95% CI 1.45-3.35). CONCLUSIONS: Preterm birth is associated with an increased risk of hospitalization for femur fractures and assault-related fractures. Associations are stronger before 18 months of age. Families of preterm children may benefit from counseling and support for fracture prevention during early childhood.

Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia. METHODS: Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline. RESULTS: The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10). DISCUSSION: In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.

Effectiveness and Safety of Apixaban versus Rivaroxaban in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus.

AIMS: To evaluate the effectiveness and safety of apixaban versus rivaroxaban among patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Using the United Kingdom's Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository, and the Office for National Statistics database, we identified a cohort of patients with NVAF and T2DM newly treated with apixaban or rivaroxaban between 2013 and 2020. Propensity scores with standardized mortality ratio weighting were used to control for confounding. We used weighted Cox proportional hazards models to estimate separately the hazard ratios (HRs) with 95% confidence intervals (CIs) of ischemic stroke, major bleeding, and major adverse limb events associated with the use of apixaban compared with rivaroxaban. We also evaluated whether the risk was modified by age, sex, duration of diabetes, microvascular and macrovascular complications of diabetes, nephropathy, CHA2DS2-VASc and HAS-BLED scores, and by dose (standard vs. low dose). RESULTS: The cohort included 11,561 apixaban and 8,265 rivaroxaban users. Apixaban was associated with a similar risk of stroke (HR: 0.99, 95% CI: 0.79-1.23), and a 32% reduced risk of major bleeding (HR: 0.68, 95% CI: 0.59-0.78), compared with rivaroxaban. The risk of major adverse limb events was similar between apixaban and rivaroxaban (HR: 0.75, 95% CI: 0.54-1.04). Overall, the risk of ischemic stroke and major bleeding was consistent in stratified analyses. CONCLUSION: Among patients with NVAF and T2DM, apixaban was associated with a similar risk of stroke and a lower risk of major bleeding compared with rivaroxaban.

Prescribing Trends of Antidepressants and Psychotropic Coprescription for Youths in UK Primary Care, 2000-2018.

BACKGROUND: There is lack of recent information on the prescribing trends of antidepressants and coprescription with other psychotropic medications in the United Kingdom (UK) pediatric population. METHODS: Using the Clinical Practice Research Datalink, we estimated the annual rates of patients newly prescribed an antidepressant (selective serotonin reuptake inhibitors (SSRIs), other newer generation antidepressants, and tricyclic antidepressants (TCAs)) and the percentage of new users of antidepressants with a same-day coprescription for other psychotropic medications. We also estimated the prevalence of patients with antidepressant prescriptions and percentage of coprescription for other psychotropic medications. RESULTS: After a 42% decline from 2000 to 2005, the rate of patients newly prescribed an antidepressant increased from 2006 onwards. From 2008 to 2018, the rate increased from 254.3 to 471.2 per 100,000 person-years (rate ratio 1.97, 95% confidence interval 1.96-1.99). The rate was higher in females and adolescents aged 15 to 17. SSRIs were most commonly prescribed (70% of all antidepressant prescriptions). Overall, 4.7% of patients newly prescribed an antidepressant had at least one same-day coprescription for another psychotropic medication. During the study period, coprescription rose from 2.6% to 6.4% and was more frequent in males. In 2018, most coprescriptions were anxiolytics and hypnotics (63%) and antipsychotics (26%). Trends in prevalent prescriptions corresponded to trends in new prescriptions. LIMITATIONS: By using a primary care database, we did not have information on prescriptions from specialists or during hospitalizations. CONCLUSIONS: During the last decade, antidepressant prescriptions and psychotropic coprescription in primary care increased in UK children and adolescents.