Concurrent Use of Oral Anticoagulants and Sulfonylureas in Individuals With Type 2 Diabetes and Risk of Hypoglycemia: A UK Population-Based Cohort Study

ObjectiveTo investigate the association of concurrent use of oral anticoagulants (OACs) and sulfonylureas and the risk of hypoglycemia in individuals with type 2 diabetes mellitus (T2DM).Research Design and MethodsA retrospective cohort study was conducted between 2001 and 2017 using electronic primary healthcare data from the IQVIA Medical Research Data (IMRD) that incorporates data supplied by The Health Improvement Network (THIN), a propriety database of Cegedim SA. Individuals with T2DM who received OAC prescription and sulfonylureas were included. We compared the risk of hypoglycemia with sulfonylureas and OACs using propensity score matching and Cox regression.Results109,040 individuals using warfarin and sulfonylureas and 77,296 using direct oral anticoagulants (DOACs) and sulfonylureas were identified and included. There were 285 hypoglycemia events in the warfarin with sulfonylureas group (incidence rate = 17.8 per 1,000 person-years), while in the sulfonylureas only, 304 hypoglycemia events were observed (incidence rate = 14.4 per 1,000 person-years). There were 14 hypoglycemic events in the DOACs with sulfonylureas group (incidence rates = 14.8 per 1,000 person-years), while in the sulfonylureas alone group, 60 hypoglycemia events were observed (incidence rate =23.7 per 1,000 person-years). Concurrent use of warfarin and sulfonylureas was associated with increased risk of hypoglycemia compared with sulfonylureas alone (HR 1.38; 95% CI 1.10–1.75). However, we found no evidence of an association between concurrent use of DOACs and sulfonylureas and risk of hypoglycemia (HR 0.54; 95% CI, 0.27–1.10) when compared with sulfonylureas only.ConclusionsWe provide real-world evidence of possible drug-drug interactions between warfarin and sulfonylureas. The decision to prescribe warfarin with coexistent sulfonylureas to individuals with T2DM should be carefully evaluated in the context of other risk factors of hypoglycemia, and availability of alternative medications

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring:population based cohort study

textabstractObjective To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Design Population based cohort study. Setting Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. Participants 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Main outcome measure Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Results Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). Conclusions The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously

Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack

BACKGROUND: To manage the risk factors and to improve clinical outcomes, patients with stroke commonly receive multiple cardiovascular medications. However, there is a lack of evidence on the optimum combination of medication therapy in the primary care setting after ischemic stroke. Therefore, this study aimed to investigate the effect of multiple cardiovascular medications on long-term survival after an incident stroke event (ischemic stroke or transient ischemic attack (TIA)). METHODS: This study consisted of 52,619 patients aged 45 and above with an incident stroke event between 2007 and 2016 in The Health Improvement Network database. We estimated the risk of all-cause mortality in patients with multiple cardiovascular medications versus monotherapy using a marginal structural model. RESULTS: During an average follow-up of 3.6 years, there were 9230 deaths (7635 in multiple cardiovascular medication groups and 1595 in the monotherapy group). Compared with patients prescribed monotherapy only, the HRs of mortality were 0.82 (95% CI 0.75-0.89) for two medications, 0.65 (0.59-0.70) for three medications, 0.61 (0.56-0.67) for four medications, 0.60 (0.54-0.66) for five medications and 0.66 (0.59-0.74) for ≥ six medications. Patients with any four classes of antiplatelet agents (APAs), lipid-regulating medications (LRMs), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers, diuretics and calcium channel blockers (CCBs) had the lowest risk of mortality (HR 0.51, 95% CI 0.46-0.57) versus any one class. The combination containing APAs, LRMs, ACEIs/ARBs and CCBs was associated with a 61% (95% CI 53-68%) lower risk of mortality compared with APAs alone. CONCLUSION: Our results suggested that combination therapy of four or five cardiovascular medications may be optimal to improve long-term survival after incident ischemic stroke or TIA. APAs, LRMs, ACEIs/ARBs and CCBs were the optimal constituents of combination therapy in the present study

The association between dementia and the risk of hypoglycaemia events among patients with diabetes mellitus: a propensity-score matched cohort analysis

BackgroundHypoglycaemia commonly occurs in patients diagnosed with diabetes mellitus (DM) and dementia. The impact of dementia on hypoglycaemic events is controversial. Thus, we evaluated whether dementia increases the risk of hypoglycaemic events in older patients diagnosed with DM.DesignA retrospective cohort study.SettingWe used the IQVIA Medical Research Data (IMRD-UK) database (formerly known as the THIN database).ParticipantsAll patients aged ≥55 years and diagnosed with DM who were prescribed at least two prescriptions of antidiabetic medication between 2000 and 2017. Two groups of patients, dementia and non-dementia group, were propensity-score (PS) matched at 1:2. The risk of hypoglycaemia was assessed through a Cox regression analysis.Main outcome and measuresHypoglycaemic events were determined during the follow-up period by Read codes.ResultsFrom the database, 133,664 diabetic patients were identified, with a mean follow-up of 6.11 years. During the study period, 7,762 diabetic patients diagnosed with dementia were matched with 12,944 diabetic patients who had not been diagnosed with dementia. The PS-matched Cox regression analysis showed that patients diagnosed with dementia were at a 2-fold increased risk for hypoglycaemic events compared with those not diagnosed with dementia (hazard ratio [HR], 2.00; 95% CI, 1.63–2.66). A similar result was shown for a multivariable analysis using all patient data (adjusted HR, 2.25; 95% CI, 2.22–2.32).ConclusionOur findings suggest that diabetic patients with a diagnosis of dementia have a statistically significant higher risk of experiencing hypoglycaemia

A Longitudinal Study of the Relation between Childhood Activities and Psychosocial Adjustment in Early Adolescence

Background: Although an increasing body of research shows that excessive screen time could impair brain development, whereas non-screen recreational activities can promote the development of adaptive emotion regulation and social skills, there is a lack of comparative research on this topic. Hence, this study examined whether and to what extent the frequency of early-life activities predicted later externalizing and internalizing problems. Methods: In 2012/13, we recruited Kindergarten 3 (K3) students from randomly selected kindergartens in two districts of Hong Kong and collected parent-report data on children’s screen activities and parent–child activities. In 2018/19, we re-surveyed the parents of 323 students (aged 11 to 13 years) with question items regarding their children’s externalizing and internalizing symptoms in early adolescence. Linear regression analyses were conducted to examine the associations between childhood activities and psychosocial problems in early adolescence. Results: Early-life parent–child activities (β = −0.14, p = 0.012) and child-alone screen use duration (β = 0.15, p = 0.007) independently predicted externalizing problems in early adolescence. Their associations with video game exposure (β = 0.19, p = 0.004) and non-screen recreational parent–child activities (β = −0.14, p = 0.004) were particularly strong. Conclusions: Parent–child play time is important for healthy psychosocial development. More efforts should be directed to urge parents and caregivers to replace child-alone screen time with parent–child play time