Use of dabigatran, an inhibitor of thrombin, increases the risk of gastrointestinal bleeding (GIB). However, it is not clear whether gastroprotective agents (GPAs) prevent GIB in dabigatran users. We investigated the risk of GIB and the role of gastroprotective agents (including proton pump inhibitors and histamine type-2–receptor antagonists) in patients using dabigatran. We performed a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly prescribed dabigatran from 2010 through 2013 were included in the analysis. Poisson regression was used to assess the risk of GIB in dabigatran users by incidence rate ratio (IRR), adjusted for patient characteristics, comorbidities, and concurrent medications. Among the 5041 patients newly prescribed dabigatran, 124 (2.5%) developed GIB during follow-up evaluation (4.2/100 patient-years). The risk of GIB in this population increased among patients 75 years and older (IRR, 2.47; 95% confidence interval [CI], 1.66–3.68), patients with a history of peptic ulcers or GIB (IRR, 2.31; 95% CI, 1.54–3.46), and patients who used aspirin (IRR, 1.52; 95% CI, 1.03–2.24). Concomitant use of gastroprotective agents was associated with a reduced risk of GIB (IRR, 0.52; 95% CI, 0.35–0.77). Subcategory analysis showed that use of proton pump inhibitors (IRR, 0.53; 95% CI, 0.31–0.91) or histamine type-2–receptor antagonists (IRR, 0.61; 95% CI, 0.40–0.94) were associated with a lower risk of GIB. Further analysis showed that the risk reduction by gastroprotective agents was significant for only upper GIB (IRR, 0.29; 95% CI, 0.15–0.54), and only for patients with a prior history of peptic ulcers or GIB (IRR, 0.14; 95% CI, 0.06–0.30). In the Hong Kong population, use of gastroprotective agents was associated with a reduced risk of GIB in patients taking dabigatran. The association was stronger for upper GIB than lower GIB, and in patients with a prior history of peptic ulcers or GIB.

Importance The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown. Objective To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF. Design, Setting, and Participants Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016. Exposures Dabigatran or warfarin use during the study period. Main Outcomes and Measures Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated. Results Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, −0.68 [95% CI, −0.38 to −0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, −3.15 [95% CI, −2.40 to −3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, −0.04 [95% CI, 0.67 to −0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (Pvalue for interaction, <.001). Conclusions and Relevance Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.

Previous studies have reported an extremely unbalanced global access to opioid analgesics. We aimed to determine contemporary trends and patterns of opioid analgesic consumption at the global, regional, and national levels. We analysed the global pharmaceutical sales data of 66 countries or regions from the IQVIA-Multinational Integrated Data Analysis System database on opioid analgesics between 2015 and 2019. Opioid analgesic consumption was measured in milligram morphine equivalent per 1000 inhabitants per day (MME per 1000/day). The global, regional, and national trend changes were estimated using linear regressions. Factors associated with consumption patterns and trend changes were explored in multivariable linear regression analyses. Overall opioid analgesic sales in the 66 countries or regions increased from 27·52 MME per 1000/day (16·63-45·54) in 2015 to 29·51 MME per 1000/day (17·85-48·79) in 2019 (difference per year 3·96%, 95% CI 0·26 to 7·80). Sales reduced yearly in North America (-12·84%; 95% CI -15·34 to -10·27) and Oceania (-2·96%; -4·20 to -1·70); increased in South America (28·69%; 7·18 to 54·53), eastern Europe (7·68%; 3·99 to 11·49), Asia (5·74%; 0·61 to 11·14), and western and central Europe (1·64%; 0·52 to 2·78); and did not differ in Africa or central America and the Caribbean. The global opioid consumption patterns were associated with country-level Human Development Index (p=0·040), cancer death rate excluding leukaemia (p=0·0072), and geographical location (p<0·0001). In 2019, opioid analgesic consumption ranged from 0·01 MME per 1000/day to 5·40 MME per 1000/day in the 17 countries and regions in the lowest consumption quartile, despite high income levels and cancer death rates in some of them. Global opioid analgesic consumption increased from 2015 to 2019. The trend changes were distinctive across regions, which could reflect the different actions in response to known issues of opioid use and misuse. Disparities in opioid analgesic consumption remained, indicating potential inadequate access to essential pain relief in countries with low consumption. None.

Studies have demonstrated a reduction for otitis media (OM) following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7), but this has not been evaluated in the United Kingdom (UK). Moreover, there are limited data on any additional impact of PCV13 introduction in 2010. We conducted an observational cohort study to investigate the trends in OM incidence and associated antibiotic prescriptions in children aged <10 year-olds during 2002-2012 using a national primary care database. Three time-periods were defined to estimate monthly incidence: pre-PCV7 (January 2002-August 2006), post-PCV7 (September 2007-March 2010), and post-PCV13 (April 2011-December 2012). Overall annual OM incidence declined by 51.3% from 135.8 episodes/1000 person-years in 2002 to 66.1 episodes/1000 person-years in 2012; antibiotic prescription rates for OM declined by 72.9% from 57.9 prescriptions/1000 person-years to 15.7 prescriptions/1000 person-years, respectively. PCV7 introduction was associated with significant decline in OM rates across all age-groups (21.8%; 95% CI, 20.2-23.4), including <2 year-olds (19.8%; 95% CI, 16.0-23.5%); 2-4 year-olds (23.0%; 95% CI, 20.4-25.4%) and 5-9 year-olds (20.2%; 95% CI, 17.6-22.7%). There was an additional significant reduction in OM (18.5%; 95% CI, 16.7-20.2%) and associated antibiotic prescribing (12.2%; 95% CI, 8.6-15.6%) after the introduction of PCV13 across all age-groups. The introduction of PCV7 was associated with a 22% significant reductions in OM in children aged <10 year-olds with an additional 19% reductions after PCV13 introduction. These declines are equivalent to 592,000 and 15,700 fewer consultations and OM-related hospitalizations, respectively, in England and Wales every year. Although the continuing decline in OM rates in our study suggests that further reduction may continue to occur, it is important to monitor long-term trends in all pneumococcal diseases, including OM and pneumonia, because of increasing replacement of non-vaccine pneumococcal serotypes in carriage and disease.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children, with worldwide prevalence rates in school-aged children estimated at 5% to 7%.^1,2 In Hong Kong (HK), the reported prevalence of ADHD is estimated to be 6.1% in schoolboys and 3.9% in early adolescents.^3,4 Attention-deficit/hyperactivity disorder is associated with a diverse range of mental health comorbidities and adverse health, academic, and psychosocial outcomes.^5-8 Individuals with ADHD are at increased risk of both attempted and completed suicide, even if comorbid psychiatric disorders are clinically treated.⁹

Objective 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.