Study question What is the association between clarithromycin use and cardiovascular outcomes?Methods In this population based study the authors compared cardiovascular outcomes in adults aged 18 or ...more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or amoxicillin (n=217 793). The self controlled case series and case crossover analysis included those who received Helicobacter pylori eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke.Study answer and limitations The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of H pylori eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of H pylori eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients.What this study adds Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population.Funding, competing interests, data sharing ID was funded by grants from the Medical Research Council for this project. LS was funded by a grant from the Wellcome Trust. The authors have no competing interests. No additional data are available.
Abstract Background 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. Methods 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). Results 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. Conclusion 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.
Abstract
Context
Previous studies suggested a potential link of maternal thyroid dysfunction with adverse neurocognitive outcomes and impaired development of internal organs in offspring.
Objective
...To review the association between maternal thyroid dysfunction and the risk of adverse outcomes in offspring.
Data Sources
PubMed, EMBASE, and Cochrane Library.
Study Selections
Eligible studies reported the association between maternal thyroid hormone function and the risk of adverse outcomes in their children.
Data Extraction
Reviewers extracted data on study characteristics and results independently.
Data Synthesis
Estimates were pooled and reported as odds ratio (OR) with 95% confidence interval (CI). I2 tests were applied to assess the heterogeneity across studies.
Results
We identified 29 eligible articles and found an association between maternal hyperthyroidism and attention deficit hyperactivity disorder (ADHD) (OR: 1.18, 95% CI: 1.04-1.34, I2 = 0%) and epilepsy (OR: 1.19, 95% CI: 1.08-1.31, I2 = 0%) in offspring; as well as an association of maternal hypothyroidism with increased risk of ADHD (OR: 1.14, 95% CI: 1.03-1.26, I2 = 25%), autism spectrum disorder (OR: 1.41, 95% CI: 1.05-1.90, I2 = 63%), and epilepsy (OR: 1.21, 95% CI: 1.06-1.39, I2 = 0%) in offspring.
Conclusion
Routine measurement and timely treatment on thyroid function should be considered for pregnant women.
BASCULE syndrome is an uncommon vasomotor dermatosis that occurs most frequently in females aged 12-15 years. It can be mistaken for urticaria, but the triad of clinical signs are differentiating and ...diagnostic. Bier anemic spots result from a poor venoarteriolar reflex in the dermal ascending arterioles, and the central urticaria-like lesions are secondary to mast cell degranulation induced by hypoxia. Cyanosis is attributed to arterial hypoxia secondary to accumulation of venous blood from standing. The eruption is triggered by standing but resolves with lying down or walking. Pruritus, pain and edema may be present and may warrant treatment. Here, Liu et al examine the case of 19-year-old woman with BASCULE syndrome.
To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates.
Systematic review and meta-analysis of head-to-head ...randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic.
We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty).
The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims 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. Methods 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. Results 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). Conclusions 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.
Whether ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers modify colorectal cancer risk remains controversial. We aimed to determine association between their use and ...colorectal cancer risk after a negative baseline colonoscopy. This is a territory-wide retrospective cohort study recruiting patients aged ≥40 who had undergone colonoscopy between 2005 and 2013. Exclusion criteria included colorectal cancer detected <6 months of index colonoscopy, prior colorectal cancer, inflammatory bowel disease, and prior colectomy. The primary outcome was colorectal cancer diagnosed between 6 and 36 months after index colonoscopy. Sites of colorectal cancer were categorized as proximal (proximal to splenic flexure) and distal cancer. The adjusted hazard ratio of colorectal cancer with ACE inhibitor/angiotensin receptor blocker use (≥180-day use within 5 years before index colonoscopy) was derived by propensity score regression adjustment of 23 covariates (including patient’s factors, concurrent medication use, and endoscopy center’s performance). Of 187 897 eligible patients, 30 856 (16.4%) were ACE inhibitors/angiotensin receptor blocker users. Eight hundred fifty-four (0.45%) developed colorectal cancer between 6 and 36 months after index colonoscopy (proximal cancer147 17.2%). These drugs were associated with lower risk of colorectal cancer that developed <3 years after index colonoscopy (adjusted hazard ratio, 0.78 95% CI, 0.64–0.96), but not colorectal cancer that developed >3years (adjusted hazard ratio, 1.18 95% CI, 0.88–1.57); every single year increase in the drug use was associated with 5% reduction in adjusted hazard ratio risk. ACE inhibitors/angiotensin receptor blocker were associated with a lower colorectal cancer risk in a duration-response manner.
IMPORTANCE: The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear. OBJECTIVE: To evaluate the association between prenatal antipsychotics exposure ...and the risk of birth and neurodevelopmental problems. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication. EXPOSURES: Prenatal antipsychotic exposure. MAIN OUTCOMES AND MEASURES: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children. RESULTS: The cohorts included 333 749 mother-child pairs for ADHD (mean SD maternal age at delivery, 31.46 5.03 years) and 411 251 pairs for ASD, preterm birth, and small for gestational age analyses (mean SD maternal age at delivery, 31.56 5.01 years). There were 13 196 children (3.95%) with a diagnosis of ADHD, 8715 (2.12%) with ASD, 33 891 (8.24%) preterm, and 7009 (1.70%) who were small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% CI, 0.83-1.61) for ADHD and 1.06 (95% CI, 0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95% CI, 1.13-1.75) for preterm birth and 1.36 (95% CI, 0.86-2.14) for small for gestational age when comparing gestationally exposed with gestationally nonexposed individuals. Additional analyses showed no association when comparing gestationally exposed individuals with those with past exposure (ADHD: wHR, 0.99; 95% CI, 0.60-1.61; ASD: wHR, 1.10; 95% CI, 0.58-2.08; preterm birth: wOR, 0.93; 95% CI, 0.70-1.24; small for gestational age: wOR, 1.21; 95% CI, 0.66-2.20) and in a sibling-matched analysis (ADHD: wHR, 0.41; 95% CI, 0.04-4.93; ASD: wHR, 0.90; 95% CI, 0.40-2.01; preterm birth: wOR, 1.25; 95% CI, 0.85-1.82; small for gestational age: wOR, 0.86, 95% CI, 0.32-2.31). CONCLUSIONS AND RELEVANCE: In this cohort study, the findings did not suggest that prenatal antipsychotics exposure increased the risk of ADHD, ASD, or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestationally exposed individuals with those with past exposure and comparing gestationally exposed with gestationally nonexposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to discontinue receipt of their regular antipsychotic treatment during pregnancy.
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) (P value 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.
The goal was to investigate the epidemiologic features of antipsychotic prescribing to children and adolescents in general practice in the United Kingdom.
A total of 384 participating general ...practices from the United Kingdom General Practice Research Database were used to identify patients 0 to 18 years of age who were prescribed > or = 1 antipsychotic medication between January 1, 1992, and December 31, 2005. Annual age-specific prevalences and incidences of antipsychotic prescribing were calculated.
The overall prevalence of use of all antipsychotics increased from 1992 (0.39 users per 1000 patient-years) to 2005 (0.77 users per 1000 patient-years). The prescribing prevalence for patients 7 to 12 years of age almost tripled between 1992 (0.23 users per 1000 patient-years) and 2005 (0.61 users per 1000 patient-years). Atypical antipsychotic prescribing increased 60-fold from 1994 (0.01 users per 1000 patient-years) to 2005 (0.61 users per 1000 patient-years). However, typical antipsychotic prescribing decreased significantly from 2000 (0.44 users per 1000 patient-years) to 2005 (0.18 users per 1000 patient-years). The incidences for typical and atypical antipsychotics showed trends similar to those of the respective prevalences. However, the overall incidence (number of new starters) for all antipsychotics was relatively stable between 1992 and 2005, which suggests that patients remain on treatment longer.
The overall prevalence of antipsychotics almost doubled between 1992 and 2005; however, the rate of increase was much lower than the reported figures in the United States. The prescribing of atypical antipsychotic drugs has increased despite the lack of conclusive evidence showing their superiority over older conventional antipsychotics. Additional investigation is required to evaluate their efficacy and safety in children and adolescents.
PDF
