Angel Y. S. Wong

Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs) and narrative review on short-term RCTs

Lorcaserin is a new anti‐obesity drug recently approved by US Food and Drug Administration. We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) to evaluate the association of lorcaserin therapy with weight loss and adverse events in obese adults (18–65 years old). Weight loss of 3.23 kg (95% confidence interval [CI]: 2.70, 3.75) and body mass index reduction of 1.16 kg m−2 (95% CI: 0.98, 1.34) was observed compared with placebo in RCTs of 1 year duration. The use of lorcaserin for 8 and 12 weeks reduced weight of 1.60 kg (95% CI: 0.34, 2.86) and 2.9 kg (95% CI: 2.2, 3.5), respectively. In comparison to placebo, lorcaserin decreased waist circumference, blood pressure, total cholesterol, low‐density lipoprotein‐cholesterol and triglycerides, however did not statistically affect heart rate or high‐density lipoprotein‐cholesterol. Headache, nausea and dizziness were found to be significantly higher in the patients receiving lorcaserin than patients receiving placebo, whereas diarrhoea is no more likely than in patients receiving placebo. In conclusion, lorcaserin achieves modest weight loss and appears to be well tolerated. Clinical and pharmacovigilance studies with longer study duration are needed to inform of the long‐term efficacy and safety of lorcaserin.

Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study

Objective Proton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy. Designs This study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure. Result Among the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years. Conclusion Long-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.

Cardiovascular outcomes associated with use of clarithromycin: population based study

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.

The Variation of Psychopharmacological Prescription Rates for People With Autism Spectrum Disorder (ASD) in 30 Countries

There is significant variation in prescriptions among countries in clinical practice for the treatment of comorbidities associated with autism spectrum disorder (ASD). It has been suggested that many people with mental health disorders in low‐/middle‐income countries do not receive adequate treatment. Hence, this study investigated psychopharmacological treatment patterns for ASD comorbidities in 30 countries and the association between countrys income and prescription rates.

Association between oral fluoroquinolones and seizures: A self-controlled case series study.

Objectives: The aim of this study was to investigate the association and to estimate the crude absolute risk of seizure among patients exposed to fluoroquinolones (FQs) in Hong Kong and the United Kingdom. Methods: A self-controlled case series study was conducted. Data were collected from the Hong Kong Clinical Data Analysis and Reporting System database and the Clinical Practice Research Datalink. Patients who were prescribed any oral FQ and had an incident seizure diagnosis from 2001 to 2013 were included. The risk windows were defined as pre-FQ start, FQ-exposed, and post-FQ completion. Incidence rate ratios were estimated in all risk windows and compared with baseline periods. A post hoc subgroup analysis was conducted to examine the effect of patients with a history of seizure. Results: An increased incidence rate ratio was found in the pre-FQ start periods and no association was found in the post-FQ completion periods in both databases. The crude absolute risk of an incident seizure in 10,000 oral FQ prescriptions was 0.72 (95% confidence interval 0.47–1.10) in the Clinical Data Analysis and Reporting System and 0.40 (95% confidence interval 0.30–0.54) in the Clinical Practice Research Datalink. The rate ratio during treatment was not higher than pre-FQ start periods among patients with a history of seizure, therefore the results did not raise serious concerns. Conclusions: This study does not support a causal association between the use of oral FQs and the subsequent occurrence of seizure. An increased risk before the FQ exposure period suggests that the clinical indication for which FQ was prescribed may have contributed to the development of seizure rather than the drug itself.

Association Between Acute Neuropsychiatric Events and Helicobacter pylori Therapy Containing Clarithromycin

IMPORTANCE There is a concern that Helicobacter pylori therapy containing clarithromycin might be associated with acute neuropsychiatric events. OBJECTIVE To examine the association between H pylori therapy containing clarithromycin and acute neuropsychiatric events. DESIGN, SETTING, AND PARTICIPANTS A self-controlled case series study was conducted using the Clinical Data Analysis and Reporting System database in Hong Kong to explore any association. The exposure of interest was H pylori therapy containing clarithromycin in the outpatient setting. Study patients, 18 years or older at cohort entry, must have had both exposure to H pylori therapy containing clarithromycin and their first recorded neuropsychiatric events between January 1, 2003, and December 31, 2012. A post hoc nested case-control analysis was also performed in patients receiving H pylori therapy containing clarithromycin. MAIN OUTCOMES AND MEASURES The primary outcome was composite neuropsychiatric events, while secondary outcomes were psychotic events and cognitive impairment. Risk periods in the self-controlled case series analysis were defined as 14-day preexposure period, current use (days 1-14 since prescription start date) and recent use (days 15-30). Age-adjusted incidence rate ratios (IRR) were estimated using the conditional Poisson regression. RESULTS Of 66 559 patients who had at least 1 outpatient prescription of H pylori therapy containing clarithromycin. Their mean (SD) age at cohort entry was 50.8 (14.8 years); their mean age at first exposure was 55.4 (14.8) years, and 30 910 were male (46.4%). A total of 1824 patients had their first recorded composite neuropsychiatric events during the study period. An increased IRR of 4.12 (35 composite neuropsychiatric events during 72 person-years; 95% CI, 2.94-5.76) during current use was observed but not in recent use (9 events during 82 person-years; IRR, 0.95; 95% CI, 0.49-1.83) and 14-day preexposure period (14 events during 72 person-years; IRR, 1.63; 95% CI, 0.96-2.77) vs baseline (1766 events during 16 665 person-years). Similarly, both the risk of psychotic events and cognitive impairment increased during current use vs baseline, although this subsequently returned to baseline incidence levels during recent use. The crude absolute risks of composite neuropsychiatric events, psychotic events, and cognitive impairment during current use were 0.45, 0.12, and 0.12 per 1000 prescriptions, respectively. The nested case-control analysis also gave similar results to that of the self-controlled case series analysis. CONCLUSIONS AND RELEVANCE This study shows evidence of a short-term increased risk of neuropsychiatric events associated with H pylori therapy containing clarithromycin.

Aspirin and Risk of Gastric Cancer After Helicobacter pylori Eradication: A Territory-Wide Study.

Background Despite successful H. pylori (HP) eradication, some individuals remain at risk of developing gastric cancer (GC). Previous studies showed that aspirin was associated with a reduced GC risk. However, whether aspirin can reduce GC risk in HP-eradicated subjects remains unknown. We aimed to determine the chemopreventive effect of aspirin in HP-eradicated subjects. Methods We identified subjects who had received a prescription of clarithromycin-based triple therapy for HP between 2003 and 2012 from a territory-wide health care database. The observation period started from commencement of HP therapy (index date), and the follow-up was censored at the end of the study (December 2015), death, or GC diagnosis. Aspirin use was defined as use once or more often weekly. Subjects who failed HP eradication or were diagnosed with GC within 12 months of HP therapy were excluded. The hazard ratio (HR) of GC with aspirin use was calculated by Cox model with Propensity Score adjustment for age, sex, comorbidities, and concurrent medications. All statistical tests were two-sided. Results The median follow-up was 7.6 years (interquartile range [IQR] = 5.1-10.3 years), and 169 (0.27%) out of 63 605 patients developed GC. The incidence rate of GC was 3.5 per 10 000 person-years. Aspirin use was associated with a reduced GC risk (HR = 0.30, 95% confidence interval [CI] = 0.15 to 0.61). The risk of GC decreased with increasing frequency, duration, and dose of aspirin (all Ptrend < .001). Conclusions Aspirin use was associated with a frequency-, dose-, and duration-dependent reduction in GC risk after HP eradication. The effect was most prominent in those who used aspirin daily or for five or more years.

Evaluation of the risk of cardiovascular events with clarithromycin using both propensity score and self-controlled study designs.

Abstract Aim Some previous studies suggest a long term association between clarithromycin use and cardiovascular events. This study investigates this association for clarithromycin given as part of Helicobacter pylori treatment (HPT). Methods Our source population was the Clinical Practice Research Datalink (CPRD), a UK primary care database. We conducted a self‐controlled case series (SCCS), a case–time–control study (CTC) and a propensity score adjusted cohort study comparing the rate of cardiovascular events in the 3 years after exposure to HPT containing clarithromycin with exposure to clarithromycin free HPT. Outcomes were first incident diagnosis of myocardial infarction (MI), arrhythmia and stroke. For the cohort analysis we included secondary outcomes all cause and cardiovascular mortality. Results Twenty‐eight thousand five hundred and fifty‐two patients were included in the cohort. The incidence rate ratio of first MI within 1 year of exposure to HPT containing clarithromycin was 1.07 (95% CI 0.85, 1.34, P = 0.58) and within 90 days was 1.43 (95% CI 0.99, 2.09 P = 0.057) in the SCCS analysis. CTC and cohort results were consistent with these findings. Conclusions There was some evidence for a short term association for first MI but none for a long term association for any outcome.

Neuropsychiatric Events Associated with Leukotriene-Modifying Agents: A Systematic Review

IntroductionLeukotriene-modifying agents (LTMAs) including montelukast, zafirlukast, and zileuton are approved by the US Food and Drug Administration (FDA) for the treatment of asthma and allergic rhinitis. Various neuropsychiatric events (NEs) have been reported; however, the evidence of the association is conflicting. This systematic review investigates the association between NEs and LTMAs by assessing the relevant published literature.MethodsPubMed, EMBASE, MEDLINE, and Cochrane Library were searched using keywords. Studies designed to investigate the association were eligible for inclusion without restriction to any study design or language. The primary outcome was defined as suicidal conditions, while secondary outcomes included all other NEs.ResultsThirty-three studies were included for a narrative review. Four observational studies did not find a significant association, while ten pharmacovigilance studies using different global databases detected the signals. Notably, some studies suggest that the FDA warning issued in 2008 might have influenced the reporting rate of NEs as a result of increased awareness.LimitationsThe risk of NEs was not quantified, because of the lack of randomized controlled trials and observational studies investigating the association.ConclusionMany pharmacovigilance studies have been conducted to determine the association between NEs and LTMAs, but there is limited evidence from observational studies. High-quality epidemiological studies should be conducted to evaluate the association and quantify the risk, not only in children, but also in adults.

Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication.

BACKGROUND Although prior studies showed metformin could reduce gastric cancer (GC) risk in patients with diabetes mellitus, they failed to adjust for Helicobacter pylori infection and glycemic control. We aimed to investigate whether metformin reduced GC risk in H. pylori-eradicated diabetic patients and its association with glycemic control. METHODS This was a territory-wide cohort study using hospital registry database, recruiting all diabetic patients who were prescribed clarithromycin-based triple therapy for H. pylori infection from 2003 to 2012. Subjects were observed from H. pylori therapy prescription until GC diagnosis, death, or end of study (December 2015). Exclusion criteria included GC diagnosed within first year of H. pylori therapy, prior history of GC or gastrectomy, and failure of H. pylori eradication. The hazard ratio (HR) of GC with metformin (defined as at least 180-day use) was estimated by Cox model with propensity score adjustment for covariates (age, sex, comorbidities, medications [including insulin], and time-weighted average hemoglobin A1c [HbA1c]). All statistical tests were two-sided. RESULTS During a median follow-up of 7.1 years (IQR = 4.7-9.8), 37 (0.51%) of 7266 diabetic patients developed GC at a median age of 76.4 years (IQR = 64.8-81.5 years). Metformin use was associated with a reduced GC risk (adjusted HR = 0.49, 95% CI = 0.24 to 0.98). There was a trend towards a lower GC risk with increasing duration (Ptrend = .01) and dose of metformin (Ptrend = .02). HbA1c level was not an independent risk factor for GC. CONCLUSIONS Metformin use was associated with a lower GC risk among H. pylori-eradicated diabetic patients in a duration- and dose-response manner, which was independent of HbA1c level.