Medication safety research by observational study design

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Dosage Effects of Histamine-2 Receptor Antagonist on the Primary Prophylaxis of Non-Steroidal Anti-Inflammatory Drug (NSAID)-Associated Peptic Ulcers: A Retrospective Cohort Study

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Mothers’ Preferences and Willingness to Pay for Human Papillomavirus Vaccination for Their Daughters: A Discrete Choice Experiment in Hong Kong

Objectives: To determine the preference of mothers in Hong Kong and their willingness to pay (WTP) for human papillomavirus (HPV) vaccination for their daughters. Method: A discrete choice experiment survey with a two-alternative study design was developed. Data were collected from pediatric specialist outpatient clinics from 482 mothers with daughters aged between 8 and 17 years. Preferences of the four attributes of HPV vaccines (protection against cervical cancer, protection duration, side effects, and out-of-pocket costs) were evaluated. The marginal and overall WTP were estimated using multinomial logistic regression. A subgroup analysis was conducted to explore the impact of socioeconomic factors on mothers’ WTP. Results: Side effects, protection against cervical cancer, protection duration, and out-of-pocket cost determined the decision to receive or not receive the vaccine. All attributes had a statistically significant effect on the preference of and the WTP for the vaccine. Maximum WTP for ideal vaccines (i.e., 100% protection, lifetime protection duration, and 0% side effects) was HK$8976 (US$1129). The estimated WTP for vaccines currently available was HK$1620 (US$208), lower than the current market price. Among those who had a monthly household income of more than HK$100,000 (US$12,821), the WTP for vaccines currently offered was higher than the market price. Conclusions: This study provides new data on how features of the HPV vaccine are viewed and valued by mothers by determining their perception of ideal or improved and current vaccine technologies. These findings could contribute to future policies on the improvement of HPV vaccine and be useful for the immunization service in Hong Kong

Databases in the Asia-Pacific Region: The Potential for a Distributed Network Approach

Background: This study describes the availability and characteristics of databases in Asian-Pacific countries and assesses the feasibility of a distributed network approach in the region. Methods: A web-based survey was conducted among investigators using healthcare databases in the Asia-Pacific countries. Potential survey participants were identified through the Asian Pharmacoepidemiology Network. Results: Investigators from a total of 11 databases participated in the survey. Database sources included four nationwide claims databases from Japan, South Korea, and Taiwan; two nationwide electronic health records from Hong Kong and Singapore; a regional electronic health record from western China; two electronic health records from Thailand; and cancer and stroke registries from Taiwan. Conclusions: We identified 11 databases with capabilities for distributed network approaches. Many country-specific coding systems and terminologies have been already converted to international coding systems. The harmonization of health expenditure data is a major obstacle for future investigations attempting to evaluate issues related to medical costs.postprin

Prescription sequence symmetry analysis: assessing risk, temporality, and consistency for adverse drug reactions across datasets in five countries

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

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.published_or_final_versio

Associations between prenatal exposure to antipsychotics and attention-deficit/hyperactivity disorder, autism spectrum disorder, preterm birth and small for gestational age: a population-based cohort study

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, Participants: This population-based cohort study included children born between 2001–2015 with follow-up to 2019, identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestational-exposed and gestational non-exposed with propensity score fine-stratification. Additional analyses included gestational-exposed versus past-exposed and 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 and 411,251 pairs for ASD/preterm birth/small for gestational age analyses. There were 13,196 children (3.95%) diagnosed with ADHD, 8,715 (2.12%) with ASD, 33,891 (8.24%) preterm, and 7,009 (1.70%) small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% confidence interval [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 gestational-exposed to gestational non-exposed. Additional analyses showed no association when comparing gestational-exposed to past-exposed (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 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: We found no evidence 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 gestational-exposed to past-exposed and comparing gestational exposed to gestational non-exposed 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 stop their regular antipsychotic treatment during pregnancy

Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis

Background: Research showing an association between proton pump inhibitors (PPIs) and Clostridium difficile infections has largely been undertaken in Europe and North America. Clostridium difficile strains vary by region and may influence risk estimates across regions. Aim: To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countries Method: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random sample data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/ outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest. Results: 54,957 patients were included. Positive associations were observed in Australia; adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Asian countries. Results did not vary by individual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation. Conclusion: When analysis was limited to the Asian countries, pooled risk estimates were higher than those which had been observed in European and North American populations. Research to identify reasons underpinning any risk difference in the Asian region is required.postprin

Leukotriene receptor antagonists and suicide: a self-controlled case series study

Oral Presentation - Paediatrics – Mental and General HealthConference Theme: Applying pharmacoepidemiology to improve health care in AsiaAim/Objective: In March 2008 the suicide of a 15 year old boy captured media attention. The suicide was attributed to the exposure of montelukast, a leukotriene receptor antagonist (LTRA) used to treat asthma and allergies. The presence of, unknown and unmeasured confounders are limitations in observational studies, particularly in the study of suicide which has several risk factors. The self-controlled case series (SCCS) method automatically controls for fi xed confounders. Objectives: To investigate the association of suicide and LTRAs using the SCCS method in the UK. Method: Electronic healthcare records of patients with a record of suicide attempt (including suicide and self -harm, poisoning-selfinfl icted, injury–self infl icted, cause of overdose-deliberate) and exposure to LTRAs during the period of 1st January 1998 to 1st January 2011 were extracted from the Health Improvement Network (THIN) database of anonymised records from contributing UK general practices. A risk period of thirty days before and after exposure to LTRA and control periods within the observation time of each patient were identifi ed. A Poisson analysis conditioned on the event was used to calculate the Incidence Rate Ratio (IRR). Results: A total of 236 cases of fi rst attempts of suicide were identifi ed. The IRR for a risk period of 30 days after the start of treatment with LTRA was 0.32 (95% CI 0.04-2.42; P=0.268). Conclusion: Our study does not support the association between the use of LTRA and suicide attempts within the fi rst thirty days of exposure to LTRA. Further studies with larger number of cases are needed