Author Correction: Hospital Admissions due to Dysglycaemia and Prescriptions of Antidiabetic Medications in England and Wales: An Ecological Study.

In the original publication, the fifth author's name was incorrectly published as Simon J. Bell. The correct name should read as 'J. Simon Bell'.

Hospital Admissions due to Dysglycaemia and Prescriptions of Antidiabetic Medications in England and Wales: An Ecological Study.

INTRODUCTION: Hypoglycaemia and hyperglycaemia are common adverse events associated with antidiabetic medications. They are also a common cause of hospital admissions for people with diabetes. The objective of the study was to explore the trends in hospital admissions due to hypoglycaemia and hyperglycaemia and in the prescriptions of antidiabetic medications in England and Wales. METHODS: We conducted an observational study during the period 1999-2016. Hospital admission data for patients from all age groups were extracted from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Data on prescriptions of antidiabetic medications were extracted from the Prescription Cost Analysis database from 2004 to 2016. RESULTS: Between 1999 and 2016, the hospital admission rate increased by 173.0% [from 17.2 (95% CI 16.9-17.6) to 47.1 (95% CI 46.5-47.6) per 100,000 persons] for hypoglycaemia and by 147.0% [from 22.8 (95% CI 22.4-23.2) to 56.3 (95% CI 55.7-56.9) per 100,000 persons] for hyperglycaemia. The prescription rate for all antidiabetic medications increased between 2004 and 2016 by 116.0% [from 373.0 (95% CI 373.0-373.0) to 806.0 (95% CI 806.0-806.0) prescriptions per 1000 persons]. There was a parallel increase in the rate of antidiabetic medication prescriptions during the same study period, with correlation coefficients of 0.94 for hypoglycaemia and 0.98 for hyperglycaemia, respectively. CONCLUSIONS: There have been parallel increases in the rate of admissions due to dysglycaemia and the rate of antidiabetic prescriptions in England and Wales. Further analytical studies are required to investigate whether increased admission for dysglycaemia is associated with increased use of antidiabetic medications.

Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia.

UNLABELLED: There is a lack of knowledge regarding the incidence of serious adverse drug reactions (ADR) to the oral iron chelator deferiprone in Chinese children with transfusion-dependent thalassaemia. In this retrospective population-based cohort study, paediatric thalassaemia patients in Hong Kong were screened for serious and medically important adverse events related to deferiprone therapy using diagnosis codes, laboratory data and hospital admissions. Potential ADRs were assessed by reviewing concomitant medications, diagnoses and laboratory data and evaluated using standardised causality assessment. Eighty-seven patients contributing 169.8 person-years were included. Thirty ADRs were identified in 21 patients. Most ADRs (56.0%) occurred in the first three months of therapy. Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient-years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%, incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe arthropathy, elevated liver enzymes and mild thrombocytopenia. In conclusion, the safety profile of DFP therapy in Chinese children suffering from transfusion-dependent thalassaemia is in line with previous studies of non-Chinese children. However, unlike previous studies, we observed a relatively high incidence of agranulocytosis and neutropenia in patients with simultaneous combined therapy. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. Further prospective clinical and pharmacogenetic studies are required to better evaluate this important safety signal. KEY POINTS: • Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy.

Experiences of adolescents and young adults with ADHD in Hong Kong: treatment services and clinical management.

BACKGROUND: Specialist services for the treatment of attention deficit hyperactivity disorder (ADHD) in adulthood in Hong Kong are yet to be developed. This study aims to explore the experiences of adolescents and young adults with ADHD in accessing treatment and services, coping with ADHD-related impairment, and their expectations of future treatment in Hong Kong. METHOD: Qualitative interviews were conducted with a semi-structured guide. Forty young adult patients aged between 16 and 23 were included in the study. The interview recordings were transcribed verbatim and anonymised. Data were analysed with a thematic approach based on key principles of Grounded Theory. RESULTS: Four meta-themes were developed: Accessing ADHD diagnosis and treatment services; ADHD-related impairment; Experience of ADHD treatments; and Attitudes and expectations of future ADHD treatment. The role of parents and schools were highly significant in accessing services for patients diagnosed with ADHD in childhood. In general, ADHD affected every aspect of patients' lives including academic outcome, employment, family and social relationships. Medications were the principal treatment for ADHD amongst the interviewees and were reported to be generally effective. Half of the patients received non-pharmacological treatments in childhood but these effects were reported to be temporary. There was general consensus that the needs of patients with ADHD could not be met by the current service. In particular, there is a lack of specialist service for adults with ADHD, follow-up by different clinicians, and insufficient provision of non-pharmacological treatments. CONCLUSION: The findings suggest that further development of specialist ADHD services and non-pharmacological options for young adults are essential to meet their diverse needs with a holistic approach.

Adverse drug reactions - examples of detection of rare events using databases.

It is recognised that randomised controlled trials are not feasible for capturing rare adverse events. There is an increasing trend towards observational research methodologies using large population-based health databases. These databases offer more scope for adequate sample sizes, allowing for comprehensive patient characterisation and assessment of the associated factors. While direct causality cannot be established and confounders cannot be ignored, databases present an opportunity to explore and quantify rare events. The use of databases for the detection of rare adverse events in the following conditions, sudden death associated with attention deficit hyperactivity disorder (ADHD) treatment, retinal detachment associated with the use of fluoroquinolones and toxic epidermal necrolysis associated with drug exposure, are discussed as examples. In general, rare adverse events tend to have immediate and important clinical implications and may be life-threatening. An understanding of the causative factors is therefore important, in addition to the research methodologies and database platforms that enable the undertaking of the research.

Association between oral fluoroquinolone use and the development of retinal detachment: a systematic review and meta-analysis of observational studies.

OBJECTIVES: Several observational studies have been published investigating the association between oral fluoroquinolone use and the development of retinal detachment; however, the findings are not concordant. This study is a meta-analysis of the existing literature and estimates the overall absolute risk of such an event. METHODS: Electronic databases were searched for observational studies on the association between oral fluoroquinolone and retinal detachment up to August 2014. Studies that did not meet the criteria for meta-analysis were narratively reviewed. Cases of retinal detachment during current fluoroquinolone use were also extracted for absolute risk calculation. RESULTS: Seven observational studies were included. Three (case-control and self-controlled case series studies) were eligible for meta-analysis and four (cohort studies) were narratively reviewed. The rate ratio of the case-control studies was 1.82 (95% CI 0.67-4.93), I(2) =96% and the incidence rate ratio of the self-controlled case series was 1.03 (95% CI 0.84-1.27), I(2) =36%. Three of the four cohort studies found no significant association between oral fluoroquinolone use and the development of retinal detachment. The pooled absolute risk of retinal detachment whilst on current oral fluoroquinolone treatment is estimated to be 4.85 per 1000000 prescriptions (95% CI 0.78-8.91). CONCLUSIONS: The findings of this systematic review and meta-analysis do not support an association between oral fluoroquinolone use and the development of retinal detachment. Given the low absolute risk, such an event would be rare if there were an association. The current prescribing practice for fluoroquinolones should not be altered because of a previously suggested potential risk of retinal detachment.

Exposure to selective serotonin reuptake inhibitors during pregnancy and risk of autism spectrum disorder in children: a systematic review and meta-analysis of observational studies.

This study is a critical analysis of the association between selective serotonin reuptake inhibitors (SSRIs) exposure during pregnancy and autism spectrum disorder (ASD) risk in children. Electronic databases were searched for observational studies published from January 1946 to June 2014 related to the association between SSRI exposure during pregnancy and ASD in children. Studies relevant to the association between SSRI exposure during pregnancy and ASD in children were extracted and compiled for meta-analysis evaluation. Ninety-five citations were identified and seven observational studies were included. Four case-control studies were eligible for the meta-analysis and two cohort studies were narratively reviewed. The pooled crude and adjusted odds ratios of the case-control studies were 2.13 (95% CI 1.66-2.73) and 1.81 (95% CI 1.47-2.24) respectively. Low heterogeneity was observed between studies. The two population-based cohort studies, utilizing the same Denmark data set, have conflicting results. The findings of this meta-analysis and narrative review support an increased risk of ASD in children of mothers exposed to SSRIs during pregnancy; however, the causality remains to be confirmed.

Pharmacovigilance in China: current situation, successes and challenges.

With the integration of the global pharmaceutical economy and the gradual transformation of the healthcare insurance system in China, the legislative framework for a comprehensive regulatory system monitoring the whole process including drug development, manufacture, distribution and use has been established by the China Food and Drug Administration (CFDA) to ensure the safety and effectiveness of medication use. China has established a relatively comprehensive pharmacovigilance system covering regulation, organisation and technology from 1989 to 2014. As of 2013, one national centre, 34 provincial centres and more than 400 municipal centres for adverse drug reaction (ADR) monitoring were included in the four-level pharmacovigilance network (national, provincial, municipal and county) with more than 200,000 grassroot organisation users. The China Adverse Drug Reaction Monitoring System (CADRMS) is an online spontaneous reporting system which connects the four-level pharmacovigilance network. By 2013, CADRMS had received over 6.6 million ADR case reports. After integrating and analysing pharmacovigilance data, the National Centre for ADR Monitoring (NCADRM) publishes medication safety information by releasing ADR bulletins, National ADR Annual Reports and International Pharmacovigilance Newsletters. The NCADRM also routinely provides CADRMS data feedback to manufacturers. The CFDA implemented risk management through several approaches, including arranging 'manufacturer communication meetings', modification of medication package inserts, and restriction, suspension or withdrawal of marketing authorisations. Seamless information exchange with overseas regulatory authorities and organisations remains an area for improvement. Further development of the China pharmacovigilance system in terms of signal generation, post-marketing pharmacoepidemiology research and education is also needed.