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COPD is the third leading cause of death in the world and its global burden is predicted to increase further. Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner. In a prospective populationbased cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV₁/FVC < 0.70). In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician. Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk. In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones. The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4. The IR was higher in males and in smokers. The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males. The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers. The proportion of never-smokers among female COPD cases is substantial.

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified. A further cohort consisted of people with no prior COVID-19 vaccination who were infected with SARS-Cov-2 identified by a first positive PCR test between 1 September 2020 and 2 May 2021. The fourth general population cohort for background rates included those people in the database as of 1 January 2017. In total, we included 3,768,517 ChAdOx1 and 1,832,841 BNT162b2 vaccinees, 401,691 people infected with SARS-CoV-2, and 9,414,403 people from the general population. An increased risk of venous thromboembolism was seen after first dose of ChAdOx1 (standardized incidence ratio: 1.12 [95% CI: 1.05 to 1.20]), BNT162b2 (1.12 [1.03 to 1.21]), and positive PCR test (7.27 [6.86 to 7.72]). Rates of cerebral venous sinus thrombosis were higher than otherwise expected after first dose of ChAdOx1 (4.14 [2.54 to 6.76]) and a SARS-CoV-2 PCR positive test (3.74 [1.56 to 8.98]). Rates of arterial thromboembolism after vaccination were no higher than expected but were increased after a SARS-CoV-2 PCR positive test (1.39 [1.21 to 1.61]). Rates of venous thromboembolism with thrombocytopenia were higher than expected after a SARS-CoV-2 PCR positive test (5.76 [3.19 to 10.40]). Population-based studies can provide information on the safety of COVID-19 vaccines. Here the authors report the rates thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom and compare them with the background (expected) rates in the general population.

Individual case safety reports (ICSRs) are a cornerstone in drug safety surveillance. The knowledge on using these data specifically for children is limited. We studied characteristics of pediatric ICSRs reported to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Public available ICSRs reported in children (0-18 years) to FAERS were downloaded from the FDA-website for the period Jan 2004-Dec 2011. Characteristics of these ICSRs, including the reported drugs and events, were described and stratified by age-groups. We included 106,122 pediatric ICSRs (55% boys and 58% from United States) with a median of 1 drug [range 1-3] and 1 event [1-2] per ICSR. Mean age was 9.1 years. 90% was submitted through expedited (15-days) (65%) or periodic reporting (25%) and 10% by non-manufacturers. The proportion and type of pediatric ICSRs reported were relatively stable over time. Most commonly reported drug classes by decreasing frequency were 'nervous system drugs' (58%), 'antineoplastics' (32%) and 'anti-infectives' (25%). Most commonly reported system organ classes were 'general' (13%), 'nervous system' (12%) and 'psychiatric' (11%) disorders. Duration of use could be calculated for 19.7% of the reported drugs, of which 14.5% concerned drugs being used long-term (>6 months). Knowledge on the distribution of the drug classes and events within FAERS is a key first step in developing pediatric specific methods for drug safety surveillance. Because of several differences in terms of drugs and events among age-categories, drug safety signal detection analysis in children needs to be stratified by each age group.

Urinary retention is a condition in which impaired emptying of the bladder results in postvoidal residual urine. It is generally classified into ‘acute’ or ‘chronic’ urinary retention. Because of the complex mechanism of micturition, many drugs can interact with the micturition pathway, all via different modes of action. Although the incidence of urinary retention, in particular acute urinary retention, has been well studied in observational studies and randomized controlled trials, data on the incidence of drug-induced urinary retention are scarce. Data from observational studies suggest that up to 10% of episodes might be attributable to the use of concomitant medication. Urinary retention has been described with the use of drugs with anticholinergic activity (e.g. antipsychotic drugs, antidepressant agents and anticholinergic respiratory agents), opioids and anaesthetics, α-adrenoceptor agonists, benzodiazepines, NSAIDs, detrusor relaxants and calcium channel antagonists. Elderly patients are at higher risk for developing drug-induced urinary retention, because of existing co-morbidities such as benign prostatic hyperplasia and the use of other concomitant medication that could reinforce the impairing effect on micturition. Drug-induced urinary retention is generally treated by urinary catheterization, especially if acute, in combination with discontinuation or a reduction in dose of the causal drug. Studies have been carried out examining the effects of preventive measures for anaesthesia-related urinary retention, both during and after surgery, particularly into the effect of using opioids in combination with non-opioid analgesic drugs on the incidence of postoperative urinary retention. Although combination therapy reduces the opioid-related adverse events, the effect on urinary retention yields contradictory results. This article reviews the literature on drug-induced urinary retention and focuses on its incidence, the different classes of drugs that have been associated with it, and options for its management and prevention.

Introduction A 6-month course of isoniazid, 300 mg daily, was programmatically introduced in Eritrea in 2014 as tuberculosis preventive therapy in people living with human immunodeficiency virus (PLHIV). The rollout of isoniazid preventive therapy (IPT) in PLHIV was successful in the first 2–3 years. After 2016, rumours based on rare but real incidents of liver injuries following use of IPT spread widely across the country and created concerns amongst healthcare professionals and consumers, that ultimately caused dramatic decline in the rollout of the intervention. Decision makers have been demanding better evidence as previously conducted local studies had inherent methodological limitations. This real-world observational study was conducted to evaluate the risk of liver injury associated with IPT among PLHIV attending Halibet national referral hospital, Asmara, Eritrea. Methods A prospective cohort study, that consecutively enrolled PLHIV attending Halibet hospital, was conducted between 1 March and 30 October 2021. Those exposed to anti-retroviral therapy (ART) plus IPT were considered as exposed and those taking only ART were considered as unexposed. Both groups were prospectively followed up for 4–5 months with monthly liver function tests (LFTs). A Cox proportional hazard model was used to explore whether there was increased risk of drug-induced liver injury (DILI) associated with IPT. Probability of survival without DILI was also estimated using Kaplan–Meier curves. Results A total of 552 patients, 284 exposed and 268 unexposed, completed the study, with a mean follow-up time of 3.97 (SD 0.675) months for the exposed and 4.06 (SD 0.675) months for the unexposed. Twelve patients developed drug-induced liver injury (DILI), with a median time-to-onset of 35 days (interquartile range: 26.8, 60 days). All cases were from the exposed group and all except two cases were asymptomatic. The incidence rate of DILI in the exposed group was 10.6 cases per 1000 person–months and zero for the unexposed group ( p  = 0.002). Conclusion DILI in PLHIV taking IPT was common; therefore, liver function should be closely monitored to safely administer the product. Despite high levels of deranged liver enzymes, the majority had no symptoms of DILI, emphasising the importance of close laboratory monitoring, especially during the first 3 months of treatment.

Previous safety issues involving medical devices have stressed the need for better safety signal detection. Various European Union (EU) national competent authorities have started to focus on strengthening the analysis of vigilance data. Consequently, article 90 of the new EU regulation states that the European Commission shall put in place systems and processes to actively monitor medical device safety signals. A systematic literature review was conducted to synthesize the current state of knowledge and investigate the present tools used for medical device safety signal detection. An electronic literature search was performed in Embase, Medline, Cochrane, Web of science, and Google scholar from inception until January 2017. Articles that included terms related to medical devices and terms associated with safety were selected. A further selection was based on the abstract review. A full review of the remaining articles was conducted to decide on which articles finally to consider relevant for this review. Completeness was assessed based on the content of the articles. Our search resulted in a total of 20,819 articles, of which 24 met the inclusion criteria and were subject to data extraction and completeness scoring. A wide range of data sources, especially spontaneous reporting systems and registries, used for the detection and assessment of product problems and patient harms associated with the use of medical devices, were studied. Coding is remarkably heterogeneous, no agreement on the preferred methods for signal detection exists, and no gold standard for signal detection has been established thus far. Data source harmonization, the development of gold standard signal detection methodologies and the standardization of coding dictionaries are amongst the recommendations to support the implementation of a new proactive approach to signal detection. The new safety surveillance system will be able to use real-world evidence to support regulatory decision-making across all jurisdictions.

Summary We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. Purpose To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. Methods We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. Results Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52–73% at 6 months to 29–53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50–66% at 6 months and decreased to 30–44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40–73% and decreased to 25–59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50–85% (6 month), 30–63% (12 month) and with teriparatide 40–75% (6 month) decreasing to 21–54% (12 month). Switching occurred most frequently in the alendronate group (2.8–5.8%) and in the teriparatide group (7.1–14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. Conclusion Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.

Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL-4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab. Methods: Spontaneous reports were used from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities ® (MedDRA ® ). Safety signal strength was assessed by the Reporting Odds Ratio (ROR). Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24–63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4–29.3). Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation.

Asthma drugs are amongst the most frequently used drugs in childhood, but international comparisons on type and indication of use are lacking. The aim of this study was to describe asthma drug use in children with and without asthma in the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a retrospective analysis of outpatient medical records of children 0–18 years from 1 January 2000 until 31 December 2005. For all children, prescription rates of asthma drugs were studied by country, age, asthma diagnosis, and off-label status. One-year prevalence rates were calculated per 100 children per patient-year (PY). The cohort consisted of 671,831 children of whom 49,442 had been diagnosed with asthma at any time during follow-up. ß2-mimetics and inhaled steroids were the most frequently prescribed asthma drug classes in NL (4.9 and 4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY), respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and anti-allergics were prescribed in less than one child per 100 per year. In patients without asthma, ß2-mimetics were used most frequently. Country differences were highest for steroids, (Italy highest), and for ß2-mimetics (the UK highest). Off-label use was low, and most pronounced for ß2-mimetics in children <18 months (IT) and combined ß2-mimetics + anticholinergics in children <6 years (NL). Conclusion: This study shows that among all asthma drugs, ß2-mimetics and inhaled steroids are most often used, also in children without asthma, and with large variability between countries. Linking multi-country databases allows us to study country specific pediatric drug use in a systematic manner without being hampered by methodological differences. This study underlines the potency of healthcare databases in rapidly providing data on pediatric drug use and possibly safety.

Objective: To provide an overview of drug use in children in three European countries. Design: Retrospective cohort study, 2000-5. Setting: Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet). Participants: 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands). Main outcome measure: Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of \"recurrent/chronic\" use (three or more prescriptions a year) and \"non-recurrent\" or \"acute\" use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class. Results: Three levels of drug use could be distinguished in the study population: high (>10/100 children per year, moderate (1-10/100 children per year), and low (<1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label. Conclusion: This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs.