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Weaknesses Missing data The primary aim of data collection by GPs is patient management, and the data are therefore not customized for medical research purposes This implies that only information deemed to be relevant to the patient's care is collected and entered into the patient's file. Key Features The Integrated Primary Care Information Project (IPCI) database contains longitudinal data of patients of a group of general practitioners (GPs) in The Netherlands. Data validity Because data in the GP systems are collected with patient management as the main goal, caution is needed when using IPCI data for research purposes. The Integrated Primary Care Information database The Integrated Primary Care Information (IPCI) database is a database containing longitudinal, routinely collected data from computer-based patient records of around 350 GP practices throughout The Netherlands. [Extracted from the article]

Aim Electronic healthcare record (EHR)-based surveillance systems are increasingly being developed to support early detection of safety signals. It is unknown what the power of such a system is for surveillance among children and adolescents. In this paper we provide estimates of the number and classes of drugs, and incidence rates (IRs) of events, that can be monitored in children and adolescents (0-18 years). Methods Data were obtained from seven population-based EHR databases in Denmark, Italy, and the Netherlands during the period 1996-2010. We estimated the number of drugs for which specific adverse events can be monitored as a function of actual drug use, minimally detectable relative risk (RR) and IRs for 10 events. Results The population comprised 4 838 146 individuals (25 575 132 person years (PYs)), who were prescribed 2170 drugs (1 610 631 PYs drug-exposure). Half of the total drug-exposure in PYs was covered by only 18 drugs (0.8%). For a relatively frequent event like upper gastrointestinal bleeding there were 39 drugs for which an association with a RR ≥4, if present, could be investigated. The corresponding number of drugs was eight for a rare event like anaphylactic shock. Conclusion Drug use in children is rare and shows little variation. The number of drugs with enough exposure to detect rare adverse events in children and adolescents within an EHR-based surveillance system such as EU-ADR is limited. Use of additional sources of paediatric drug exposure information and global collaboration are imperative in order to optimize EHR data for paediatric safety surveillance. [ABSTRACT FROM AUTHOR]

Antiepileptic drug (AED) use in young people is increasing. However, evidence of its use at a multinational level is limited. This study aims to characterize AED prescribing in the young in three European countries and to assess the capacity of drug safety surveillance. A retrospective cohort study was conducted in 2001–2005 using primary care databases: PEDIANET (Italy, 0–11 years), IPCI (The Netherlands, 0–18 years), and IMS Disease Analyzer (United Kingdom, 0–18 years). Prescribing prevalence was calculated by country, patient age, and drug type. In 2005, AED prevalence in children (0–11 years) was highest in Italy [3.9 subjects/1,000 person-years (PY)] followed by the United Kingdom (3.0 subjects/1,000 PY) and The Netherlands (2.2 subjects/1,000 PY). Over the study period, prescribing prevalence in 0–11 year olds was stable in all countries. In contrast, a steady rise of AED prevalence was observed in adolescents (12–18 years) in the United Kingdom (p = 0.0003) but not in The Netherlands (p = 0.88). All countries showed a slight increase in prevalence for newer AEDs. Simultaneously, the prevalence of conventional AEDs decreased in The Netherlands and Italy, but not in the United Kingdom. In 2005, lamotrigine use was highest in The Netherlands and the United Kingdom, whereas topiramate was favored in Italy. In Europe, conventional AEDs are still the main treatment choice for children with epilepsy, and the use of newer AEDs remains low. Our study highlights a lack of research capacity to conduct multinational AED safety studies in children. Further work should explore large databases and other health care settings to meet these research needs. [ABSTRACT FROM AUTHOR]

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Chronic cough is a debilitating medical condition that is often complicated by psychomorbidities such as depressive symptoms. Nevertheless, little is known about the impact of chronic cough on the risk of developing depression. Therefore, we investigated the association between chronic cough and prevalent, incident and recurrent depression in a population-based sample of middle-aged and older persons., Methods: Within the Rotterdam Study, a population-based cohort, we defined chronic cough as reporting daily coughing for ⩾3 months. Depression was assessed using the Center for Epidemiologic Studies Depression scale, clinical interviews and medical records. Associations between chronic cough and depression were determined with linear, logistic and Cox regression analyses., Results: The study included 5877 participants (mean±sd age 72±8 years, 59% female) who contributed 37 287 person-years of follow-up. At baseline, participants with chronic cough reported more depressive symptoms (adjusted standardised mean difference 0.15, 95% CI 0.07-0.22) compared to those without chronic cough. Over time, chronic cough was associated with an increased risk of depression in participants with a history of depression (hazard ratio (HR) 1.45, 95% CI 1.13-1.84), but not in those without a history of depression (HR 0.91, 95% CI 0.68-1.22)., Conclusions: Adults with chronic cough have a disproportionate burden of depressive symptoms and an increased risk of recurrent depression. This highlights the importance of screening for depression in patients with chronic cough., Competing Interests: Conflict of interest: J.T. Arinze reports support for the present manuscript received from Merck Sharp and Dohme (MSD), support for attending meetings and/or travel received from Lung Foundation Netherlands (Long Fonds), outside the submitted work. G.G. Brusselle reports support for the present manuscript received from MSD, and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events received from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Chiesi, Sanofi and Teva, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

Background: Increasing evidence suggests that sarcopenia and a higher systemic immune-inflammation index (SII) are linked with morbidity in patients with COPD. However, whether these two conditions contribute to all-cause mortality in middle-aged and older patients with COPD or asthma is unclear. Therefore, we investigated the association between sarcopenia, SII, COPD or asthma and all-cause mortality in a large-scale population-based setting., Methods: Between 2009 and 2014, 4482 participants (aged >55 years; 57.3% female) from the population-based Rotterdam Study were included. COPD and asthma patients were diagnosed clinically and based on spirometry. Six study groups were defined according to the presence or absence of COPD or asthma and sarcopenia. Cox regression models were used to assess all-cause mortality in the study groups, adjusted for sex, age, body mass index, SII, smoking, oral corticosteroid use and comorbidities. In addition, all participants were categorised into sex-specific quartiles of SII, and mortality in these groups was compared., Results: Over a median follow-up of 6.1 years (interquartile range 5.0-7.2 years), 466 (10.4%) persons died. Independent of the presence of sarcopenia, participants with COPD had a higher risk of all-cause mortality (hazard ratio (HR) 2.13, 95% CI 1.46-3.12 and HR 1.70, 95% CI 1.32-2.18 for those with and without sarcopenia, respectively). Compared to lower SII levels, higher SII levels increased mortality risk even in people without sarcopenia, COPD or asthma., Conclusion: Middle-aged and older people with COPD, higher SII levels or sarcopenia had an independently increased mortality risk. Our study suggests prognostic usefulness of routinely evaluating sarcopenia and SII in older people with COPD or asthma., Competing Interests: Conflict of interest: E. Benz has nothing to disclose. Conflict of interest: S.R.A. Wijnant reports grants from GlaxoSmithKline outside the submitted work. Conflict of interest: K. Trajanoska has nothing to disclose. Conflict of interest: J.T. Arinze reports a doctoral research grant from Merck Sharp & Dohme, paid to their institution, outside the submitted work. Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: M. de Ridder has nothing to disclose. Conflict of interest: R. Williams has nothing to disclose. Conflict of interest: F. van Rooij has nothing to disclose. Conflict of interest: K.M.C. Verhamme reports that they work for a research department that receives or has received unconditional grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis, GSK, UCB, Amgen and Chiesi, none of which are related to the content of this paper. Conflict of interest: M.A. Ikram has nothing to disclose. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: F. Rivadeneira has nothing to disclose. Conflict of interest: L. Lahousse reports financial support for the current manuscript from the Fund for Scientific Research Flanders (grant 3G037618), and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Institute for Continuing Study of Pharmacists, outside the submitted work. Conflict of interest: G.G. Brusselle reports receiving fees for advisory boards or lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi and Teva, outside the submitted work., (Copyright ©The authors 2022.)

Aim: The aim of this study was to investigate occurrence and determinants of asthma exacerbations in an ageing general population., Methods: Subjects aged 45 years or above with physician-diagnosed asthma in the Rotterdam Study, a population-based prospective cohort from January 1991 to May 2018, were assessed for asthma exacerbations. Exacerbations were defined as acute episodes of worsening asthma treated with oral corticosteroids. Cox proportional hazards analysis was used to investigate risk factors for a future exacerbation., Results: Out of 763 participants with asthma (mean age 61.3 years, 69.2% female), 427 (56.0%) experienced at least one exacerbation, in a mean follow-up time of 13.9 years. The mean annual exacerbation rate was 0.22. Most exacerbations occurred during winter months. Risk factors for exacerbations were a history of previous exacerbations (HR 4.25; 95% CI 3.07-5.90, p<0.001)), respiratory complaints (HR 2.18; 95% CI 1.48-3.21, p<0.001), airflow obstruction (HR 1.52; 95% CI 1.07-2.15, p=0.019), obesity (HR 1.38; 95% CI 1.01-1.87, p=0.040) and depressive symptoms (HR 1.55; 95% CI 1.05-2.29, p=0.027). Compared to those not using respiratory medication, we observed higher hazard ratios for those on short-acting β 2 -agonists (SABA, i.e. rescue medication) only (HR 3.08, 95% CI 1.61-5.90, p=0.001) than those on controller medication (HR 2.50, 95% CI 1.59-3.92, p<0.001)., Conclusion: Many older adults with asthma suffer from at least one severe exacerbation. Previous exacerbations, use of SABA without concomitant controller medication, respiratory complaints, obesity, airway obstruction and depression are independent risk factors for exacerbations., Competing Interests: Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: L. Lahousse has nothing to disclose. Conflict of interest: K.M.C. Verhamme works for a research group that received/receives unconditional research grants from Yamanouchi, Pfizer–Boehringer Ingelheim, Novartis, GSK, Chiesi and Amgen. Conflict of interest: G-J. Braunstahl reports grants from GSK, AstraZeneca, Chiesi and Teva, personal fees from Novartis and Sanofi, and grants and personal fees from ALK Abello, outside the submitted work. Conflict of interest: J.J.C.C.M. in ‘t Veen reports faculty grants from Teva, Chiesi, Boehringer Ingelheim and AstraZeneca, and speaker bureau and advisory board fees from Sanofi, outside the submitted work. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: G.G.O. Brusselle reports advisory board fees from Amgen, Boehringer Ingelheim, Novartis, Sanofi and Teva, and advisory board and lecture fees from AstraZeneca, Chiesi and GlaxoSmithKline, outside the submitted work., (Copyright ©The authors 2021.)

Observational studies report a reduction of COPD exacerbations in patients treated with β-blockers. In contrast, the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK COPD) randomised controlled trial which excluded COPD patients with cardiovascular conditions showed an increase in COPD exacerbations. It is unclear whether this discrepancy could be explained by underlying cardiovascular comorbidity. We examined whether the association between use of β-blockers and risk of COPD exacerbations differed between patients with and without a cardiovascular indication for β-blockers use. Within the Rotterdam Study, we followed COPD subjects until the first COPD exacerbation, or end of follow-up. Cardiovascular indication for β-blockers use was defined as a history of hypertension, coronary heart disease, atrial fibrillation and/or heart failure at baseline. The association between β-blockers use and COPD exacerbations was assessed using Cox proportional hazards models adjusted for age, sex, smoking, incident cardiovascular disease ( i.e. heart failure, hypertension, atrial fibrillation and/or coronary heart disease during follow-up), respiratory drugs and nitrates. In total, 1312 COPD patients with a mean age of 69.7±9.2 years were included. In patients with a cardiovascular indication (n=755, mean age of 70.4±8.8 years), current use of cardioselective β-blockers was significantly associated with a reduced risk of COPD exacerbations (HR 0.69, 95% CI 0.57-0.85). In contrast, in subjects without a cardiovascular indication (n=557, mean age of 68.8±9.7 years), current use of cardioselective β-blockers was not associated with an altered risk of COPD exacerbations (HR 0.94, 95% CI 0.55-1.62). Use of cardioselective β-blockers reduced the risk of exacerbations in COPD patients with concomitant cardiovascular disease. Therefore, the potential benefits of β-blockers might be confined to COPD patients with cardiovascular disease., Competing Interests: Conflict of interest: L. Karimi has nothing to disclose. Conflict of interest: L. Lahousse reports grants from AstraZeneca and Chiesi (both awards), and expert consultation for Boehringer Ingelheim GmbH and Novartis, outside the submitted work. Conflict of interest: P. De Nocker has nothing to disclose. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: G.G. Brusselle reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, GlaxoSmithKline, Sanofi and Teva, outside the submitted work. Conflict of interest: K.M.C. Verhamme works for a research group that, in the past, has received unconditional research grants from Pfizer, Boehringer Ingelheim, Yamanouchi and GSK, none of which is related to the content of this paper., (Copyright ©The authors 2021.)

Rationale: Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies., Methods: A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed., Results: 10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10 -6 ). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found., Conclusions: The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response., Competing Interests: Conflict of interest: N. Hernandez-Pacheco reports grants from Instituto de Salud Carlos III (ISCIII, FI16/00136) and co-funded by the European Social Funds from the European Union (ESF) “ESF invests in your future”, during the conduct of the study. Conflict of interest: S.J. Vijverberg has nothing to disclose. Conflict of interest: E. Herrera-Luis reports grants from the Spanish Ministry of Science, Innovation, and Universities (PRE2018-083837), during the conduct of the study. Conflict of interest: J. Li has nothing to disclose. Conflict of interest: Y.Y. Sio has nothing to disclose. Conflict of interest: R. Granell has nothing to disclose. Conflict of interest: A. Corrales has nothing to disclose. Conflict of interest: C. Maroteau has nothing to disclose. Conflict of interest: R. Lethem has nothing to disclose. Conflict of interest: J. Perez-Garcia has nothing to disclose. Conflict of interest: N. Farzan has nothing to disclose. Conflict of interest: K. Repnik has nothing to disclose. Conflict of interest: M. Gorenjak has nothing to disclose. Conflict of interest: P. Soares has nothing to disclose. Conflict of interest: L. Karimi has nothing to disclose. Conflict of interest: M. Schieck has nothing to disclose. Conflict of interest: L. Pérez-Méndez has nothing to disclose. Conflict of interest: V. Berce has nothing to disclose. Conflict of interest: R. Tavendale has nothing to disclose. Conflict of interest: C. Eng has nothing to disclose. Conflict of interest: O. Sardon has nothing to disclose. Conflict of interest: I. Kull has nothing to disclose. Conflict of interest: S. Mukhopadhyay reports grants from The Gannochy Trust, Perth and Kinross City Council and Scottish Enterprises Tayside, during the conduct of the study. Conflict of interest: M. Pirmohamed reports grants from UK Department of Health and UK Medical Research Council, during the conduct of the study; grants from MRC Clinical Pharmacology Training Scheme (joint funding by MRC and Roche, UCB, Eli Lilly and Novartis), Joint PhD studentship funded by EPSRC and Astra Zeneca and grants from Bristol Myers Squibb, outside the submitted work. Conflict of interest: K.M.C. Verhamme reports grants from ZonMw, during the conduct of the study; and works for a department who in the past received unconditional research grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis and GSK. Conflict of interest: E.G. Burchard reports grants from the National Heart, Lung, and Blood Institute (NHLBI) of the US National Institutes of Health (NIH) (X01HL134589, X01HL134589,R01HL128439, R01HL135156, R01HL141992 and R01HL141845), the National Institute of Environmental Health Sciences (NIEHS) (R01ES015794 and R21ES24844), the National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443 and R56MD013312), the National Institute of General Medical Sciences (NIGMS) (RL5GM118984), the Tobacco-Related Disease Research Program (award numbers 24RT-0025 and 27IR-0030), the National Human Genome Research Institute (NHGRI) (U01HG009080), the Sandler Family Foundation, the American Asthma Foundation, the Amos Medical Faculty Development Program from the Robert Wood Johnson Foundation, the Harry Wm. and Diana V. Hind Distinguished Professorship in Pharmaceutical Sciences II, during the conduct of the study. Conflict of interest: M. Kabesch reports grants from European Union, German Ministry of Education and Research, German Research Foundation, during the conduct of the study; personal fees for consultancy from Bionorica, Sanofi, Novartis and Bencard, personal fees for lectures from ERS, EAACI, ATS, Novartis, Glaxo, Nutricia, Hipp and Allergopharma, outside the submitted work. Conflict of interest: D.B. Hawcutt has nothing to disclose. Conflict of interest: E. Melén has nothing to disclose. Conflict of interest: U. Potočnik reports grants from Slovenian Research Agency (P3-0067) and Ministry of Education, Science and Sport Slovenia (MIZS) (SysPharmPediA grant C3330-16-500106), during the conduct of the study. Conflict of interest: F.T. Chew reports grants from Singapore Ministry of Education Academic Research Fund, Singapore Immunology Network, National Medical Research Council (NMRC) (Singapore), Biomedical Research Council (BMRC) (Singapore), and the Agency for Science Technology and Research (A*STAR) (Singapore), during the conduct of the study; and consulting fees from Sime Darby Technology Centre, First Resources Ltd, Genting Plantation and Olam International, outside the submitted work. Conflict of interest: K.G. Tantisira reports grants from U.S. National Institutes of Health, during the conduct of the study. Conflict of interest: S. Turner has nothing to disclose. Conflict of interest: C.M. Palmer has nothing to disclose. Conflict of interest: C. Flores has nothing to disclose. Conflict of interest: M. Pino-Yanes reports grants from Spanish Ministry of Economy, Industry and Competitiveness (funded by the Ramón y Cajal Program, RYC-2015-17205), and Instituto de Salud Carlos III (ISCIII) (funded by ISCIII through AES and EC within AAL framework, and the SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020, AC15/00015), during the conduct of the study. Conflict of interest: A.H. Maitland-van der Zee reports grants from GSK, during the conduct of the study; grants from Boehringer Ingelheim, personal fees for advisory board work from AstraZeneca and Boehringer Ingelheim, outside the submitted work., (Copyright ©ERS 2021.)

Since chronic cough has common neurobiological mechanisms and pathophysiology with chronic pain, both clinical disorders might be interrelated. Hence, we examined the association between chronic cough and chronic pain in adult subjects in the Rotterdam Study, a large prospective population-based cohort study.Using a standardised questionnaire, chronic pain was defined as pain lasting up to 6 months and grouped into a frequency of weekly/monthly or daily pain. Chronic cough was described as daily coughing for at least 3 months duration. The longitudinal and cross-sectional associations were investigated bi-directionally.Of 7141 subjects in the study, 54% (n=3888) reported chronic pain at baseline. The co-prevalence of daily chronic pain and chronic cough was 4.4%. Chronic cough was more prevalent in subjects with daily and weekly/monthly chronic pain compared with those without chronic pain (13.8% and 10.3% versus 8.2%; p<0.001). After adjustment for potential confounders, prevalent chronic pain was significantly associated with incident chronic cough (OR 1.47, 95% CI 1.08-1.99). The association remained significant in subjects with daily chronic pain (OR 1.49, 95% CI 1.06-2.11) with a similar effect estimate, albeit non-significant in those with weekly/monthly chronic pain (OR 1.43, 95% CI 0.98-2.10). After adjustment for covariables, subjects with chronic cough had a significant risk of developing chronic pain (OR 1.63, 95% CI 1.02-2.62) compared with those without chronic cough.Chronic cough and chronic pain confer risk on each other among adult subjects, indicating that both conditions might share common risk factors and/or pathophysiologic mechanisms., Competing Interests: Conflict of interest: J.T. Arinze reports grants from MSD (doctoral research grant), outside the submitted work. Conflict of interest: K.M.C. Verhamme works for a research group who in the past received unconditional grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis and GSK, none of which relate to the content of this work. Conflict of interest: A.I. Luik has nothing to disclose. Conflict of interest: B. Stricker has nothing to disclose. Conflict of interest: J.B.J. van Meurs has nothing to disclose. Conflict of interest: G.G. Brusselle reports personal fees from Astra Zeneca (advisory boards and speaker's fees), Boehringer-Ingelheim (advisory boards and speaker's fees), Chiesi (advisory boards and speaker's fees), GlaxoSmithKline (advisory boards and speaker's fees), Novartis (advisory boards and speaker's fees), Sanofi (advisory boards) and Teva (advisory boards and speaker's fees), and grants from MSD, outside the submitted work., (Copyright ©ERS 2021.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Josep Pane and Dorian Villegas are employees of Alcon. Laura Gamez and Irene Rebollo are employees of Novartis. Katia M.C. Verhamme reports working for a research group that received/receives unconditional research grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis, GSK, and Chiesi, none of which are related to the content of this manuscript. Miriam C.J.M. Sturkenboom reports being a principal investigator on post-authorization safety studies for Novartis, non-related to this study. The authors report no other potential conflicts of interest for this work., (© 2021 Pane et al.)

Introduction: The amount of mandatory data that needs to be analyzed as part of a medical device postmarket surveillance (PMS) system has grown exponentially in recent times. This is a consequence of increasingly demanding and complex regulatory requirements from Health Authorities, aimed at a better understanding of the medical device safety evaluation. Proactive approaches to PMS processes are becoming more necessary as regulators increase the scrutiny of device safety. New technologies have been explored to address some of the challenges associated with this changing regulatory environment., Areas Covered: This paper focuses on the different technical aspects of blockchain and how this new technology has the potential to support the ongoing efforts to improve the PMS system for medical devices., Expert Opinion: To address these challenges, we suggest to generate a private PMS data permissioned blockchain with a proof-of-authority consensus mechanism, to which only a restricted number of designated and audited participants have authorization to validate transactions and add them to the PMS data blockchain ledger. Blockchain has the potential to support a more efficient approach, which could offer many advantages to the different stakeholders involved in the PMS process, such as supporting with new regulatory initiatives.

Chronic cough is a common complaint in the general population but there are no precise data on the incidence of, and prospectively examined risk factors for chronic cough in a population-based setting. Therefore, we investigated the period prevalence, incidence and risk factors for chronic cough in adult subjects. In a prospective population-based cohort study among subjects aged ≥45 years, data on chronic cough were collected on two separate occasions using a standardised questionnaire. Chronic cough was defined as daily coughing for at least 3 months duration during the preceding 2 years. Potential risk factors were gathered by interview, physical examination and several investigations. Of the 9824 participants in this study, 1073 (10.9%) subjects had chronic cough at baseline. The prevalence of chronic cough increased with age and peaked in the eighth decade. In subjects aged <70 years, chronic cough was more common in women. During an average follow-up of 6 years, 439 incident cases of chronic cough occurred with an overall incidence rate of 11.6 per 1000 person-years (95% CI 10.6-12.8). In current smokers, the incidence of chronic cough was higher in men. In the multivariable analysis, current smoking, gastro-oesophageal reflux disease (GORD), asthma and COPD were identified as risk factors for chronic cough. Chronic cough is common among adults and highly prevalent in the older population. Current smoking, GORD, asthma and COPD are independent risk factors for chronic cough. Individuals at risk of developing chronic cough may benefit from smoking cessation and control of the underlying disease., Competing Interests: Conflict of interest: J.T. Arinze has nothing to disclose. Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: L. Karimi has nothing to disclose. Conflict of interest: K.M.C. Verhamme works for a research group that, in the past, received unconditional grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis and GSK, none of which relate to the content of this work. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: G.G. Brusselle reports advisory boards and speaker's fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva; and advisory board fees from Sanofi, outside the submitted work., (Copyright ©ERS 2020.)

Background: Guidelines recommend omalizumab in patients with uncontrolled severe allergic asthma. We investigated real-life use of omalizumab, the proportion of patients fulfilling eligibility criteria, its costs and its effectiveness., Method: In a cohort of asthma patients initiating treatment with omalizumab in Belgium between 2010 and 2016, we investigated fulfilment of eligibility criteria (chronic use of high-dose inhaled corticosteroids (ICSs) plus long-acting β 2 -agonists (LABAs) and ≥2 severe asthma exacerbations in previous year), and compared hospitalisations and systemic corticosteroid consumption in the year before and after omalizumab initiation. We computed healthcare costs in the respective time periods and compared the cost per prevented hospitalisation in patients fulfilling eligibility criteria versus those who did not., Results: Between 2010 and 2016, omalizumab treatment was initiated in 2068 patients with asthma; only 24% fulfilled the eligibility criteria, mainly due to nonadherence to high-dose ICSs + LABAs. The proportion of patients hospitalised for asthma decreased from 41% to 21% in eligible patients (absolute risk reduction, 20%), whereas the absolute risk reduction was 5% (from 19% to 14%) in noneligible patients. The cost per prevented hospitalisation was €44 238 versus €139 495, respectively. Chronic use of systemic corticosteroids was discontinued in 35% of eligible patients versus 15% of noneligible patients., Conclusion: In Belgium, omalizumab is mostly initiated in uncontrolled asthma patients who are nonadherent to ICSs + LABAs. Omalizumab decreases hospitalisations and the use of systemic corticosteroids, but at a high cost. Careful management of patients with difficult-to-treat asthma should be a priority before prescribing omalizumab., Competing Interests: Conflict of interest: K.M.C. Verhamme works for a research group that, in the past, received unconditional research grants from Pfizer/Boehringer Ingelheim, Yamanouchi, Novartis and GSK. None of these are related to the content of this manuscript. Conflict of interest: C. Lucet has nothing to disclose. Conflict of interest: A. Van Meerhaeghe has nothing to disclose. Conflict of interest: G.G.O. Brusselle reports personal fees for advisory boards and lectures from Astra Zeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, and for advisory boards from Sanofi, outside the submitted work. Conflict of interest: M-L. Lambert has nothing to disclose., (Copyright ©ERS 2019.)