The direct disease burden of COVID-19 in Belgium in 2020 and 2021.

BACKGROUND: Burden of disease estimates have become important population health metrics over the past decade to measure losses in health. In Belgium, the disease burden caused by COVID-19 has not yet been estimated, although COVID-19 has emerged as one of the most important diseases. Therefore, the current study aims to estimate the direct COVID-19 burden in Belgium, observed despite policy interventions, during 2020 and 2021, and compare it to the burden from other causes. METHODS: Disability-adjusted life years (DALYs) are the sum of Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) due to disease. DALYs allow comparing the burden of disease between countries, diseases, and over time. We used the European Burden of Disease Network consensus disease model for COVID-19 to estimate DALYs related to COVID-19. Estimates of person-years for (a) acute non-fatal disease states were calculated from a compartmental model, using Belgian seroprevalence, social contact, hospital, and intensive care admission data, (b) deaths were sourced from the national COVID-19 mortality surveillance, and (c) chronic post-acute disease states were derived from a Belgian cohort study. RESULTS: In 2020, the total number of COVID-19 related DALYs was estimated at 253,577 [252,541 - 254,739], which is higher than in 2021, when it was 139,281 [136,704 - 142,306]. The observed COVID-19 burden was largely borne by the elderly, and over 90% of the burden was attributable to premature mortality (i.e., YLLs). In younger people, morbidity (i.e., YLD) contributed relatively more to the DALYs, especially in 2021, when vaccination was rolled out. Morbidity was mainly attributable to long-lasting post-acute symptoms. CONCLUSION: COVID-19 had a substantial impact on population health in Belgium, especially in 2020, when COVID-19 would have been the main cause of disease burden if all other causes had maintained their 2019 level.

Impact of the COVID-19 pandemic on community antibiotic consumption in the EU/European Economic Area: a changepoint analysis.

OBJECTIVES: A decrease in community antibiotic consumption in Europe has been observed during the COVID-19 pandemic. The magnitude of this decrease, how fast after the outbreak it occurred, whether it was sustained during the pandemic and whether the seasonal variation in antibiotic consumption was affected, have not yet been evaluated in detail. METHODS: Data on community antibiotic consumption were available from the European Surveillance of Antimicrobial Consumption Network for 28 EU/European Economic Area (EEA) countries between 2010 and 2021. Antibiotic consumption was expressed as DDDs per 1000 inhabitants per day (DID). The impact of the pandemic on antibiotic consumption was investigated using descriptive statistics and non-linear mixed changepoint models for quarterly and yearly data. RESULTS: The decrease in overall antibiotic consumption between 2019 and 2020 (-3.4 DID; -18.6%) was mainly due to a decrease in the consumption of penicillins [Anatomical Therapeutic Chemical (ATC) code J01C] (-1.9 DID; -23.0%), other ß-lactam antibacterials (J01D) (-0.6 DID; -25.8%) and macrolides, lincosamides and streptogramins (J01F) (-0.5 DID; -17.4%) and was sustained during 2021. The changepoint analysis of yearly data (28 countries) estimated a decrease of 3.3 DID in overall antibiotic consumption (J01) between 2019 and 2020. The analysis of quarterly data (16 countries) estimated a decrease in overall antibiotic consumption (J01) of 4.0 DID and a decrease in seasonal variation of 1.2 DID between the first and second quarters of 2020. CONCLUSIONS: The changepoint analysis indicated a significant, sudden and steep decrease in community antibiotic consumption in the EU/EEA immediately after the start of the COVID-19 outbreak in Europe, as well as a decrease in its seasonal variation.

Determinants of life-expectancy and disability-adjusted life years (DALYs) in European and Organisation for Economic Co-operation and Development (OECD) countries: A longitudinal analysis (1990-2019).

•We relate 68 factors to population health observed in 61 countries over 30 years.•Using random forests, multiple imputation and generalized estimating equations.•GDP per capita and demographics are key; income inequality is not.•Health and social expenditure are more influential than freedom and corruption.•On the macro-level, life-style effects appear to be mediated by cultural context.

Economic burden and health-related quality-of-life among infants with respiratory syncytial virus infection: A multi-country prospective cohort study in Europe.

BACKGROUND: Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. METHODS: Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). RESULTS: Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. CONCLUSION: This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs.

An approximate Bayesian approach for estimation of the instantaneous reproduction number under misreported epidemic data.

In epidemic models, the effective reproduction number is of central importance to assess the transmission dynamics of an infectious disease and to orient health intervention strategies. Publicly shared data during an outbreak often suffers from two sources of misreporting (underreporting and delay in reporting) that should not be overlooked when estimating epidemiological parameters. The main statistical challenge in models that intrinsically account for a misreporting process lies in the joint estimation of the time-varying reproduction number and the delay/underreporting parameters. Existing Bayesian approaches typically rely on Markov chain Monte Carlo algorithms that are extremely costly from a computational perspective. We propose a much faster alternative based on Laplacian-P-splines (LPS) that combines Bayesian penalized B-splines for flexible and smooth estimation of the instantaneous reproduction number and Laplace approximations to selected posterior distributions for fast computation. Assuming a known generation interval distribution, the incidence at a given calendar time is governed by the epidemic renewal equation and the delay structure is specified through a composite link framework. Laplace approximations to the conditional posterior of the spline vector are obtained from analytical versions of the gradient and Hessian of the log-likelihood, implying a drastic speed-up in the computation of posterior estimates. Furthermore, the proposed LPS approach can be used to obtain point estimates and approximate credible intervals for the delay and reporting probabilities. Simulation of epidemics with different combinations for the underreporting rate and delay structure (one-day, two-day, and weekend delays) show that the proposed LPS methodology delivers fast and accurate estimates outperforming existing methods that do not take into account underreporting and delay patterns. Finally, LPS is illustrated in two real case studies of epidemic outbreaks.

Economic Burden and Health-Related Quality of Life of Respiratory Syncytial Virus and Influenza Infection in European Community-Dwelling Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus infections result in a considerable mortality and morbidity among the aging population globally. Influenza vaccination for older adults before the seasonal influenza epidemic has been evaluated to be cost-effective in many countries. Interventions against RSV in older adults are in the pipeline, and evaluating their cost-effectiveness is crucial for decision making. To inform such evaluations, our aim was to estimate average costs and health-related quality of life (HRQoL) in older adults with RSV and influenza infection. METHODS: The European RESCEU observational cohort study followed 1040 relatively healthy community-dwelling older adults aged 60 years and older during 2 consecutive winter seasons. Health care resource use and HRQoL were collected and analyzed during RSV episodes, and also during influenza episodes. Country-specific unit cost data were mainly obtained from national databases. Direct costs were estimated from a patient, health care provider, and health care payers' perspective, whereas indirect costs were estimated from a societal perspective. Due to small sample size, no formal statistical comparisons were made. RESULTS: Thirty-six RSV and 60 influenza episodes were reported, including 1 hospitalization. Means (median; first-third quartile) of €26.4 (€5.5; 0-47.3) direct and €4.4 (€0; 0-0) indirect costs were reported per nonhospitalized RSV episode, and €42.5 (€36; 3.3-66.7) direct and €32.1 (€0; 0-0) indirect costs per nonhospitalized influenza episode. For RSV episodes, the utility value decreased from 0.896 (0.928; 0.854-0.953) to 0.801 (0.854; 0.712-0.937) from preseason to 1 week after symptom onset; for influenza, the change was from 0.872 (0.895; 0.828-0.953) to 0.664 (0.686; 0.574-0.797). CONCLUSIONS: The average costs and HRQoL estimates of older adults treated outside the hospital can be used to inform the design of future studies and the decision making regarding interventions to prevent RSV infection in older adults. Larger studies are needed to provide better country-specific and complementary cost estimates and to allow for formal statistical comparison of costs between RSV and influenza. CLINICAL TRIALS REGISTRATION: NCT03621930.

Laplacian-P-splines for Bayesian inference in the mixture cure model.

The mixture cure model for analyzing survival data is characterized by the assumption that the population under study is divided into a group of subjects who will experience the event of interest over some finite time horizon and another group of cured subjects who will never experience the event irrespective of the duration of follow-up. When using the Bayesian paradigm for inference in survival models with a cure fraction, it is common practice to rely on Markov chain Monte Carlo (MCMC) methods to sample from posterior distributions. Although computationally feasible, the iterative nature of MCMC often implies long sampling times to explore the target space with chains that may suffer from slow convergence and poor mixing. Furthermore, extra efforts have to be invested in diagnostic checks to monitor the reliability of the generated posterior samples. A sampling-free strategy for fast and flexible Bayesian inference in the mixture cure model is suggested in this article by combining Laplace approximations and penalized B-splines. A logistic regression model is assumed for the cure proportion and a Cox proportional hazards model with a P-spline approximated baseline hazard is used to specify the conditional survival function of susceptible subjects. Laplace approximations to the posterior conditional latent vector are based on analytical formulas for the gradient and Hessian of the log-likelihood, resulting in a substantial speed-up in approximating posterior distributions. The spline specification yields smooth estimates of survival curves and functions of latent variables together with their associated credible interval are estimated in seconds. A fully stochastic algorithm based on a Metropolis-Langevin-within-Gibbs sampler is also suggested as an alternative to the proposed Laplacian-P-splines mixture cure (LPSMC) methodology. The statistical performance and computational efficiency of LPSMC is assessed in a simulation study. Results show that LPSMC is an appealing alternative to MCMC for approximate Bayesian inference in standard mixture cure models. Finally, the novel LPSMC approach is illustrated on three applications involving real survival data.

Dual Use of Public and Private Health Care Services in Brazil.

(1) Background: Brazil has a universal public healthcare system, but individuals can still opt to buy private health insurance and/or pay out-of-pocket for healthcare. Past research suggests that Brazilians make combined use of public and private services, possibly causing double costs. This study aims to describe this dual use and assess its relationship with socioeconomic status (SES). (2) Methods: We calculated survey-weighted population estimates and descriptive statistics, and built a survey-weighted logistic regression model to explore the effect of SES on dual use of healthcare, including demographic characteristics and other variables related to healthcare need and use as additional explanatory variables using data from the 2019 Brazilian National Health Survey. (3) Results: An estimated 39,039,016 (n = 46,914; 18.6%) persons sought care in the two weeks before the survey, of which 5,576,216 were dual users (n = 6484; 14.7%). Dual use happened both in the direction of public to private (n = 4628; 67.3%), and of private to public (n = 1855; 32.7%). Higher income had a significant effect on dual use (p < 0.0001), suggesting a dose-response relationship, even after controlling for confounders. Significant effects were also found for region (p < 0.0001) and usual source of care (USC) (p < 0.0001). (4) Conclusion: A large number of Brazilians are seeking care from a source different than their regular system. Higher SES, region, and USC are associated factors, possibly leading to more health inequity. Due to its high prevalence and important implications, more research is warranted to illuminate the main causes of dual use.

Impact of Adding Oseltamivir to Usual Care on Quality-Adjusted Life-Years During Influenza-Like Illness.

OBJECTIVES: The ALIC4E trial has shown that oseltamivir reduces recovery time while increasing the risk of nausea. This secondary analysis of the ALIC4E trial aimed to determine the gain in quality-adjusted life-years (QALYs) associated with adding oseltamivir to usual primary care in patients presenting with influenza-like illness (ILI). METHODS: Patients with ILI were recruited during the influenza season (2015-2018) in 15 European countries. Patients were assigned to usual care with or without oseltamivir through stratified randomization (age, severity, comorbidities, and symptom onset). Patients' health status was valued with the EQ-5D and visual analog scale (VAS) for up to 28 days. Average EQ-5D and VAS scores over time were estimated for both treatment groups using one-inflated beta regression in children (<13 years old) and adults (≥13 years old). QALY gain was calculated as the difference between the groups. Sensitivity analysis considered the value set to convert EQ-5D answers to summary scores and the follow-up period. RESULTS: In adults, oseltamivir gained 0.0006 (95% confidence interval 0.0002-0.0010) QALYs, whereas no statistically significant gain was found in children (14-day follow-up, EQ-5D). QALY gains were statistically significant in patients aged ≥65 years, patients without relevant comorbidities, or patients experiencing symptoms for ≤48 hours. Using VAS and accounting for 28-day follow-up resulted in higher QALY gain. CONCLUSIONS: QALY gain owing to oseltamivir is limited compared with other diseases, and its clinical meaningfulness remains to be determined. Further analysis is needed to evaluate whether QALY gain and its impact on ILI treatment cost render oseltamivir cost-effective.

Pertussis Immunization During Pregnancy: Assessment of the Role of Maternal Antibodies on Immune Responses in Term and Preterm-Born Infants.

BACKGROUND: Limited data exist on the impact of maternal tetanus, diphtheria, acellular pertussis (Tdap) vaccination for preterm born infants. We report its effect at birth and on antibody-mediated immune responses to a DTaP-IPV-HB-PRP~T vaccine in preterm compared with term infants. METHODS: Women delivering at term or prematurely were either vaccinated with a Tdap vaccine (Boostrix; GSK) during pregnancy or not vaccinated in the last 5 years. Cord and maternal blood were collected at delivery. Infants were vaccinated with DTaP-IPV-HB-PRP~T vaccine (Hexyon; Sanofi Pasteur) and blood collected before and 1 month after primary (8-12-16 weeks) and before and 1 month after booster vaccination (13 or 15 months for preterm and term, respectively). Immunoglobulin G antibodies against all antigens included in DTaP-IPV-HB-PRP~T vaccine were measured (NCT02511327). RESULTS: Cord blood geometric mean concentrations (GMCs) in preterm infants from Tdap-vaccinated women were significantly higher than in term and preterm infants from unvaccinated women. A longer time interval between maternal vaccination and delivery resulted in higher cord blood GMCs in preterm infants. Equal GMCs in term and preterm infants from Tdap-vaccinated women were observed after primary vaccination. After boosting, significantly lower GMCs were seen for pertussis toxin, filamentous hemagglutinin, and tetanus toxoid in preterm compared with term infants from Tdap-vaccinated women, yet still comparable to GMCs in both term and preterm infants from unvaccinated women. CONCLUSIONS: Preterm infants profit from maternal Tdap vaccination. Prematurity did not influence primary immune responses in the presence of maternal antibodies but was associated with a lower booster immune response.

Belgian population norms for the EQ-5D-5L, 2018.

PURPOSE: Health-related quality of life outcomes are increasingly used to monitor population health and health inequalities and to assess the (cost-) effectiveness of health interventions. The EQ-5D-5L has been included in the Belgian Health Interview Survey, providing a new source of population-based self-perceived health status information. This study aims to estimate Belgian population norms for the EQ-5D-5L by sex, age, and region and to analyze its association with educational attainment. METHODS: The BHIS 2018 provided EQ-5D-5L data for a nationally representative sample of the Belgian population. The dimension scores and index values were analyzed using logistic and linear regressions, respectively, accounting for the survey design. RESULTS: More than half of respondents reported problems of pain/discomfort, while over a quarter reported problems of anxiety/depression. The average index value was 0.84. Women reported more problems on all dimensions, but particularly on anxiety/depression and pain/discomfort, resulting in significantly lower index values. Problems with mobility, self-care, and usual activities showed a sharp increase after the age of 80 years. Consequently, index values decreased significantly by age. Lower education was associated with a higher prevalence of problems for all dimensions except anxiety/depression and with a significantly lower index value. CONCLUSION: This paper presents the first nationally representative Belgian population norms using the EQ-5D-5L. Inclusion of the EQ-5D in future surveys will allow monitoring over time of self-reported health, disease burden, and health inequalities.

Consumption of antibiotics in the community, European Union/European Economic Area, 1997-2017: data collection, management and analysis.

OBJECTIVES: This article introduces a series of articles on antibiotic consumption in the community between 1997 and 2017, which provide an update of previous articles covering the periods 1997-2003 and 1997-2009. METHODS: In this article, differences in participating countries, the ATC/DDD classification system, and data collection, validation and analysis between the current and previous series are described. RESULTS: In the previous series, 33 European countries provided valid data for further analysis, while the current series focused on 30 countries belonging to the EU or the European Economic Area (EEA). For both series, data were collected in accordance with the WHO ATC classification system. While the previous series reported data in accordance with the ATC/DDD index 2011, the current series employed the ATC/DDD index 2019. Both series focused on consumption of antibacterials for systemic use (ATC J01) and collected data expressed in DDD per 1000 inhabitants per day and packages per 1000 inhabitants per day. When studying consumption expressed in packages per 1000 inhabitants per day, countries reporting total care data, i.e. community and hospital sector combined, were included in the previous series but excluded in the current series. While the previous series used non-linear mixed models to evaluate time trends in antibiotic consumption, the current series allowed for inclusion of change-points with a data-driven location. In addition, both series assessed the composition and quality of antibiotic consumption in the EU/EEA. CONCLUSIONS: The updated analyses of two decades of ESAC-Net data provide the most comprehensive and detailed description of antibiotic consumption in the community in Europe.

Consumption of quinolones in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Data on quinolone consumption in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of main subgroups of quinolones. METHODS: For the period 1997-2017, data on consumption of quinolones, i.e. ATC group J01M, in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Quinolone consumption was analysed by subgroups based on pharmacokinetic profile, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, quinolone consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 8.2 between countries with the highest (Bulgaria) and the lowest (Norway) consumption. The second-generation quinolones accounted for >50% of quinolone consumption in most countries. Quinolone consumption significantly increased up to 2001, and did not change significantly afterwards. Seasonal variation increased significantly over time. Proportional consumption of third-generation quinolones significantly increased over time relative to that of second-generation quinolones, while proportional consumption of both third- and second-generation quinolones significantly increased relative to that of first-generation quinolones. Levofloxacin and moxifloxacin represented >40% of quinolone consumption in the community in southern EU/EEA countries. CONCLUSIONS: Quinolone consumption in the community is no longer increasing in the EU/EEA, but its seasonal variation continues to increase significantly as is the proportion of quinolones to treat respiratory infections.

Consumption of macrolides, lincosamides and streptogramins in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Data on the consumption of macrolides, lincosamides and streptogramins (MLS) in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in composition of the main subgroups of MLS. METHODS: For the period 1997-2017, data on consumption of MLS, i.e. ATC group J01F, in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of MLS was analysed and presented as trends, seasonal variation, presence of change-points and compositional changes, using a classification based on mean plasma elimination half-life for macrolides. RESULTS: In 2017, consumption of MLS in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 13 between countries with the highest (Greece) and the lowest (Sweden) consumption. Consumption of MLS did not change significantly up to 2003, after which it significantly increased up to 2007. No significant change was observed after 2007. Consumption of MLS showed high seasonal variation. The proportional consumption of long-acting macrolides significantly increased over time compared with that of intermediate-acting macrolides, and proportional consumption of the latter increased compared with that of short-acting macrolides. CONCLUSIONS: Consumption of MLS did not change significantly over time during 2007-2017, while the proportional consumption of long-acting macrolides increased. Seasonal variation remained high, which suggests that MLS are still prescribed inappropriately in many countries.

Consumption of antibiotics in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Data on antibiotic consumption in the community were collected from 30 EU/EEA countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main antibiotic groups. METHODS: For the period 1997-2017, data on consumption of antibiotics, i.e. antibacterials for systemic use (ATC group J01), in the community, aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Antibiotic consumption was analysed based on ATC-3 groups, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, antibiotic consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor 3.6 between countries with the highest (Greece) and the lowest (the Netherlands) consumption. Antibiotic consumption in the EU/EEA did not change significantly over time. Antibiotic consumption showed a significant seasonal variation, which decreased over time. The number of DDD per package significantly increased over time. The proportional consumption of sulphonamides and trimethoprim (J01E) relative to other groups significantly decreased over time, while the proportional consumption of other antibacterials (J01X) relative to other groups significantly increased over time. CONCLUSIONS: Overall, antibiotic consumption in the community in the EU/EEA did not change during 1997-2017, while seasonal variation consistently decreased over time. The number of DDD per package increased during 1997-2017.

Consumption of penicillins in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Data on consumption of penicillins in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main subgroups of penicillins. METHODS: For the period 1997-2017, data on consumption of penicillins, i.e. ß-lactam antibacterials, penicillins (ATC group J01C), in the community aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of penicillins was analysed based on ATC-4 subgroups, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, consumption of penicillins in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 4.9 between countries with the highest (Spain) and the lowest (the Netherlands) consumption. An increase in consumption of penicillins, which was not statistically significant, was observed between 1997 and 2003 and up to 2010. A decrease, which was not statistically significant, was observed from 2010 onwards. Proportional consumption of combinations of penicillins, including ß-lactamase inhibitors (J01CR) increased during 1997-2017, which coincided with a decrease in the proportional consumption of extended-spectrum penicillins (J01CA) and narrow-spectrum penicillins (J01CE). CONCLUSIONS: Considerable variation in the patterns of consumption of penicillins was observed between EU/EEA countries. The consumption of penicillins in the EU/EEA community did not change significantly over time, while the proportional consumption of combinations of penicillins increased.

Quality appraisal of antibiotic consumption in the community, European Union/European Economic Area, 2009 and 2017.

OBJECTIVES: The quality of antibiotic consumption in the community can be assessed using 12 drug-specific quality indicators (DSQIs) developed by the European Surveillance of Antimicrobial Consumption (ESAC) project. We compared quality in 2009 and 2017 in the EU/European Economic Area (EEA) and evaluated the impact of using different DDD values (ATC/DDD indices 2011 and 2019) for the 2009 quality assessment using these DSQIs and a joint scientific opinion (JSO) indicator. METHODS: We calculated the 12 DSQIs and the JSO indicator for 2017 and for 2009 for EU/EEA countries able to deliver values. For each of the indicators we grouped the 2017 and 2009 indicator values into four quartiles. To evaluate changes in quality between 2009 and 2017, we used the quartile distribution of the 2009 indicator values in 30 EU/EEA countries as benchmarks. In addition, we compared the quality assessment for 2009 using the ATC/DDD indices 2011 and 2019. RESULTS: In 2017, a difference in the quality of antibiotic consumption in the community between northern and southern EU/EEA countries remained, but also several eastern EU/EEA countries shifted towards lower quality. Quality of antibiotic consumption decreased between 2009 and 2017 in particular indicator values for penicillin, quinolone, relative ß-lactam and broad- versus narrow-spectrum antibiotic consumption, and seasonal variation. Using different ATC/DDD indices did not substantially change countries' ranking based on their DSQI values. CONCLUSIONS: The quality of antibiotic consumption in the community as measured by the DSQIs further decreased between 2009 and 2017, especially in Southern and Eastern European countries. A continuous effort to improve antibiotic consumption is essential to reduce antibiotic consumption in general and the use of broad-spectrum antibiotics in particular.

Consumption of cephalosporins in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Data on cephalosporin consumption in the community were collected from 30 EU/EEA countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main subgroups of cephalosporins. METHODS: For the period 1997-2017, data on consumption of cephalosporins (i.e. first-, second-, third- and fourth-generation cephalosporins; ATC subgroups J01DB, J01DC, J01DD and J01DE, respectively) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Cephalosporin consumption was analysed based on ATC-4 subgroup, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, cephalosporin consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 285 between countries with the highest (Greece) and the lowest (the Netherlands) consumption. Cephalosporin consumption did not change significantly between the first quarter of 1997 and the last quarter of 2017. Seasonal variation decreased significantly over time. Proportional consumption of second- and third-generation cephalosporins significantly increased over time compared with that of first-generation cephalosporins, and proportional consumption of fourth-generation cephalosporins significantly decreased compared with that of second- and third-generation cephalosporins. CONCLUSIONS: Despite considerable variation between countries in the composition of cephalosporin consumption and trends over time, a significant shift towards consumption of more broad-spectrum cephalosporins in the community was observed across the EU/EEA during 1997-2017.

Change-points in antibiotic consumption in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Surveillance of antibiotic consumption in the community is of utmost importance to inform and evaluate control strategies. Data on two decades of antibiotic consumption in the community were collected from 30 EU/European Economic Area (EEA) countries. This article reviews temporal trends and the presence of abrupt changes in subgroups of relevance in antimicrobial stewardship. METHODS: For the period 1997-2017, data on yearly antibiotic consumption in the community, aggregated at the level of the active substance, were collected using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. We applied a range of non-linear mixed models to assess the presence of changes in the consumption of antibacterials for systemic use (ATC group J01) and eight antibiotic subgroups. RESULTS: For the majority of the studied groups, a country-specific change-point model provided the best fit. Depending on the antibiotic group/subgroup and on the country, change-points were spread out between 2000 and 2013. CONCLUSIONS: Due to the heterogeneity in antibiotic consumption in the community across EU/EEA countries, a country-specific change-point model provided the better fit. Given the limitations of this model, our recommendation for the included countries is to carefully interpret the country-specific results presented in this article and to use the tutorial included in this series to conduct their own change-point analysis when evaluating the impact of changes in regulations, public awareness campaigns, and other national interventions to improve antibiotic consumption in the community.

Consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Data on consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of main subgroups of tetracyclines, sulphonamides and trimethoprim and other antibacterials. METHODS: For the period 1997-2017, data on consumption of tetracyclines (ATC group J01A), sulphonamides and trimethoprim (ATC group J01E), and other antibacterials (ATC group J01X) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials was analysed based on ATC-4 subgroups and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in the community expressed in DDD per 1000 inhabitants per day varied considerably between countries. Between 1997 and 2017, consumption of tetracyclines did not change significantly, while its seasonal variation significantly decreased over time. Consumption of sulphonamides and trimethoprim significantly decreased until 2006, and its seasonal variation significantly decreased over time. The consumption of other antibacterials showed no significant change over time or in seasonal variation. CONCLUSIONS: Consumption and composition of tetracyclines, sulphonamides and trimethoprim, and other antibacterials showed wide variations between EU/EEA countries and over time. This represents an opportunity to further reduce consumption of these groups in some countries and improve the quality of their prescription.