Ondansetron use in nausea and vomiting during pregnancy:A descriptive analysis of prescription patterns and patient characteristics in UK general practice

AIMS: The objective of this study was to describe ondansetron drug utilization patterns during pregnancy to treat nausea and vomiting in pregnancy (NVP). Moreover, we aimed to describe the maternal factors associated with NVP and antiemetic use. METHODS: The data consist of pregnancies with a live birth(s) within an IMRD‐UK registered GP practice. Descriptive statistics were used to investigate patterns of ondansetron use in pregnancy and to describe maternal characteristics associated with NVP and antiemetic drug utilization. We differentiate first‐ from second‐line use during pregnancy using antiemetic prescription pathways. RESULTS: The dataset included 733 633 recorded complete pregnancies from 2005 to 2019. NVP diagnosis and ondansetron prescription prevalence increased from 2.7% and 0.1% in 2005 to 4.8% and 2.5% in 2019 respectively. Over the period 2015–2019, the most common oral daily dosages were 4 mg/d (8.5%), 8 mg/d (37.1%), 12 mg/d (37.5%) and between 16 and 24 mg/d (16.9%). Prescription of ondansetron was initiated during the first trimester of pregnancy in 40% of the cases and was moderately used as a first‐line therapy (2.8%), but preferred choice of second‐line therapy. Women with mental health disorders, asthma and/or prescribed folic acid were more likely to experience NVP and use antiemetics in pregnancy than their counterparts. CONCLUSION: This study confirms that ondansetron is increasingly used off‐label to treat NVP during pregnancy, also in the first trimester and before other prescription antiemetics have been prescribed. Several maternal comorbidities and folic acid use were more common among women experiencing NVP and using antiemetics, including ondansetron

Potential adjustment methodology for missing data and reporting delay in the HIV Surveillance System, European Union/European Economic Area, 2015

HIV remains one of the most important public health concerns in the European Union and European Economic Area (EU/EEA). Accurate data are therefore crucial to appropriately direct and evaluate public health response. The European Centre for Disease Prevention and Control (ECDC) and the World Health Organization Regional Office for Europe (WHO/Europe) have jointly coordinated enhanced HIV/AIDS surveillance in the European Region since 2008. The general objectives of the surveillance system in EU/EEA countries include monitoring of trends over time and across countries. Specific HIV-related objectives include the monitoring of testing patterns, late HIV diagnoses, defined by low CD4+ counts (<350 cells/mm3), and mortality, as well estimating HIV incidence and prevalence stratified by key populations, e.g. transmission category and migrant status [1]. To meet these objectives, the long-term strategy states that improving the quality of surveillance data is needed [2]. Achieving this in practice poses challenges, especially given the heterogeneous national surveillance systems in the EU/EEA and that the routinely collected data are known to suffer from important quality limitations. The limitations originating from national data collection systems may include under-reporting or duplication of cases, delays in reporting, incompleteness of data and misclassification. Accounting for some of these limitations (e.g. assessment of under-reporting) requires additional data such as cohort studies or registries, while other issues, such as incompleteness and reporting delay, may be addressed directly within the surveillance datasets. Missing data are a well-recognised problem within surveillance systems. When values for some variables are missing and cases with missing values are excluded from analysis, it may lead to biased and potentially less precise estimates [3,4]. In principle, whenever there are missing data or reporting delays, the accuracy of epidemiological distributions and trends should be interpreted with caution. Reporting delay, the time from case diagnosis to notification, can lead to problems when analysing the most recent years, given that the information on some cases or variables may not have been collected yet because of national reporting process characteristics. This phenomenon is common in disease surveillance and also applies to HIV [5-8]. Rough adjustments for reporting delay were already implemented in the past in Europe [8,9], but further refinement of the existing applied methodology is needed to address this issue across more countries’ data. The main purpose of this paper is to explore the issues of missing data and reporting delay in EU/EEA HIV surveillance data. We aim to quantify the extent to which these problems are present and to identify specific data characteristics that are relevant for data adjustments. Taking these characteristics into account, we also propose methods to adjust for missing data and reporting delay based on literature and existing national practices in EU/EEA countries.Peer Reviewe

Marketing Authorization Applications Made to the European Medicines Agency in 2018-2019:What was the Contribution of Real-World Evidence?

Information derived from routinely collected real-world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real-world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019. For MAAs, 63 of 158 products (39.9%) contained RWE with a total of 117 studies. For 31.7% of these products, the RWE submitted was derived from data collected before the planned authorization. The most common data sources were registries (60.3%) followed by hospital data (31.7%). RWE was mainly included to support safety (87.3%) and efficacy (49.2%) with cohort studies being the most frequently used study design (88.9%). For EOIs, 28 of 153 products (18.3%) contained RWE with a total of 36 studies. For 57.1% of these products, studies were conducted prior to the EOIs. RWE sources were mainly registries (35.6%) and hospital data (27.0%). RWE was typically used to support safety (82.1%) and efficacy (53.6%). Cohort studies were the most commonly used study design (87.6%). We conclude that there is widespread use of RWE to support evaluation of MAAs and EOIs submitted to the EMA and identify areas where further research is required

Prescribing Patterns of Codeine and Alternative Medicines in Children in Europe

INTRODUCTION: Concerns over serious respiratory depression in children led to two European Union (EU) referral procedures (in 2013 and 2015) to review the benefit–risk balance of codeine in this population when used for pain relief, cough or cold. Consequently, codeine should no longer be used in children aged < 12 years and restrictions were introduced for treatment in children ≥ 12 years. OBJECTIVE: This multinational collaborative study aimed to assess the effectiveness of these risk minimisation measures by evaluating changes in prescribing of codeine and alternative treatments. METHOD: Children under 12 and 12–18 years old were followed between 2010 and 2017 to analyse quarterly trends in prescribing of codeine and alternative treatments in electronic health records from France, Germany, Norway, Spain and the United Kingdom using interrupted time series analysis. RESULTS: Overall prescribing of codeine in children decreased in all five countries, reaching near zero prevalence in children under 12 years of age. This was accompanied by an increase in use of other opioid analgesics in France (from 0.15 to 0.56 prevalence per 100 person-years immediately after the first referral), Norway (from 0.0006 to 0.0013 at the end of the study), the United Kingdom (from 0.018 to 0.05 at the end of the study), and an increase in non-opioid analgesics in Norway (from 0.045 to 0.075 at the end of the study) after the referral on pain relief indication. The referral on cough/cold indication led to a decrease in use of opioid and non-opioid antitussives in children aged < 12 years in France (from 10 to 7 and 20 to 16, respectively) and had no impact in other countries. Overall prescribing trends for codeine and alternatives were similar across both age groups within each country. CONCLUSION: The decrease in use of codeine shows that healthcare professionals followed the adopted measures and switched prescribing practices for pain management in children aged < 18 years towards opioid or non-opioid analgesics depending on national clinical and reimbursement settings. Whist the magnitude of the first referral on pain differed between countries, the second referral on cough/cold had only a minimal impact on the use of codeine and antitussives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-022-01214-y

Estimating HIV incidence and number of undiagnosed individuals living with HIV in the European Union/European Economic Area, 2015

Helena Cortes Martins, Departamento de Doenças Infeciosas do Instituto Nacional de Saúde Doutor Ricardo Jorge, IPSince 2011, human immunodeficiency virus (HIV) incidence appears unchanged in the European Union/European Economic Area with between 29,000 and 33,000 new cases reported annually up to 2015. Despite evidence that HIV diagnosis is occurring earlier post-infection, the estimated number of people living with HIV (PLHIV) who were unaware of being infected in 2015 was 122,000, or 15% of all PLHIV (n=810,000). This is concerning as such individuals cannot benefit from highly effective treatment and may unknowingly sustain transmission.Members of the ECDC HIV/AIDS Surveillance and Dublin Declaration Monitoring Networks: Portugal: Kamal Mansinho, Helena Cortes Martins, Teresa Melo.info:eu-repo/semantics/publishedVersio

Estimating HIV Incidence, Time to Diagnosis, and the Undiagnosed HIV Epidemic Using Routine Surveillance Data.

BACKGROUND: Estimates of the size of the undiagnosed HIV-infected population are important to understand the HIV epidemic and to plan interventions, including "test-and-treat" strategies. METHODS: We developed a multi-state back-calculation model to estimate HIV incidence, time between infection and diagnosis, and the undiagnosed population by CD4 count strata, using surveillance data on new HIV and AIDS diagnoses. The HIV incidence curve was modelled using cubic splines. The model was tested on simulated data and applied to surveillance data on men who have sex with men in The Netherlands. RESULTS: The number of HIV infections could be estimated accurately using simulated data, with most values within the 95% confidence intervals of model predictions. When applying the model to Dutch surveillance data, 15,400 (95% confidence interval [CI] = 15,000, 16,000) men who have sex with men were estimated to have been infected between 1980 and 2011. HIV incidence showed a bimodal distribution, with peaks around 1985 and 2005 and a decline in recent years. Mean time to diagnosis was 6.1 (95% CI = 5.8, 6.4) years between 1984 and 1995 and decreased to 2.6 (2.3, 3.0) years in 2011. By the end of 2011, 11,500 (11,000, 12,000) men who have sex with men in The Netherlands were estimated to be living with HIV, of whom 1,750 (1,450, 2,200) were still undiagnosed. Of the undiagnosed men who have sex with men, 29% (22, 37) were infected for less than 1 year, and 16% (13, 20) for more than 5 years. CONCLUSIONS: This multi-state back-calculation model will be useful to estimate HIV incidence, time to diagnosis, and the undiagnosed HIV epidemic based on routine surveillance data

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

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.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.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.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

The European gonococcal antimicrobial surveillance programme (Euro-GASP) appropriately reflects the antimicrobial resistance situation for Neisseria gonorrhoeae in the European Union/European Economic Area.

BACKGROUND: European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA). METHODS: We compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p  90%). EQA performance was also good;  4-fold from the modal MIC of the EQA isolate. CONCLUSIONS: The overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea

The Added Value of Analyzing Pooled Health-Related Quality of Life Data: A Review of the EORTC PROBE Initiative

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes and Behavioural Evidence (PROBE) initiative was established to investigate critical topics to better understand health-related quality of life (HRQOL) of cancer patients and to educate clinicians, policy makers, and healthcare providers. METHODS: The aim of this paper is to review the major research outcomes of the pooled analysis of HRQOL data along with the clinical data. We identified 30 pooled EORTC randomized controlled trials (RCTs), 18 NCIC-Clinical Trials Group RCTs, and two German Ovarian Cancer Study Group RCTs, all using the EORTC QLQ-C30. All statistical tests were two-sided. RESULTS: Evidence was found that HRQOL data can offer prognostic information beyond clinical measures and improve prognostic accuracy in cancer RCTs (by 5.9%-8.3%). Moreover, models that considered both patient- and clinician-reported scores gained more prognostic overall survival accuracy for fatigue (P < .001), vomiting (P = .01), nausea (P < .001), and constipation (P = .01). Greater understanding of the association between symptom and/or functioning scales was developed by identifying physical, psychological, and gastrointestinal clusters. Additionally, minimally important differences in interpreting HRQOL changes for improvement and deterioration were found to vary across different patient populations and disease stages. Finally, HRQOL scores are statistically significantly affected by deviations from the intended time point at which the questionnaire is completed. CONCLUSIONS: The use of existing pooled data shows that it is possible to learn about general aspects of cancer HRQOL and methodology. Our work shows that setting up international pooled datasets holds great promise for understanding patients' unmet psychosocial needs and calls for additional empirical investigation to improve clinical care and understand cancer through retrospective HRQOL analyses

The effects of age on health-related quality of life in cancer populations: A pooled analysis of randomized controlled trials using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 involving 6024 cancer patients.

Cancer incidence increases exponentially with advancing age, cancer patients live longer than in the past, and many new treatments focus on stabilizing disease and HRQOL. The objective of this study is to examine how cancer affects patients' HRQOL and whether their HRQOL is age-dependent.Data from 25 EORTC randomized controlled trials was pooled. EORTC QLQ-C30 mean scores for the cancer cohort and five general population cohorts were compared to assess the impact of cancer on patients' HRQOL. Within the cancer cohort, multiple linear regressions (two-sided level P-value = 0.05 adjusted for multiple testing.) were used to investigate the association between age and HRQOL, adjusted for gender, WHO performance status (PS), distant metastasis and stratified by cancer site. A difference of 10 points on the 0-100 scale was considered clinically important.Cancer patients generally have worse HRQOL compared to the general population, but the specific HRQOL domains impaired vary with age. When comparing the cancer versus the general population, young cancer patients had worse financial problems, social and role functioning, while the older cancer groups had more appetite loss. Within the cancer cohort, HRQOL was worse with increasing age for physical functioning and constipation, and better with increasing age for social functioning, insomnia and financial problems (all p < 0.05).HRQOL is impaired in cancer patients compared to the general population, but the impact on specific HRQOL domains varies by age. Within the cancer population, some HRQOL components improve with age while others deteriorate. Optimal care for older cancer patients should target HRQOL domains most relevant to this population