Cost-savings and potential cost-savings through the distribution of generic antiretroviral drugs within the statutory health insurance market of Germany between January 2017 and June 2019.

BACKGROUND: Recent patent losses for antiretroviral drugs (ARV) have led to the debate of cost-saving through the replacement of patented drugs with generic drugs. The split of recommended single-tablet regimens (STR) into their single substance partners is one of the considerations mentioned in said debate. Particularly, generic tenofovir disoproxil/emtricitabine (TDF/FTC) is expected to hold untapped cost-saving potential, which may curb increasing overall expenditures for combined antiretroviral therapy (cART) within the statutory health insurance (SHI) of Germany. METHODS: Data of ARV reimbursed by the SHI were used to describe the trends of defined daily doses (DDD) as well as the revenue within the German ARV market. They were also used to determine the cost-savings of moving to generic drugs. The time period observed was between January 2017 and June 2019. The potential cost-savings were determined with following assumption in mind: the maximum possible use of generic ARV, including 1) the split of STR and replacing all substance partners with generic ones, and 2) replacing patented tenofovir alafenamide/emtricitabine (TAF/FTC) with generic TDF/FTC. RESULTS: Throughout the observation period, the DDD of generic ARV increased nearly five-fold while their revenue increased more than four-fold. Total cost-saving showed a sharp increase over the same period, with generic TDF/FTC accounting for a share of around 70%. The largest potential cost-saving could have been achieved through replacing patented TAF/FTC with generic TDF/FTC, peaking at nearly 10% of total revenue, but showing decreasing trends in general. CONCLUSION: The progressive distribution of generic ARV ensured increasing cost-savings, but consequently curbed the potential cost-savings. Unique price reductions of generic TDF/FTC have played a pivotal role for these effects. In any case, substituting with generic ARV should not fail to adhere to the treatment guidelines and continue to consider the medical requirements for the treatment.

Complement-binding anti-HLA antibodies and kidney-allograft survival.

BACKGROUND: Anti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure. METHODS: We enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed. RESULTS: The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97). CONCLUSIONS: Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.

Longitudinal association of carotid plaque presence and intima-media thickness with depressive symptoms in the elderly: the three-city study.

OBJECTIVE: To investigate prospectively whether subclinical vascular disease is associated with future depressive symptoms in the elderly. APPROACH AND RESULTS: A multicenter cohort of community-dwelling individuals aged 65 to 85 years was examined for carotid plaque presence and common carotid artery intima-media thickness at baseline and followed up after 2, 4, 7, and 10 years. At baseline and follow-up examinations, depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). High level of depressive symptoms was defined as a CES-D score >16 in men and >22 in women. Among 4125 participants (58% women) at baseline, men more frequently showed carotid plaque presence and had higher mean common carotid artery intima-media thickness than women. After adjustment for major cardiovascular risk factors, carotid plaque presence was associated with a higher CES-D score at the 10-year follow-up in men (+1.46; 95% confidence interval, 0.71-2.20; P<0.001), but not in women. When restricting analyses to individuals without cardiovascular disease at baseline, carotid plaque presence increased the likelihood of high level of depressive symptoms at follow-up examinations in men (odds ratio, 1.47; 95% confidence interval, 1.06-2.05; P=0.022), but not in women. One SD increase in log-transformed common carotid artery intima-media thickness was associated with a higher CES-D score at the 10-year follow-up in women (+0.55; 95% confidence interval, 0.16-0.95; P=0.006) and men (+0.40; 95% confidence interval, 0.02-0.78; P=0.037). Common carotid artery intima-media thickness did not increase the likelihood of high level of depressive symptoms at follow-up in both sexes. CONCLUSIONS: Subclinical vascular disease is associated with the progression of depressive symptoms in elderly men and women and the occurrence of high level of depressive symptoms in elderly men.

All-Cause Mortality up to and After Coronary Heart Disease and Stroke Events in European Middle-Aged Men: The PRIME Study.

BACKGROUND AND PURPOSE: The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men. METHODS: The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates. RESULTS: A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke. CONCLUSIONS: These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease.

Passive smoking and smoking cessation among patients with coronary heart disease across Europe: results from the EUROASPIRE III survey.

AIMS: Passive smoking is the inhalation of environmental tobacco smoke (ETS) and is a risk factor for coronary heart disease (CHD). We aimed to describe the frequency of passive smoking among patients with CHD and to investigate the association between ETS exposure and smoking cessation. METHODS AND RESULTS: The EUROASPIRE III survey was conducted in 2006-07 among CHD patients up to 80 years of age from 22 European regions. Patients were interviewed and examined on average 15 months after hospital admission for CHD. Information was obtained on smoking prior to hospital admission, smoking at interview, and ETS exposure at home, at work, and at other locations. Breath carbon monoxide was measured to validate self-reported non-smoking. Among 8729 patients, 6060 (69.4%) were non-smokers prior to hospital admission, of whom 10.3% reported ETS exposure at home, 7.2% at work, and 13.8% at other locations. Overall, 24.2% of non-smokers were exposed to ETS at any place. Among the 2669 patients who were smoking prior to hospital admission, the likelihood of cessation at interview was lower in those with ETS exposure at home than in those without [25.3 vs. 58.1%; adjusted odds ratio (OR) 0.26, 95% confidence interval (CI) 0.20-0.33]. This finding applied also to ETS exposure at work (32.2 vs. 52.7%; adjusted OR 0.56, 95% CI 0.42-0.76) and at other locations (38.0 vs. 52.8%; adjusted OR 0.63, 95% CI 0.48-0.84). CONCLUSION: A noteworthy proportion of non-smokers with CHD are exposed to ETS. Passive smoking may jeopardize smoking cessation among CHD patients.

Multiple biomarkers for the prediction of ischemic stroke: the PRIME study.

OBJECTIVE: To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke, including biomarkers of hemostasis, inflammation, and endothelial activation as well as chemokines and adipocytokines. METHODS AND RESULTS: The Prospective Epidemiological Study on Myocardial Infarction (PRIME) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years. In a nested case-control study, 95 ischemic stroke cases were matched with 190 controls. After multivariable adjustment for traditional risk factors, fibrinogen (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03-2.28), E-selectin (OR, 1.76; 95% CI, 1.06-2.93), interferon-γ-inducible-protein-10 (OR, 1.72; 95% CI, 1.06-2.78), resistin (OR, 2.86; 95% CI, 1.30-6.27), and total adiponectin (OR, 1.82; 95% CI, 1.04-3.19) were significantly associated with ischemic stroke. Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 (95% CI, 0.612-0.745) to 0.785 and 0.788, respectively, and yielded a categorical net reclassification improvement of 29.9% (P=0.001) and 28.4% (P=0.002), respectively. Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 (95% CI, 0.770-0.877) and resulted in an net reclassification improvement of 41.4% (P<0.001). Results were confirmed when using continuous net reclassification improvement. CONCLUSIONS: Among multiple biomarkers from distinct biological pathways, E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke.

Major regional disparities in outcomes after sudden cardiac arrest during sports.

AIMS: Characteristics of sudden cardiac arrest (SCA) during sports offers a novel (and unexplored) setting to assess factors associated with disparities in outcomes across regions. METHODS AND RESULTS: From a prospective 5-year community-based French registry concerning SCA during sports in 10-75 year-olds, we evaluated whether outcomes differed significantly between geographic regions. We then determined the extent to which variations in community-related early interventions were associated with regional variations in survival. Among 820 SCA cases studied, overall survival at hospital discharge was 15.7% (95% confidence interval, 13.2-18.2%), with considerable regional disparities (from 3.4 to 42.6%, P < 0.001). Major differences were noted regarding bystander initiation of cardiopulmonary resuscitation (15.3-80.9%, P < 0.001) and presence of initial shockable rhythm (28.6-79.1%, P < 0.001), with higher values of these being associated with better survival rates. The proportion of survivors with favourable neurological outcome at discharge was fairly uniform among survival groups (CPC-1/2, varying from 77.4 to 90.0%, P = 0.83). No difference was observed regarding subjects' characteristics and circumstances of SCA occurrence, including delays in resuscitation (collapse-to-call period). With a comparable in-hospital mortality (P = 0.44), survival at hospital discharge was highly correlated with that at hospital admission (regional variations from 7.4 to 75.0%, P < 0.001). CONCLUSION: Major regional disparities exist in survival rates (up to 10-fold) after SCA during sports. SCA cases from regions with the highest levels of bystander resuscitation had the best survival rates to hospital admission and discharge.

Access to automated external defibrillators and first responders: Associations with socioeconomic factors and income inequality at small spatial scales.

Aim: The 2021 European Resuscitation Council (ERC) guidelines recommend two automated external defibrillators (AEDs)/km2 and at least 10 first responders/km2. We examined 1) access to AEDs and volunteer first responders in line with these guidelines and 2) its associations with socioeconomic factors and income inequality, focusing on small spatial scales. Method: We considered data on 776 AEDs in February 2022 and 1,173 out-of-hospital cardiac arrests (OHCAs) including 713 OHCA with app-alerted volunteer first responders from February to September 2022 in Berlin. We fit multilevel models to analyse AED area coverage and Poisson models to examine first responder availability across 12 districts and 536 neighbourhoods. Results: Median AED area coverage according to the 2021 ERC guidelines was 43.1% (interquartile range (IQR) 2.3-87.2) at the neighbourhood level and median number of available first responders per OHCA case was one (IQR 0.0-1.0). AED area coverage showed a positive association with average income tax per capita, with better coverage in the highest compared to the lowest quartile neighbourhoods (coefficient: 0.13, 95% confidence interval (CI): 0.01-0.25). First responder availability was not associated with income tax. AED area coverage and first responder availability were positively associated with income inequality, with better coverage (coefficient: 0.13, 95% CI: 0.04-0.23) and availability (rate ratio: 1.31, 95% CI: 1.03-1.67) in quartiles of highest as compared to lowest inequality. Conclusion: Access to resuscitation resources is neither equitable nor in accordance with the 2021 ERC guidelines. Ensuring better access necessitates understanding of socioeconomic factors and income inequality at small spatial scales.

Effect of elevated depressive symptoms during adolescence on health-related quality of life in young adulthood-a six-year cohort study with repeated exposure measurements.

Objectives: Depression is a major contributor of young people's burden of disease. In this study we aim to estimate the effect of elevated depressive symptoms on physical health-related quality of life. Design: We used self-reported information from the prospective BELLA cohort study, which included adolescents selected from the general population in Germany. The baseline assessment (2003-2006) and the 1-, 2-, and 6-year follow-up waves provide the data basis. Participants: The baseline study population consisted of 1,460 adolescents between the ages of 12 and 17 who, according to their caregivers, did not suffer from depression. Variables: The primary outcome, as measured by the physical component score (PCS) of the SF-36 at a 6-year follow-up (range: 0-100), is physical health-related quality of life. The exposure of interest is depressive symptoms, as measured by the Center for Epidemiological Studies Depression Scale for Children (CES-DC) at baseline, 1-year follow-up and 2-year follow-ups (range: 0-60). We dichotomized the exposure into subthreshold (≤15) and elevated depressive symptoms (>15). For the main analyses we considered a cumulative index for elevated depressive symptoms across the three time points (range: 0-3). Considered confounders are sex, age, socioeconomic status, migrant background, social support, anxiety symptoms, physical activity, chronic diseases, and sleeping problems. Statistical methods: We used multiple imputation to account for missing values. Within each imputed dataset, we applied inverse probability weighting (IPW) to estimate the effect of the cumulative index for elevated depressive symptoms at baseline, 1- and 2-year follow-up on physical health-related quality of life at 6-year follow-up. We derived 95% confidence intervals by bootstrapping. Results: After adjusting with IPW, the effect of the cumulative index per one unit increase of elevated depressive symptoms on the physical component score was -1.71 (95% CI: -3.51 to -0.04). The adjusted effect estimates of single exposure of elevated depressive symptoms on physical health-related quality of life were -0.83 (95% CI: -3.69 to 1.87) at baseline, -2.96 (95% CI: -4.94 to -0.52) at 1-year follow-up and -1.32 (95% CI: -3.85 to 1.15) at 2-year follow-up. Conclusion: Findings suggest that elevated depressive symptoms during adolescence decrease physical health-related quality of life in young adulthood.

Association between changes in cardiovascular health and the risk of multimorbidity: community-based cohort studies in the UK and Finland.

Background: Better cardiovascular health is associated with lower risk of various chronic diseases, but its association with multimorbidity is poorly understood. We aimed to examine whether change in cardiovascular health is associated with multimorbidity risk. Methods: The primary analysis was conducted in the Whitehall II multiwave prospective cohort study (UK) and the validation analysis in the Finnish Public Sector cohort study (Finland). Change in cardiovascular health was assessed using the American Heart Association Life's Simple 7 (LS7) and Life's Essential 8 (LE8) at baseline and re-assessments, using objective measures in Whitehall II and self-reports and pharmacy claims in the Finnish Public Sector cohort study, respectively. Multimorbidity was defined as the presence of two or more of 12 chronic diseases during follow-up. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox's proportional hazard models with age as time scale, adjusting for sex, education, occupation, marital status, and ethnicity. Findings: In the primary analysis among 9715 participants, mean age was 44.8 (standard deviation 6.0) years and 67.6% participants were men at baseline. During the median follow-up of 31.4 (interquartile range 26.8-32.3) years, 2751 participants developed multimorbidity. The hazard of multimorbidity decreased by 8% (HR 0.92, 95% CI 0.88-0.96) per ideal LS7 metric increment over 5 years and by 14% (HR 0.86, 95% CI 0.80-0.93) per ten points increase in LE8 score over 10 years. These findings were replicated in the validation analysis among 75,377 participants in terms of 4-year change in cardiovascular health. Interpretation: Improvement in cardiovascular health was associated with lower multimorbidity risk in two community-based cohort studies. Interventions improving cardiovascular health of the community may contribute to multimorbidity prevention. Funding: None.

Adipocytokines and the risk of ischemic stroke: the PRIME Study.

OBJECTIVE: Adipocytokines are hormones secreted from adipose tissue that possibly link adiposity and the risk of cardiovascular disease, but limited prospective data exist on plasma adipocytokines and ischemic stroke risk. We investigated associations and predictive properties of 4 plasma adipocytokines, namely resistin, adipsin, leptin, and total adiponectin, with regard to incident ischemic stroke in the PRIME Study. METHODS: A cohort of 9,771 healthy men 50 to 59 years of age at baseline was followed up over a period of 10 years. In a nested case-control study, 95 ischemic stroke cases were matched with 190 controls on age, study center, and date of examination. Hazard ratios (HRs) per standard deviation increase in plasma adipocytokine levels were estimated using conditional logistic regression analysis. The additive value of adipocytokines in stroke risk prediction was evaluated by discrimination and reclassification metrics. RESULTS: Resistin (HR, 1.88; 95% confidence interval [CI], 1.16-3.03), adipsin (HR, 2.01; 95% CI, 1.33-3.04), and total adiponectin (HR, 1.53; 95% CI, 1.01-2.34), but not leptin, were independent predictors of ischemic stroke. The performance of a traditional risk factor model predicting ischemic stroke was significantly improved by the simultaneous inclusion of resistin, adipsin, and total adiponectin (c-statistic: 0.673 [95% CI, 0.631-0.766] vs 0.826 [95% CI, 0.792-0.892], p < 0.001; net reclassification improvement: 38.1%, p < 0.001). INTERPRETATION: Higher plasma levels of resistin, adipsin, and total adiponectin were associated with an increased 10-year risk of ischemic stroke among healthy middle-aged men. Resistin, adipsin, and total adiponectin provided incremental value over traditional risk factors for the prediction of ischemic stroke risk.

Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.

BACKGROUND: Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management. AIMS: This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population. METHODS AND RESULTS: Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people ≥30 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively. CONCLUSION: Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.

We linked data available for 1.31 million people seen by English general practitioners in 2010 with data from hospital admissions and death certificates up to 2016 to investigate the risk of death in people who suffered from any of 12 common cardiovascular diseases (CVDs) compared with those who did not. The results show heterogeneously increased risks of death in people who suffered from any of 12 common CVD when compared with people who remained CVD free. The results support efforts of prevention for the entire spectrum of CVD including alleged minor types such as stable angina and transient ischaemic attack.

Reporting quality for abstracts of randomised trials on child and adolescent depression prevention: a meta-epidemiological study on adherence to CONSORT for abstracts.

OBJECTIVES: This study aimed to investigate adherence to Consolidated Standards of Reporting Trials (CONSORT) for abstracts in reports of randomised trials on child and adolescent depression prevention. Secondary objective was to examine factors associated with overall reporting quality. DESIGN: Meta-epidemiological study. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, PsycArticles and CENTRAL. ELIGIBILITY CRITERIA: Trials were eligible if the sample consisted of children and adolescents under 18 years with or without an increased risk for depression or subthreshold depression. We included reports published from 1 January 2003 to 8 August 2020 on randomised controlled trials (RCTs) and cluster randomised trials (CRTs) assessing universal, selective and indicated interventions aiming to prevent the onset of depression or reducing depressive symptoms. DATA EXTRACTION AND SYNTHESIS: As the primary outcome measure, we assessed for each trial abstract whether information recommended by CONSORT was adequately reported, inadequately reported or not reported. Moreover, we calculated a summative score of overall reporting quality and analysed associations with trial and journal characteristics. RESULTS: We identified 169 eligible studies, 103 (61%) RCTs and 66 (39%) CRTs. Adequate reporting varied considerably across CONSORT items: while 9 out of 10 abstracts adequately reported the study objective, no abstract adequately provided information on blinding. Important adverse events or side effects were only adequately reported in one out of 169 abstracts. Summative scores for the abstracts' overall reporting quality ranged from 17% to 83%, with a median of 40%. Scores were associated with the number of authors, abstract word count, journal impact factor, year of publication and abstract structure. CONCLUSIONS: Reporting quality for abstracts of trials on child and adolescent depression prevention is suboptimal. To help health professionals make informed judgements, efforts for improving adherence to reporting guidelines for abstracts are needed.

An evolutionary machine learning algorithm for cardiovascular disease risk prediction.

INTRODUCTION: This study developed a novel risk assessment model to predict the occurrence of cardiovascular disease (CVD) events. It uses a Genetic Algorithm (GA) to develop an easy-to-use model with high accuracy, calibrated based on the Isfahan Cohort Study (ICS) database. METHODS: The ICS was a population-based prospective cohort study of 6,504 healthy Iranian adults aged ≥ 35 years followed for incident CVD over ten years, from 2001 to 2010. To develop a risk score, the problem of predicting CVD was solved using a well-designed GA, and finally, the results were compared with classic machine learning (ML) and statistical methods. RESULTS: A number of risk scores such as the WHO, and PARS models were utilized as the baseline for comparison due to their similar chart-based models. The Framingham and PROCAM models were also applied to the dataset, with the area under a Receiver Operating Characteristic curve (AUROC) equal to 0.633 and 0.683, respectively. However, the more complex Deep Learning model using a three-layered Convolutional Neural Network (CNN) performed best among the ML models, with an AUROC of 0.74, and the GA-based eXplanaible Persian Atherosclerotic CVD Risk Stratification (XPARS) showed higher performance compared to the statistical methods. XPARS with eight features showed an AUROC of 0.76, and the XPARS with four features, showed an AUROC of 0.72. CONCLUSION: A risk model that is extracted using GA substantially improves the prediction of CVD compared to conventional methods. It is clear, interpretable and can be a suitable replacement for conventional statistical methods.

Public Access Defibrillators and Socioeconomic Factors on the Small­Scale Spatial Level in Berlin­a Cross-Sectional Analysis

BACKGROUND: The use of a public access defibrillator (PAD) increases the probability of surviving an out-of-hospital cardiac arrest (OHCA). No strategies exist, however, for the optimal distribution of PADs in an urban area in order to meet existing needs and ensure equal access for all potential users. It thus seems likely that the accessibility of PADs on the spatial level varies widely as a function of living circumstances. METHODS: This cross-sectional study is based on registry data concerning PAD (2022, n = 776) and OHCA (2018-2020, n = 4051), along with data on socioeconomic factors on the spatial level in Berlin (12 districts and 137 subdistricts). Associations of socioeconomic factors with the number of PADs per 10 000 inhabitants and the PAD coverage rate of sites of previous OHCAs were investigated. RESULTS: The median number of PADs per 10 000 inhabitants ranged from 0.46 to 2.67 at the district level, and only five districts had a median PAD coverage rate of sites of previous OHCAs above 0%, after aggregation of the analyses at the subdistrict level. Subdistricts with a more favorable economic status and a greater income disparity had a higher PAD density. Socially disadvantaged subdistricts had no association with PAD density. CONCLUSION: There are large deficits in the distribution of PADs at the small-scale spatial level in Berlin with respect to the goals of meeting existing needs and ensuring equal access for all potential users. The findings presented here will be of importance for the planning of future PAD programs so that the distributional efficiency and fairness of PAD in urban areas can be improved.

Assessing the probability of risk factor control in patients with coronary heart disease: results from the ESC-EORP EUROASPIRE V survey.

AIMS: In patients with coronary heart disease (CHD), we investigated whether it is possible to accurately assess the probability of short-term control of risk factors (blood pressure, cholesterol, smoking) based on individual and large-area residential characteristics. METHODS AND RESULTS: We merged individual data of participants from EUROASPIRE V who were hospitalized for CHD (2014-2017) and interviewed and examined for risk factor control (2016-2017), with large-area residential data provided by Eurostat for Nomenclature of Territorial Units for Statistics (NUTS) regions using postal codes. Data from 2562 CHD patients in 16 countries were linked to data from 60 NUTS 2 and 121 NUTS 3 regions. The median time between hospitalization and interview was 14 months. We developed prediction models to assess the probability of risk factor control at interview using data from the time of hospitalization: (i) baseline models including 35 variables on patients' demographic, clinical, and socio-economic characteristics and (ii) extended models additionally considering nine variables on large-area residential characteristics. We calculated and internally validated c-indices to assess the discriminative ability of prediction models. Baseline models showed good discrimination with c-indices of 0.69, 0.70, and 0.76 for blood pressure control, cholesterol control, and smoking cessation, respectively. Extended models for blood pressure, cholesterol, and smoking yielded improved c-indices of 0.72, 0.71, and 0.78, respectively. CONCLUSION: Our results indicate that the probability of risk factor control in CHD patients can be accurately assessed using individual and large-area residential characteristics, allowing for an identification of patients who are less likely to achieve risk factor targets.

Malariological baseline survey and in vitro antimalarial drug resistance in Gulu district, Northern Uganda.

A comprehensive, representative malaria survey has been carried out in a population of internally displaced persons (IDP) in the district of Gulu, Northern Uganda. It included 74 households and 390 persons, and covered socio-economic and environmental information, individual physical data, malaria and the drug sensitivity of Plasmodium falciparum. The prevalence of infections with Plasmodium falciparum was 54.4% at a geometric mean asexual parasitaemia of 229/microl blood, typical for hyperendemic conditions. P. falciparum turned out to be highly resistant to chloroquine and amodiaquine. It showed also reduced sensitivity against lumefantrine and artemisinin, obviously the result of the liberal use of the lumefantrine-artemether combination without evidence-based indication.

Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies.

OBJECTIVES:  To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. DESIGN:  Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. SETTING:  Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. MAIN OUTCOME MEASURES:  Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. RESULTS:  Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. CONCLUSIONS:  Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians' reporting behaviours of adverse drug reactions.

Regular exercise behaviour and intention and symptoms of anxiety and depression in coronary heart disease patients across Europe: Results from the EUROASPIRE III survey.

BACKGROUND: Regular exercise lowers the risk of cardiovascular death in coronary heart disease (CHD) patients. We aimed to investigate regular exercise behaviour and intention in relation to symptoms of anxiety and depression in CHD patients across Europe. DESIGN: This study was based on a multicentre cross-sectional survey. METHODS: In the EUROpean Action on Secondary and Primary Prevention through Intervention to Reduce Events (EUROASPIRE) III survey, 8966 CHD patients <80 years of age from 22 European countries were interviewed on average 15 months after hospitalisation. Whether patients exercised or intended to exercise regularly was assessed using the Stages of Change questionnaire in 8330 patients. Symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. Total physical activity was measured by the International Physical Activity Questionnaire in patients from a subset of 14 countries. RESULTS: Overall, 50.3% of patients were not intending to exercise regularly, 15.9% were intending to exercise regularly, and 33.8% were exercising regularly. Patients with severe symptoms of depression less frequently exercised regularly than patients with symptoms in the normal range (20.2%, 95% confidence interval (CI) 14.8-26.8 vs 36.7%, 95% CI 29.8-44.2). Among patients not exercising regularly, patients with severe symptoms of depression were less likely to have an intention to exercise regularly (odds ratio 0.62, 95% CI 0.46-0.85). Symptoms of anxiety did not affect regular exercise intention. In sensitivity analysis, results were consistent when adjusting for total physical activity. CONCLUSIONS: Lower frequency of regular exercise and decreased likelihood of exercise intention were observed in CHD patients with severe depressive symptoms. Severe symptoms of depression may preclude CHD patients from performing regular exercise.