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/emtricit- abine (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 con- sider the medical requirements for the treatment.Peer Reviewe

An Update Based on the SCORE-Deutschland Risk Charts

Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008–11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40–65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29% and the estimated proportion of high risk people (10-year risk > = 5%) by 50% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk

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

Summary: 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

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

Serotonin and norepinephrine reuptake inhibitors antidepressant use is related to lower baroreflex sensitivity independently of the severity of depressive symptoms. A community-study of 9213 participants from the Paris Prospective Study III

n/

Epidemiology and prevention of cardiovascular diseases: investigation of novel approaches, determinants, and relationships in the general population and in patient populations

Kardiovaskuläre Erkrankungen entstehen häufig auf der Basis subklinischer arterieller Gefäßveränderungen, die aufgrund atherothrombotischer Prozesse zu einer koronaren Herzkrankheit (KHK) oder einem ischämischen Schlaganfall (ISA) führen und in der Folge die kardiovaskuläre und Gesamtsterblichkeit langfristig erhöhen. Entsprechend dieser Entwicklung der Krankheitslast beschäftigt sich diese Arbeit mit der Epidemiologie und Prävention kardiovaskulärer Erkrankungen und untersucht neue Ansätze, Determinanten und Zusammenhänge in der Allgemeinbevölkerung und in Patientenkollektiven. In der PRIME Studie (Etude Prospective de l’Infarctus du Myocarde) wurde die Gesamtsterblichkeit vor und nach dem Auftreten einer KHK und eines ISA über einen Zeitraum von 10 Jahren untersucht. Der gewählte einheitliche Ansatz basiert auf einer Unterscheidung zwischen Perioden vor und nach kardiovaskulären Ereignissen innerhalb derselben Studienbevölkerung. Die Ergebnisse zeigen, dass das Auftreten von KHK bzw. ISA das Risiko für Gesamtsterblichkeit in der PRIME Studie um 60% erhöht bzw. verdreifacht. Im Rahmen der PRIME Studie wurde in einer eingebetteten Fall-Kontroll-Studie der Prädiktivwert neuer Biomarker der Hämostase, Inflammation und Endothelaktivierung sowie von Chemokinen und Adipozytokinen für das 10-Jahres Risiko für ISA untersucht. Die Ergebnisse weisen darauf hin, dass von insgesamt 14 neuen Biomarkern, die mögliche Determinanten des kardiovaskulären Risikos sind, ein Biomarker der Endothelaktivierung (E-Selectin) und ein Adipozytokin (Resistin) die Prädiktion des ISA-Risikos verbessern. Anhand von Daten des EUROASPIRE III Surveys (EUROpean Action on Secondary and Primary Prevention through Intervention to Reduce Events) wurden neue Zusammenhänge bei der Kontrolle des Risikofaktors Rauchen bei KHK-Patienten untersucht. Es zeigte sich, dass Passivrauch exponierte Patienten eine wesentlich geringere Wahrscheinlichkeit haben, mit dem Rauchen aufzuhören. Zudem wurden Patientengruppen identifiziert, deren Bereitschaft zum Rauchstopp besonders eingeschränkt ist. In der Three-City (3C) Studie wurde die vaskuläre Depressionshypothese getestet, indem der Zusammenhang zwischen subklinischen Gefäßveränderungen und depressiven Symptomen im Alter untersucht wurde. Über einen Zeitraum von 10 Jahren waren Plaques und Intima-Media-Dicke der Halsschlagader mit einer Progression depressiver Symptome bei Männern und Frauen und mit dem Auftreten hoher depressiver Symptome bei Männern assoziiert. Die Ergebnisse dieser Arbeit liefern Argumente für die Stärkung der Primär- und Sekundärprävention kardiovaskulärer Erkrankungen, verweisen auf die Möglichkeit einer verbesserten Identifikation von Personen mit einem erhöhten ISA-Risiko in der Primärprävention, zeigen mögliche Ansätze auf für eine intensivierte Kontrolle des Risikofaktors Rauchen in der Sekundärprävention der KHK und bieten Hinweise für einen Zusammenhang zwischen kardiovaskulären und depressiven Erkrankungen im Alter.Cardiovascular diseases develop on the basis of subclinical vascular alterations due to atherothrombotic processes that lead to coronary heart disease (CHD) and ischaemic stroke (IS) and subsequently increase cardiovascular and all-cause mortality in the long term. According to this progression of the disease burden, the present work deals with the epidemiology and prevention of cardiovascular diseases and investigates novel approaches, determinants, and relationships in the general population and in patient populations. In the PRIME Study (Etude Prospective de l’Infarctus du Myocarde), all-cause mortality was investigated prior and after the occurrence of CHD and stroke over a period of 10 years. The chosen approach is based on the distinction between periods prior and after cardiovascular events within the same study population. The results show a 60% and 3-fold increased risk of all-cause mortality in the PRIME Study after the occurrence of CHD and stroke, respectively. In a nested case-control study within the PRIME Study, the predictive value for IS of novel biomarkers of haemostasis, inflammation, and endothelial activation, chemokines, and adipocytokines was investigated. The results indicate that out of a total of 14 biomarkers possibly determining cardiovascular risk, one biomarker of endothelial activation (E-selectin) and one adipocytokine (resistin) improve risk prediction of IS. Using data from the EUROASPIRE III Survey (EUROpean Action on Secondary and Primary Prevention through Intervention to Reduce Events), novel relationships in the control of smoking were examined among CHD patients. It was demonstrated that patients exposed to environmental tobacco smoke had a substantially decreased likelihood to quit smoking. Furthermore, patient groups were identified whose readiness to stop smoking was particularly limited. In the Three-City (3C) Study, the vascular depression hypothesis was tested investigating the relationship between subclinical vascular disease and depressive symptoms in the elderly. Over a period of 10 years, carotid plaque presence and intima media thickness were associated with the progression of depressive symptoms among men and women and the occurrence of high depressive symptoms among men. The results of this work provide arguments in favour of strengthening primary and secondary prevention of cardiovascular disease, point towards the possibility of an improved identification of persons with an increased IS risk in primary prevention, indicate possible novel approaches for an intensified control of smoking in secondary prevention of CHD, and provide evidence for a relationship between cardiovascular disease and depression in the elderly

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

Wiehn J, Nonte J, Prugger C. Reporting quality for abstracts of randomised trials on child and adolescent depression prevention: a meta-epidemiological study on adherence to CONSORT for abstracts. BMJ Open . 2022;12(8): e061873.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. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Reporting quality of randomised controlled and cluster randomised trial abstracts in childhood depression prevention: A meta-epidemiologic study

This meta-epidemiologic study aimed primarily to examine the extent of adherence to CONSORT-A and CONSORT-C in abstracts of childhood depression prevention trials. Secondarily, this study aimed to examine associated factors of overall report quality

Predicting 10-Year Risk of Fatal Cardiovascular Disease in Germany: An Update Based on the SCORE-Deutschland Risk Charts

Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008–11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40–65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29% and the estimated proportion of high risk people (10-year risk > = 5%) by 50% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk