Development of a risk score to identify patients at high risk for a severe course of COVID-19.

Aim: We aimed to develop a risk score to calculate a person's individual risk for a severe COVID-19 course (POINTED score) to support prioritization of especially vulnerable patients for a (booster) vaccination. Subject and methods: This cohort study was based on German claims data and included 623,363 individuals with a COVID-19 diagnosis in 2020. The outcome was COVID-19 related treatment in an intensive care unit, mechanical ventilation, or death after a COVID-19 infection. Data were split into a training and a test sample. Poisson regression models with robust standard errors including 35 predefined risk factors were calculated. Coefficients were rescaled with a min-max normalization to derive numeric score values between 0 and 20 for each risk factor. The scores' discriminatory ability was evaluated by calculating the area under the curve (AUC). Results: Besides age, down syndrome and hematologic cancer with therapy, immunosuppressive therapy, and other neurological conditions were the risk factors with the highest risk for a severe COVID-19 course. The AUC of the POINTED score was 0.889, indicating very good predictive validity. Conclusion: The POINTED score is a valid tool to calculate a person's risk for a severe COVID-19 course. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01884-7.

Does uptake of specialty care affect HRQoL development in COPD patients beneficially? A difference-in-difference analysis linking claims and survey data.

BACKGROUND: There is an evidence gap on whether the choice of specialty care beneficially affects health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD). This study analyzes how newly initiated pulmonologist care affects the generic and disease-specific HRQoL in COPD patients over a period of 1 year. METHODS: We linked claims data with data from two survey waves to investigate the longitudinal effect of specialty care on HRQoL using linear Difference-in-Difference models based on 1:3 propensity score matched data. Generic HRQoL was operationalized by EQ-5D-5L visual analog scale (VAS), and disease-specific HRQoL by COPD assessment test (CAT). Subgroup analyses examined COPD patients with low (GOLD AB) and high (GOLD CD) exacerbation risk. RESULTS: In contrast to routine care patients, pulmonologists' patients (n = 442) experienced no significant deterioration in HRQoL (VAS - 0.0, p = 0.9870; CAT + 0.5, p = 0.0804). Models unveiled a small comparative advantage of specialty care on HRQoL (mean change: CAT - 0.8, VAS + 2.9), which was especially pronounced for GOLD AB (CAT - 0.7; VAS + 3.1). CONCLUSION: The uptake of pulmonologist care had a statistically significant, but not clinically relevant, beneficial impact on the development of HRQoL by slowing down overall HRQoL deterioration within 1 year. Including specialty care more appropriately in COPD management, especially at lower disease stages (GOLD AB), could thus improve patients' health outcome.

Characteristics and Cost of Unscheduled Hospitalizations in Patients Treated with New Oral Anticancer Drugs in Germany: Evidence from the Randomized AMBORA Trial.

Drug-related problems (e.g., adverse drug reactions, ADR) are serious safety issues in patients treated with oral anticancer therapeutics (OAT). The previously published randomized AMBORA trial showed that an intensified clinical pharmacological/pharmaceutical care program within the first 12 weeks of treatment reduces the number and severity of ADR as well as hospitalization rates in 202 patients. The present investigation focused on unscheduled hospitalizations detected within AMBORA and analyzed the characteristics (e.g., frequency, involved OAT) and cost of each hospital stay. To estimate the potential savings of an intensified care program in a larger group, the absolute risk for OAT-related hospitalizations was extrapolated to all insureds of a leading German statutory health insurance company (AOK Bayern). Within 12 weeks, 45 of 202 patients were hospitalized. 50% of all unscheduled hospital admissions were OAT-related (20 of 40) and occurred in 18 patients. The mean cost per inpatient stay was EUR 5873. The intensified AMBORA care program reduced the patients' absolute risk for OAT-related hospitalization by 11.36%. If this care program would have been implemented in the AOK Bayern collective (3,862,017 insureds) it has the potential to reduce hospitalization rates and thereby cost by a maximum of EUR 4.745 million within 12 weeks after therapy initiation.

Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany.

BACKGROUND: Long-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults. METHODS AND FINDINGS: We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias. CONCLUSIONS: In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults. TRIAL REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

Routine data-based quality indicators for the treatment of gonarthrosis and coxarthrosis patients in the ambulatory care sector - A study protocol for a cluster-randomised pilot trial to evaluate the MobilE-ARTH study.

BACKGROUND: In 2019, Germany had the highest rate of hip replacement surgery and the fourth highest rate of knee replacement surgery among more than 30 OECD countries. The age-standardised rates were estimated at 174 hip joint and 137 knee joint replacements per 100,000 population. Against this background, the contrast between financial incentives for surgery and missing incentives for non-surgical treatment options is repeatedly discussed. Quality indicators (QIs) can serve to measure and transparently present the quality of evidence-based care. Comparing results in the form of audit and feedback has been shown to improve e.g. guideline-compliant ambulatory care. Existing QIs targeting the care of gon- and coxarthrosis mainly focus on discharge management after joint replacement surgery and/or require additional data collection. Therefore, as part of the MobilE-ARTH project, a set of QIs for ambulatory care prior to joint replacement surgery calculable based on routine data is being developed. The present study's aim is to evaluate the impact of this QI set in terms of providing feedback on the quality of care. METHODS: The MobilE-ARTH project comprises (Phase 1) developing a QI set following the RAND/UCLA Appropriateness Method, (Phase 2) implementing the QIs in established physician networks of a German statutory health insurance (SHI) within a prospective, non-blinded, cluster-randomised pilot study, and (Phase 3) evaluating the QI set's effectiveness. The physicians in the intervention networks will (a) receive feedback reports providing information about the routine data-based QIs of their gon- and/or coxarthrosis patients and aggregated results for their network, and (b) be invited to two voluntary, facilitated network meetings. In these network meetings, the physicians can use the information provided on the feedback reports to discuss multiprofessional care pathways for patients with gon- and/or coxarthrosis. Selected indicators of the QI set will serve as primary and secondary outcome measures. Routine data will be analysed within multi-level models using an intention-to-treat approach. DISCUSSION: Feedback reports help maintaining clinical standards and closing the gap between evidence and medical practice, thus enabling an overall improvement in health care. Providing physicians with QI-based information on quality of care promotes identifying strengths and weaknesses in medical treatments. TRIAL REGISTRATION: German Clinical Trials Register, number DRKS00027516 , Registered 25th January 2022 - Prospectively registered.

[Economic aspects in the care of patients with new oral anticancer drugs: findings from the AMBORA trial]. / Ökonomische Aspekte bei der Versorgung von Patient*innen mit neuen oralen Tumortherapeutika: Erkenntnisse aus der AMBORA-Studie.

INTRODUCTION: The number of prescriptions and costs of oral anticancer drugs are increasing. Therapy discontinuation due to, for example, side effects, progression, or death, often lead to medication wastage. While evidence exists for the economic value of wasted injectable chemotherapeutics, there is a lack of data for oral anticancer drugs in Germany. METHODS: The multicenter AMBORA trial investigated 202 patients, who had been newly started on new oral anticancer drugs, over 12 weeks and analyzed the outpatient prescription data of patients who discontinued treatment. The amount of medicines wasted and their costs were determined using the pharmacy retail price. Defined daily doses and prescription data from the AOK Bayern, a German statutory health care insurance company, were used to extrapolate these costs. RESULTS: Within 12 weeks, 24.8 % of the AMBORA patients discontinued oral anticancer treatment (50 of 202). Prescription data of 34 patients were evaluable. In total, 1,693 tablets/capsules with a value of 112,212 euros were wasted. The approximate extrapolation to the prescription volume of the AOK Bayern resulted in an estimated wastage of 3.49 million euros in 12 weeks. DISCUSSION: Medication wastage due to discontinuation of new oral anticancer drug therapy leads to a considerable financial burden. Regarding rising prescription numbers and therapy costs in oncology, measures to reduce wastage of oral anticancer drugs should be initiated. CONCLUSION: Clinical pharmacological / pharmaceutical care including medication reconciliation and review, side effect management and patient counseling to optimize adherence and medication intake behavior, contributes to a reduction of therapy discontinuations, thereby reducing drug wastage. To further reduce drug wastage small (initiation) packages, which are currently not always available for an economic prescription, play an important role. The practice of partial prescription fills, which is already practiced internationally, should also be further discussed in Germany.

Covid-19 risk factors: statistical learning from German healthcare claims data.

BACKGROUND: Precise individual risk quantification of severe courses of Covid-19 is needed to prioritize protective measures and to assess population risks in a phase of increased immunization. So far, results for the German population are lacking. Furthermore, existing studies pre-specify comorbidity risks by broad categories rather than deriving them from the data using statistical learning techniques. METHODS: Risk factors for severe, critical and lethal courses of Covid-19 are identified from a large German claims dataset covering more than 4 million individuals. To avoid prior grouping and pre-selection of risk factors, fine-grained hierarchical information from medical classification systems for diagnoses, pharmaceuticals and procedures are used, resulting in more than 33,000 covariates. These are processed using a LASSO approach. RESULTS: We identify relevant risk factors, among which hypertensive diseases, heart disease and the corresponding medications are most relevant at population level. Prior use of diuretics is the strongest single medical predictor for severe course (e.g. Torasemide, odds ratio (OR) 1.801), but also for a critical course (OR 2.304) and death (OR 2.523). To assess risk profiles at the individual level, our approach sums up many such factors and has better predictive ability than using pre-specified morbidity groups (AUC for predicting critical course 0.875 versus AUC ≤ 0.865). CONCLUSIONS: The proposed method can help to identify risk factors and assess risk at the individual level for other infectious diseases. The results can be used by administrative data holders to guide protective policies, while a risk index can be applied in clinical studies with a narrower focus.

Can Adherence to and Persistence with Inhaled Long-acting Bronchodilators Improve the Quality of Life in Patients with Chronic Obstructive Pulmonary Disease? Results from a German Disease Management Program.

BACKGROUND AND OBJECTIVE: Adherence to and persistence with inhaled long-acting bronchodilators (ILAB), is commonly considered to be a relevant driver of perceived health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD), but the topic is rarely studied with real-world data. Using survey and health insurance claims data, this study investigates the effect of adherence to and persistence with ILAB on EQ-5D-5L visual analog scale (VAS) in ILAB users who were enrolled in the German disease management programs (DMP) for COPD. METHODS: Included ILAB users were aged ≥ 18 years, continuously insured with AOK Bavaria and enrolled in the DMP for COPD. Adherence to ILAB [proportion of days covered (PDC); PDC ≥ 80%], and persistence (days of uninterrupted ILAB therapy) were assessed in the year preceding the study's HRQoL questionnaire. In a cross-sectional design we applied quasi-Poisson models with log link function and subgroup analyses. The robustness of results was analyzed with comprehensive sensitivity analyses. RESULTS: Patients with PDC ≥ 80% had 2.96% higher VAS scores than patients with lower PDCs. From all analyses, patients with GOLD stage III had the highest effects from PDC ≥ 80% (5.33% increased VAS). Patients without heart failure profited significantly more from PDC ≥ 80% (+ 4.34% vs - 2.88%) and from an additional persistent day (+ 0.01% vs - 0.01%) than patients with heart failure. CONCLUSIONS: Overall, ILAB users significantly profited from PDC ≥ 80%, but not from continuous PDC or persistent days. In secondary subgroup analyses, patients with GOLD stage III and patients without heart failure particularly profited from PDC ≥ 80%. Only patients without heart failure particularly profited from more persistent days. Because identified effects were small and often not robust, advancing adherence and persistence alone may not improve the German DMP for COPD substantially.

Impact of Lung Function and Exacerbations on Health-Related Quality of Life in COPD Patients Within One Year: Real-World Analysis Based on Claims Data.

PURPOSE: Real-world evidence on the impact of forced expiratory volume in one second (FEV1) and exacerbations on health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD) is sparse especially with regard to GOLD ABCD groups. This study investigates how changes in FEV1 and exacerbations affect generic and disease-specific HRQoL in COPD patients over one year. METHODS: Using German claims data and survey data, we classified 3016 COPD patients and analyzed their health status by GOLD groups AB and CD. HRQoL was measured with the disease-specific COPD assessment test (CAT) and the visual analog scale (VAS) from the generic Euro-Qol 5D-5L. We applied change score models to assess associations between changes in FEV1 (≥100 mL decrease/no change/≥100 mL increase) or the development of severe exacerbations with change in HRQoL. RESULTS: FEV1 decrease was associated with a significant but not minimal important difference (MID) deterioration in disease-specific HRQoL (mean change [95% CI]: CAT +0.74 [0.15 to 1.33]), while no significant change was observed in the generic VAS. Experiencing at least one severe exacerbation also had a significant impact on CAT deterioration (+1.58 [0.52 to 2.64]), but again not on VAS. Here, GOLD groups AB showed not only a statistically but also a clinically relevant MID deterioration in CAT (+2.1 [0.88 to 3.32]). These particular patient groups were further characterized by a higher probability of being male, having a higher mMRC and Charlson index, and a lower probability of having higher FEV1 or BMI values. CONCLUSION: FEV1 decline and the occurrence of ≥1 severe exacerbation are significantly associated with overall deterioration in disease-specific HRQoL. Preventing severe exacerbations particularly in patients without previous severe exacerbations (ABCD groups A and B) may help to stabilize the key patient-reported outcome HRQoL.

Long-term weight gain in obese COPD patients participating in a disease management program: a risk factor for reduced health-related quality of life.

BACKGROUND: Little is known about how long-term weight gain affects the health perception of COPD patients. OBJECTIVES: The aim is to evaluate the long-term association of BMI change and health-related quality of life (HRQoL) in obese COPD patients. METHODS: Claims and survey data from a COPD disease management program were used to match two groups of COPD patients with BMI ≥ 30 who have differing weight trajectories over a 5-year timespan via propensity score and genetic matching. EQ-5D-5L, including visual analog scale (VAS) and COPD Assessment Test (CAT), were used as outcomes of interest. Sociodemographic and disease-based variables were matched. RESULTS: Out of 1202 obese COPD patients, 126 with a weight increase of four or more BMI points were matched separately with 252 (propensity score matching) and 197 (genetic matching) control subjects who had relatively stable BMI. For the EQ-5D-5L, patients with BMI increase reported significantly worse health perception for VAS and all descriptive dimensions except pain/discomfort. For the CAT, especially the perception of ability to complete daily activities and overall energy results were significantly worse. VAS differences reach the range of minimal important differences. Stopping smoking and already being in obesity class II were the most influential risk factors for BMI increase. CONCLUSION: Obese COPD patients who gain four or more BMI points over 5 years report significantly lower results in different dimensions of generic and disease-specific HRQoL than their peers with stable BMI. To improve real-world outcomes, tracking and preventing specific BMI trajectories could constitute a clinically relevant aspect of managing COPD patients.

Effects of adherence to pharmacological secondary prevention after acute myocardial infarction on health care costs - an analysis of real-world data.

BACKGROUND: Acute myocardial infarction (AMI), a major source of morbidity and mortality, is also associated with excess costs. Findings from previous studies were divergent regarding the effect on health care expenditure of adherence to guideline-recommended medication. However, gender-specific medication effectiveness, correlating the effectiveness of concomitant medication and variation in adherence over time, has not yet been considered. METHODS: We aim to measure the effect of adherence on health care expenditures stratified by gender from a third-party payer's perspective in a sample of statutory insured Disease Management Program participants over a follow-up period of 3-years. In 3627 AMI patients, the proportion of days covered (PDC) for four guideline-recommended medications was calculated. A generalized additive mixed model was used, taking into account inter-individual effects (mean PDC rate) and intra-individual effects (deviation from the mean PDC rate). RESULTS: Regarding inter-individual effects, for both sexes only anti-platelet agents had a significant negative influence indicating that higher mean PDC rates lead to higher costs. With respect to intra-individual effects, for females higher deviations from the mean PDC rate for angiotensin-converting enzyme (ACE) inhibitors, anti-platelet agents, and statins were associated with higher costs. Furthermore, for males, an increasing positive deviation from the PDC mean increases costs for ß-blockers and a negative deviation decreases costs. For anti-platelet agents, an increasing deviation from the PDC-mean slightly increases costs. CONCLUSION: Positive and negative deviation from the mean PDC rate, independent of how high the mean was, usually negatively affect health care expenditures. Therefore, continuity in intake of guideline-recommended medication is important to save costs.

The relationship between body mass index and health-related quality of life in COPD: real-world evidence based on claims and survey data.

BACKGROUND: Body mass index (BMI) is an important parameter associated with mortality and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD). However, informed guidance on stratified weight recommendations for COPD is still lacking. This study aims to determine the association between BMI and HRQoL across different severity grades of COPD to support patient management. METHODS: We use conjunct analysis of claims and survey data based on a German COPD disease management program from 2016 to 2017. The EQ-5D-5L visual analog scale (VAS) and COPD Assessment Test (CAT) are used to measure generic and disease-specific HRQoL. Generalized additive models with smooth functions are implemented to evaluate the relationship between BMI and HRQoL, stratified by COPD severity. RESULTS: 11,577 patients were included in this study. Mean age was 69.4 years and 59% of patients were male. In GOLD grades 1-3, patients with BMI of around 25 had the best generic and disease-specific HRQoL, whereas in GOLD grade 4, obese patients had the best HRQoL using both instruments when controlled for several variables including smoking status, income, COPD severity, comorbidities, emphysema, corticosteroid use, and days spent in hospital. CONCLUSION: This real-world analysis shows the non-linear relationship between BMI and HRQoL in COPD. HRQoL of obese patients with mild to severe COPD might improve following weight reduction. For very severe COPD, a negative association of obesity and HRQoL could not be confirmed. The results hint at the need to stratify COPD patients by disease stage for optimal BMI management.

Effect of BMI on health care expenditures stratified by COPD GOLD severity grades: Results from the LQ-DMP study.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation, which is progressive and not fully reversible. In patients with COPD, body mass index (BMI) is an important parameter associated with health outcomes, e.g. mortality and health-related quality of life. However, so far no study evaluated the association of BMI and health care expenditures across different COPD severity grades. We used claims data and documentation data of a Disease Management Program (DMP) from a statutory health insurance fund (AOK Bayern). Patients were excluded if they had less than 4 observations in the 8 years observational period. Generalized additive mixed models with smooth functions were used to evaluate the association between BMI and health care expenditures, stratified by severity of COPD, indicated by GOLD grades 1-4. We included 30,682 patients with overall 188,725 observations. In GOLD grades 1-3 we found an u-shaped relation of BMI and expenditures, where patients with a BMI of 30 or slightly above had the lowest and underweight and obese patients had the highest health care expenditures. Contrarily, in GOLD grade 4 we found an almost linear decline of health care expenditures with increasing BMI. In terms of expenditures, the often reported obesity paradox in patients with COPD was clearly reflected in GOLD grade 4, while in all other severity grades underweight as well as severely obese patients caused the highest health care expenditures. Reduction of obesity may thus reduce health care expenditures in GOLD grades 1-3.

Patients with coronary artery disease after acute myocardial infarction: effects of continuous enrollment in a structured Disease Management Program on adherence to guideline-recommended medication, health care expenditures, and survival.

OBJECTIVE: Acute myocardial infarction (AMI) carries increased risk of mortality and excess costs. Disease Management Programs (DMPs) providing guideline-recommended care for chronic diseases seem an intuitively appealing way to enhance health outcomes for patients with chronic conditions such as AMI. The aim of the study is to compare adherence to guideline-recommended medication, health care expenditures and survival of patients enrolled and not enrolled in the German DMP for coronary artery disease (CAD) after an AMI from the perspective of a third-party payer over a follow-up period of 3 years. METHODS: The study is based on routinely collected data from a regional statutory health insurance fund (n = 15,360). A propensity score matching with caliper method was conducted. Afterwards guideline-recommended medication, health care expenditures, and survival between patients enrolled and not enrolled in the DMP were compared with generalized linear and Cox proportional hazard models. RESULTS: The propensity score matching resulted in 3870 pairs of AMI patients previously and continuously enrolled and not enrolled in the DMP. In the 3-year follow-up period the proportion of days covered rates for ACE-inhibitors (60.95% vs. 58.92%), anti-platelet agents (74.20% vs. 70.66%), statins (54.18% vs. 52.13%), and ß-blockers (61.95% vs. 52.64%) were higher in the DMP group. Besides that, DMP participants induced lower health care expenditures per day (€58.24 vs. €72.72) and had a significantly lower risk of death (HR: 0.757). CONCLUSION: Previous and continuous enrollment in the DMP CAD for patients after AMI is a promising strategy as it enhances guideline-recommended medication, reduces health care expenditures and the risk of death.

Healthcare costs associated with breast cancer in Germany: a claims data analysis.

PURPOSE: This study estimates the healthcare costs associated with breast cancer (BC) for different treatment phases (initial, intermediate, terminal) in Germany from the payer's perspective. METHODS: The analysis uses claims data from the AOK Bayern covering 2011-2014 for continuously insured BC patients identified through inpatient and outpatient diagnoses. We calculate the healthcare costs attributable to BC using a control group design comparing the target population to a 1:2 matched control group adjusted for age, gender, and comorbidities. For incident and prevalent BC cases, we calculate age-standardized phase-specific incremental costs stratified by cost domain. RESULTS: The initial, intermediate, and terminal phases comprise 3841, 28,315, and 1767 BC cases, respectively. BC-related incremental costs follow a u-shaped curve, with costs highest near diagnosis and death, and lower in between. With average costs of €33,237 per incident and €28,211 per prevalent case in the remaining 11 months before death, the highest BC-related incremental healthcare costs can be found in the terminal phase. In the initial phase, there were mean incremental costs of €21,455 the first 11 months after diagnosis. In the intermediate phase, incremental costs totaled €2851 per incident and €2387 per prevalent case per year. Healthcare costs decreased with age in most phases. The cost drivers depend on the treatment phase, with cytostatic drugs and inpatient treatment showing the highest economic impact in most phases. CONCLUSION: The study concludes that BC care costs impose a relevant economic burden on statutory health insurance and vary substantially depending on the treatment phase.

Measuring quality of life in COPD patients: comparing disease-specific supplements to the EQ-5D-5L.

Objectives: Patients with chronic obstructive pulmonary disease (COPD) show impairments in health-related quality of life (HRQL). We aimed to find a disease-specific questionnaire for routine application in large cohorts and to assess its additional explanatory power to generic HRQL tool (EQ-5D-5L). Methods: 1,350 participants of the disease management program COPD received the EQ-5D-5L combined with one of the three disease-specific tools: COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) or St. George's Respiratory Disease Questionnaire (SGRQ) (450 participants each). We compared metric properties and evaluated the Germany-specific experience-based values (EBVS) and utilities in comparison to the Visual Analogue Scale (VAS). We calculated the additional explanatory power of the identified disease-specific tool on VAS through regression analysis. Results: 344 patients returned the questionnaire. CAT, CCQ, and SGRQ group did not differ regarding baseline characteristics. The questionnaire specific response rates were 33.7% for CAT, 30.5% for CCQ, and 34.6% SGRQ, thereof 94.0%, 94.3%, and 65.6% valid answers, respectively. EBVS was better suited to reflect VAS than utilities. CAT increased the explanatory power by 10%. Conclusion: CAT outperformed CCQ and SGRQ, and it increased the explanatory power of VAS. EBV combined with CAT seems superior to only generic or disease-specific approaches.

Direct and indirect costs of COPD progression and its comorbidities in a structured disease management program: results from the LQ-DMP study.

BACKGROUND: Evidence on the economic impact of chronic obstructive pulmonary disease (COPD) for third-party payers and society based on large real world datasets are still scarce. Therefore, the aim of this study was to estimate the economic impact of COPD severity and its comorbidities, stratified by GOLD grade, on direct and indirect costs for an unselected population enrolled in the structured German Disease Management Program (DMP) for COPD. METHODS: All individuals enrolled in the DMP COPD were included in the analysis. Patients were only excluded if they were not insured or not enrolled in the DMP COPD the complete year before the last DMP documentation (at physician visit), had a missing forced expiratory volume in 1 s (FEV1) measurement or other missing values in covariates. The final dataset included 39,307 patients in GOLD grade 1 to 4. We used multiple generalized linear models to analyze the association of COPD severity with direct and indirect costs, while adjusting for sex, age, income, smoking status, body mass index, and comorbidities. RESULTS: More severe COPD was significantly associated with higher healthcare utilization, work absence, and premature retirement. Adjusted annual costs for GOLD grade 1 to 4 amounted to €3809 [€3691-€3935], €4284 [€4176-€4394], €5548 [€5328-€5774], and €8309 [€7583-9065] for direct costs, and €11,784 [€11,257-€12,318], €12,985 [€12,531-13,443], €15,805 [€15,034-€16,584], and €19,402 [€17,853-€21,017] for indirect costs. Comorbidities had significant additional effects on direct and indirect costs with factors ranging from 1.19 (arthritis) to 1.51 (myocardial infarction) in direct and from 1.16 (myocardial infarction) to 1.27 (cancer) in indirect costs. CONCLUSION: The findings indicate that more severe GOLD grades in an unselected COPD population enrolled in a structured DMP are associated with tremendous additional direct and indirect costs, with comorbidities significantly increase costs. In direct cost category hospitalization and in indirect cost category premature retirement were the main cost driver. From a societal perspective prevention and interventions focusing on disease control, and slowing down disease progression and strengthening the ability to work would be beneficial in order to realize cost savings in COPD.

Real-world effectiveness and safety of oral anticoagulation strategies in atrial fibrillation: a cohort study based on a German claims dataset.

OBJECTIVE: To compare the real-world effectiveness and safety of non-vitamin-K-antagonist oral anticoagulant (NOAC) treatment in atrial fibrillation (AF) patients with a vitamin-K-antagonist (VKA)-based treatment. METHODS: This was a retrospective analysis of an anonymized claims dataset from 3 German health insurance funds covering the period from January 01, 2010 to June 30, 2014, with a minimum observation time of 12 months. All continuously insured patients with at least 2 outpatient AF diagnoses and/or 1 inpatient respective diagnosis who received at least 1 outpatient prescription of a NOAC or VKA were included. OUTCOMES AND MEASURES: Death, ischemic strokes (IS), non-specified strokes, transient ischemic attacks (TIAs), myocardial infarctions (MIs), arterial embolism (AE), hemorrhagic strokes, severe bleedings, and composite outcomes. Main comparisons were done based on propensity score-matched (PSM) cohorts. Results were reported as incidence rate ratios and hazard ratios (HRs). RESULTS: We assigned 37,439 AF patients to each PSM cohort (NOAC cohort: mean age 78.2 years, mean CHA2DS2VASc score 2.96, mean follow-up 348.5 days; VKA cohort: mean age 78.2 years, mean CHA2DS2VASc 2.95, mean follow-up 365.5 days). NOAC exposure was associated with significantly higher incidence rate ratios; 95% CI/HRs; 95% CI for the following outcomes: death (1.22; 1.17-1.28/1.22; 1.17-1.28), IS (1.90; 1.69-2.15/1.92; 1.69-2.19), non-specified strokes (2.04; 1.16-3.70/1.93; 1.13-3.32), TIAs (1.52; 1.29-1.79/1.44; 1.21-1.70), MIs (1.26; 1.10-1.15/1.31; 1.13-1.52), AE (1.75; 1.32-2.32/1.81; 1.36-2.34) and severe bleeding (1.92; 1.71-2.15/1.95; 1.74-2.20). Multivariable Cox regression analyses and additional sensitivity analysis, including analysis of PSM-matched NOAC/VKA treatment-naive patients, only confirmed the above results. The study was documented under clinicaltrials.gov (NCT02657616). CONCLUSION AND RELEVANCE: A VKA therapy seems to be more effective and safer than a NOAC therapy in a real-world cohort of German AF patients.

Dehydroevodiamine and hortiamine, alkaloids from the traditional Chinese herbal drug Evodia rutaecarpa, are IKr blockers with proarrhythmic effects in vitro and in vivo.

Evodiae fructus is a widely used herbal drug in traditional Chinese medicine. Evodia extract was found to inhibit hERG channels. The aim of the current study was to identify hERG inhibitors in Evodia extract and to investigate their potential proarrhythmic effects. Dehydroevodiamine (DHE) and hortiamine were identified as IKr (rapid delayed rectifier current) inhibitors in Evodia extract by HPLC-microfractionation and subsequent patch clamp studies on human embryonic kidney cells. DHE and hortiamine inhibited IKr with IC50s of 253.2±26.3nM and 144.8±35.1nM, respectively. In dog ventricular cardiomyocytes, DHE dose-dependently prolonged the action potential duration (APD). Early afterdepolarizations (EADs) were seen in 14, 67, 100, and 67% of cells after 0.01, 0.1, 1 and 10µM DHE, respectively. The proarrhythmic potential of DHE was evaluated in 8 anesthetized rabbits and in 8 chronic atrioventricular block (cAVB) dogs. In rabbits, DHE increased the QT interval significantly by 12±10% (0.05mg/kg/5min) and 60±26% (0.5mg/kg/5min), and induced Torsade de Pointes arrhythmias (TdP, 0.5mg/kg/5min) in 2 rabbits. In cAVB dogs, 0.33mg/kg/5min DHE increased QT duration by 48±10% (P<0.05*) and induced TdP in 2/4 dogs. A higher dose did not induce TdP. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), methanolic extracts of Evodia, DHE and hortiamine dose-dependently prolonged APD. At 3µM DHE and hortiamine induced EADs. hERG inhibition at submicromolar concentrations, APD prolongation and EADs in hiPSC-CMs and dose-dependent proarrhythmic effects of DHE at micromolar plasma concentrations in cAVB dogs should increase awareness regarding proarrhythmic effects of widely used Evodia extracts.

Natural products as potential human ether-a-go-go-related gene channel inhibitors - outcomes from a screening of widely used herbal medicines and edible plants.

Inhibition of the human ether-a-go-go-related gene channel is the single most important risk factor leading to acquired long QT syndrome. Drug-induced QT prolongation can cause severe cardiac complications, including arrhythmia, and is thus a liability in drug development. Considering the importance of the human ether-a-go-go-related gene channel as an antitarget and the daily intake of plant-derived foods and herbal products, surprisingly few natural products have been tested for channel blocking properties. In an assessment of possible human ether-a-go-go-related gene liabilities, a selection of widely used herbal medicines and edible plants (vegetables, fruits, and spices) was screened by means of a functional two-microelectrode voltage-clamp assay with Xenopus oocytes. The human ether-a-go-go-related gene channel blocking activity of selected extracts was investigated with the aid of a high-performance liquid chromatography-based profiling approach, and attributed to tannins and alkaloids. Major European medicinal plants and frequently consumed food plants were found to have a low risk for human ether-a-go-go-related gene toxicity.