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Abstract Background Phenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment. The management of PKU should start as soon as possible after diagnosis to prevent irreversible damage and be maintained throughout life. The aim of this study was to assess the burden of illness in PKU patients in general and in PKU patients born before and after the introduction of newborn screening in Germany. Methods This retrospective matched cohort analysis used the Institut für angewandte Gesundheitsforschung Berlin (InGef) research database containing anonymized healthcare claims of approximately 4 million covered lives. PKU patients were compared with matched controls from the general population within the same database (1:10 ratio via direct, exact matching on age and gender without replacement). PKU patients were included if they were aged ≥18 years on 01/01/15 and were continuously enrolled from 01/01/10 to 31/12/15. The 50 most commonly reported comorbidities and 50 most commonly prescribed medications in the PKU population were analyzed. Differences between groups were tested using 95% confidence interval (CI) of prevalence ratio (PR) values. Results The analysis included 377 adult PKU patients ( 1.5 vs controls included major depressive disorders (PR = 2.3), chronic ischemic heart disease (PR = 1.7), asthma (PR = 1.7), dizziness and giddiness (PR = 1.8), unspecified diabetes mellitus (PR = 1.7), infectious gastroenteritis and colitis (PR = 1.7), and reaction to severe stress and adjustment disorders (PR = 1.6). The most commonly prescribed Anatomical Therapeutic Chemical (ATC) subcodes among PKU patients (vs the control population) are for systemic antibacterials (34.7% vs 32.8%), anti-inflammatory and antirheumatic (29.4% vs 27.5%), renin-angiotensin agents (30.0% vs 27.0%), acid-related disorders (29.4% vs 20.2%), and beta-blockers (24.9% vs 19.9%). Conclusion The overall clinical burden on patients with PKU is exacerbated by a significantly higher risk of numerous comorbidities and hence, prescribing of the requisite medication, both for recognized (e.g. major depressive disorders) and more unexpected comorbidities (e.g. ischemic heart disease).

Background and Purpose: It is unestablished whether andexanet alfa, compared with guideline-based usual care including prothrombin complex concentrates, is associated with reduced hematoma expansion (HE) and mortality in patients with factor-Xa inhibitor-related intracerebral hemorrhage (ICH). We compared the occurrence of HE and clinical outcomes in patients treated either with andexanet alfa or with usual care during the acute phase of factor-Xa inhibitor-related ICH., Methods: Data were extracted from the multicenter, prospective, single-arm ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) and a multicenter observational cohort study, RETRACE-II (German-Wide Multicenter Analysis of Oral Anticoagulant-Associated Intracerebral Hemorrhage - Part Two). HE was based on computed tomography scans performed within 36 hours from baseline imaging. Inverse probability of treatment weighting was performed to adjust for baseline comorbidities and ICH severity. Patients presenting with atraumatic ICH while receiving apixaban or rivaroxaban within 18 hours of admission were included. Patients with secondary ICH or not fulfilling the inclusion criteria for the ANNEXA-4 trial were excluded. We compared ANNEXA-4 patients, who received andexanet alfa for hemostatic treatment, with RETRACE-II patients who were treated with usual care, primarily administration of prothrombin complex concentrates. Primary outcome was rate of HE defined as relative increase of ≥35%. Secondary outcomes comprised mean absolute change in hematoma volume, as well as in-hospital mortality and functional outcome., Results: Overall, 182 patients with factor-Xa inhibitor-related ICH (85 receiving andexanet alfa versus 97 receiving usual care) were selected for analysis. There were no relevant differences regarding demographic or clinical characteristics between both groups. HE occurred in 11 of 80 (14%) andexanet alfa patients compared with 21 of 67 (36%) usual care patients (adjusted relative risk, 0.40 [95% CI, 0.20-0.78]; P =0.005), with a reduction in mean overall hematoma volume change of 7 mL. There were no statistically significant differences among in-hospital mortality or functional outcomes. Sensitivity analysis including only usual care patients receiving prothrombin complex concentrates demonstrated consistent results., Conclusions: As compared with usual care, andexanet alfa was associated with a lower rate of HE in atraumatic factor-Xa inhibitor-related ICH, however, without translating into significantly improved clinical outcomes. A comparative trial is needed to confirm the benefit on limiting HE and to explore clinical outcomes across patient subgroups and by time to treatment. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT02329327 and NCT03093233.

This retrospective matched-cohort analysis compared health-economic burdens of adults (≥18 years; n  = 377) with phenylketonuria (PKU) and age/gender-matched non-PKU controls ( n  = 3770) in Germany. Healthcare costs and resource-utilization were analyzed for the year 2015. Differences between groups were tested using 95% CI of mean differences (MD). PKU patients had significantly higher mean costs in total (MD €3307, 95% CI €1736-€4879), for pharmaceuticals (MD €1912, 95% CI €1195-€2629) [including dietary amino-acid supplements (MD €1268, 95% CI €864-€1672)], and outpatient costs (MD €395, 95% CI €115-€675). Inpatient costs (MD €904, 95% CI -€293 to €2100) and costs for aids and remedies (MD €97, 95% CI -€10 to €203) were also higher in PKU patients. PKU patients had more outpatient visits and stayed longer in hospital. Adult PKU patients incur higher total healthcare costs than non-PKU controls, especially regarding pharmaceuticals and outpatient costs, and more frequent resource-utilization, resulting in higher health-economic burden for the statutory healthcare system., (© 2021 The Authors.)

Background: The EQ-5D-5L questionnaire is used in oncology to generate health-related quality of life (HRQoL) weights and corresponding health states. The purpose was to explore the relationship between demographic and clinical characteristics and HRQoL among advanced or metastatic colorectal cancer (CRC) patients by linking clinical data of a German CRC registry to self-reported HRQoL measures from the EQ-5D-5L., Methods: The study sample included patients with advanced or metastatic CRC currently recruited in the German Tumor Registry Colorectal Cancer. The EQ-5D-5L was administered once to patients who were at the start or at later stages of palliative treatment. Data on comorbidities, disease-specific health states, symptoms, and treatment status were drawn from the registry. Multivariate regression analyses were performed to explore the impact of patient and disease characteristics on HRQoL., Results: In total, n = 433 questionnaires were included in the data analysis. Mean age of patients was 66.3 years and 61.2% were male. The mean EQ-5D-5L utility score was 0.82 and the mean EQ-5D-5L VAS score was 62.05. The regression analyses revealed that none of the demographic characteristics and few of the clinical characteristics, such as fatigue and pain, had a significant impact on the HRQoL., Conclusions: The study demonstrated a reduced HRQoL of patients with advanced or metastatic CRC when compared to the general population. The symptoms fatigue and pain negatively affected the HRQoL, whereas other characteristics such as age, gender, and comorbidities did not have a significant impact on HRQoL.

People living with human immunodeficiency virus (PLHIV) are at high risk of developing non-HIV related comorbidities, particularly at older ages. In a retrospective claims database analysis, we compared PLHIV to a matched, non-HIV cohort to assess the prevalence of comorbidities and healthcare costs in PLHIV and the general non-HIV population in Germany. In total, 2,132 adult patients with HIV were identified in the InGef research database with HIV ICD-10 diagnosis within each year from 2011 to 2014. Of these, 1,969 could be matched to a control cohort of 3,938 individuals (1:2 ratio). Matching criteria included age, gender and socio-economic variables. The prevalence of acute renal disease (0.5% vs. 0.2%, p = 0.045), bone fractures due to osteoporosis (6.4% vs. 2.1%, p<0.001), chronic renal disease (4.3% vs. 2.4%, p<0.001), cardiovascular disease (12.8% vs. 10.4%, p = 0.006), Hepatitis B (5.9% vs. 0.3%, p<0.001) and Hepatitis C infection (8.8% vs. 0.3%, p<0.001) was significantly higher in PLHIV compared to the matched non-HIV cohort. Mean costs excluding costs for antiretroviral therapy (ART) were significantly higher in the HIV cohort (8,049€ vs. 3,658€, p<0.05). On average, PLHIV incurred excess costs of 16,441€ for ART, 2,747€ for pharmaceuticals excluding ART (p<0.05), 1,441€ for outpatient care (p<0.05) and 321€ for inpatient care (p<0.05). Devices and remedies' costs were significantly higher in the control cohort with excess costs of 113€ (p<0.05). Considering mean total costs, excluding ART, excess costs for PLHIV amounted to 8,049€ (p<0.05). This analysis demonstrated an increased comorbidity and economic burden of PLHIV compared to matched controls. Our findings suggest that HIV remains an area of high unmet medical need. To improve patient outcomes, adequate HIV management including regular monitoring, screening for comorbidities and optimal ART selection throughout the life course of PLHIV are of key importance., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SC has received honoraria and/or travel grants for consulting or speaking at educational events from Abbvie, Gilead, Indivior, Janssen-Cilag, MSD and ViiV. EW has received honoraria and/or travel grants for consulting or speaking at educational events from AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hexal, Janssen-Cilag, MSD SHARP & DOHME, Roche, and ViiV Healthcare. MUC Research has received support for clinical research from AbbVie, Gilead Sciences, MSD Sharp and Dohme, Pfizer und ViiV Healthcare. JA is an employee of Xcenda GmbH, a company which received funding from Gilead Sciences Europe Ltd for developing and conducting this study. HDC is a Gilead Sciences Europe Ltd employee.

Aims: The aim of this study was to assess the burden of heart failure (HF) patients with/without iron deficiency/iron deficiency anaemia (ID/A) from the health insurance perspective., Methods and Results: We conducted a retrospective claims database analysis using the Institut für angewandte Gesundheitsforschung Berlin research database. The study period spanned from 1 January 2012 to 31 December 2014. HF patients were identified by International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification codes (I50.-, I50.0-, I50.00, I50.01, I50.1-, I50.11, I50.12, I50.13, I50.14, I50.19, and I50.9). HF patients were stratified into HF patients without ID/A and HF patients with ID/A (D50.-, D50.0, D50.8, D50.9, and E61.1). HF patients with ID/A were stratified into three subgroups: no iron treatment, oral iron treatment, and intravenous iron treatment. A matching approach was applied to compare outcomes for HF patients without ID/A vs. HF patient with untreated incident ID/A without iron treatment and for HF patients receiving no iron treatment vs. oral iron treatment vs. intravenous iron treatment. Matching parameters included exact age, sex, and New York Heart Association functional class. An optimization algorithm was used to balance total health care costs in the baseline period for the potential matched pairs without sample size reduction. In total, 172 394 (4537.4 per 100 000) HF patients were identified in the Institut für angewandte Gesundheitsforschung Berlin research database in 2013. Of these, 11.1% (19 070; 501.9 per 100 000) were diagnosed with ID/A and/or had a prescription for iron medication in 2013. The mean age of HF patients was 77.0 years (±12.0 years). Women were more frequently diagnosed with HF (54.6%). HF patients with untreated incident ID/A (1.77%) had a significantly higher all-cause mortality than HF patients without ID/A (33.1% vs. 24.1%, P < 0.01). The analysis of health care utilization revealed significant differences in the rate of all-cause hospitalization (72.9% vs. 50.5%, P < 0.01). The annual health care costs for HF patients with untreated incident ID/A amounted to €17 347 with incremental costs of €849 (P < 0.01) attributed to ID/A., Conclusions: Heart failure is associated with a major burden for patients and the health care system in terms of health care resource utilization, costs, and mortality. Our findings suggest that there is an unmet need for treating more HF patients with ID/A with iron medication., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Phenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment. The management of PKU should start as soon as possible after diagnosis to prevent irreversible damage and be maintained throughout life. The aim of this study was to assess the burden of illness in PKU patients in general and in PKU patients born before and after the introduction of newborn screening in Germany., Methods: This retrospective matched cohort analysis used the Institut für angewandte Gesundheitsforschung Berlin (InGef) research database containing anonymized healthcare claims of approximately 4 million covered lives. PKU patients were compared with matched controls from the general population within the same database (1:10 ratio via direct, exact matching on age and gender without replacement). PKU patients were included if they were aged ≥18 years on 01/01/15 and were continuously enrolled from 01/01/10 to 31/12/15. The 50 most commonly reported comorbidities and 50 most commonly prescribed medications in the PKU population were analyzed. Differences between groups were tested using 95% confidence interval (CI) of prevalence ratio (PR) values., Results: The analysis included 377 adult PKU patients (< 5 of which were receiving sapropterin dihydrochloride) and 3,770 matched controls. Of the 50 most common comorbidities in the PKU population, those with a statistically significant PR > 1.5 vs controls included major depressive disorders (PR = 2.3), chronic ischemic heart disease (PR = 1.7), asthma (PR = 1.7), dizziness and giddiness (PR = 1.8), unspecified diabetes mellitus (PR = 1.7), infectious gastroenteritis and colitis (PR = 1.7), and reaction to severe stress and adjustment disorders (PR = 1.6). The most commonly prescribed Anatomical Therapeutic Chemical (ATC) subcodes among PKU patients (vs the control population) are for systemic antibacterials (34.7% vs 32.8%), anti-inflammatory and antirheumatic (29.4% vs 27.5%), renin-angiotensin agents (30.0% vs 27.0%), acid-related disorders (29.4% vs 20.2%), and beta-blockers (24.9% vs 19.9%)., Conclusion: The overall clinical burden on patients with PKU is exacerbated by a significantly higher risk of numerous comorbidities and hence, prescribing of the requisite medication, both for recognized (e.g. major depressive disorders) and more unexpected comorbidities (e.g. ischemic heart disease).

Aims: Several psychosocial factors have been shown to increase the risk of Type 2 diabetes mellitus. This study investigated the association between structural social support and incidence of Type 2 diabetes mellitus in men and women., Methods: Data were derived from three population-based MONICA/KORA surveys conducted in 1984-1995 in the Augsburg region (southern Germany) and followed up by 2009. The study population comprised 8952 participants (4669 men/4283 women) aged 30-74 years without diabetes at baseline. Structural social support was assessed using the Social Network Index. Sex-specific hazard ratios were estimated from Cox proportional hazard models., Results: Within follow-up, 904 incident Type 2 diabetes mellitus cases (558 men, 346 women) were observed. Crude incidence rates for Type 2 diabetes mellitus per 10 000 person-years were substantially higher in poor compared with good structural social support (men: 94 vs. 69, women: 58 vs. 43). After adjustment for age, survey, parental history of diabetes, smoking status, alcohol intake, physical activity, hypertension, dyslipidaemia, BMI, education, sleep complaints and depressed mood, risk of Type 2 diabetes mellitus for participants with poor compared with good structural social support was 1.31 [95% confidence interval (CI) = 1.11-1.55] in men and 1.10 (95% CI = 0.88-1.37) in women. Stratified analyses revealed a hazard ratio of 1.50 (95% CI = 1.23-1.83) in men with a low level of education and 0.87 (95% CI = 0.62-1.22) in men with a high level of education (P for interaction: 0.0082)., Conclusions: Poor structural social support is associated with Type 2 diabetes mellitus in men. This association is independent of risk factors at baseline and is particularly pronounced in men with a low level of education., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Background: Patient satisfaction is a relevant prognostic factor in young persons with chronic disease and may be both age and disease specific. To assess health care quality from the patient's view in young persons with inflammatory bowel disease, an easy to use, valid, reliable and informative specific instrument was needed., Methods: All parts of the study were directed at persons with inflammatory bowel disease aged 15 to 24 ("youth"). A qualitative internet patient survey was used to generate items, complemented by a physician survey and literature search. A 2nd internet survey served to reduce items based on perceived importance and representativeness. Following pilot testing to assess ease of use and face validity, 150 respondents to a postal survey in patients from a paediatric clinical registry were included for validation analyses. Construct validity was assessed by relating summary scores to results from global questions on satisfaction with care using ANOVA. To assess test-retest reliability using intraclass correlation coefficients (ICC), a subset of patients were assessed twice within 3 months., Results: 302 persons with IBD and 55 physicians participated in the item generating internet survey, resulting in 3,954 statements. After discarding redundancies 256 statements were presented in the 2nd internet survey. Of these, 32 items were retained. The resulting instrument assesses both the perceived relevance (importance) of an item as well as the performance of the care giver for each item for calculation of a summary satisfaction score (range 0 to 1). Sensibility testing showed good acceptance for most items. Construct validity was good, with mean scores of 0.63 (0.50 to 0.76), 0.71 (0.69 to 0.74) and 0.81 (0.79 to 0.83) for no, some and good global satisfaction (ANOVA, p < 0.001). Test-retest reliability was satisfactory (ICC 0.6 to 0.7)., Conclusions: We developed an easy to use, patient oriented, valid instrument to assess satisfaction with care in young persons with IBD for use in survey research.