Comorbidities, healthcare resource utilization & treatment pattern among patients with prurigo nodularis, compared to a benchmark in Germany: A real-world evidence claims data study.

BACKGROUND: Prurigo nodularis (PN) is a rare chronic inflammatory skin disease with a high disease burden, but data on clinical and economic burden are still scarce. OBJECTIVE: To describe the real-world epidemiologic, clinical and therapeutic characteristics and related economic burden of patients with PN compared to a benchmark population in Germany. METHODS: This retrospective study was based on an excerpt of German Statutory Health Insurance data of patients with an initial PN diagnosis between 2012 and 2016. PN cohort contained no record of PN in eight quarters before the index quarter and was followed up for eight quarters (unless deceased). Benchmark cohort without PN was calculated using direct standardization and 1:1 matching to PN cohort. RESULTS: Out of 4,536,002 insured patients, 2309 incident patients with PN were identified and matched to the benchmark cohort out of 3,018,382 patients without PN. Patients were mostly between 45 and 80 years when diagnosed with PN. Higher comorbidity rates were reported for PN than benchmark, with a rising disease burden at follow-up. Most patients with PN (91.3%) were diagnosed outpatient and had >50% more outpatient visits than the benchmark cohort. Hospitalization rates were higher in PN (53.9%) versus benchmark (35.1%), yielding twice longer mean hospital stays for PN (12 days) compared to benchmark (6 days) (p < 0.001). The most common initial therapy for patients with PN was topical corticosteroids (47.6%); ≥10% of patients were treated with antidepressants, antihistamines or systemic corticosteroids. Therapy rates were higher for PN compared to benchmark (p < 0.001). Mean initial costs were twofold higher in PN versus benchmark for outpatient, inpatient and drugs. During follow-up, an increase of >70% in mean PN costs compared to benchmark was identified for outpatient, inpatient and concomitant treatments (p < 0.001). CONCLUSION: This study highlights the significantly higher clinical and economic burden incurred by PN compared to benchmark patients in Germany, reflecting the unmet medical need for PN.

Retrospective German claims data study on initial treatment of bladder carcinoma (BCa) by transurethral bladder resection (TURB): a comparative analysis of costs using standard white light- (WL-) vs. blue light- (BL-) TURB.

PURPOSE: Photodynamic diagnosis using hexaminolevulinate (HAL)-guided BL-TURB may reduce the recurrence risk in non-muscle invasive BCa compared to standard WL-TURB due to more sensitive tumor detection. The impact of the initial use of WL- vs. BL-TURB on follow-up costs was evaluated in this real-world data analysis. METHODS: Anonymous claims data of German statutory health insurances (GKV) from 2011 to 2016 were analyzed in a primary and adjusted study population. Selection criteria included five quarters before enrolment, one index quarter (InQ) of initial TURB and BCa diagnosis, either within two years for the primary analysis or within four years for the adjusted analysis, and a follow-up period (FU) of either eleven or three quarters, respectively. RESULTS: In the primary analysis (n = 2331), cystectomy was identified as an important cost driver masking potential differences between cohorts. Therefore, patients undergoing cystectomy (InQ + FU) were excluded from the adjusted study population of n = 4541 patients (WL: 79%; BL: 21%). Mean total costs of BL-TURB were initially comparable to WL-TURB (WL: EUR 4534 vs. BL: EUR 4543) and tended to be lower compared to WL-TURB in the first two quarters of FU. After one year (3rd FU quarter), costs equalized. Considering total FU, mean costs of BL-TURB were significantly lower compared to WL-TURB (WL: EUR 7073 vs BL: EUR 6431; p = 0.045). CONCLUSION: This retrospective analysis of healthcare claims data highlights the comparability of costs between BL-TURB and WL-TURB.

Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study.

AIMS: We compared the new use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP4i) and the risk of cardiorenal disease, heart failure (HF) or chronic kidney disease (CKD), in patients with type 2 diabetes without a history of prevalent cardiovascular and renal disease, defined as cardiovascular and renal disease (CVRD) free, managed in routine clinical practice. MATERIALS AND METHODS: In this observational cohort study, patients were identified from electronic health records from England, Germany, Japan, Norway, South Korea and Sweden, during 2012-2018. In total, 1 006 577 CVRD-free new users of SGLT2i or DPP4i were propensity score matched 1:1. Unadjusted Cox regression was used to estimate hazard ratios (HRs) for outcomes: cardiorenal disease, HF, CKD, stroke, myocardial infarction (MI), cardiovascular and all-cause mortality. RESULTS: Baseline characteristics were well balanced between the treatment groups (n = 105 130 in each group) with total follow-up of 187 955 patient years. Patients had a mean age of 56 years, 43% were women and they were indexed between 2013 and 2018. The most commonly used agents were dapagliflozin (91.7% of exposure time) and sitagliptin/linagliptin (55.0%), in the SGLT2i and DPP4i, groups, respectively. SGLT2i was associated with lower risk of cardiorenal disease, HF, CKD, all-cause and cardiovascular mortality; HR (95% confidence interval), 0.56 (0.42-0.74), 0.71 (0.59-0.86), 0.44 (0.28-0.69), 0.67 (0.59-0.77), and 0.61 (0.44-0.85), respectively. No differences were observed for stroke [0.87 (0.69-1.09)] and MI [0.94 (0.80-1.11)]. CONCLUSION: In this multinational observational study, SGLT2i was associated with a lower risk of HF and CKD versus DPP4i in patients with type 2 diabetes otherwise free from both cardiovascular and renal disease.

[Prevalence, Costs of Medical Treatment and Modalities of Dialysis-dependent Chronic Renal Failure in Germany: Comparison of Dialysis Care of Nursing Home Residents and in Outpatient Units]. / Prävalenz, Kosten der Versorgung und Formen des dialysepflichtigen chronischen Nierenversagens in Deutschland: Vergleich der Dialyseversorgung innerhalb und außerhalb stationärer Pflegeeinrichtungen.

STUDY OBJECTIVES: Current estimates on the prevalence of chronic renal failure and the costs of dialysis in Germany's population are not available. The aim of this study was to assess the prevalence of dialysis-dependent chronic renal failure and treatment costs of dialysis-dependent patients in Germany as well as differences between those residing in nursing homes and those treated in outpatient units. METHODS: Health insurance claims from 4.5 million anonymized patients in the WIG2 research database were analyzed. Patients of all ages who had received outpatient dialysis treatment for chronic renal failure in 2017 (using uniform value scale code 13602) were included. These insurance claims were extrapolated to the German statutory health insurance population and, using official statistics, further to the entire population of Germany. Data on comorbidities, use of health resources, and costs were compared among patients residing in nursing homes and those treated in outpatient units. RESULTS: In 2017, there were 87,255 dialysis-dependent statutory health insurance patients (≙1,054 person/1 million population, pmp), and 100,202 in Germany's whole population (≙1,210 pmp). About 8% of dialysis-dependent patients (n=7,676) were living in nursing homes. Our analyses predict an increase in dialysis-dependent patients of about 20-23% (up to 120,000-123,000), with an increase of dialysis-dependent nursing home residents of 37-44% (up to 10,500-11,000) by 2040. Almost all dialysis-dependent patients were treated with hemodialysis; peritoneal dialysis was rarely observed. The average annual treatment costs for dialysis-dependent patients residing in nursing homes amounted to 57,205 Euro and 53,996 Euro per patient respectively, with total annual statutory health insurance treatment costs amounting to about 4.73 billion Euro in 2017. CONCLUSION: This study presents current estimates for dialysis-dependent chronic renal failure in Germany. Our findings on prevalence are comparable to data from other European countries and suggest a considerable increase in dialysis dependency by 2040, particularly for nursing home residents, resulting in a further increase in dialysis care costs. Hemodialysis was the most commonly used dialysis modality in patients living both in and out of nursing care facilities, with peritoneal dialysis rarely being used.

Epidemiology of Prurigo Nodularis compared with Psoriasis in Germany: A Claims Database Analysis.

Prurigo nodularis is an itchy skin disease with unknown epidemiology. This study aimed to describe the epidemiology of prurigo nodularis compared with that of psoriasis. The German sickness fund claims database, with 2,783,175 continuously insured patients, included 1,720 patients diagnosed with prurigo nodularis and 51,390 with psoriasis. Patients with prurigo nodularis were averagely 8 years older than psoriasis patients and more often were women (p < 0.001). Annual incidence was a constant 0.02% in prurigo nodularis, and decreased steadily from 0.53 to 0.42% in psoriasis; cumulative incidence was 0.1% for prurigo nodularis and 1.9% for psoriasis. Prevalence was 0.1% for prurigo nodularis and 4.7% for psoriasis, with a 1-year mortality of 5.4% for prurigo nodularis and 1.2% for psoriasis (p < 0.001). The most frequent pre-existing comorbidities in patients with prurigo nodularis were inflammatory dermatoses and depression. This epidemiological study found a low prevalence of prurigo nodularis, manifesting different demographics and comorbidities compared with psoriasis.

Treatment Patterns and Adherence to Guidelines for Uncomplicated Urinary Tract Infection in Germany: A Retrospective Cohort Study.

INTRODUCTION: Understanding antibiotic prescribing for uncomplicated urinary tract infection (uUTI) could help to optimize management. However, data on uUTI treatment patterns in the European Union are scarce. We used real-world data to evaluate adherence to antibiotic prescribing guidelines for femalepatients with uUTI in Germany. METHODS: This retrospective cohort study used anonymized German statutory health insurance claims data from the Wissenschaftliches Institut für Gesundheitsökonomie und Gesundheitssystemforschung from January 2013 to December 2019. Patients were female, aged ≥ 12 years, with an index uUTI diagnosis. Patient characteristics and treating physician specialties were examined overall and in sub-cohorts for recommended/non-recommended treatment (based on initial therapy adherence to German uUTI treatment guidelines) and optimal/sub-optimal outcome (based on a prescription of different antibiotics or a urinary tract infection-related episode). RESULTS: Overall, 144,645 uUTI cases in 124,971 patients were analyzed; 51,230 (35.4%) and 93,415 (64.6%) cases were assigned to the recommended/non-recommended treatment sub-cohorts, respectively. Clinically meaningful differences in age and comorbidities were observed between these sub-cohorts. Most cases had an optimal outcome (n = 122,823; 84.9%); of these, a higher proportion received antibiotics that were recommended but not as first-choice versus first-choice therapies as their initial treatment (58.6% vs. 35.3%). In the sub-optimal outcome cohort, 49.1% received antibiotics that were recommended but not as first-choice and 41.1% received first-choice therapies as their initial treatment. Most uUTIs were treated by general practitioners (GPs; 82.3%), followed by gynecologists (13.3%), and urologists (6.8%). Notably, 64.5% of initial therapy prescriptions filled by gynecologists and 32.1% by GPs were first-choice antibiotics. CONCLUSION: A high proportion of prescribed treatments for the initial uUTI episode were not recommended by German uUTI guidelines as first-choice antibiotics. Prescribing adherence varied by physician specialty; specialists showed greater adherence to treatment guidelines versus GPs. This study provides a novel and multi-dimensional picture of uUTI treatment in Germany.

Uncomplicated urinary tract infections are one of the most common infections in women. Doctors around the world use different types of antibiotics to treat people with uncomplicated urinary tract infections. We performed this study to find out more about how doctors in Germany use antibiotics to treat uncomplicated urinary tract infections. We looked at health records from female patients (aged 12+) in Germany. Overall, we examined 144,645 records. We found that around one in ten women use antibiotics to treat an uncomplicated urinary tract infection every year. We then checked to see if the doctors were giving people the right type of antibiotic, the right dose, and the right length of course. To do this, we checked against guidelines that were written by experts in Germany. We found that only one in three patients (35%) received treatment that met the guidelines. We also looked to see what differences there were between different types of doctors. For example, if general practitioners (family doctors) used different antibiotics to specialist doctors in hospitals. Four out of five patients (82%) were treated by general practitioners. We found that specialists were more likely to stick to the guidelines than general practitioners. Finally, we looked at how many patients recovered well after their first course of antibiotics. More than four out of five patients (80%) recovered well. Interestingly, more than half of the patients who had a good recovery (59%) received antibiotics that were not recommended by the guidelines.

Elucidating the risk of cardiopulmonary consequences of an exacerbation of COPD: results of the EXACOS-CV study in Germany.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) represent a period of vulnerability. This study explored the association between time periods following an exacerbation and the risk of severe cardiovascular (CV) events or death in Germany. METHODS: A longitudinal cohort study was conducted using routinely collected healthcare data. Individuals with COPD were identified between 2014 and 2018. Exposure was moderate or severe exacerbation of COPD. Periods at risk were the 1-7, 8-14, 15-30, 31-180 and 181-365 days following each exacerbation onset occurring after cohort entry. The main outcome of interest was the first hospitalisation for a CV event or all-cause death. Time-dependent Cox proportional hazards models estimated the HR for the association between subperiods versus periods outside exacerbations, and the risk of outcome. RESULTS: Among 126 795 patients, 58 720 (46.3%) exacerbated at least once and 48 982 (38.6%) experienced at least one CV event or died during a median follow-up of 36 months. The rate of outcome was increased during 1-7 days following a severe exacerbation onset (HR 15.84, 95% CI 15.26 to 16.45), and remained elevated for up to a year (181-365 days HR 1.17, 95% CI 1.11 to 1.23). In the 1-7 days following a moderate exacerbation onset, the increased rate was HR 1.17, 95% CI 1.05 to 1.31). CONCLUSION: The risk of a CV event or death increased in time periods following both moderate and severe exacerbations of COPD, emphasising the need to promptly manage the risk of CV events following the onset of an exacerbation, to prevent exacerbations of any severity, and more generally, to address the cardiopulmonary risk in patients with COPD.

Incidence of Lyme Borreliosis in Germany: A retrospective observational healthcare claims study.

Lyme borreliosis (LB) is the most common tick-borne disease in Germany. Although the incidence of LB in Germany has been assessed in several studies, those studies either used data from statutory surveillance, which frequently underreport cases, or data from health claims databases, which may overestimate cases due to non-specific LB case definitions. Here, using a more specific case definition, we describe the incidence of medically-attended LB by disease manifestation, age group, and federal state for the period 2015-2019. Both inpatient and outpatient cases were analyzed from a claims database. To be eligible for inclusion, patients were required to have an LB specific ICD-10 GM diagnosis code plus an antibiotic prescription, and for disseminated manifestations, a laboratory test order additionally. LB cases were classified as erythema migrans (EM), or disseminated disease including Lyme arthritis (LA), Lyme neuroborreliosis (LNB), and all other disease manifestations (OTH). Between 2015 and 2019, the incidence of medically-attended LB cases ranged from 195.7/100,000 population per year (95% confidence interval [CI], 191.0 - 200.5) to 254.5/100,000 population per year (95% CI, 249.0 - 260.0) per year. The majority of cases (92.2%) were EM, while 2.8% presented as LA, 3.8% as LNB, and 1.2% as OTH. For both EM and disseminated disease, the incidence peaked in children aged 5-9 years and in older adults. By federal state, the incidence of medically-attended EM ranged from 74.4/100,000 population per year (95% CI, 71.9 - 77.0) per year in Hamburg, to 394.1/100,000 population per year (95% CI, 370.7 - 417.6) per year in Saxony, whereas for medically-attended disseminated disease, the highest incidence was in Thuringia, Saxony, and Bavaria (range: 22.0 [95% CI, 19.9 - 24.0] to 35.7 [95% CI, 34.7 - 36.7] per 100,000 population per year). This study comprehensively estimated the incidence of all manifestations of medically-attended LB and showed a high incidence of LB throughout Germany. Results from the study support performing epidemiological studies in all federal states to measure the burden of LB and to invest in public health interventions for prevention.

Evaluation of Adherence and Persistence to Triple Therapy in Patients with COPD: A German Claims Data Study.

Purpose: Triple therapy (long-acting muscarinic antagonist/long-acting ß2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany. Patients and Methods: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year's continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence. Results: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users. Conclusion: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.

Respiratory syncytial virus immunization patterns in Germany, 2015-2020.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in infants and young children worldwide. Using routine statutory health insurance claims data including patients from all regions of Germany, we investigated the health-care resource use and costs associated with RSV prophylaxis with palivizumab in Germany. In the database, infants from the birth cohorts 2015-2019 eligible for palivizumab immunization were identified using codes of the 10th revision of the International Classification of Diseases (ICD-10). Health-care resource use and costs related to immunization were determined by inpatient and outpatient administrations. Over the study period, only 1.3% of infants received at least one dose of palivizumab in their first year of life. The mean number of doses per immunized infant was 4.6. From a third-party payer perspective, the mean costs of palivizumab per infant who received at least one dose in the first year of life was €5,435 in the birth cohorts 2015-2019. Despite the substantial risk of severe RSV infection, we found low rates of palivizumab utilization. Novel preventive interventions, featuring broader indications and single-dose administration per season, contribute to mitigating the burden of RSV disease across a more extensive infant population.

Impact of COPD on mortality: An 8-year observational retrospective healthcare claims database cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality. Here we present a large observational study on the association of COPD and exacerbations with mortality (AvoidEx Mortality). METHODS: A real-world, observational cohort study with longitudinal analyses of German healthcare claims data in patients ≥40 years of age with a COPD diagnosis from 2011 to 2018 (n = 250,723) was conducted. Patients entered the cohort (index date) upon the first COPD diagnosis. To assess the impact of COPD on all-cause death, a propensity score-matched control group of non-COPD patients was constructed. The number and severity of exacerbations during a 12-month pre-index period were used to form subgroups. For each exacerbation subgroup the exacerbations during 12 months prior to death were analysed. RESULTS: COPD increases the all-cause mortality risk by almost 60% (HR 1.57 (95% CI 1.55-1.59)) in comparison to matched non-COPD controls, when controlling for other baseline covariates. The cumulative risk of death after 8 years was highest in patients with a history of more than one moderate or severe exacerbation. Among all deceased COPD patients, 17.2% had experienced a severe, and 34.8% a moderate exacerbation, within 3 months preceding death. Despite increasing exacerbation rates towards death, more than the half of patients were not receiving any recommended pharmacological COPD therapy in the year before death. CONCLUSION: Our study illustrates the impact of COPD on mortality risk and highlights the need for consequent COPD management comprising exacerbation assessment and treatment.

Hyperkalemia-Related RAASi Reduction and Estimated Number Needed to Treat to Avoid a First Hospitalization by Maintaining RAASi.

BACKGROUND: Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy provides cardiorenal protection but is often down-titrated or discontinued following a hyperkalemia episode. This observational study describes the extent of hyperkalemia-related RAASi reduction in patients with chronic kidney disease (CKD) and/or heart failure (HF), and estimates the number needed to treat (NNT) to avoid a first hospitalization if RAASi had been maintained at the prior dose. METHODS: Healthcare registers and claims data from Germany, Spain, Sweden, and the UK were used to identify non-dialysis patients with CKD and/or HF who had a hyperkalemia episode while on RAASi. Patients whose RAASi therapy was reduced (down-titrated/discontinued) after the hyperkalemia episode were propensity score (PS)-matched to those with maintained RAASi, and their risks of a hospitalization within 6 months were estimated using the Kaplan-Meier method. Based on the absolute difference in this 6-month risk, the NNT framework was applied to estimate the number of patients who needed to have maintained instead of reduced their RAASi to avoid a first hospitalization during this period. RESULTS: Overall, 40,059 patients from Germany, Spain, Sweden, and the UK were included. Presence of CKD at baseline was similar across countries (72%-92%), while HF was less common in Spain (18%) versus other countries (32%-71%). After the hyperkalemia episode, RAASi was reduced in 25%-57% of patients. Following PS matching, the 6-month risk of hospitalization was consistently higher in those with reduced versus maintained RAASi; the absolute risk difference ranged from 2.7% to 7.3%. Applying the NNT framework, these data suggest that a first hospitalization within 6 months could potentially have been avoided if 25 patients had maintained instead of reduced their RAASi. CONCLUSIONS: Our findings suggest a potential for avoiding a first hospitalization, even within a short time frame, by increasing adherence to guidelines to maintain instead of reduce RAASi after a hyperkalemia episode.

Health Care for Inpatients with a Proximal Humeral Fracture - an Analysis of Health Insurance Data. / Versorgungsrealität stationär behandelter Patienten mit proximaler Humerusfraktur ­ Eine Analyse auf Basis von GKV-Daten.

The proximal humeral fracture is one of the most common fractures in the elderly. While epidemiological factors have been well studied, the influence of a proximal humeral fracture on morbidity, mortality and associated costs has not yet been adequately analysed.On a basis of 4.1 million insurance holders of the German public health insurance (GKV), patients with (study population, SP) and without (comparison group, VG) a proximal humeral fracture (pHF) were compared with regard to comorbidity, rehospitalisation, mortality, drug and aid needs as well as number of physician contacts. Study period was between 2012 and 2016.6068 patients of the SP met the inclusion and exclusion criteria (age 69.4 ± 14.3 years; male : female = 28.2% : 71.8%). 4781 patients (78.8%) received surgical, 1287 patients (21.2%) conservative treatment of the pHF. Rehospitalisations and visits to the general practitioner occurred more frequently in the SP vs. VG (p < 0.01). Contacts with specialists after pHF varied according to specialty, as did newly occurring diseases. Typical specialities for preventive examinations were significantly less common (gynaecology p < 0.01, pathology p < 0.01, dermatology p < 0.01). According to pHF, the costs of SP for drugs (2490.76 ± 1395.51 € vs. 2167.86 ± 1314.43 €; p = 0.04), medical therapies (867.01 ± 238.67 € vs. 393.26 ± 217.55 €; p < 0.01) and aids (821.02 ± 415.73 € vs. 513.52 ± 368.76 €; p < 0.01) were significantly above the VG. The two-year survival after pHF is lower in the SP than in the VG (p < 0.01).The results show increased morbidity and mortality as well as medical costs after a proximal humeral fracture. Preventive examinations and treatments are rarer. In the future, care concepts for patients with proximal humeral fractures should not only be optimised with regard to functional scores and reduced complication rates, but also with regard to quality of life and preservation of general health.

Pneumococcal vaccination rates in immunocompromised patients in Germany: A retrospective cohort study to assess sequential vaccination rates and changes over time.

BACKGROUND: Pneumococcal vaccination is recommended by the German Standing Committee on Vaccination (STIKO) for infants, elderly 60+ years and patients at risk. In 2016, a sequential pneumococcal vaccination schedule (conjugate vaccine followed by polysaccharide vaccine 6-12 months later) supplemented this recommendation for immunocompromised patients ≥2 years of age. Previous research showed low pneumococcal vaccination rates (pnc-VR) in this vulnerable group. Moreover, no evidence is available on adherence to the newer sequential schedule. This study aimed to analyze the development of pnc-VRs in immunocompromised patients and rates of sequential vaccinations according to the STIKO recommendations. METHODS: Using a representative health claims database, we assigned incident immunocompromised patients ≥2 years of age to one of two successive cohorts to observe trends over time: cohort A (first diagnosis of immunocompromised condition between 01/2013 and 12/2014), and cohort B (first diagnosis between 01/ 2015 and 12/2017). Pnc-VR within two years after first diagnosis and cumulative pnc-VR was compared among both cohorts. In cohort B, we assessed sequential pnc-VR within 15 months of the first vaccination. For additional analyses, patients were stratified by age, gender and immunocompromising condition. RESULTS: Cohort A and B comprised 193,521 and 289,279 patients, respectively. Overall pnc-VR increased over time from 4.3% (cohort A; 95%-confidence interval: 4.3%-4.4%) to 6.0% (cohort B; 5.9%-6.1%), with highest pnc-VRs in men ≥60 years (11.3%: 11.1%-11.6%) and HIV patients (15.2%: 13.1%-17.4%). Cumulative pnc-VRs in cohort B were higher in any quarter following diagnosis when compared with cohort A. Overall sequential pnc-VR in cohort B was 4.0% (3.7%-4.3%), with a higher rate observed in patients aged 16-59 (6.8%: 6.0%-7.7%) vs. patients aged ≥60 years (3.1%: 2.8%-3.4%). CONCLUSION: While some improvements were seen over time, pnc-VRs remain very low in immunocompromised patients, as did sequential vaccination rates. Current recommendations to protect immunocompromised patients from pneumococcal infections are not being sufficiently implemented.

Real-world effectiveness of osteoporosis treatments in Germany.

This observational study assessed the impact on the fracture incidence of osteoporosis medications in postmenopausal women in Germany. Continued treatment with osteoporosis medications was associated with reductions of fracture rates in a real-world setting. PURPOSE: The efficacy of osteoporosis medications has been demonstrated in clinical trials, but a lack of evidence exists of their real-world effectiveness. This real-world study assessed the treatment patterns and impact on the fracture incidence of osteoporosis medications in postmenopausal women in Germany. METHODS: This cohort study used data from the WIG2 benchmark database, a German anonymised healthcare claims database. All women ≥ 50 years of age with ≥ 1 prescription for osteoporosis medication between 1 January 2013 and 31 December 2017 were included. The primary outcome was treatment effectiveness, evaluated as the change in fracture incidence after initiating treatment. Fracture types included all fractures, clinical vertebral, hip and wrist/forearm. Fracture incidence was assessed during the early-treatment period (0-3 months) and the on-treatment period (4-12, 13-24, 25-36 and 37-48 months). RESULTS: Baseline covariates and treatment patterns were determined for 41,861 patients. The median duration of therapy was longer with denosumab (587 days) than with intravenous ibandronate (451 days), intravenous zoledronate (389 days) or oral bisphosphonates (258 days). The baseline incidence rate of all fractures was higher in patients receiving denosumab than in those receiving other treatments (87.6, 78.2, 56.6 and 66.0 per 1000 person-years for denosumab, oral bisphosphonates, intravenous ibandronate and intravenous zoledronate, respectively). Rates of all fractures declined with continued denosumab (by 38%, 50%, 56% and 67% at 12, 24, 36 and 48 months, respectively) and oral bisphosphonates (by 39%, 44%, 49% and 42%, respectively) treatment. CONCLUSION: Continued treatment with osteoporosis medications was associated with reductions of fracture rates in a real-world setting.

Machine learning-based identification of risk-factor signatures for undiagnosed atrial fibrillation in primary prevention and post-stroke in clinical practice.

AIMS: Atrial fibrillation (AF) carries a substantial risk of ischemic stroke and other complications, and estimates suggest that over a third of cases remain undiagnosed. AF detection is particularly pressing in stroke survivors. To tailor AF screening efforts, we explored German health claims data for routinely available predictors of incident AF in primary care and post-stroke using machine learning methods. METHODS AND RESULTS: We combined AF predictors in patients over 45 years of age using claims data in the InGef database (n = 1 476 391) for (i) incident AF and (ii) AF post-stroke, using machine learning techniques. Between 2013-2016, new-onset AF was diagnosed in 98 958 patients (6.7%). Published risk factors for AF including male sex, hypertension, heart failure, valvular heart disease, and chronic kidney disease were confirmed. Component-wise gradient boosting identified additional predictors for AF from ICD-codes available in ambulatory care. The area under the curve (AUC) of the final, condensed model consisting of 13 predictors, was 0.829 (95% confidence interval (CI) 0.826-0.833) in the internal validation, and 0.755 (95% CI 0.603-0.890) in a prospective validation cohort (n = 661). The AUC for post-stroke AF was of 0.67 (95% CI 0.651-0.689) in the internal validation data set, and 0.766 (95% CI 0.731-0.800) in the prospective clinical cohort. CONCLUSION: ICD-coded clinical variables selected by machine learning can improve the identification of patients at risk of newly diagnosed AF. Using this readily available, automatically coded information can target AF screening efforts to identify high-risk populations in primary care and stroke survivors.

Glycaemic variability is associated with all-cause mortality in COVID-19 patients with ARDS, a retrospective subcohort study.

There is high mortality among intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID-19). Important factors for COVID-19 mortality are diabetes status and elevated fasting plasma glucose (FPG). However, the effect of glycaemic variability on survival has not been explored in patients with COVID-19 and ARDS. This single-centre cohort study compared several metrics of glycaemic variability for goodness-of-fit in patients requiring mechanical ventilation due to COVID-19 ARDS in the ICU at University Hospital Aachen, Germany. 106 patients had moderate to severe ARDS (P/F ratio median [IQR]: 112 [87-148] mmHg). Continuous HRs showed a proportional increase in mortality risk with daily glycaemic variability (DGV). Multivariable unadjusted and adjusted Cox-models showed a statistically significant difference in mortality for DGV (HR: 1.02, (P) < 0.001, LR(P) < 0.001; HR: 1.016, (P) = 0.001, LR(P) < 0.001, respectively). Kaplan-Meier estimators yielded a shorter median survival (25 vs. 87 days) and a higher likelihood of death (75% vs. 31%) in patients with DGV ≥ 25.5 mg/dl (P < 0.0001). High glycaemic variability during ICU admission is associated with significant increase in all-cause mortality for patients admitted with COVID-19 ARDS to the ICU. This effect persisted even after adjustment for clinically predetermined confounders, including diabetes, median procalcitonin and FPG.

COPD Exacerbation History and Impact on Future Exacerbations - 8-Year Retrospective Observational Database Cohort Study from Germany.

Background: Recent studies evaluating the predictive value of different variables on future exacerbations suggest exacerbation history as the strongest predictor. We examined the effect of exacerbation history on subsequent events in a large sample population with over 250,000 COPD patients using up to 8 years of longitudinal healthcare data from Germany. Methods: Patients 40 years or older with any COPD diagnosis in primary or secondary care were included from 2011 to 2017 (index period) from healthcare insurance claims (Germany; WIG2 research database), with 12 months before index date as baseline and at least 12-month follow-up. Exacerbations during baseline were defined as moderate (treatment with oral corticosteroids or antibiotics, J01AA, J01CA) or severe (emergency visit or hospitalization). Results: Patients without (category A), with one moderate (category B), or with either one severe or several baseline exacerbations (category C) experienced an average of 0.9 (CI 0.9-0.9), 1.9 (CI 1.9-1.9), and 6.3 (CI 6.1-6.3) exacerbations during the first 3 years of follow-up, respectively. By 8 years, 87.0% (CI 86.6-87.4), 70.5% (CI 69.9-71.0) and 49.1% (CI 48.9-49.3) of category C, B and A patients had experienced a subsequent exacerbation. Conclusion: Baseline exacerbations increased the likelihood of, and reduced time to subsequent exacerbations. Even patients without baseline exacerbations experienced exacerbations within three years, emphasizing the importance of adequate treatment in patients with less severe disease presentation as well.

Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19.

BACKGROUND: Some patients with Corona Virus Disease 2019 (COVID-19) develop a severe clinical course with acute respiratory distress syndrome (ARDS) and fatal outcome. Clinical manifestations and biomarkers in early stages of disease with relevant predictive impact for outcomes remain largely unexplored. We aimed to identify parameters which are significantly different between subgroups. DESIGN: 125 patients with COVID-19 were analysed. Patients with ARDS (N = 59) or non-ARDS (N = 66) were compared, as well as fatal outcome versus survival in the two groups. KEY RESULTS: ARDS and non-ARDS patients did not differ with respect to comorbidities or medication on developing a fatal outcome versus survival. Body mass index was higher in patients with ARDS versus non-ARDS (p = 0.01), but not different within the groups in survivors versus non-survivors. Interleukin-6 levels on admission were higher in patients with ARDS compared to non-ARDS as well as in patients with fatal outcome versus survivors, whereas lymphocyte levels were lower in the different subgroups (all p<0.05). There was a highly significant 3.5-fold difference in fever load in non-survivors compared to survivors (p<0.0001). Extrapulmonary viral spread was detected more often in patients with fatal outcome compared to survivors (P = 0.01). Further the detection of SARS-CoV-2 in serum showed a significantly more severe course and an increased risk of death (both p<0.05). CONCLUSIONS: We have identified early risk markers for a severe clinical course, like ARDS or fatal outcome. This data might help develop a strategy to address new therapeutic options early in patients with COVID-19 and at high risk for fatal outcome.

[Retrospective SHI (Statutory Health Insurances) real-world study on initial GnRH antagonist and agonist therapy for advanced prostate cancer: prescription patterns and hospital costs in Germany]. / Retrospektive GKV-Versorgungsforschungsstudie über GnRH-Antagonisten/-Agonisten zur initialen Therapie des fortgeschrittenen Prostatakarzinoms ­ Verordnungsmuster und Krankenhauskosten in Deutschland.

INTRODUCTION: Androgen deprivation therapy (ADT) plays a pivotal role in the treatment of advanced or metastasised prostate cancer (PCa). The aim of this health services research was to compare real-world data on the initial use of different GnRH agonists and antagonists (GnRHa) with regard to prescription patterns, hospitalisation rates and costs. MATERIAL AND METHODS: Anonymised claims data from > 70 German health insurance funds between 2010 and 2015 (n = 4 205 227) were analysed (1 year pre-observation period, 1 index quarter with initial GnRHa prescription, ≥ 2 years of follow-up (FU)). RESULTS: The study population included 2382 PCa patients (mean age 75 years). Leuprolide (Leu) was prescribed most frequently (56.6 %). At initial GnRHa administration, 70 % of patients neither had lymph node nor distant metastases. Around 11.2 % of all patients stopped GnRHa treatment after the first prescription, 17.6 % switched their initial therapy to another substance after a mean of 457 days (median: 399 days); in the hybrid (hyb) group 100 days earlier on average than in the agonist group (p = 0.016). The prevalence ranking of the most common comorbidities was consistent over time: hypertension, hyperlipidaemia, cardiovascular disease (CVD) and diabetes. The prevalence of hypertension increased significantly in the agonist group (16.4 %) compared with the antagonist (6.9 %, p = 0.022) and hyb group (11.6 %, p = 0.006). With regard to CVD, there were no significant differences in the relative growth rate between the 3 combined therapy classes. In total, 23.9 % of all patients died within the 3-year FU. The mortality rate was lowest for triptorelin (Trp, 22.1 %) and highest for goserelin (Gos, 29.4 %, n.s.). In the index quarter, 26.4 % of patients had at least one inpatient hospitalisation [min-max: Trp 22.4 %; Gos 30.3 %], with an average length of hospital stay/patient of 3 days [Trp 2.4; Gos 4.5]. The annual hospitalisation rate was between 36.2 and 40.7 %, the average length of hospital stay in the entire FU was between 17.6 (Trp) and 20.8 days (hyb). The average hospital costs in the index quarter were approx. EUR 1200 [Trp 988; Gos 1803] and per FU year approx. EUR 3000. In the Trp cohort, total costs (index quarter + 3 years) were more than EUR 1000 below the average costs of EUR 9476 [Trp 8116; Leu 9779; n.s.]. CONCLUSION: This comparative retrospective analysis provides real-world information on initial GnRHa treatment for advanced prostate cancer, revealing differences in treatment patterns, hospitalisation rates and hospital costs in Germany.