Association between treatment and improvements in overall survival of patients with advanced/metastatic non-small cell lung cancer since 2011: A study in the United States, Canada, and Germany using retrospective real-world databases.

BACKGROUND: This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) in three countries between 2011 and 2020. METHODS: Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS. FINDINGS: We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months. CONCLUSIONS: Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation.

Myelofibrosis and anemia: A German claims data analysis to describe epidemiology and current treatment.

OBJECTIVES: There is limited data on the incidence, prevalence, and treatments for myelofibrosis (MF) in Germany. This retrospective study examined claims data from 3.3 million insured individuals, spanning from 2010 to 2021. METHODS: Four sensitivity scenarios were explored to identify cases of MF. Point prevalence and cumulative incidence of MF were determined as of December 31, 2021, and within 2021, respectively. A cross-sectional analysis used the main scenario definition of MF to identify cases and evaluate the period prevalence of patients receiving treatment for symptoms and/or splenomegaly, including first-line (1L) Janus kinase inhibitor (JAKi), second-line, or further (2L+) MF-related treatment therapies during 2021. The prevalence of anemia treatment was also reported. RESULTS: The estimated standardized point prevalence of MF on December 31, 2021, was 9.9-12.4 cases per 100 000 persons, and cumulative incidence in 2021 was 1.2-1.8 cases per 100 000 persons. Standardized period prevalence in 2021 for MF patients receiving 1L JAKi and/or 2L+ MF-related treatment was 4.0 cases per 100 000. Among these patients, 47.1%-53.7% required treatment for anemia, resulting in a period prevalence of 1.9-2.2 cases per 100 000 individuals. CONCLUSION: The data reveal gaps in MF treatments and the need to improve patient quality of life.

Assessing the performance of group-based trajectory modeling method to discover different patterns of medication adherence.

It is well known that medication adherence is critical to patient outcomes and can decrease patient mortality. The Pharmacy Quality Alliance (PQA) has recognized and identified medication adherence as an important indicator of medication-use quality. Hence, there is a need to use the right methods to assess medication adherence. The PQA has endorsed the proportion of days covered (PDC) as the primary method of measuring adherence. Although easy to calculate, the PDC has however several drawbacks as a method of measuring adherence. PDC is a deterministic approach that cannot capture the complexity of a dynamic phenomenon. Group-based trajectory modeling (GBTM) is increasingly proposed as an alternative to capture heterogeneity in medication adherence. The main goal of this paper is to demonstrate, through a simulation study, the ability of GBTM to capture treatment adherence when compared to its deterministic PDC analogue and to the nonparametric longitudinal K-means. A time-varying treatment was generated as a quadratic function of time, baseline, and time-varying covariates. Three trajectory models are considered combining a cat's cradle effect, and a rainbow effect. The performance of GBTM was compared to the PDC and longitudinal K-means using the absolute bias, the variance, the c-statistics, the relative bias, and the relative variance. For all explored scenarios, we find that GBTM performed better in capturing different patterns of medication adherence with lower relative bias and variance even under model misspecification than PDC and longitudinal K-means.

IQSEC2 disorder: A new disease entity or a Rett spectrum continuum?

IQSEC2 mutations are associated with IQSEC2-related intellectual disability (ID). Phenotypic spectrum has been better defined in the last few years by the increasing number of reported cases although the genotype-phenotype relationship for IQSEC2 remains overall complex. As for IQSEC2-related ID a wide phenotypic diversity has been described in Rett syndrome (RTT). Several patients harboring IQSEC2 mutations present with clinical symptoms similar to RTT and some cases meet most of the criteria for classic RTT. With the aim of establishing a genotype-phenotype correlation, we collected data of 16 patients harboring IQSEC2 point mutations (15 of them previously unreported) and of five novel patients carrying CNVs encompassing IQSEC2. Most of our patients surprisingly shared a moderate-to-mild phenotype. The similarities in the clinical course between our mild cases and patients with milder forms of atypical RTT reinforce the hypothesis that also IQSEC2 mutated patients may lay under the wide clinical spectrum of RTT and thus IQSEC2 should be considered in the differential diagnosis. Our data confirm that position, type of variant and gender are crucial for IQSEC2-associated phenotype delineation.

Burden of Staphylococcus aureus infections after orthopedic surgery in Germany.

BACKGROUND: This study assessed incidence, risk factors, and outcomes of Staphylococcus aureus infections (SAI) following endoprosthetic hip or knee, or spine surgeries. METHODS: Adult patients with at least one of the selected surgeries from 2012 to 2015 captured in a German sickness fund database were included. SAI were identified using S. aureus-specific ICD-10 codes. Patients with certain prior surgeries and infections were excluded. Cumulative incidence and incidence density of post-surgical SAI were assessed. Risk factors, mortality, healthcare resource utilization and direct costs were compared between SAI and non-SAI groups using multivariable analyses over the 1 year follow-up. RESULTS: Overall, 74,327 patients who underwent a knee (28.6%), hip (39.6%), or spine surgery (31.8%) were included. The majority were female (61.58%), with a mean age of 69.59 years and a mean Charlson Comorbidity Index (CCI) of 2.3. Overall, 1.92% of observed patients (20.20 SAI per 1000 person-years (PY)) experienced a SAI within 1 year of index hospitalization. Knee surgeries were associated with lower SAI risk compared with hip surgeries (Hazard Ratio (HR) = 0.8; p = 0.024), whereas spine surgeries did not differ significantly from hip surgeries. Compared with non-SAI group, the SAI group had on average 4.4 times the number of hospitalizations (3.1 vs. 0.7) and 7.7 times the number of hospital days (53.5 vs. 6.9) excluding the index hospitalization (p < 0.001). One year post-orthopedic mortality was 22.38% in the SAI and 5.31% in the non-SAI group (p < 0.001). The total medical costs were significantly higher in the SAI group compared to non-SAI group (42,834€ vs. 13,781€; p < 0.001). Adjusting for confounders, the SAI group had nearly 2 times the all-cause direct healthcare costs (exp(b) = 1.9; p < 0.001); and 1.72 times higher risk of death (HR = 1.72; p < 0.001). CONCLUSIONS: SAI risk after orthopedic surgeries persists and is associated with significant economic burden and risk of mortality. Hence, risk reduction and prevention methods are of utmost importance.

Comparison of the effect of membrane sizes and fibre arrangements of two membrane oxygenators on the inflammatory response, oxygenation and decarboxylation in a rat model of extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has gained widespread acceptance for the treatment of critically ill patients suffering from cardiac and/or respiratory failure. Various animal models have been developed to investigate the adverse effects induced by ECMO. Different membrane oxygenators have been used with varying priming volumes and membrane surfaces (Micro-1, small animal membrane oxygenator (SAMO)). METHODS: Sixteen male Lewis rats (350-400 g) were randomly assigned to receive ECMO with Micro-1 or SAMO (n = 8, respectively). Venoarterial ECMO was established after cannulation of the femoral artery and the jugular vein. The cardiac output was measured using a left-ventricular conductance catheter. The oxygen fraction of the ECMO was set to 1.0, 0.75, 0.5 and 0.21 after a stabilisation period of 15 min. Further, arterial blood gas analyses were performed at baseline, and during the first hour every 15 min after commencing the ECMO, and subsequently every 30 min. Dilutional anaemia was calculated using haemoglobin concentration at baseline, and 15 min after the start of ECMO therapy. Moreover, inflammation was determined by measuring tumour necrosis factor alpha, interleukin-6 and -10 at baseline and every 30 min. RESULTS: Animals of the Micro-1 group showed a significantly lower dilutional anaemia (ΔHaemoglobin t0 - t0.25: SAMO 6.3 [5.6-7.5] g/dl vs. Micro-1 5.6 [4.6-5.8] g/dl; p = 0.028). Further, significantly higher oxygen partial pressure was measured in the SAMO group, at an oxygen fraction of 0.75, 0.5 and 0.21 (380 [356-388] vs. 314 [263-352] mmHg, p = 0.002; 267 [249-273] mmHg vs. 197 [140-222] mmHg, p = 0.002; 87 [82-106] mmHg vs. 76 [60-79] mmHg, p = 0.021, respectively). However, no differences were found regarding the oxygen fraction of 1.0, in terms of carbon-dioxide partial pressure and cardiac output. Moreover, in the Micro-1 group tumour necrosis factor alpha was increased after 60 min and interleukin-6 after 120 min. CONCLUSION: While the dilutional anaemia was increased after commencing the ECMO, the oxygenation was augmented in the SAMO group. The inflammatory response was elevated in the Micro-1 group.

Primary data, claims data, and linked data in observational research: the case of COPD in Germany.

BACKGROUND: Real-world evidence (RWE) can inform patient management decisions, but RWE studies are associated with limitations. Linkage of different RWE data types could address such limitations by enriching data and improving scientific quality. Using the example of chronic obstructive pulmonary disease (COPD) in Germany, this study assessed the value of data linkage between primary and secondary data sources for RWE. METHODS: Post hoc analysis of data from an observational RWE study, which used prospectively collected data and data from an insurance claims database to assess treatment adherence and persistence in patients with COPD in Germany. Patient-level primary data were collected from the prospective observational study (primary dataset, N = 636), and claims data from the sickness fund AOK Nordost (claims dataset, N = 74,916). Primary and claims data were linked at a patient level using insurance numbers (linked dataset). Patients in the linked dataset were indexed at date of study inclusion for primary data and matched calendar date for claims data. Agreement between primary and claims data was examined for patients in the linked dataset based on comparisons between recorded sociodemographic data at index, comorbidities (primary: any recorded; claims: pre-index), prescriptions for COPD therapies (type and date) and exacerbations in the 12-month post-index period. RESULTS: The linked dataset included primary and claims data for 536 patients. Fewer comorbid patients were reported in primary data compared with claims data (p < 0.001), with overall agreement between 63.6% (hypertension) and 90.5% (osteoporosis). Number of prescriptions for COPD therapies per patient was lower in primary versus claims data (3.7 vs 10.3 prescriptions, respectively), with only 24.5% of prescriptions recorded in both datasets. Only 11.5% of exacerbations (moderate or severe) were recorded in both datasets, with 15.5% recorded only in primary data and 73.0% recorded only in claims data. CONCLUSION: Our study highlighted discrepancies between primary and claims data capture for this population of German patients with COPD, with lower reporting of comorbidities, COPD therapy prescriptions and exacerbations in primary versus claims data. Study findings suggest that data linkage of primary and claims data could provide enrichment and be useful in fully describing COPD endpoints.

Adaption and validation of the adherence barriers questionnaire for HIV patients on antiretroviral therapy (ABQ-HIV).

BACKGROUND: Despite substantial advances in antiretroviral therapy (ART) for human immunodeficiency virus (HIV) in the last decades, non-adherence (NA) continues to be a major challenge in the real-life treatment. To meet this challenge, adherence-promoting interventions with a tailored approach towards patient-specific adherence barriers that are identified using a reliable and practicable questionnaire are needed. The aim of this investigation was to develop and validate a respective questionnaire (Adherence Barriers Questionnaire for HIV: ABQ-HIV), based on an earlier version of the ABQ. METHODS: The existing ABQ was discussed by an expert panel and revised according to the specifications of ART therapy for HIV patients. Initially, the ABQ-HIV consisted of 17 items formulated as statements (4-point-Likert-scale ranging from "strongly agree" to "strongly disagree"). A higher score indicates a higher influence of a certain barrier on patient's perceptions. The ABQ-HIV was applied in a cross-sectional survey of German HIV patients. Evaluation of the questionnaire included an assessment of internal consistency as well as factor analysis. Convergent validity was assessed by comparing the ABQ-HIV score with the degree of self-reported adherence measured by the 8-item Morisky Medication Adherence Scale (MMAS-8©). RESULTS: Three hundred seventy patients were able to be included in all validation analyses. The included patients had a mean age of 51.2 years, and 15.7% were female. The mean HIV infection time was 11.7 years, and the mean duration of treatment since first starting ART was 8.7 years. Twenty-five patients - excluded from all further analyses - were not able/willing to answer all ABQ-HIV questions. The results of the reliability analysis showed a Cronbach's α of 0.708 for the initial 17-items in the ABQ-HIV draft. Two items were eliminated from the initial questionnaire, resulting in a Cronbach's α of 0.720 and a split-half reliability of 0.724 (Spearman-Brown coefficient). Based on the reduced 15-item scale, the factor analysis resulted in three different components of the questionnaire. Component 1, with seven items, represents the unintentional adherence barriers. The second component, which contains five items, can be labelled as a subscale describing barriers associated with disease/treatment knowledge. Finally, three items, which can be summarized as intentional adherence barriers, show maximum loading in the third component. The score of the reduced 15-item ABQ-HIV scale, as well as the scores of the three subscales, correlated significantly with the MMAS score. All correlation coefficients were negative, indicating that higher burdens of adherence barriers measured by ABQ-HIV or its subscales were associated with a lower MMAS score and thus, with a lower adherence level. The ROC analysis using the MMAS low adherence classification as its state variable provided a cut-off for the ABQ-HIV scale of > 28 (sensitivity: 61.5%, specificity: 83.3%). In our sample, 85 patients (23.0%) reached a score of > 28 and appeared to face a high non-adherence risk. CONCLUSIONS: The ABQ-HIV is a practical, reliable, and valid instrument for identifying patient-specific barriers to adherence in the HIV treatment. It is also useful in identifying HIV patient subgroups, according to adherence barriers specific to these patients.

Drug survival of second biological DMARD therapy in patients with rheumatoid arthritis: a retrospective non-interventional cohort analysis.

BACKGROUND: Since persistence to first biological disease modifying anti-rheumatic drugs (bDMARDs) is far from ideal in rheumatoid arthritis (RA) patients, many do receive a second and/or third bDMARD treatment. However, little is known about treatment persistence of the second-line bDMARD and it is specifically unknown whether the mode of action of such a treatment is associated with different persistence rates. We aimed to assess discontinuation-, re-initiation- or continuation-rates of a 2nd bDMARD therapy as well as switching-rates to a third biological DMARD (3rd bDMARD) therapy in RA patients. METHOD: Analysis was based on German claims data (2010-2013). Patients were included if they had received at least one prescription for an anti-TNF and at least one follow-up prescription of a 2nd bDMARD different from the first anti-TNF. Patient follow-up started on the date of the first prescription for the 2nd bDMARD and lasted for 12 months or until a patient's death. RESULTS: 2667 RA patients received at least one anti-TNF prescription. Of these, 451 patients received a second bDMARD (340 anti-TNF, mean age 52.6 years; 111 non-anti-TNF, mean age 55.9 years). During the follow-up, 28.8% vs. 11.7% of the 2nd anti-TNF vs. non-anti-TNF patients (p < 0.001) switched to a 3rd bDMARD; 14.1% vs. 19.8% (p = 0.179) discontinued without re-start; 3.8% vs.1.8% (p = 0.387) re-started and 53.5 vs. 66.7% (p < 0.050) continued therapy. Patients in the non-anti-TNF group demonstrated longer drug survival (295 days) than patients in the anti-TNF group (264 days; p = 0.016). Independent variables associated with earlier discontinuation (including re-start) or switch were prescription of an anti-TNF as 2nd bDMARD (HR = 1.512) and a higher comorbidity level (CCI, HR = 1.112), whereas previous painkiller medication (HR = 0.629) was associated with later discontinuation or switch. CONCLUSIONS: Only 56.8% of RA patients continued 2nd bDMARD treatment after 12 months; 60% if re-start was included. Non-anti-TNF patients had a higher probability of continuing 2nd bDMARD therapy.

Patient Preferences in the Treatment of Neovascular Age-Related Macular Degeneration: A Discrete Choice Experiment.

PURPOSE: The objective of our study was to investigate preferences of patients with neovascular age-related macular degeneration (nAMD) for different anti-vascular endothelial growth factor (VEGF) treatment schemes. DESIGN: We used a discrete choice experiment (DCE) design as part of a telephone interview. PARTICIPANTS: Patients with nAMD aged at least 50 years were included in the study. METHODS: Telephone interviews were done between November 2012 and October 2013. MAIN OUTCOME MEASURES: In our DCE survey, we measured patient preferences toward specific levels of attributes that describe different options in the everyday intravitreal injection treatment setting: (1) treatment scheme; (2) change of visual acuity (VA); and (3) time the patient needs for each visit to the eye specialist. RESULTS: A total of 284 patients with nAMD with a mean age of 77.4±7.1 years (women: 59.9%) completed the DCE interviews. Of them, 22.9% had poor VA at study inclusion, 54.9% had moderate VA, and 14.1% had good VA; VA was not available for 8.1% of the patients. Generally, patients preferred the attribute levels "improvement in VA" and "short time per specialist visit." The results for the attribute "treatment scheme" were inconclusive because none of the attribute levels (injections every 4 weeks, every 8 weeks, and pro re nata) were associated with statistically significant utility differences. This also mirrors the relative importance of the different attributes in patient decisions: "Change of VA" influenced decision making for a treatment option in 73.6% of cases; "waiting, treatment, and travel time" influenced decision making in 21.0% of cases; and "treatment scheme" influenced decision making for a treatment option in 5.4% of cases. To obtain improved VA instead of a worsening VA, patients in our study stated to be willing to accept a very long time needed per physician visit of 21.2 hours (8.5 hours for improved rather than stable VA and 12.7 hours for stable VA rather than worsening VA). CONCLUSIONS: To prevent deterioration of VA, patients with nAMD seem to be willing to accept a high treatment burden with regular intravitreal injections at short intervals and long periods of waiting, treatment, and traveling for their consultations.

Treatment-dependent and treatment-independent risk factors associated with the risk of diabetes-related events: a retrospective analysis based on 229,042 patients with type 2 diabetes mellitus.

BACKGROUND: The aim of this study was to analyse which factors predict the real-world macro-/microvascular event, hospitalisation and death risk in patients with type 2 diabetes mellitus. Furthermore, we aimed to investigate whether there exists both an under- and over-treatment risk of these patients. METHODS: We used a German claims/clinical data set covering the years 2010-12. Diabetes-related events were defined as (1) macro-, (2) microvascular events leading to inpatient hospitalisation, (3) other hospitalisations with type 2 diabetes mellitus as main diagnosis, (4) all-cause death and (5) a composite outcome including all event categories 1-4. Factors associated with event risk were analysed by a Kaplan-Meier curve analysis and by multivariable Cox regression models. RESULTS: 229,042 patients with type 2 diabetes mellitus (mean age 70.2 years; mean CCI 6.03) were included. Among factors that increased the event risk were patients' age, male gender, the adapted Charlson Comorbidity Index, the adapted Diabetes Complication Severity Index, previous events, and number of prescribed chronic medications. For systolic blood pressure/HbA1C, a double-J/U-curve pattern was detected: HbA1C of 6-6.5% (42-48 mmol/mol) and systolic blood pressure of 130-140 mmHg (17.3-18.7kPa) were associated with the lowest event risk, values below/above that range were associated with higher risk. However, this pattern was mainly driven by the death risk and was much less clearly observed for the macrovascular/microvascular/hospitalization risk and for young/less comorbid patients. CONCLUSIONS: Both blood pressure and HbA1C seem to be very important treatment targets, especially in comorbid old patients. It is of particular clinical importance that both over- and under-treatment pose a threat to patients with type 2 diabetes mellitus.

Adaptation and validation of the Adherence Barriers Questionnaire for HIV Patients on Antiretroviral Therapy (ABQ-HIV) for the Brazilian context.

Despite significant advancements in antiretroviral therapy (ART) for HIV, adherence remains a challenge. While Brazil has validated scales for treatment adherence, few assess treatment adherence barriers. This underscores the necessity for validated questionnaires on adherence barriers to identify patient-specific challenges and enhance strategies for ART adherence. This study aimed to adapt and validate the Adherence Barriers Questionnaire for HIV Patients on Antiretroviral Therapy (ABQ-HIV), a 17-item questionnaire assessing the adherence barriers to ART, for the Brazilian context and to evaluate its psychometric properties in HIV patients. A methodological study on the psychometric properties and factorial structure of ABQ-HIV was conducted. The study followed seven steps: consent of the original authors, two translations, synthesis of the translations, expert committee, back-translation, pre-test, and reliability test. A high content validity index (0.93) was achieved with the expert committee. The study sample consisted of 230 adults with HIV, with 37.0 (29.3-45.0) years as the median age (IQR), and 52.2% were male. The exploratory factor analysis with a three subscales structure of 17 items showed good interpretability (Bartlett's sphericity (1167.2 [136]; p < 0.001) and Kaiser-Meyer-Olkin = 0.602) and internal consistency (α = 0.76; Ω = 0.76). The fit indicators were satisfactory (χ2 = 89.931; df = 88; p > 0.005; RMSEA = 0.010; RMSR = 0.07; CFI = 0.996; GFI = 0.940; AGFI = 0.907; NNFI = 0.995). The Brazilian version of ABQ-HIV is a potential instrument for identifying specific barriers to adherence to ART in adults living with HIV in Brazil.

Switching within versus out of class following first-line TNFi failure in ulcerative colitis: real-world outcomes from a German claims data analysis.

Background: Biologic agents have demonstrated efficacy in treating ulcerative colitis (UC); however, treatment failure to tumor necrosis factor inhibitors (TNFi) is common in the real world. Data on preferential sequencing in clinical practice after failure remain limited. Objectives: This study aimed to evaluate real-world outcomes of patients cycling to TNFis or switching to non-TNFi biologics following first-line failure with TNFis. Design: Retrospective cohort study in Germany. Methods: Adult patients with UC were identified using administrative claims data from 1 May 2014 to 30 June 2022 provided by a statutory sickness fund. Patients newly initiating first-line therapy with TNFis and then switching to another agent were identified. Patients were defined as within-class switched (WCS), if they cycled to another TNFi, or outside-class switchers (OCS), if they switched to a non-TNFi biologic [ustekinumab (UST) or vedolizumab (VDZ)] and followed from index (switch date) to death, insurance end, or study end on 30 June 2022. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline characteristics between groups, and weighted Cox regression models were used to compare primary (time to discontinuation and second treatment switch) and secondary outcomes (corticosteroid-free drug survival). Results: We identified 166 patients initiating TNFis and switching to a subsequent treatment (mean age: 42.9 years, 49.4% female). Following IPTW, there were 71 and 76 patients in the WCS and OCS groups, respectively. Compared to OCS, WCS were more likely to discontinue the new therapy [hazard ratio (HR), 1.82, 95% confidence interval (CI), 1.14-2.89, p = 0.012], and switch a second time (HR, 3.46, 95% CI, 1.89-6.36, p < 0.001). Moreover, WCS showed an increased likelihood of initiating prolonged corticosteroid therapy (HR, 1.42, 95% CI, 0.77-2.59, p = 0.260); however, the results were not significant. Conclusion: Following first-line TNFi failure, this study suggests that real-world outcomes among patients with UC are less favorable when cycling to another TNFi, compared to switching to a non-TNFi such as UST or VDZ.

Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients.

AIMS: Based on an analysis of claims-based data of 8.298 million members of two German statutory health insurance funds, the aim of this contribution is to quantify age-/gender-specific prevalence/incidence of atrial fibrillation (AF) in a German setting. METHODS AND RESULTS: Patients were classified as AF prevalent, if they had received at least two outpatient diagnoses of AF (ICD10-Code I48.1-) in two different quarters of the year and/or had received at least one main AF diagnosis during inpatient treatment between 1 January 2007 and 12 December 2008. They were considered to have had new onset AF in 2008 under the following conditions; first, there was no AF diagnosis in 2007; secondly, patients had not received oral anticoagulant medication in 2007; and thirdly, patients had received either one inpatient/two outpatient diagnoses of AF in 2008. In our sample, a total of 176 891 patients had AF. AF prevalence was 2.132%. The average age of these AF patients was 73.1 years, and 55.5% (98 190 patients) were male. The incidence of AF in our sample was 4.358 cases/1000 person-years in men and 3.868 cases/1000 person-years in women. CONCLUSION: A comparison of the distribution of AF prevalence/incidence in our population with that in already published studies showed that our figures were higher, especially in the age groups above 70 years. Our data show that in a large industrial nation such as Germany care provision structures are going to be challenged by a requirement to treat more AF patients in the future.

Association between asthma control and healthcare costs: Results from a German linked data study.

Background: This study aimed to evaluate differences in healthcare resource utilization and cost among patients with controlled and uncontrolled asthma.Methods: Claims data from a German sickness fund was linked to patient survey data. Outpatient physicians enrolled patients and assessed asthma control using the ACTTM questionnaire. All-cause and asthma-specific healthcare resource use (HCRU)/costs were compared descriptively and based on multivariable models using a continuous ACTTM score.Results: Overall, 492 asthma patients were included (mean age: 53.8, 73.8% female). The mean/median ACTTM score was 19.9/20.7, with 183 patients (37.2%) classified as having uncontrolled asthma (mean ACTTM score<20) Patients with uncontrolled asthma had significantly more hospitalizations (p = .035) and medication prescriptions (p < .001), which resulted in higher total healthcare costs for asthma-related (€1785 vs. €1615; p = .004) and all-cause care (€4695 vs. €4117; p = .009). While controlling for baseline characteristics, multivariable models confirmed a negative association between asthma control and total all-cause healthcare costs (p = .008), total asthma-related costs (p = .008), and costs of medication prescriptions (p = .001). However, no significant association was found for all-cause (p = .062) and asthma-related hospitalization costs (p = .576).Conclusion: Considering continuous patient care, improving asthma control is not only desirable from a clinical perspective, but could also be an effective approach to reduce asthma-related HCRU and cost burden.

Everolimus in combination with cyclosporin a as pre- and posttransplantation immunosuppressive therapy in nonmyeloablative allogeneic hematopoietic stem cell transplantation.

Everolimus (RAD001) is an mTOR inhibitor that has been successfully used as an immunosuppressant in solid-organ transplantation. Data in allogeneic hematopoietic stem cell transplantation (HSCT) is limited. This study aimed to investigate pharmacokinetics, safety, and efficacy of RAD001 in a canine allogeneic HSCT model. First, pharmacokinetics of RAD001 were performed in healthy dogs in order to determine the appropriate dosing. Doses of 0.25 mg RAD001 twice daily in combination with 15 mg/kg cyclosporin A (CsA) twice daily were identified as appropriate starting doses to achieve the targeted range of RAD001 (3-8 µg/L) when orally administered. Subsequently, 10 dogs were transplanted using 2 Gy total body irradiation (TBI) for conditioning and 0.25 mg RAD001 twice daily plus 15 mg/kg CsA twice daily for pre- and posttransplantation immunosuppression. Seven of the 10 transplanted dogs were maintained at the starting RAD001 dose throughout the study. For the remaining 3 dogs, dose adjustments were necessary. RAD001 accumulation over time did not occur. All dogs initially engrafted. Five dogs eventually rejected the graft (weeks 10, 10, 13, 27, and 56). Two dogs died of pneumonia (weeks 8 and 72) but were chimeric until then. Total cholesterol rose from median 4.1 mmol/L (3.5-5.7 mmol/L) before HSCT to 6.0 mmol/l (5.0-8.5 mmol/l) at day 21 after HSCT, but remained always within normal range. Changes in creatinine and triglyceride values were not observed. Long-term engraftment rates were inferior to sirolimus/CsA and mycophenolate mofetil (MMF)/CsA regimen, respectively. RAD001/CsA caused a more pronounced reduction of platelet counts to median 2 × 10(9)/L (range: 0-21 × 10(9)/L) and longer time to platelet recovery of 21 days (range: 14-24 days) compared with MMF/CsA. CsA c(2h) levels were significantly enhanced in the RAD001/CsA regimen, but c(0h) and area under the curve from 0 to 12 hours (AUC(0-12h)) values did not differ compared with an MMF/CsA immunosuppression. In summary, immunosuppression consisting of RAD001 and CsA is well tolerated but not as efficient as with other established immunosuppressants in a canine nonmyeloablative HSCT regimen. Hence, our study does not support the application of RAD001/CsA as standard practice in this setting.

Are head cues necessary for goats (Capra hircus) in recognising group members?

In this study, we investigated whether goats can distinguish a member of their own group from one belonging to a different group even when the head of the goat in question cannot be seen. In the experiment, a total of 45 adult female goats (walkers) were trained to walk along a passageway at the end of which they learnt to expect food (trial run). Walking down this corridor, they passed another adult female goat (stimulus goat) whose trunk and hind legs alone were visible. Using 19 individuals, ten pairs of stimulus goats consisting of one goat from the walker's group and one from a different group were matched in terms of body size, constitution, colour and coat length. In addition, the stimulus goat from the same group as the walker had to be higher ranking than the latter to avoid being attacked. The walkers completed two, four or six trial runs depending on the number of pairs suitable for a given walker. The walker's exploratory behaviour (observing and sniffing at the stimulus goat) was recorded. Data from 109 trial runs were analysed using generalised linear mixed-effects models with crossed random effects. On average, the walker spent a total of 8.7 s exploring the stimulus goat visually and olfactorily if the latter was from a different group and only about half as long (4.2 s) if it was from her own group. In particular, the time a walker spent observing a stimulus goat whilst approaching the latter was significantly longer if the stimulus goat belonged to a different group than to her own (2.5 s as opposed to 1.4 s). Moreover, a stimulus goat from a different group was sniffed at significantly longer (4.6 s) than one from the same group (1.9 s). Results suggest that goats can easily discriminate between members of their own group and those of a different group even when the latter's heads are hidden. Olfactory and visual cues are probably important for identifying group members.

Hospitalized with stroke at the weekend: Higher cost and risk of early death?

OBJECTIVES: Previous studies have shown that weekend hospitalizations are associated with poorer health outcomes and higher mortality ("weekend effect"). However, few of these studies have adjusted for disease severity and little is known about the effect on costs. This work investigates the weekend effect and its costs for patients with cerebral infarction in Germany, adjusting for patient characteristics and proxies of stroke severity. METHODS: Adult patients with a cerebral infarction hospitalization 10th revision of the International statistical classification of diseases and related health problems (ICD-10: I63) between 01 January 2014 and 30 June 2017 were included from German health claims (AOK PLUS dataset). Propensity score matching was used to match patients hospitalized on weekends or on public holidays (weekend group) with patients hospitalized during the working week (workday group), based on baseline characteristics and proxies for disease severity such as concomitant diagnoses of aphasia, ataxia, and coma, or peg tube at index hospitalization. Matched cohorts were compared in terms of in-hospital, 7-day, and 30-day mortality, as well as risk and costs of stroke and rehabilitation stays in the year after first stroke. RESULTS: Of 32,311 patients hospitalized with cerebral infarction between 01 January 2014 and 30 June 2017, 8409 were in the weekend group and 23,902 in the workday group. After propensity score matching, 16,730 patients were included in our study (8365 per group). Matched cohorts did not differ in baseline characteristics or stroke severity. In the weekend group, the risk of in-hospital death (11.2%) and the seven-day mortality rate (6.8%) were 13.1% and 17.2% higher than in the workday group, respectively (both p < 0.01). The hazard ratio for death in the weekend group was 1.1 (p = 0.043). The risks of subsequent stroke hospitalization and rehabilitation stays for a stroke were 8.4% higher and 5.5% higher in the weekend group (both p = 0.02). As a result, the stroke-related hospitalization and rehabilitation costs per patient year were, respectively, 5.6% and 8.0% higher in the weekend group (both p = 0.01). CONCLUSIONS: A significant weekend effect emerged after controlling for observable patient characteristics and proxies of stroke severity. This effect also resulted in higher costs for patients admitted on weekends.

Effects of Single Pill Combinations Compared to Identical Multi Pill Therapy on Outcomes in Hypertension, Dyslipidemia and Secondary Cardiovascular Prevention: The START-Study.

AIM: Current guidelines for the treatment of arterial hypertension (AH) or cardiovascular (CV) prevention recommend combination drug treatments with single pill combinations (SPC) to improve adherence to treatment. We aimed to assess whether the SPC concept is clinically superior to multi pill combination (MPC) with identical drugs. METHODS AND RESULTS: In an explorative study, we analyzed anonymized claims data sets of patients treated with CV drugs for hypertension and/or CV disorders who were insured by the German AOK PLUS statutory health fund covering 01/07/2012-30/06/2018. Patients at age ≥18 years who received either a SPC or MPC with identical drugs were followed for up to one year. A one to one propensity score matching (PSM) was applied within patient groups who started identical drug combinations, and results were reported as incidence rate ratios (IRRs) as well as hazard ratios (HRs). After PSM, data from 59,336 patients were analyzed. In 30 out of 56 IRR analyses, superiority of SPC over MPC was shown. In 5 out of 7 comparisons, the HR for the composite outcome of all-cause death and all-cause hospitalizations was in favor of the SPC regimen (SPC versus MPC): valsartan/amlodipine: HR=0.87 (95% CI: 0.84-0.91, p ≤ 0.001); candesartan/amlodipine: 0.77 (95% CI: 0.65-0.90, p = 0.001); valsartan/amlodipine/hydrochlorothiazide: HR=0.68 (95% CI: 0.61-0.74, p ≤ 0.001); ramipril/amlodipine: HR=0.80 (95% CI: 0.77-0.83, p ≤ 0.001); acetylsalicylic acid (ASA)/atorvastatin/ramipril: HR=0.64 (95% CI: 0.47-0.88, p = 0.005). CONCLUSION: SPC regimens are associated with a lower incidence of CV events and lower all-cause mortality in clinical practice. SPC regimens should generally be preferred to improve patient's prognosis.

Diabetes-Related Effectiveness and Cost of Liraglutide or Insulin in German Patients with Type 2 Diabetes: A 5-Year Retrospective Claims Analysis.

INTRODUCTION: Liraglutide is a glucagon-like peptide-1 analogue used to treat type 2 diabetes mellitus (T2DM). To date, limited long-term data (> 2 years) exist comparing real-world diabetes-related effectiveness and costs for liraglutide versus insulin treatment. METHODS: This retrospective claims data analysis covered the period from 1 January 2010 to 31 December 2017 and included continuously insured patients with T2DM who initiated insulin or liraglutide and had 3.5 or 5 years' follow-up data, identified using the German AOK PLUS dataset. Propensity score matching (PSM) was used to adjust for patient characteristics. RESULTS: After PSM, there were 825 and 436 patients in the liraglutide and insulin groups at 3.5 and 5 years' follow-up, respectively. Baseline characteristics were similar between compared cohorts. The respective change from baseline to follow-up in mean glycated haemoglobin for liraglutide and insulin patients was - 0.88% and - 0.81% (p > 0.100) after 3.5 years and - 1.15%/ - 1.02% (p > 0.100) after 5 years. Mean respective changes in body mass index (kg/m2) were - 1.21/+ 1.14 (p < 0.001) after 3.5 years and - 1.29/+ 1.13 after 5 years (p < 0.001). Liraglutide- versus insulin-treated patients were less likely to have an early T2DM-related hospitalisation (3.5-year hazard ratio [HR]: 0.414 [95% confidence interval (CI) 0.263-0.651]; 5-year HR: 0.448 [95% CI 0.286-0.701]). At 5 years' follow-up, there was no statistically significant difference in total direct costs between treatment groups (cost ratio: 1.069 [95% CI 0.98-1.13]; p > 0.100). CONCLUSION: The clinical effectiveness of liraglutide is maintained long term (up to 5 years). Liraglutide treatment is not associated with higher total direct healthcare costs.