Safety and survival of docetaxel and cabazitaxel in metastatic castration-resistant prostate cancer

Objectives: To investigate real-world haematological toxicity, overall survival (OS) and the treatment characteristics of docetaxel and cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods: This retrospective claims data study followed patients with mCRPC receiving cabazitaxel or docetaxel from their first chemotherapy infusion. Haematological toxicities were measured using treatment codes and inpatient diagnoses. OS was estimated using the Kaplan–Meier method. A multivariable Cox regression analysis was used to identify OS predictors. Results: Data from 539 patients administered docetaxel and 240 administered cabazitaxel were analysed. Regarding adverse events, within 8 months of treatment initiation, some kind of treatment for haematological toxicity was documented in 31% of patients given docetaxel and in 61% of patients given cabazitaxel. In the same period, hospitalization associated with haematological toxicity was documented in 11% of the patients in the docetaxel cohort and in 15% of the patients in the cabazitaxel cohort. In the docetaxel cohort, 9.9% of patients required reverse isolation and 13% were diagnosed with sepsis during hospitalization. In the cabazitaxel cohort, the cumulative incidence was 7.9% and 15%, respectively. The median OS was reached at 21.9 months in the docetaxel cohort and, because of a later line of therapy, at 11.3 months in the cabazitaxel cohort. A multivariate Cox regression revealed that indicators of locally advanced and metastatic disease, severe comorbidities, and prior hormonal/cytotoxic therapies were independent predictors of early death. Conclusion: Cabazitaxel patients face an increased risk of haematological toxicities during treatment. Together with their short survival time, this calls for a strict indication when using cabazitaxel in patients with mCRPC. © 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International

Treatment-Related Healthcare Costs of Metastatic Castration-Resistant Prostate Cancer in Germany: A Claims Data Study

Purpose: Treatments for patients with metastatic castration-resistant prostate cancer (mCRPC) have expanded rapidly. They include the chemotherapies docetaxel and cabazitaxel, hormonal drugs abiraterone and enzalutamide, and best supportive care (BSC). Cabazitaxel has proven to be the last life-prolonging option, associated with a significant risk of serious adverse events. Given the lack of real-world evidence, we aimed to compare healthcare resource utilization (HRU) and costs in patients with mCRPC treated with cabazitaxel, docetaxel, abiraterone, enzalutamide, and BSC. Methods: We used 2014–2017 claims data from a large German statutory health insurance fund, the Techniker Krankenkasse, to identify patients with mCRPC. Patient allocation to individual therapy regimens was based on clinical knowledge and included therapy cycles, duration of therapy, and continuous treatment. The study period lasted from the first claim until death, the end of data availability, a drug switch, or discontinuation of therapy, whichever came first. Multivariate regression models were used to compare monthly all-cause and mCRPC-related HRU and costs across cohorts by adjusting for baseline covariates (including age and comorbidities). Results: The 3944 identified patients with mCRPC initiated treatment with cabazitaxel (n = 240), docetaxel (n = 539), abiraterone (n = 486), enzalutamide (n = 351), or BSC (n = 2328). In most domains, HRU was highest in the cabazitaxel cohort and lowest in the BSC group. Accordingly, the highest all-cause and mCRPC-related costs per month, respectively, were observed in patients receiving cabazitaxel (€7631/€6343), followed by abiraterone (€5226/€4579), enzalutamide (€5079/€4416), docetaxel (€2392/€1580), and BSC (€959/€438). Cost variations were mostly attributable to drugs, inpatient treatment, and sick leave payments. Conclusion: mCRPC treatment imposes a high economic burden on statutory health insurance. Cabazitaxel is associated with substantially higher expenses, resulting from higher drug costs and a greater need for inpatient treatment. As mCRPC continues to be incurable, decision makers and clinician leaders should carefully evaluate public access to innovative agents and optimal treatment strategies

Use of guideline-recommended drug therapy in patients undergoing percutaneous coronary intervention for stable coronary heart disease in Germany: a multilevel analysis of nationwide routine data

Objectives: To determine the prescription of guideline recommended drug therapy in patients with stable coronary heart disease (sCHD) prior to percutaneous coronary intervention (PCI) in Germany and to examine the role of patient characteristics and features of regional healthcare supply in a multilevel model. Design Secondary data analysis of factors associated with the prescription of guideline recommended drug therapy using a multilevel model to analyse regional-level effects, over and above the effects of patient-level demographic and health status. Setting Office-based prescriptions in the year prior to the invasive procedure. Participants A linked nationwide dataset from Germany's three largest statutory health insurance funds of all patients receiving PCI in the year 2016. Main outcome measures Patients' odds of receiving optimal medical therapy and symptom-oriented therapy within 1 year prior to PCI. Results 68.6% of patients received at least one lipid-lowering drug and one symptom-oriented therapy prior to PCI. 43.6% received at least two agents to control their symptoms. Patients who received treatment in accordance with the recommendations had a greater number of diagnosed risk factors, a more severe history of cardiac disease and used a higher volume of ambulatory office-based physician services. The prescriptions prevalence for the symptom-oriented therapies differed significantly between eastern and western Germany, with a higher prevalence in the eastern districts. Conclusions: Guidelines can only provide decision-making corridors, and the applicability of recommendations must always be assessed on a case by case basis. Nevertheless, our analysis indicates that the prevalence of prescriptions in routine practice is subject to substantial variation and that conservative therapy options are not fully exhausted prior to PCI. This suggests that there might be room for improvement in the care of patients with sCHD

Health literacy in patients with pulmonary embolism: development and validation of the HeLP (Health Literacy in Pulmonary Embolism)-Questionnaire

Background: Pulmonary embolism (PE) is a common cardiovascular disease and health literacy is necessary to deal with its consequences after the acute event. The aim of this study was to develop and validate a new questionnaire to measure PE-specific health literacy. Methods: A mixed-methods design with qualitative and quantitative elements was used in the development process. A literature review about health literacy concepts and instruments and interviews with patients with PE and clinicians were conducted. Quantitative analyses included factor analyses, item response theory with a graded partial credit model, and reliability analyses in different test and validation samples. Furthermore, convergent and known-groups validity and responsiveness were assessed. Results: The qualitative results supported a concept of PE-related health literacy with four main topics: dealing with PE-related health information, disease management, health-related selfcare, and social support. An initial item pool of 91 items was developed. Further interviews and an online survey with patients with PE (n = 1,013) were used to reduce the number of items and to confirm structural validity. Confirmatory factor analyses in the final evaluation study with patients with PE (n = 238) indicated a good model fit of the four-factor structure. The Health Literacy in Pulmonary Embolism (HeLP)-Questionnaire showed good reliability (Cronbach’s alpha: 0.82 to 0.90). All four subscales were responsive toward receiving a brochure with PE-related health information. Conclusion: The newly developed German HeLP Questionnaire comprises 23 items in four domains and showed good psychometric properties. Further evaluation of the questionnaire in different samples of patients with PE is needed

Gute Praxis Datenlinkage (GPD) : Good Practice Data Linkage

Das personenbezogene Verknüpfen verschiedener Datenquellen (Datenlinkage) für Forschungszwecke findet in den letzten Jahren in Deutschland zunehmend Anwendung. Jedoch fehlen hierfür konsentierte methodische Standards. Ziel dieses Beitrages ist es, solche Standards für Forschungsvorhaben zu definieren. Eine weitere Intention ist es, dem Lesenden eine Checkliste zur Bewertung geplanter Forschungsvorhaben und Artikel bereitzustellen. Zu diesem Zweck hat eine aus Mitgliedern verschiedener Fachgesellschaften zusammengesetzte Expertengruppe seit 2016 insgesamt 7 Leitlinien mit 27 konkreten Empfehlungen erstellt. Die Gute Praxis Datenlinkage beinhaltet die folgenden Leitlinien: (1) Forschungsziele, Fragestellung, Datenquellen und Ressourcen, (2) Dateninfrastruktur und Datenfluss, (3) Datenschutz, (4) Ethik, (5) Schlüsselvariablen und Linkageverfahren, (6) Datenprüfung/Qualitätssicherung sowie (7) Langfristige Datennutzung für noch festzulegende Fragestellungen. Jede Leitlinie wird ausführlich diskutiert. Zukünftige Aktualisierungen werden wissenschaftliche und datenschutzrechtliche Entwicklungen berücksichtigen

External validity from routine data of statutory health insurance (SHI)

Einleitung Für wissenschaftliche Analysen der Versorgungsforschung wird zunehmend auf GKV-Routinedaten zurückgegriffen. Da diese Daten primär zur Leistungsabrechnung erhoben worden sind, können diese nur als Sekundärdaten für andere Fragestellungen herangezogen werden. Hierbei stellt sich Frage, wie valide eine derartige Datengrundlage ist. Methodik Es wird untersucht, wie valide der Krankheitsverlauf und -umfang der Versicherten über die bei gesetzlichen Krankenkassen vorhandenen (Sekundär-) Daten abgebildet werden kann im Vergleich zu Angaben aus Primärdaten. Als Primärdaten werden von Ärzten und Patienten dokumentierte Angaben aus Follow-up-Fragebögen im Rahmen eines Modellvorhabens der Techniker Krankenkasse (TK) herangezogen (n = 363 Patienten mit Koronarstenose) und mit den dazugehörigen GKV-Routinedaten verglichen. Es werden die Parameter Arbeitsunfähigkeit (AU), Arzneimittelinanspruchnahmen und Krankenhausaufenthalte untersucht. Ergebnisse Arbeitsunfähigkeit: Eine AU-Übereinstimmung von Krankenkassen- und Patienten- Daten beträgt aus TK-Perspektive im Untersuchungszeitraum FU1 (0-3 Monate) 61,8%, FU2 (4-6 Monate) 82,2% und FU3 (7-12 Monate) 81,3%. Der größte Anteil für die Übereinstimmung (> 95%) geht auf gesunde Versicherte (ohne AU-Tage) zurück. Fokussiert man nur auf Versicherte mit AU-Tagen, beträgt die Übereinstimmung in FU1 0% (n = 132 Versicherte), in FU2 10% (n = 60) und in FU3 4,9% (n = 61). Arzneimittelinanspruchnahmen: Beim Vergleich einzelner Medikamente stimmt die bei den Ärzten dokumentierte Einnahme von Clopidogrel mit den TK- und Patienten-Daten in hohem Ausmaß (> 90%) überein. Für Acetylsalicylsäure liegt die Übereinstimmung in den Patientendaten bei 90%, in den TK-Daten bei 50%. Über den Gesamtzeitraum hinweg (0-12 Monate) beträgt der Patientenanteil mit einer 100%-Übereinstimmung der Gesamtmedikation aus TK- Perspektive gemittelt 28,8%, aus Patientenperspektive 52,1%. Krankenhausaufenthalte: Im Gesamtzeitraum sind in den TK-Daten 1.976 Krankenhaustage dokumentiert, in den Patientendaten 3.109 Tage und in den Arztdaten 1.156 Tage. Aus TK-Perspektive beträgt die Übereinstimmung mit den Patientendaten hinsichtlich der stationären Verweildauer in FU1 für alle Patienten mit Krankenhausaufenthalt 37,8%, in FU2 66,4% und in FU3 61,0%. Schlussfolgerung Das Ausmaß der Übereinstimmung zwischen den drei Datenquellen Arzt, Patient und TK fällt in Abhängigkeit vom untersuchten Parameter (AU, Medikamente, Krankenhausaufenthalte) und Zeitpunkt sehr different aus. Globale Aussagen zur Validität der TK-Sekundär-Datenbasis sind somit nicht möglich. Jeder Schwerpunkt kann nur individuell unter Berücksichtigung seiner jeweiligen methodische Limitationen interpretiert werden. Zu berücksichtigen ist, dass die beiden Vergleichsdatenquellen Arzt und Patient selbst nur eingeschränkt valide sind und somit nicht per se als Goldstandard für einen Vergleich herangezogen werden können. Je einfacher die Operationalisierung unter Berücksichtigung der jeweiligen methodischen Limitationen in den Primärdatenquellen vorgenommen wird, desto höher ist die Übereinstimmung zwischen den drei betrachteten Datenquellen.Background Scientific analyses in healthcare research increasingly base on secondary data of the Statutory Health Insurance (SHI). These data are primarily collected for billing of medical benefits and can therefore only be used as secondary data for possible other issues. The question here is how valid such a data basis can be. Methods It is examined how valid progression and extent of diseases for insured persons may be displayed by means of secondary data available within the SHI in comparison to information from primary data. Primary data from 363 patients with coronary stenosis are derived from follow-up questionnaires filled in by doctors and patients within a pilot project of one health insurance fund, the Techniker Krankenkasse (TK). Sickness absence, medication and hospitalizations are analyzed. Results The agreement of TK data and patient data regarding sickness absence was 61.8% in investigation period FU1 (0-3 months), 82.2% in FU2 (4-6 months) and 81.3% in FU3 (7-12 months) from TK-perspective. The highest conformity (>95%) arises from patients without sick leave days. Focusing just on patients with sickness absence, compliance was 0% (n=132 patients) in FU1, 10% (n=60) in FU2 and 4.9% (n= 61) in FU3. Comparisons for Clopidogrel show a high level of agreement between the medication documented by doctors and that indicated within TK and patients’ data (>90%). For acetylsalicylic acid, the agreement was 90% in the patients' data and 50% in the TK data. For the whole observation period, there was a compliance of 100% regarding the entire medication of 28.8% from perspective of TK and of 52.1% from perspective of the patients. In the whole observation period, 1,976 hospital days are documented in TK data, com-pared to 3,109 days in the patients' data and 1,156 days in the doctors' data, respectively. From TK-perspective the conformity with the patients’ data concerning the length of stay in FU1 for all patients with hospitalization was 37.8%, 66.4% in FU2 and 61.0% in FU3. Conclusion The level of agreement between the three data sources differs much depending on the investigated parameter (sickness absence, drugs, hospitalizations) and the observation period. This complicates global statements regarding validity of the TK secondary data. Respective methodological limitations have to be taken into account. In addition the data sources from doctor and patient themselves are restricted as regards validity. Therefore, they cannot be used without restrictions as a gold standard for a comparison

Follow-up of 3 Million Persons Undergoing Colonoscopy in Germany: Utilization of Repeat Colonoscopies and Polypectomies Within 10 Years

INTRODUCTION: Given the sparsity of longitudinal studies on colonoscopy use, we quantified utilization of repeat colonoscopy within 10 years and the proportion of persons with polypectomies at first repeat colonoscopy using a large German claims database. METHODS: Based on the German Pharmacoepidemiological Research Database, we identified persons who underwent colonoscopy between 2006 and 2015 (index colonoscopy) and assessed colonoscopies and polypectomies during follow-up. We defined 3 subcohorts based on available procedure/diagnosis codes at index colonoscopy: persons with snare polypectomy, which is reimbursable for lesions ≥5 mm in size (cohort 1), with a forceps polypectomy (cohort 2), and without such procedures/diagnoses (cohort 3). We stratified all analyses by diagnostic vs screening index colonoscopy. RESULTS: Overall, we included 3,076,657 persons (cohort 1–3: 15%, 13%, 72%). Among persons with screening index colonoscopy (30%), the proportions with a repeat colonoscopy within 10 years in cohorts 1, 2, and 3 were 78%, 66%, and 43%, respectively, and a snare polypectomy at first repeat colonoscopy was performed in 27%, 17%, and 12%, respectively. In cohort 1, 32% of persons with a (first) repeat colonoscopy after 9 years had a snare polypectomy (after 3 years: 25%). Among persons with diagnostic index colonoscopies, 80%, 78%, and 65% had a repeat colonoscopy, and 27%, 17%, and 10% had a snare polypectomy at first repeat colonoscopy, respectively. DISCUSSION: Our study suggests substantial underuse of repeat colonoscopy among persons with previous snare polypectomy and overuse among lower risk groups. One-quarter of persons with a snare polypectomy at baseline had another snare polypectomy at first repeat colonoscopy

Pressure to provide milk among mothers of very low birth weight infants: an explorative study

Abstract Background Pump-dependent mothers of very low birth weight (VLBW, < 1500g) infants experience specific challenges achieving sufficient milk supply in the neonatal intensive care unit (NICU) and are therefore less frequently able to achieve (exclusive) breast milk feeding. Stress due to the limitations on participating in the infant’s care may contribute to this problem. Some explorative studies suggest that pressure to provide milk may be an additional stressor in mothers. However, the type of pressure to provide milk perceived by mothers of VLBW infants has rarely been examined. Methods A retrospective and anonymous questionnaire was conducted with mothers of VLBW infants aged 6 to 24 months at the time of data collection. Quantitative data and written comments were used to examine the mothers’ perceptions. Descriptive and bivariate tests (Spearman´s rho, Pearson’s chi2) were performed to show correlations between pressure to provide breast milk, parental stress (PSS:NICU: role alteration subscale), milk volume, and maternal factors. Pressure to provide milk was measured through two self-developed single items to differentiate between internal and external pressures. Results Data of n = 533 mothers of VLBW infants was analysed. More than 70% of the mothers agreed that they pressured themselves to provide milk for their infant. In contrast, 34% of the mothers agreed that they felt pressure from outside to provide milk. Higher milk volume 14 days post-partum was significantly correlated with less internal (Spearman´s rho = 0.2017, p = 0.000) and less external pressure to provide milk (Spearman´s rho = 0.2991; p = 0.000). Higher PSS:NICU parental role alteration scores were significantly correlated with more internal (Spearman´s rho = -0.2865, p = 0.000) and more external pressure to provide milk (Spearman´s rho = -0.1478; p = 0.002). Milk volume 14 days post-partum and the PSS:NICU were not significantly correlated (Spearman´s rho = -0.0190; p = 0.701). Qualitative analyses highlighted these results and enhanced the bidirectional relationships between maternal pressure to provide milk and milk volume. Conclusions Especially internal pressure to provide milk is perceived by many mothers, being mutually dependent on milk supply and parental stress. Pressure to provide milk may be an important factor to decrease maternal stress in the NICU and, therefore, lead to more positive pumping and breastfeeding experiences. More research and validated instruments are needed to adequately measure pressure to provide milk with its different psychological, social, and environmental dimensions