Background: Hitherto only studies with selected populations have found an increased all-cause mortality of some selected opioids compared to selected non-opioids for chronic non-cancer pain (CNCP). We have examined the allcause mortality for CNCP associated with all established opioids compared to non-opioid analgesic therapy (anticonvulsants, antidepressants, dipyrone, non-steroidal agents). Methods: The study used the InGef (Institute for Applied Health Research Berlin) database which is an anonymized healthcare claims database including 4,711,668 insured persons who were covered by 61 German statutory health insurances between 2013 and 2017.The health insurance companies are the owners of the database. All-cause mortality was determined from death certificates. Adjusted hazard ratios (HRs) including age, gender, comorbidity index, and propensity score as covariates and risk differences (RD) in incidence of death between patients with long-term opioid therapy (LTOT) and control-drug therapy were calculated. Results: The mean age of participants was 66 years; 55% were women. There were 554 deaths during 10,435 person-years for the LTOT patients, whereas there were 340 deaths during 11,342 person-years in the control group. The HR for all-cause mortality was 1.59 (95% CI, 1.38-1.82) with a risk difference of 148 excess deaths (95% CI 99-198) per 10,000 person-years. The elevated risk of death for LTOT was confined to the out-of-hospital deaths: LTOT patients had 288 out-of-hospital deaths during 10,435 person-years (276 per 10,000 person-years) whereas there were 110 deaths during 11,342 person-years (97 per 10,000 person-years) in the control group. HR was 2.29 (95% CI 1.86, 2.83). Although our propensity score matching model indicated a good classification, residual confounding cannot be fully excluded. The opioid group had a higher prevalence of heart failure and a higher use of antithrombotic and antiplatelet agents and of psycholeptics.

<b><i>Objectives:</i></b> Buprenorphine (BUP) is used in opioid maintenance treatment (OMT) for opioid-dependent patients. Previous real-world evidence suggests that many patients receive lower BUP dosage than recommended, with 38% of patients receiving &#x3c;6 mg BUP per day. The goal of this research is to evaluate the impact of BUP dosage on the risk of relapses in the real world. <b><i>Methods:</i></b> This study was based on German claims data of 4 million patients. Patients identified by International Classification of Diseases, 10th Edition F11.2 (opioid dependence) between 2011 and 2012 and at least one BUP prescription were selected for this study (<i>n</i> = 364) and followed up over 4 years. Patients were assigned to 6 dosage groups, with &#x3c;6 mg/day serving as low dosage/reference category. The impact of dosage on the occurrence of relapses (indicated by treatment interruption of &#x3e;3 months without OMT prescription or hospital admissions) was examined using multivariate logistic regression. Age, gender, comorbidities, fixed/variable dosing, and up-dosing were used as covariates. <b><i>Results:</i></b> Results showed a protective effect of higher BUP as higher BUP dosages were significantly associated with a lower risk of relapse. Using low dosage (&#x3c;6 mg/day) as the reference category, ORs were 0.40 (95% CI 0.19–0.87) at 6–&#x3c;8 mg/day, 0.28 (0.15–0.56) at 8–&#x3c;10 mg/day, 0.26 (0.10–0.67) at 10–&#x3c;12 mg/day, 0.40 (0.18–0.92) at 12–&#x3c;16 mg/day, and 0.18 (0.09–0.37) at ≥16 mg/day. No covariate showed a significant effect on the probability of relapse. <b><i>Conclusions:</i></b> The present study used a large German health claims dataset to confirm that higher BUP dosages are a protective factor for avoiding relapses in opioid-dependent patients, thus highlighting the importance of adequate BUP dosing in relapse prevention.

Introduction Cartilage defects in the knee can be caused by injury, various types of arthritis, or degeneration. As a long-term consequence of cartilage defects, osteoarthritis can develop over time, often leading to the need for a total knee replacement (TKR). The treatment alternatives of chondral defects include, among others, microfracture, and matrix-associated autologous chondrocyte implantation (M-ACI). The purpose of this study was to determine cost-effectiveness of M-ACI in Germany with available mid- and long-term outcome data, with special focus on the avoidance of TKR. Materials and methods We developed a discrete-event simulation (DES) that follows up individuals with cartilage defects of the knee over their lifetimes. The DES was conducted with a status-quo scenario in which M-ACI is available and a comparison scenario with no M-ACI available. The model included 10,000 patients with articular cartilage defects. We assumed Weibull distributions for short- and long-term effects for implant failures. Model outcomes were costs, number of TKRs, and quality-adjusted life years (QALYs). All analyses were performed from the perspective of the German statutory health insurance. Results The majority of patients was under 45 years old, with defect sizes between 2 and 7 cm2 (mean: 4.5 cm2); average modeled lifetime was 48 years. In the scenario without M-ACI, 26.4% of patients required a TKR over their lifetime. In the M-ACI scenario, this was the case in only 5.5% of cases. Thus, in the modeled cohort of 10,000 patients, 2700 TKRs, including revisions, could be avoided. Patients treated with M-ACI experienced improved quality of life (22.53 vs. 21.21 QALYs) at higher treatment-related costs (18,589 vs. 14,134 € /patient) compared to those treated without M-ACI, yielding an incremental cost‐effectiveness ratio (ICER) of 3376 € /QALY. Conclusion M-ACI is projected to be a highly cost‐effective treatment for chondral defects of the knee in the German healthcare setting.

Introduction Real-world data on usage of 1st, 2nd and 3rd generation tyrosine kinase inhibitor (TKIs) in chronic myeloid leukemia (CML) is scarce. This study therefore aimed to analyze the use of different TKIs used in 1st- and 2nd-line treatment and the frequency of TKI switches in CML. Methods This observational study was based on the InGef research database, an anonymized representative claims dataset in Germany (n= 4 million). An incidence and prevalence patient CML cohort was followed for 5 and 3 years. Analyses regarding incidence, prevalence and therapy distribution were performed descriptively. Results 151 patients were included in the incidence and 636 patients in the prevalence cohort. This resulted in an incidence of 1.8 (95%-confidence interval [CI]: 1.34 – 2.20) and a prevalence of 14.9 (95%-CI 13.70 – 16.03) per 100,000 inhabitants. For the incidence cohort, data on 1st-line therapy was available for 124 patients and distributed across imatinib (N=52), nilotinib (N=44), dasatinib (N=12), chemotherapies as hydroxycarbamide (N=11) and ponatinib/bosutinib (N=5). 26% of patients switched TKI therapy at least once in three years. In the prevalence cohort, 423 patients (66.5%) had claims on existing or newly emerged cardiovascular diseases (CD). No significant differences (p=0.32) between TKIs in patients with CD were found. Discussion Every fourth patient switched TKI therapy within the first three years after treatment initiation. Switches were more likely when hints of disease progression or intolerability were observable in the database.

BackgroundOpioid Use Disorder (OUD) is a substance use disorder with a chronic course associated with comorbid mental and somatic disorders, a high burden of psychosocial problems and opioid maintenance treatment (OMT) as a standard treatment. In the US, OUD imposes a significant economic burden on society, with annual societal costs estimated at over 55 billion dollars. Surprisingly, in Europe and especially in Germany, there is currently no detailed information on the healthcare costs of patients with OUD. The goal of the present research is to gather cost information about OUD patients in OMT with a focus on maintenance medication and relapses.MethodsWe analysed health claims data of four million persons covered by statutory health insurance in Germany, applying a cost-of-illness approach and aimed at examining the direct costs of OMT patients in Germany. Patients with an ICD-10 code F11.2 and at least one claim of an OMT medication were stratified into the treatment groups buprenorphine, methadone or levomethadone, based on the first prescription in each of the follow-up years. Costs were stratified for years with and without relapses. Group comparisons were performed with ANOVA.ResultsWe analysed 3165 patient years, the total annual sickness funds costs were on average 7470 € per year and patient. Comparing costs of levomethadone (8400 €, SD: 11,080 €), methadone (7090 €, SD: 10,900 €) and buprenorphine (6670 €, SD: 7430 €) revealed significant lower costs of buprenorphine compared to levomethadone (p < 0.0001). In years with relapses, costs were higher than in years without relapses (8178 € vs 7409 €; SD: 11,622, resp. 10,378 €). In years with relapses, hospital costs were the major cost driver.ConclusionsThe present study shows the costs of OUD patients in OMT for the first time with a German dataset. Healthcare costs for patients with an OUD in OMT are associated with more than two times the cost of an average German patients. Preventing relapses might have significant impact on costs. Patients in different OMT were dissimilar which may have affected the cost differences.