Bone evaluation study-2: update on the epidemiology of osteoporosis in Germany.

Osteoporosis is the most common bone disorder. Our data gives an estimate of around 5.87 million cases of osteoporosis in the general German population in 2018. Only 30% of insured individuals who suffered an osteoporotic fracture and/or had a confirmed diagnosis of osteoporosis, received an appropriate prescription. PURPOSE: Osteoporosis is the most common bone disorder. It particularly affects elderly people and increases the risk of atraumatic fractures. The aim of this study was to estimate the prevalence of osteoporosis in the general German population aged ≥ 50 years and to collect data on the frequency of prescription of osteoporosis-specific medication in order to assess the treatment gap. METHODS: Retrospective analysis of anonymized data of individuals aged ≥ 50 years insured under statutory healthcare schemes from the database of the Institute for Applied Health Research Berlin (InGef) for 2018 (study population). Insured individuals with osteoporosis were identified based on osteoporosis diagnoses, osteoporosis-specific prescriptions, or osteoporotic fractures. Thus, we estimated the prevalence of osteoporosis in the general German population aged ≥ 50 years. The prevalence of diagnoses, fractures, and prescriptions was determined for the study population and stratified by age and gender. RESULTS: Within the study population of 1,599,299 insured individuals, a prevalence of osteoporosis of 15.9% was determined. This estimated approximately 5.87 million cases of osteoporosis for the general German population. 81.6% of the cases were women. Osteoporosis-specific prescriptions were received by 30.0% of the insured individuals in the study population who had been diagnosed with osteoporosis and/or suffered an osteoporotic fracture. CONCLUSIONS: Germany has a high prevalence of osteoporosis. Only a small portion of individuals who may require osteoporosis-specific treatment actually receive it.

A Systematic Literature Review of Injection Site Pain Perception in Adult Patients Treated with Citrate-Free and Citrate-Containing Biologic Agents.

OBJECTIVE: To investigate injection site pain (ISP) and other injection site outcomes caused by biologics administered alongside citrate-free (CF) and citrate-containing (CC) formulations. METHODS: Electronic literature databases (Medline, Embase, and Cochrane Library) were systematically searched for clinical trials and observational studies reporting on injection site outcomes after subcutaneous administration of biologics. Studies with unknown excipient formulations were excluded. The primary outcome was ISP, and secondary outcomes included any other reported injection site reactions (ISRs). Meta-analysis approaches were used to aggregate evidence identified via the conducted systematic literature review. RESULTS: A total of two observational studies, two cross-over/sequential trials, and three head-tohead comparison trials directly comparing CF with CC biologics were identified, as well as seven placebo-controlled trials. Evidence from five of the seven direct comparison studies suggested reduced pain perception at the injection site when CF formulations were applied. Findings for other ISRs were balanced between both formulations, with slightly favorable results for preparations without citrate. A meta-analysis of placebo-controlled trials found no significant difference between arms with CF formulations and placebo regarding the proportion of patients experiencing ISP (OR 0.62, 95% CI 0.30-1.28). CONCLUSION: Excipient formulations are rarely specified in studies assessing pain and other ISRs of subcutaneously administered biologics. The available data indicate that subcutaneous administration of biologic agents without citrate may be associated with lower pain perception outcomes compared with treatment using CC formulations. Importantly, ISP is influenced by many factors which may have affected the results. More research is needed to assess how formulation excipients influence ISRs.

Excitation function of 54Fe(p,α)51Mn from 9.5 MeV to 18 MeV.

Excitation function of the 54Fe(p,α)51Mn reaction was measured from 9.5 to 18 MeV E 0 , p + by activating a foil stack of 54Fe electrodeposited on copper substrates. Residual radionuclides were quantified by HPGe gamma ray spectrometry. Both 51Mn (t 1/2 = 46.2 min, 〈 E ß + 〉 = 963.7 keV , I ß + = 97 % ; E γ = 749.1 keV, I γ = 0.265%) and its radioactive daughter, 51Cr (t 1/2 = 27.704d, E γ = 320.1 keV, I γ = 9.91%), were used to indirectly quantify formation of 51Mn. Results agree within uncertainty to the only other measurement in literature and predictions of default TALYS theoretical code. Final relative uncertainties are within ±12%.

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.

Assessment of Metastatic Colorectal Cancer Patients' Preferences for Biologic Treatments in Germany Using a Discrete Choice Experiment.

BACKGROUND: Current treatment regimens for metastatic colorectal cancer (mCRC) include biologics such as epidermal growth factor receptor and vascular endothelial growth factor inhibitors, which have specific side-effect profiles. There is a lack of information on mCRC patient preference in Germany regarding biologics in combination with chemotherapy. This study aims to identify German mCRC patients' preference for these treatments PATIENTS AND METHODS: This was a multicenter cross-sectional discrete choice experiment (DCE). Data were collected using electronic case report forms and structured phone interviews. DCE attributes were related to efficacy, side effects, frequency of administration, and distance to treating physicians' practice. Patients' characteristics and choices were analyzed descriptively. Choice data was modeled using a random utility maximization framework. RESULTS: All attributes, except distance to treating physicians' practice, had a significant impact on patients' decision. The most important driver of patients' treatment decision was overall survival, followed by safety-related attributes and frequency of administration. Overall survival was the main driver in all subgroups analyzed. Risk of severe skin toxicities was more important to women, than men. In patients with prior experience of side effects, the risk of side effects accounted for 45% of a patient's decision, compared to 35% in those without prior experience. CONCLUSION: Overall survival remains the most important driver in mCRC patients' preferences for biologic treatment in combination with chemotherapy. Attributes related to safety were less important to patients when considering their treatment decision. These results indicate that understanding patient preferences may lead to increased treatment compliance.

Fractures in untreated patients with osteoporosis in Germany: an InGef healthcare insurance database analysis.

Osteoporosis is a skeletal disease that may result in low-trauma fracture if untreated. Among men and women ≥ 70 years untreated for osteoporosis, 30% (43,514) sustained at least one post-index fracture. Care for patients with osteoporosis diagnosis directly contributed to a cost burden of €786 million. INTRODUCTION: Osteoporosis is a skeletal disease that manifests as bone mineral density loss and low-trauma fractures. This database analysis describes the characteristics of untreated osteoporosis patients, and their rate of fractures, health resource utilization, and cost burden. METHODS: From the InGef database (2011-2016), eligible patients (≥ 70 years) untreated for osteoporosis were identified via a recorded diagnosis of osteoporosis (ICD-10 codes M80/M81) or an initial fragility fracture (index point). All patients were followed up for fractures post index. Direct costs included inpatient, outpatient, pharmacy, and ancillary care costs. RESULTS: A total of 144,752 patients (mean age 79 years; 73% female, median follow-up of 3.2 years) met the eligibility criteria; 23% had a history of fractures. Forty-eight percent of patients had cardiac diseases, 32% diabetes, and 27% cerebrovascular disease. Thirty percent (43,514) of patients had at least one post-index fracture; two or more post-index fractures were experienced in 7% (10,262) of patients. Median time from index date to first fracture was 145.5 days. Bisphosphonates were the most prescribed osteoporosis treatment following a first fracture post-index (n = 4102, 9.2%). There was a total of 107,055 patients (74.0%) who had at least one all-cause hospital stay. The total number of fracture-related admissions was 63,595 and that of outpatient visits was 323,460. A total of 34,764 (24%) patients died during follow-up. Costs for fracture-related care for patients directly contributed to a cost burden of €786 million. CONCLUSIONS: Osteoporosis patients and patients who sustain a fragility fracture remain undertreated for osteoporosis, increasing their risk of future fractures. Diagnosing and treating this group of patients should remain a priority to alleviate the clinical and economic burden of osteoporosis-related fractures.

Do Surrogate Endpoints Better Correlate with Overall Survival in Studies That Did Not Allow for Crossover or Reported Balanced Postprogression Treatments? An Application in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: In previous studies, correlation between overall survival (OS) and surrogate endpoints like objective response rate (ORR) or progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) was poor. This can be biased by crossover and postprogression treatments. OBJECTIVES: To evaluate the relationship between these two surrogate endpoints and OS in advanced NSCLC studies that did not allow for crossover or reported balanced post-progression treatments. METHODS: A systematic review in patients with advanced NSCLC receiving second- and further-line therapy was performed. The relationship between the absolute difference in ORR or median PFS (mPFS) and the absolute difference in median OS (mOS) was assessed using the correlation coefficient (R) and weighted regression models. The analysis was repeated in predefined data cuts based on crossover and balance of postprogression treatments. When the upper limit of R's 95% confidence interval (CI) was more than 0.7, the surrogate threshold effect (STE) was estimated. RESULTS: In total, 146 randomized clinical trials (43,061 patients) were included. The mean ORR, mPFS, and mOS were 12.2% ± 11.2%, 3.2 ± 1.3 months, and 9.6 ± 4.1 months, respectively. The correlation coefficients of ORR and mPFS were 0.181 (95% CI 0.016-0.337) and 0.254 (95% CI 0.074-0.418), respectively, with mOS. Nevertheless, in trials that did not allow crossover and reported balanced postprogression treatments, the correlation coefficients of ORR and mPFS were 0.528 (95% CI 0.081-0.798) and 0.778 (95% CI 0.475-0.916), respectively, with mOS. On the basis of STE estimation, in trials showing significant treatment effect size of 41.0% or more ORR or 4.15 or more mPFS months, OS benefit can be expected with sufficient certainty. CONCLUSIONS: Crossover and postprogression treatments may bias the relationship between surrogate endpoints and OS. Presented STE calculation can be used to interpret treatment effect on either ORR or PFS when used as primary endpoints.

Investigating Treatment Outcomes Across OCD Symptom Dimensions in a Clinical Sample of OCD Patients.

Despite the heterogeneous nature of obsessive-compulsive disorder (OCD), many self-report assessments do not adequately capture the clinical picture presenting within each symptom dimension, particularly unacceptable thoughts (UTs). In addition, obsessions and ordering/arranging compulsions are often underrepresented in samples of treatment outcome studies for OCD. Such methodological discrepancies may obscure research findings comparing treatment outcomes across OCD symptom dimensions. This study aimed to improve upon previous research by investigating treatment outcomes across OCD symptom dimensions using the Dimensional Obsessive-Compulsive Scale, which offers a more comprehensive assessment of UTs. The study included a primarily residential sample of 134 OCD patients. Results indicated that there were no significant differences in treatment outcomes across symptom dimensions. However, the severity of UTs remained significantly greater than other symptom dimensions at both admission and discharge. Thus, it is possible that UTs may exhibit uniquely impairing features, compared with other symptom dimensions. It is also possible that these findings may reflect the characteristics of the residential OCD samples. These speculations as well as implications for OCD treatment and future research are discussed.