Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial.

BACKGROUND: Combinations of avelumab [anti-programmed death-ligand 1 (anti-PD-L1)] or talazoparib [poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor] with binimetinib (MEK inhibitor) were expected to result in additive or synergistic antitumor activity relative to each drug administered alone. Here, we report phase Ib results from JAVELIN PARP MEKi, which investigated avelumab or talazoparib combined with binimetinib in metastatic pancreatic ductal adenocarcinoma (mPDAC). PATIENTS AND METHODS: Patients with mPDAC that had progressed with prior treatment received avelumab 800 mg every 2 weeks plus binimetinib 45 mg or 30 mg two times daily (continuous), or talazoparib 0.75 mg daily plus binimetinib 45 mg or 30 mg two times daily (7 days on/7 days off). The primary endpoint was dose-limiting toxicity (DLT). RESULTS: A total of 22 patients received avelumab plus binimetinib 45 mg (n = 12) or 30 mg (n = 10). Among DLT-evaluable patients, DLT occurred in five of 11 patients (45.5%) at the 45-mg dose, necessitating de-escalation to 30 mg; DLT occurred in three of 10 patients (30.0%) at the 30-mg dose. Among patients treated at the 45-mg dose, one (8.3%) had a best overall response of partial response. Thirteen patients received talazoparib plus binimetinib 45 mg (n = 6) or 30 mg (n = 7). Among DLT-evaluable patients, DLT occurred in two of five patients (40.0%) at the 45-mg dose, necessitating de-escalation to 30 mg; DLT occurred in two of six patients (33.3%) at the 30-mg dose. No objective responses were observed. CONCLUSIONS: Combinations of avelumab or talazoparib plus binimetinib resulted in higher-than-expected DLT rates. However, most DLTs were single occurrences, and the overall safety profiles were generally consistent with those reported for the single agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT03637491; https://clinicaltrials.gov/ct2/show/NCT03637491.

[Ventilation Patients between Acute Care and Long-term Out-of-Hospital Ventilation - Routine Documentation based Analysis of the Care Situation]. / Beatmungspatienten zwischen Akutversorgung und außerstationärer Langzeitbeatmung.

BACKGROUND: The number of invasive and non-invasive long-term out-of-hospital ventilations has been increasing rapidly for years. At the same time, there is poor information on the quality of care of out-of-hospital ventilated patients. The present investigation was conducted as part of the OVER-BEAS study. The aim of this study was to describe the care situation of weaning patients from admission to discharge from the weaning center using existing routine documentation. MATERIAL AND METHODS: In our retrospective analysis, we included all patients admitted in 2018 via the weaning ward of the Thorax Center Münnerstadt. Descriptive analysis of routine data collected as part of quality management was performed. Data sources were the WeanNet database, the discharge letter of the weaning center, and the transfer report of the referring hospital. RESULTS: In the studied weaning center, 50.8 % of the patients (n = 31) could be completely weaned from the respirator and extubated or decannulated (category 3aI). If complete weaning was not successful, 75.0 % (n = 21) required the constant presence of specially trained staff or a specialist nurse in the further course. In this case, further care was mostly provided in inpatient care facilities (e. g., ventilator shared living community). CONCLUSION: Based on routine documentation, the care situation of weaning patients can be presented and compared with known data. In this way, the outcome quality of a weaning center can be made comparable.

[Ventilation Patients between Acute Care and Long-term Out-of-Hospital Ventilation - Routine Documentation based Analysis of the Care Situation]. / Beatmungspatienten zwischen Akutversorgung und außerstationärer Langzeitbeatmung.

BACKGROUND: The number of invasive and non-invasive long-term out-of-hospital ventilations has been increasing rapidly for years. At the same time, there is poor information on the quality of care of out-of-hospital ventilated patients. The present investigation was conducted as part of the OVER-BEAS study. The aim of this study was to describe the care situation of weaning patients from admission to discharge from the weaning center using existing routine documentation. MATERIAL AND METHODS: In our retrospective analysis, we included all patients admitted in 2018 via the weaning ward of the Thorax Center Münnerstadt. Descriptive analysis of routine data collected as part of quality management was performed. Data sources were the WeanNet database, the discharge letter of the weaning center, and the transfer report of the referring hospital. RESULTS: In the studied weaning center, 50.8 % of the patients (n = 31) could be completely weaned from the respirator and extubated or decannulated (category 3aI). If complete weaning was not successful, 75.0 % (n = 21) required the constant presence of specially trained staff or a specialist nurse in the further course. In this case, further care was mostly provided in inpatient care facilities (e. g., ventilator shared living community). CONCLUSION: Based on routine documentation, the care situation of weaning patients can be presented and compared with known data. In this way, the outcome quality of a weaning center can be made comparable.

Phase II study of pembrolizumab efficacy and safety in women with recurrent small cell neuroendocrine carcinoma of the lower genital tract.

OBJECTIVE: To investigate the efficacy and safety of pembrolizumab in women with recurrent small cell neuroendocrine tumors of the lower genital tract. METHODS: We conducted an open-label, investigator-initiated phase II basket trial of pembrolizumab 200 mg intravenously every 3 weeks in patients with rare tumors (ClinicalTrials.gov: NCT02721732). The trial had prespecified cohorts, including small cell malignancies of extrapulmonary origin. Eligibility criteria included disease progression during standard treatment in the 6 months before study enrollment. Patients were enrolled from February 2017 to February 2019. The primary endpoint was the proportion of patients alive without progression at 27 weeks. Response to pembrolizumab was evaluated every 9 weeks (3 cycles) with radiographic imaging. RESULTS: Seven women with gynecologic extrapulmonary small cell carcinoma were enrolled, 6 with cervical and 1 with vulvar carcinoma. No patient was progression free at 27 weeks. At first radiologic assessment, 1 patient had stable disease, while 6 had progression. The single patient with stable disease at 6 weeks had disease progression at 14 weeks. The median progression-free interval was 2.1 months (range 0.8-3.3 months). Severe treatment-related adverse events (≥grade 3) were seen in 2 of 7 patients (29%); 1 patient had grade 3 asymptomatic elevation of serum alkaline phosphatase, and 1 had grade 3 asymptomatic elevation of serum alanine aminotransferase. CONCLUSIONS: Pembrolizumab alone showed minimal activity in women with recurrent small cell neuroendocrine tumors of the lower genital tract. Treatment was well tolerated in the majority of study participants, and the rate of severe adverse events was low.

[Application for Inpatient Psychosomatic Rehabilitation: Frequency, Quality, and Approval Rates]. / Anträge auf psychosomatische Rehabilitation ­ Häufigkeit, Qualität und Befürwortungsrate.

BACKGROUND: There has been a steady increase in psychiatric primary diagnoses in medical rehabilitation services carried out by the statutory pension insurance (DRV). To date, no data are available regarding frequency, quality, and approval rates of applications for psychosomatic rehabilitation. Pension insurance physicians reviewing the application require sufficient information on rehabilitation-related needs, motivation, abilities, and prognosis of an insured person. Medical reports accompanying application for rehabilitation are often provided by a family physician. Psychiatric disorders are often misdiagnosed by general practitioners. METHOD: In a 2-week period, all decisions made by pension insurance physicians evaluating applications for rehabilitation were recorded. For each incoming application, the following data were documented: psychiatric and somatic primary diagnosis; availability of medical reports; information on prior treatment/therapy; request for further information; decision made by the physician. RESULTS: 1,366 applications (with 81% first-time applications) were included in the analysis. 16.2% of all applications were from insurants with psychiatric primary diagnoses. 44.0% of these applications included a medical report from the family physician only. The proportion of rejected applications (34.7%) and undecided applications (27.2%) was higher in the group of applicants with psychiatric primary diagnosis vs. somatic primary diagnosis (19.6% rejected; 12.7% undecided; χ2=79.8(4), p=0.001). Applications from patients with psychiatric primary diagnosis that lacked a medical report from a psychiatrist/psychotherapist were more likely to be rejected (45.3 vs. 32.3%) or to remain undecided (28.0 vs. 18.3%; χ2=10.2(2), p=0.006). In contrast, among applicants with a history of psychiatric/psychotherapeutic treatment, there was a higher proportion of undecided applications accompanied by a medical report from the family physician (35.7 vs. 18.2%). CONCLUSION: It might be useful to have medical reports generally provided by medical specialists. This may help both to increase the informative value of applications for psychosomatic rehabilitation and enable quicker decisions and better diagnosis.

[Optimising the rehabilitation discharge report of the German statutory pension insurance: the recipients' and users' perspectives]. / Optimierung des Reha-Entlassungsberichts der Deutschen Rentenversicherung - die Sichtweisen der Adressaten bzw. Nutzer.

BACKGROUND: Given the significance of documentation and information transfer in the health-care system as well as new technological options, there is a need for continuously modifying and enhancing the pension insurance's rehabilitation discharge report while taking into account the benefits and expenses associated with it. Among the regular discharge report recipients/users are general practitioners, medical specialists, socio-medical consultants of the German pension insurance and other health-care providers and funding agencies (e. g., statutory health insurance, federal labour agency), external socio-medical consultants, judges in charge of social legislation issues, pension insurance administrators, and rehabilitation quality assurance officials. In the context of a broader project on the optimisation of the pension insurance's rehabilitation discharge report, the specific needs and interests of its recipients/users as well as suggestions concerning the improvement of structure and content of the discharge report were assessed. METHOD: Discharge report recipients/users were asked via questionnaire to indicate how frequently they use certain information from the report for their work. They were also asked to state objections/areas of concern and sugges­tions for improvement. RESULTS: 400 recipients/users filled in the questionnaire. More than half of the respondents considered the discharge report too long. Sugges­tions for shortening the report centred on avoiding redundancies and including standardised response items instead of free text passages. User groups differed with regard to the content that should be subject to reductions. CONCLUSIONS: The non-representative sample notwithstanding, the survey's results have rendered important starting points for optimising the statutory pension insurance's discharge report.

[Acceptance and practicability of evidence-based therapy standards in child and adolescent rehabilitation: results of a user survey]. / Akzeptanz und Praktikabilität der Reha-Therapiestandards für Kinder und Jugendliche: Ergebnisse der Anwenderbefragung.

The introduction of evidence-based therapy standards in child and adolescent rehabilitation of the German statutory pension insurance scheme (Deutsche Rentenversicherung Bund, 2011) was accompanied by a user survey that gave the participating rehabilitation centres the opportunity to comment on the new therapy standards and to suggest modifications.The survey questionnaire encompassed various topics related to the therapy standards, amongst them quality, comprehensibility, and acceptance, evaluation of feedback, and reasons for noncompliance with therapy standard requirements. For each of the 3 indications, a separate questionnaire was applied to assess modification suggestions regarding KTL therapy elements, the minimum percentage of patients to be treated accordingly, and the minimum duration of therapeutic procedures for each evidence-based treatment module. Responses from 14 rehab centres (return rate 54%) were obtained and analyzed.According to the majority of the responding rehabilitation centres, the therapy standards for child and adolescent rehabilitation fulfilled the quality features of topicality, multidisciplinarity, and relevance for routine rehabilitative practice. The degree of empirical grounding was evaluated more inconsistently. Difficulties with coding of KTL therapy elements were cited as the primary reasons for failing to comply with requirements in 2008.Exemplarily, the results of the user survey regarding the rehabilitative treatment of children and adolescents with obesity (age group: 8 years and older) are presented in detail.Concluding, the modifications to the therapy standards in child and adolescent rehabilitation introduced on the basis of the user survey are set out.

[Systematic literature review on interventions in rehabilitation for children and adolescents with asthma bronchiale]. / Systematische Literaturanalyse zur rehabilitativen Behandlung von Kindern und Jugendlichen mit Asthma bronchiale.

Relevant data bases were used to collect and evaluate guidelines, meta-analyses, and reviews as well as primary studies dealing with asthma therapy for children and adolescents. Treatment approaches whose effectiveness with regard to bronchial asthma was empirically verified (i. e., evidence-based) were identified (medical and diagnostic procedures as well as drug trials were excluded from the analysis). 152 methodically sound studies referring to asthma treatment of children and adolescents were selected. Strong evidence was found for patient education, parent education, exercise therapy, inhalation, and tobacco withdrawal. Nutritional counseling and avoidance of allergens showed limited evidence. Psychotherapy, relaxation techniques, breathing exercises, climate therapy, clinical social work (social and legal counseling services, vocational reintegration counseling, aftercare) and integration counseling showed inconsistent evidence. No evidence was found for alternative medicine. Challenges regarding the development of treatment standards for children and adolescent rehabilitation are highlighted; these refer to limitations in report quality in some of the studies, the validity of treatments for comorbid conditions, a lack of differentiation for different age groups, and transferability of outpatient or international study results to inpatient rehabilitation.

Is there a secular decline in motor skills in preschool children?

Current research seems to confirm a secular decline in movement skills in school children. Only few data are available for preschool children and no clear trend can be identified. In the year 2007, height, weight, and motor performance were determined in 726 preschool children [Prevention through Activity in Kindergarten Trial (PAKT)] and compared with historical samples from 1973, 1985, and 1989. There was no difference in height and weight between the samples of 1973 and 2007. Older boys of today were smaller and lighter than those of 1989. Regardless of age, PAKT children fared significantly better in standing long jump than those assessed in 1989. Compared with the sample of 1973, PAKT children did equally well in this task. There were no differences in performance in an obstacle course between children of 1989 and 2007. In balancing backwards, PAKT children performed significantly worse than those in 1985. Regarding target throwing only the PAKT 4-year-olds achieved significantly worse results than those in 1985.Therefore, in preschool children, a secular decline is only evident in some, but not all, motor skills, which may indicate a change in behavior activity over the last decades.