Nanoliposomal Irinotecan With Fluorouracil and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Cholangiocarcinoma: A Phase II Study of the AIO Hepatobiliary-YMO Cancer Groups (NIFE-AIO-YMO HEP-0315).

PURPOSE: First-line therapy options in advanced cholangiocarcinoma (CCA) are based on the ABC-02 trial regimen (gemcitabine/cisplatin [G/C]). The NIFE trial examined nanoliposomal irinotecan/fluorouracil/leucovorin (nal-IRI/FU/LV) as alternative first-line therapy in advanced CCA. METHODS: NIFE is a prospective, open-label, randomized, multicenter phase II study that aimed at detecting efficacy comparable with the standard treatment. Patients with advanced CCA were randomly assigned (1:1) to receive nal-IRI/FU/LV (arm A) or G/C (arm B). Stratification parameters were intrahepatic versus extrahepatic CCA, sex, and Eastern Cooperative Oncology Group (ECOG; 0/1). Arm A was designed as a Simon's optimal two-stage design and arm B served as a randomized control group. The primary goal was to exclude an inferior progression-free survival (PFS) at 4 months of only 40%, while assuming a rate of 60% on G/C population. RESULTS: Between 2018 and 2020, overall 91 patients were randomly assigned to receive nal-IRI/FU/LV (n = 49) or G/C (n = 42). The NIFE trial formally met its primary end point with a 4-month PFS rate of 51% in patients receiving nal-IRI/FU/LV. The median PFS was 6 months (2.4-9.6) in arm A and 6.9 months (2.5-7.9) in arm B. Median overall survival (OS) was 15.9 months (10.6-20.3) in arm A and 13.6 months (6.5-17.7) in arm B. The exploratory comparison of study arms suggested a numerical but statistically not significant advantage for nal-IRI/FU/LV (hazard ratio for PFS, 0.85 [95% CI, 0.53 to 1.38] and for OS, 0.94 [95% CI, 0.58 to 1.50]). Analysis for stratification parameters revealed no differences for sex and ECOG, but for tumor localization. The objective response rate was 24.5% with nal-IRI/FU/LV and 11.9% with G/C. No unexpected toxicities occurred. AEs related to nal-IRI/FU/LV were mainly GI and to G/C hematologic. CONCLUSION: Treatment of advanced CCA with nal-IRI/FU/LV demonstrated efficacy in first-line therapy without new safety findings and merits further validation.

[Treatment of haemophilia in Austria]. / Hämophilie-Behandlung in Österreich.

This guideline is intended to provide practical guidance for the diagnosis and treatment of haemophilia in Austria. Few randomized controlled interventional trials are available addressing the treatment of haemophilia, therefore recommendations are usually based on low level of evidence and represent expert consensus.This guideline is based on the WFH guideline, published in 2020, and adapted according to the national circumstances and experience.It includes recommendations and suggestions for diagnosis and follow-up visits and pharmacological therapies for treatment and prophylaxis. Further topics comprise special aspects in children and adults with severe haemophilia, outcome measurement, and management of trauma, special bleedings and interventions, including dental procedures, inhibitors, management of haemophilia carriers, and psychosocial aspects.

[Four years of specialized outpatient palliative care in a rural area : Cooperation and acceptability from general practitioners' view]. / Vier Jahre spezialisierte ambulante Palliativversorgung (SAPV) im ländlichen Bereich : Zusammenarbeit und Akzeptanz aus hausärztlicher Sicht.

BACKGROUND: In 2011, a specialized palliative home care was introduced in the counties of Landshut and Dingolfing. OBJECTIVES: The aim of the current survey was to evaluate the cooperation, acceptance and need of palliative measures for patients particulary from the general practitioner's perspective. METHODS: From January to March 2015, 198 general practitioners from the counties of Landshut and Dingolfing were contacted with questionnaires. The questionnaires consisted of 16 questions covering five different issues, and drew upon the practical experiences of the authors and earlier surveys from the literature. The questionnaires were sent by post containing a self-addressed and postpaid envelope. RESULTS: Completed questionnaires from 40 out of 198 contacted general practitioners (33 % female and 53 % male). Of these 85 % had cooperated with a SAPV team, 23 % had taken part in training for palliative medicine, 10 % intended to acquire a qualification and 10 % could imagine working in a SAPV team. In addition, 75 % stated that hospitalizations were avoided through the use of SAPV while 73 % felt that time and costs were saved for their own practices. The majority of general practitioners were satisfied with the work provided by the SAPV and the cooperation. Regarding additional palliative care for geriatric patients, 60 % believed that this was sensible. One main critique was that the information about including a patient in the SAPV program was transferred to the general practitioner too late. CONCLUSION: The current data show that general practitioners recognize the need for palliative medicine skills and predominately welcome the work of a specialized palliative care team in treating their patients. However, close cooperation and communication is necessary for a successful network between generalists and specialists in palliative care.

Effectiveness of mouth-to-mouth resuscitation performed by young adolescents on a mannequin.

Bystanders are reluctant to perform basic life support (BLS) because of fear of failure and of infection, especially with mouth-to-mouth resuscitation (MTM). A possibility to enhance willingness could be the giving of MTM or BLS instructions at a very early age to the potential rescuers. The study aimed to investigate the effectiveness of MTM with respect to ventilation and the time needed for performing 5 ventilations. In this study, MTM was performed on a mannequin by 57 children and adolescents aged 10 and 14 years. This study showed that 14-year-olds effectively perform MTM, reaching the recommended tidal volumes. Ten-year-old children have already developed sufficient motor skills for MTM with no significant time differences compared with the 14-year-olds. However, physical demands may be rather high at this age. Further long-term studies are needed to investigate clinical benefits of early teaching of MTM or BLS that may lead to international guidelines with low age limits.

Comparison of mouth-to-mouth resuscitation and Combitube ventilation in a bench model.

CONTEXT: In addition to heart massage, the primary goal of cardiopulmonary resuscitation is efficient oxygenation and ventilation. OBJECTIVE: To compare the ease of learning and handling of standard mouth-to-mouth resuscitation with the Combitube (Tyco Healthcare Nellcor, Pleasanton, CA) ventilation. METHODS: After a 30 minute theoretical introduction and demonstration of mouth-to-mouth resuscitation and use of the Combitube in mannequins, following American Heart Association guidelines, 26 adolescent school children (15 of them 14 years old, 11 of them 10 years old) undertook two ventilation trials, each consisting of five single ventilations, with each technique. Only the second trial with each technique was evaluated. Qualitative implementation (grades: very good, good, failed) was evaluated, several procedure-related time points were recorded, and tidal volumes (ml) were measured. RESULTS: With mouth-to-mouth resuscitation, the time interval until start of first ventilation was 36.5 seconds shorter than with the Combitube (P < 0.001). With the Combitube, the time needed for five single ventilations was 6.4 seconds less than with mouth-to-mouth resuscitation (P < 0.001) and mean tidal volumes were higher (mouth-to-mouth resuscitation, 450 +/- 384 ml, versus Combitube, 735 +/- 358 ml; P < 0.05). CONCLUSION: Most of the school children performed both techniques to a high qualitative level. The study shows that mouth-to-mouth resuscitation and use of the Combitube have equal ease of learning, a precondition for proficient retention of skills. Tidal volumes were significantly higher with the Combitube and, not surprisingly, the time interval until the start of first ventilation was significantly shorter with mouth-to-mouth resuscitation. Regardless of the ventilation technique or device, we believe that subsequent retraining of ventilation skills is very important.