Rainald Fischer

Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator therapy approved for people with cystic fibrosis (pwCF) who have at least one phe508del mutation. However, its approval in the European Union (EU) for pwCF with non-phe508del mutations is lacking, because data on treatment response in this subgroup are scarce. Methods: This retrospective observational study evaluated six pwCF (ages 6 to 66) with responsive CFTR mutations (M1101K, R347P, 2789+5G>A, G551D) undergoing off-label ETI therapy. Evaluations were conducted at 0, 3, 6, 9, and 12 months, assessing lung function (FEV₁), sweat chloride levels, body mass index (BMI), quality of life, medication satisfaction, ear, nose and throat (ENT) symptoms, and physical activity. A control group of four pwCF with classic symptoms and no ETI treatment was included. Results: FEV₁ improved significantly after 3 and 6 months (p < 0.05) and stabilized by 12 months. Sweat chloride levels decreased significantly, with four pwCF achieving levels <60 mmol/L. Improvements in the upper and lower airway symptoms, medication satisfaction, and increased BMI were noted. Conclusions: ETI demonstrates high efficacy in this small group of pwCF with rare CFTR mutations, offering a treatment option that warrants further monitoring and evaluation.

Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator therapy approved for people with cystic fibrosis (pwCF) who have at least one phe508del mutation. However, its approval in the EU for pwCF with non-phe508del mutations is lacking, with limited data on treatment response in this subgroup. Methods: This retrospective study analyzed data from six pwCF (ages 6 to 66) with responsive CFTR mutations (M1101K, R347P, 2789+5G>A, G551D) undergoing off-label ETI therapy. Evaluations were conducted at 0, 3, 6, 9, and 12 months, assessing lung function (FEV1), sweat chloride levels, BMI, quality of life (CFQ-R), medication satisfaction (TSQM), ENT symptoms (SNOT-22), and physical performance. A control group of four pwCF with classic symptoms and no ETI treatment was included. Results: FEV1 improved significantly after 3 and 6 months (p<0.05) and stabilized by 12 months. Sweat chloride levels decreased significantly, with four pwCF achieving levels below 60 mmol/l. Improvements in ENT and respiratory symptoms, medication satisfaction, and increased BMI were noted. Conclusion: ETI demonstrates high efficacy in selected non-phe508del mutations, offering an effective treatment option that warrants further monitoring and evaluation.

High-altitude (HA) exposure affects cognitive functions, but studies have found inconsistent results. The aim of this systematic review was to evaluate the effects of HA exposure on cognitive functions in healthy subjects. A structural overview of the applied neuropsychological tests was provided with a classification of superordinate cognitive domains. A literature search was performed using PubMed up to October 2021 according to PRISMA guidelines. Eligibility criteria included a healthy human cohort exposed to altitude in the field (at minimum 2440 m [8000 ft]) or in a hypoxic environment in a laboratory, and an assessment of cognitive domains. The literature search identified 52 studies (29 of these were field studies; altitude range: 2440 m–8848 m [8000–29,029 ft]). Researchers applied 112 different neuropsychological tests. Attentional capacity, concentration, and executive functions were the most frequently studied. In the laboratory, the ratio of altitude-induced impairments (64.7%) was twice as high compared to results showing no change or improved results (35.3%), but altitudes studied were similar in the chamber compared to field studies. In the field, the opposite results were found (66.4 % no change or improvements, 33.6% impairments). Since better acclimatization can be assumed in the field studies, the findings support the hypothesis that sufficient acclimatization has beneficial effects on cognitive functions at HA. However, it also becomes apparent that research in this area would benefit most if a consensus could be reached on a standardized framework of freely available neurocognitive tests.

Zwei höhenmedizinisch erfahrene Bergsteiger (w, 52 Jahre, m, 53 Jahre) planten eine Trekkingtour durch das Helambu- und Langtanggebiet in Nepal, nördlich von Kathmandu. Sie hatten 8 Tage Zeit und wollten zuletzt eine Höhe von 5000 Hm erreichen. Da die geplanten Trekkingetappen zum Teil recht lang waren (üblich sind für diese Strecke 12–14 Tage), erfolgte eine Präakklimatisation in einem Hypoxiezelt zu Hause. Über insgesamt 14 Tage wurde die Hypoxie langsam gesteigert, zuletzt entsprechend einer normobaren Hypoxie von 4500 Hm (ca. 13 % FiO₂). Die Dauer der nächtlichen Hypoxie betrug im Schnitt 6 h. Das Intervall zwischen der letzten Hypoxienacht zu Hause und dem Beginn der Trekkingtour betrug 6 Tage. Nach dem Start der Tour im Kathmandu-Tal, 1460 Hm, und der ersten Übernachtung, 2100 Hm, folgte ein weiterer Höhenanstieg am zweiten Tag: Überquerung eines Passes kurz vor dem Schlafplatz, 3400 Hm, und Übernachtung, 3290 Hm. Am Tag 3 sollte die Überschreitung des Laurebina-Passes, 4610 HM, erfolgen und die Übernachtung danach in Gosainkund (laut Karte 3480 m). Eine Wegbeschreibung wurde nicht mitgeführt, da eine detaillierte topografische Karte in Kathmandu erworben wurde und die Bergsteiger auf die Informationen in den jeweiligen Lodges und die Gespräche mit anderen Trekkern vertrauten. Zudem waren sie bereits mehrfach in Nepal trekken gewesen. Im Langtanggebiet waren sie vor über 20 Jahren, damals erfolgte auch ein Besuch von Gosainkund. Bei der zweiten Übernachtung trafen sie eine Wandergruppe, die davon berichtete, dass sie gerade in umgekehrter Richtung von Gosainkund unterwegs gewesen waren, allerdings benötigten sie für diese Strecke 2,5 Tage. Von Gosainkund auf den Laurebina-Pass (also von 3480 bis 4610 Hm) hätten sie nur etwa 2 Stunden gebraucht. Mit diesen Informationen und der Karte machten sich beide Bergsteiger am dritten Tag auf den Weg, trotz der Meinung eines Nepalis während der ersten Teepause, 3690 Hm, dass es „impossible“ sei, von hier an einem Tag bis nach Gosainkund zu gelangen. Da Zelt und Schlafsäcke mitgeführt wurden, erschien das Risiko vertretbar, falls der Pass nicht erreichbar war, davor zu übernachten und den Anstieg am kommenden Tag zu versuchen. Allerdings war beiden Bergsteigern bewusst, dass in diesem Fall eine ziemlich rasche Steigerung der Schlafhöhe (auf etwa 4000–4200 Hm) möglicherweise mit einer Höhenkrankheit einhergehen könnte. Dies wäre nur durch den langen Abstieg nach Gosainkund (laut Karte 3480 Hm) mit Überschreitung des Passes davor zu vermeiden. Am Laurebina–Pass (4610 Hm) bemerkten beide Bergsteiger die Hypoxie trotz Präakklimatisation deutlich, das Gehen war nur langsam möglich, es bestand leichter Schwindel. Nachdem der Laurebina-Pass dann nach einem langen Tag um circa 17 Uhr erreicht war, machten sich beide auf den Weg nach unten, um eine zu hohe Schlafhöhe zu vermeiden ([Abb. 1]). Nach etwa 30 min Abstieg konnte man im letzten Abendlicht bald einen See mit mehreren, offenbar bewohnten Häusern erkennen. In diesem Moment erst wurde beiden Bergsteigern klar, dass dies Gosainkund mit den heiligen Seen sein musste ([Abb. 2]). Daher konnte die Höhe in der topografischen Karte nicht stimmen, sondern müsste offenbar nicht 3480 Hm sondern 4380 HM lauten, also knapp 900 Hm Unterschied. Das machte das Erreichen des Zielorts natürlich deutlich einfacher, allerdings auf Kosten einer zu großen Schlafhöhe, was bei beiden Bergsteigern über Nacht zu einer mäßig ausgeprägten Höhenkrankheit mit Kopfschmerzen, Schlafstörungen und leichter Übelkeit führte.

After the SMART trial evaluating the safety of salmeterol (long-acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken to promote a guideline-adherent prescribing of LABA only to patients receiving inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related prescription patterns after the SMART trial in Germany. Patients documented in the Bavarian Association of Statutory Health Insurance Physicians database (approximately 10.5 million people) were included if they had a diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004 and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane Armitage tests were used for time trend analyses. Highest annual PPRs were found for budesonide and the fixed combination of salmeterol/fluticasone. The proportion of “concomitant LABA and ICS users” increased from 52.0 to 57.6% within the study period, whereas for “LABA users without ICS” a slight decrease from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one quarter with a LABA prescription without concomitant ICS was highest in elderly, male patients (≈20%). In the majority of these patients, a concomitant diagnosis of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present. Between 2004 and 2008, we found a moderate increase in guideline-adherent LABA prescribing in a representative German population. Elderly men received a significant number of LABA prescriptions without concomitant ICS probably due to ACOS.

Health facility delivery is considered a critical strategy to improve maternal health. The Government of Nepal is promoting institutional delivery through different incentive programmes and the establishment of birthing centres. This study aimed to identify the socio-demographic, socio-cultural, and health service-related factors influencing institutional delivery uptake in rural areas of Chitwan district, where high rates of institutional deliveries co-exist with a significant proportion of home deliveries. This community-based cross-sectional study was conducted in six rural Village Development Committees of Chitwan district, which are characterised by relatively low institutional delivery rates and the availability of birthing centres. The study area represents both hilly and plain areas of Chitwan. A total of 673 mothers who had given birth during a one-year-period were interviewed using a structured questionnaire. Univariate and multivariable logistic regression analysis using stepwise backward elimination was performed to identify key factors affecting institutional delivery. Adjusting for all other factors in the final model, advantaged caste/ethnicity [aOR: 1.98; 95% CI: 1.15-3.42], support for institutional delivery by the husband [aOR: 19.85; 95% CI: 8.53-46.21], the decision on place of delivery taken jointly by women and family members [aOR: 5.43; 95% CI: 2.91-10.16] or by family members alone [aOR: 4.61; 95% CI: 2.56-8.28], birth preparations [aOR: 1.75; 95% CI: 1.04-2.92], complications during the most recent pregnancy/delivery [aOR: 2.88; 95% CI: 1.67-4.98], a perception that skilled health workers are always available [aOR: 2.70; 95% CI: 1.20-6.07] and a birthing facility located within one hour’s travelling distance [aOR: 2.15; 95% CI: 1.26-3.69] significantly increased the likelihood of institutional delivery. On the other hand, not knowing about the adequacy of physical facilities significantly decreased the likelihood of institutional delivery [aOR: 0.14; 95% CI: 0.05-0.41]. With multiple incentives present, the decision to deliver in a health facility is affected by a complex interplay of socio-demographic, socio-cultural, and health service-related factors. Family decision-making roles and a husband’s support for institutional delivery exert a particularly strong influence on the place of delivery, and this should be emphasized in the health policy as well as development and implementation of maternal health programmes in Nepal.