Wirksamkeit von Mefloquin als intermittierende präventive Behandlung der Malaria in der Schwangerschaft gegen Schistosoma haematobium-Infektionen in Gabun

Nach Malaria stellt die urogenitale Schistosomiasis mit geschätzten 112 Millionen Erkrankten und einer erheblichen Morbidität in Subsahara-Afrika die in dieser Region wichtigste Parasitenerkrankung dar. Chronische Infektionen mit S. haematobium können schwerwiegende Pathologien der Harnwege und Genitalien, wie beispielsweise Ulzerationen, Ureterstenosen bis hin zu Niereninsuffizienz und Blasenkarzinomen bedingen. Schwangere Frauen stellen eine besonders gefährdete Patientengruppe dar; perinatale und –partale Mortalitätsraten, sowie Aborte sind bei infizierten Frauen häufiger und auch das Risiko einer vertikalen HIV-Transmission scheint erhöht zu sein. Die Behandlung der urogenitalen Bilharziose basiert momentan ausschließlich auf dem Medikament Praziquantel; in tierexperimentellen Studien und in vitro konnte jedoch eine vielversprechende Aktivität des Antimalariamittels Mefloquin (MQ) gegenüber Schistosomen beschrieben werden. Im Rahmen einer multizentrischen klinischen Studie (MiPPAD) wurde dessen Wirksamkeit als intermittierende präventive Behandlung gegen Malaria während der Schwangerschaft (IPTp) untersucht und mit dem aktuell zur IPTp verwendeten Medikament Sulfadoxin-Pyrimethamin (SP) verglichen. Eingebettet in diese Studie untersuchten wir die Wirksamkeit von MQ gegen S. haematobium-Infektionen in Schwangeren, wobei die SP-Gruppe als Kontrolle fungierte. Es handelte sich hierbei um eine randomisierte kontrollierte, Untersucher-verblindete klinische Studie, die als Proof of Concept-Untersuchung erste Erkenntnisse bezüglich der Wirksamkeit von MQ gegen S. haematobium-Infektionen in Schwangeren liefern sollte. Es wurden 65 Probandinnen in die Studie eingeschlossen; davon 48 in der Interventionsgruppe (MQ) und 17 in der Kontrollgruppe (SP). Die Studienteilnehmerinnen erhielten im Abstand von vier Wochen zwei Dosen des jeweiligen Studienmedikaments; als primärer Endpunkt wurde die S. haematobium-Eierausscheidung im Urin zu Beginn der Studie, vier Wochen und zehn Wochen nach der ersten Intervention definiert. Zum finalen Messzeitpunkt konnte in der MQ-Gruppe (ITT-Population) eine deutliche Reduktion der Eierausscheidung (ERR) von 98% (IQR, 70-100) und eine Heilungsrate von 47% (IQR, 36-70) festgestellt werden. In der SP-Gruppe stieg die Eierausscheidung im gleichen Zeitraum um 20% (IQR, -186 – 75); lediglich eine Probandin konnte in dieser Gruppe geheilt werden (7% [IQR, 1-31]). MQ als IPTp führte verglichen mit SP zu signifikant höheren ERR (p=0,01) und Heilungsraten (p=0,01). Während der hier gezeigte Effekt von Mefloquin auf die Eierausscheidung durchaus von klinischer Relevanz ist, liegt die Heilungsrate klar unter den Werten des Erstlinienmedikaments Praziquantel. Eine gleichwertige Alternative zu Praziquantel scheint Mefloquin daher nicht darzustellen; angesichts seines Einsatzes als Malariamedikament und der in Subsahara-Afrika weit verbreiteten Koendemizität von P. falciparum und S. haematobium ist die antischistosomale Wirkung von Mefloquin jedoch gerade in dieser Region von klinischem Interesse. Aufgrund seiner bekannten Wirkung gegen juvenile Schistosomen könnte MQ auch als Teil einer Kombinationstherapie mit Praziquantel angewandt werden; diesbezüglich besteht jedoch weiterer Forschungsbedarf

Tackling the frailty burden with an integrative value-based approach: results from a mixed-methods study

Aim The purpose of this paper is to investigate the implementation of value-based care principles in the context of frailty in the perioperative process, highlighting the importance of an integrative perspective considering medical and patient-centric outcomes as well as costs. Subject and methods This mixed-methods study employs a sequential design. Qualitative observational data were used to identify needs and barriers for implementing value-based principles, and quantitative methods were subsequently used to demonstrate the value of employing such an approach using data gathered from n = 952 patients. Propensity score matching was applied to identify the frailty-associated costs of the inpatient setting for n = 381 non-frail and n = 381 (pre-)frail patients, in particular considering patient-centric outcomes. Results The qualitative analysis identified three main challenges when implementing value-based principles in the context of perioperative care and frailty, namely challenges related to the cost, patient-centric, and integrative perspectives. In addressing these shortcomings, a quantitative analysis of a propensity score-matched sample of patients undergoing surgery shows additional frailty-associated costs of 3583.01 [1654.92; 5511.04] EUR for (pre-)frail patients and the influence of individual patient-centric attributes. Effect size Cohen’s d was 0.26. Conclusion The results demonstrate that frailty should be considered from an integrative perspective, taking cost, patient-centered outcomes, and medical outcomes into account simultaneously. The results also show the value of a research design which uses qualitative data for the identification of needs and barriers, as well as quantitative data for demonstrating the usefulness of the conceived value-based approach to perioperative care delivery

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated

The evolving landscape of COVID‐19 and post‐COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations