University Hospital of Geneva

The field of addiction medicine is rapidly evolving due to shifting drug markets and emerging patterns of use. In Switzerland, the possible arrival of highly potent synthetic opioids highlights the need for interprofessional preparedness, particularly through wider training in naloxone use. At the same time, the rise in recreational ketamine use brings an underestimated urological complication: ketamine-induced cystitis, whose early detection is crucial. Growing digitalisation also fosters compulsive pornography use, where craving plays a key role; new tools such as the PCE-S scale help to better assess these mechanisms. Together, these trends call for strengthened monitoring, prevention, and adaptive clinical strategies.

Die gut- und bösartigen Erkrankungen des oberen Gastrointestinaltrakts weisen genderspezifische Unterschiede auf. Die häufige gastroösophageale Refluxerkrankung ist hier ein Paradebeispiel: Männer weisen häufiger eine erosive Refluxerkrankung auf als Frauen und sind zum Zeitpunkt des Auftretens zudem jünger. Auch die Progressionsrate zum metaplastischen Barrett-Ösophagus ist bei Männern höher. Bei der Achalasie gibt es Hinweise darauf, dass die operative Versorgung mittels laparoskopischer Heller-Myotomie und 180°-Semifundoplikation nach Dor bei den Frauen zu einer im Vergleich zu den Männern deutlicheren Beschwerdebesserung führt, obwohl diese eine ausgeprägtere Dilatation der tubulären Speiseröhre aufwiesen. Der weibliche Hormonstatus beeinflusst Lokalisation und Histopathologie des Karzinoms des ösophagogastralen Übergangs bzw. Magenkarzinoms. Prä- und postmenopausale Karzinome unterscheiden sich bei Frauen signifikant. Überdies ist die hohe Mikrosatelliteninstabilität (MSI-high) häufiger bei Frauen vorhanden und mit einer generell signifikant besseren Prognose assoziiert. MSI-high-Magenkarzinome von Frauen zeigen ein besseres Überleben als MSI-high-Karzinome von Männern. Der zukünftige Einschluss genderspezifischer Aspekte in Studien am oberen Gastrointestinaltrakt ist wünschenswert, um adäquate Daten zu generieren und perspektivisch auch differenzierte Therapiestratifizierungen zu ermöglichen.

Background The antipsychotic aripiprazole is mainly metabolized by the cytochrome P450 (CYP) 2D6. The main objective of this study was to evaluate the influence of CYP2D6 phenotypes on aripiprazole plasma levels and treatment duration. Design 466 patients treated with aripiprazole for up to 12 months and with at least one aripiprazole plasma level in steady-state condition were selected. CYP2D6 genotypes and phenoconversion to poor metabolizer status due to strong CYP2D6 inhibition were considered. Aripiprazole plasma level-to-dose ratios and treatment duration up to discontinuation, defined as switching to another psychotropic drug and/or stopping the follow-up, were analyzed using robust linear models and Cox regression, respectively. Akaike variable selection was applied. Results CYP2D6 poor metabolizers (genetically determined n = 19 and phenoconverted, n = 52) showed higher aripiprazole concentration-to-dose (P < .001) and aripiprazole plus dehydroaripiprazole concentration-to-dose (P < .001) ratios when compared to normal metabolizers (n = 255). CYP2D6 extreme metabolizers (ie, poor and ultrarapid metabolizers) had higher risk of treatment discontinuation versus intermediate and normal metabolizers after 3, 6, and 12 months of treatment (HR: 2.08, 1.75, 1.59, respectively; P = .013, P = .019, and P = .047, respectively). For a pharmacogenetic-guided treatment, the number of patients needed to genotype to prevent 1 patient from aripiprazole discontinuation was 15. Conclusion CYP2D6 poor metabolism was associated with increased aripiprazole and aripiprazole plus dehydroaripiprazole concentrations-to-dose. CYP2D6 extreme phenotypes were associated with increased risk of treatment discontinuation over 1 year of treatment. This finding supports the applicability of pre-emptive CYP2D6 genotyping, which is expected to decrease aripiprazole adverse events and inefficacy that would probably lead to treatment discontinuation.

Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne disease with a case fatality rate of up to 40% in humans, posing a significant health threat. This study investigates the 2022-23 CCHF outbreaks in Iraq, the highest recorded to date, and analyzes potential factors at the human-animal-environmental interface. Data from the Iraqi government, the World Health Organization, and the World Bank were used to analyze CCHF trends and affecting factors. This included epidemiological reports, clinical data, tick infestation and seroprevalence studies, and climate data. Descriptive and statistical analyses examined case trends, geographic and demographic characteristics, clinical manifestations, risk factors, seasonal patterns, and influencing factors. A sudden rise in CCHF cases began in southern Iraq in April 2022 and expanded across all governorates, with a shift toward urban areas. Higher incidence was observed among males, aged 25-44, and those involved in slaughtering. The most common clinical manifestation was fever (97%), followed by hemorrhagic symptoms (54%). Bleeding from the gums or mouth and subcutaneous bleeding were more frequent in patients with fatal outcomes. Seasonal patterns showed peaks during spring and fall, correlating with tick activity and potentially exacerbated by climate change. Tick infestation and seroprevalence studies indicated a high prevalence of Hyalomma ticks and CCHF seropositivity among domestic animals in southern Iraq (60%), consistent with the distribution of CCHF human cases. Iraq's ongoing CCHF outbreak demands multidisciplinary One Health strategies. The Iraqi government has adopted such a control strategy, contributing to regional and global efforts to enhance pandemic preparedness.