Swiss medical weekly最新文献

{"title":"Long-term levels of protection of different types of immunity against the Omicron variant: a rapid literature review.","authors":"Sabina Rodriguez Velásquez, Loza Estifanos Biru, Sandrine Marie Hakiza, Muaamar Al-Gobari, Isotta Triulzi, Jyoti Dalal, Camille Beatrice Gaza Varela, Sara Botero Mesa, Olivia Keiser","doi":"10.57187/s.3732","DOIUrl":"10.57187/s.3732","url":null,"abstract":"<p><strong>Introduction: </strong>With the emergence of newer SARS-CoV-2 variants and their substantial effects on the levels and duration of protection against infection, an understanding of these characteristics of the protection conferred by humoral and cellular immunity can aid in the proper development and implementation of vaccine and safety guidelines.</p><p><strong>Methods: </strong>We conducted a rapid literature review and searched five electronic databases weekly from 1 November 2021 to 30 September 2022. Studies that assessed the humoral or cellular immunity conferred by infection, vaccination or a hybrid (combination of both) in adults and risk groups (immunocompromised and older populations) were identified. Studies were eligible when they reported data on immunological assays of COVID-19 (related to vaccination and/or infection) or the effectiveness of protection (related to the effectiveness of vaccination and/or infection).</p><p><strong>Results: </strong>We screened 5103 studies and included 205 studies, of which 70 provided data on the duration of protection against SARS-CoV-2 infection. The duration of protection of adaptive immunity was greatly impacted by Omicron and its subvariants: levels of protection were low by 3-6 months from exposure to infection/vaccination. Although more durable, cellular immunity also showed signs of waning by 6 months. First and second mRNA vaccine booster doses increased the levels of protection against infection and severe disease from Omicron and its subvariants but continued to demonstrate a high degree of waning over time.</p><p><strong>Conclusion: </strong>All humoral immunities (infection-acquired, vaccine-acquired and hybrid) waned by 3-6 months. Cellular immunity was more durable but showed signs of waning by 6 months. Hybrid immunity had the highest magnitude of protection against SARS-CoV-2 infection. Boosting may be recommended as early as 3-4 months after the last dose, especially in risk groups.</p>","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid detection of the source of a Listeria monocytogenes outbreak in Switzerland through routine interviewing of patients and whole-genome sequencing.","authors":"Cornelia Speich, Roger Stephan, Nicola Dhima, Florian Hollenstein, Jule Horlbog, Giulia Delvento, Ekkehardt Altpeter, Meike Zuske, Michelle Raess, Helena Greter","doi":"10.57187/s.3745","DOIUrl":"https://doi.org/10.57187/s.3745","url":null,"abstract":"<p><strong>Aims of the study: </strong>Listeriosis is a notifiable disease in Switzerland. In summer 2022, the Swiss Federal Office of Public Health noticed an increase in reports of listeriosis cases, indicating a possible ongoing outbreak. Here we present the approaches applied for rapidly confirming the outbreak, detecting the underlying source of infection and the measures put in place to eliminate it and contain the outbreak.</p><p><strong>Methods: </strong>For close surveillance and early detection of outbreak situations with their possible sources, listeriosis patients in Switzerland are systematically interviewed about risk behaviours and foods consumed prior to the infection. Listeria monocytogenes isolates derived from patients in medical laboratories are sent to the National Reference Laboratory for Enteropathogenic Bacteria and Listeria, where they routinely undergo whole-genome sequencing. Interview and whole-genome sequencing data are continuously linked for comparison and analysis.</p><p><strong>Results: </strong>In summer 2022, 20 patient-derived L. monocytogenes serotype 4b sequence type 388 strains were found to belong to an outbreak cluster (≤10 different alleles between neighbouring isolates) based on core genome multilocus sequence typing analysis. Geographically, 18 of 20 outbreak cases occurred in northeastern Switzerland. The median age of patients was 77.4 years (range: 58.1-89.7), with both sexes equally affected. Rolling analysis of the interview data revealed smoked trout from a local producer as a suspected infection source, triggering an on-site investigation of the production facility and sampling of the suspected products by the responsible cantonal food inspection team on 15 July 2022. Seven of ten samples tested positive for L. monocytogenes and the respective cantonal authority ordered a ban on production and distribution as well as a product recall. The Federal Food Safety and Veterinary Office released a nationwide public alert covering the smoked fish products concerned. Whole-genome sequencing analysis confirmed the interrelatedness of the L. monocytogenes smoked trout product isolates and the patient-derived isolates. Following the ban on production and distribution and the product recall, reporting of new outbreak-related cases rapidly dropped to zero.</p><p><strong>Conclusions: </strong>This listeriosis outbreak could be contained within a relatively short time thanks to identification of the source of contamination through the established combined approach of timely interviewing of every listeriosis patient or a representative and continuous molecular analysis of the patient- and food-derived L. monocytogenes isolates. These findings highlight the effectiveness of this well-established, joint approach involving the federal and cantonal authorities and the research institutions mandated to contain listeriosis outbreaks in Switzerland.</p>","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic haematopoietic cell transplantation for chronic myeloid leukaemia in Switzerland in the face of rapid development of effective drugs.","authors":"Dominik Heim, Helen Baldomero, Michael Medinger, Stavroula Masouridi-Levrat, Urs Schanz, Gayathri Nair, Tayfun Güngör, Jörg Halter, Jakob R Passweg, Yves Chalandon","doi":"10.57187/s.3754","DOIUrl":"https://doi.org/10.57187/s.3754","url":null,"abstract":"<p><strong>Aim: </strong>Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development.</p><p><strong>Methods: </strong>All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997-2001 (Q1), 2002-2006 (Q2), 2007-2011 (Q3), 2012-2016 (Q4) and 2017-2021 (Q5), as the observation period spanned 25 years.</p><p><strong>Results: </strong>Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death.</p><p><strong>Conclusion: </strong>Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.</p>","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of and risk factors for suicidal ideation in adolescents during the COVID-19 pandemic: a cross-sectional study.","authors":"Roxane Dumont, Elsa Lorthe, Viviane Richard, Andrea Loizeau, Guillaume Fernandez, David De Ridder, Francesco Pennacchio, Julien Lamour, María-Eugenia Zaballa, Helene Baysson, Klara M Posfay-Barbe, Remy P Barbe, Silvia Stringhini, Idris Guessous","doi":"10.57187/s.3461","DOIUrl":"https://doi.org/10.57187/s.3461","url":null,"abstract":"<p><strong>Background and objectives: </strong>Pandemic-related life changes may have had a deleterious impact on suicidal behaviours. Early detection of suicidal ideation and identification of subgroups at increased risk could help prevent suicide, one of the leading causes of death among adolescents worldwide. Here, we aimed to investigate the prevalence of and risk factors for suicidal ideation in adolescents using a population-based sample from Switzerland, two years into the pandemic.</p><p><strong>Methods: </strong>Between December 2021 and June 2022, adolescents aged 14 to 17 years already enrolled in a population-based cohort study (State of Geneva, Switzerland) were asked about suicidal ideation over the previous year. In addition to a regression model, we conducted a network analysis of exposures which identified direct and indirect risk factors for suicidal ideation (i.e. those connected through intermediate risk factors) using mixed graphical models.</p><p><strong>Results: </strong>Among 492 adolescents, 14.4% (95% CI: 11.5-17.8) declared having experienced suicidal ideation over the previous year. Using network analysis, we found that high psychological distress, low self-esteem, identifying as lesbian, gay or bisexual, suffering from bullying, extensive screen time and a severe COVID-19 pandemic impact were major risk factors for suicidal ideation, with parent-adolescent relationship having the highest centrality strength in the network.</p><p><strong>Conclusion: </strong>Our results show that a significant proportion of adolescents experience suicidal ideation, yet these rates are comparable with pre-pandemic results. Providing psychological support is fundamental, with a focus on improving parent-adolescent relationships.</p>","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial.","authors":"Annalisa Marinosci, Delphine Sculier, Gilles Wandeler, Sabine Yerly, Marcel Stoeckle, Enos Bernasconi, Dominique L Braun, Pietro Vernazza, Matthias Cavassini, Marta Buzzi, Karin J Metzner, Laurent Decosterd, Huldrych F Günthard, Patrick Schmid, Andreas Limacher, Mattia Branca, Alexandra Calmy","doi":"10.57187/s.3762","DOIUrl":"10.57187/s.3762","url":null,"abstract":"<p><strong>Background: </strong>Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences.</p><p><strong>Materials and methods: </strong>The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales.</p><p><strong>Results: </strong>Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48.</p><p><strong>Conclusions: </strong>Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of li","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and cost-effectiveness of genetic counselling for all patients with newly diagnosed ovarian cancer: a single-centre retrospective study.","authors":"Saskia Schlootz, Flurina A M Saner, Manuela Rabaglio, Sara Imboden, Julian Wampfler","doi":"10.57187/s.3386","DOIUrl":"https://doi.org/10.57187/s.3386","url":null,"abstract":"<p><strong>Background and aims of the study: </strong>Due to its importance for treatment and potential prevention in family members, germline testing for BRCA1/2 in patients with newly diagnosed ovarian cancer is decisive and considered a standard of care. Maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitors substantially improves progression-free survival in patients with BRCA mutations and homologous recombination-deficient tumours by inducing synthetic lethality. In Switzerland, they are licensed only for these patients. Therefore, it is crucial to test patients early while they are receiving adjuvant chemotherapy. This study aimed to determine whether genetic counselling followed by homologous recombination deficiency testing is feasible for initialising maintenance therapy within eight weeks and cost-effective in daily practice in Switzerland compared to somatic tumour analysis of all patients at diagnosis.</p><p><strong>Methods: </strong>This single-centre retrospective study included 44 patients with newly diagnosed high-grade serous ovarian cancer of a Federation of Gynaecology and Obstetrics (FIGO) stage of IIIA-IVB diagnosed between 12/2020 and 12/2022. It collected the outcomes of genetic counselling, germline testing, and somatic Geneva test for homologous recombination deficiency. Delays in initiating maintenance therapy, total testing costs per patient, and progression-free survival were examined to assess feasibility and cost-effectiveness in clinical practice.</p><p><strong>Results: </strong>Thirty-seven of 44 patients (84%) with newly diagnosed ovarian cancer received counselling, of which 34 (77%) were tested for germline BRCA and other homologous recombination repair gene mutations. Five (15%) BRCA and three (9%) other homologous recombination deficiency mutations were identified. Eleven of the remaining 26 patients (42%) had tumours with somatic homologous recombination deficiency. The mean time to the initiation of maintenance therapy of 5.2 weeks was not longer than in studies for market authorisation (SOLO1, PAOLA, and PRIMA). The mean testing costs per patient were 3880 Swiss Franks (CHF), compared to 5624 CHF if all patients were tested at diagnosis with the myChoice CDx test (p <0.0001).</p><p><strong>Conclusion: </strong>Using genetic counselling to consent patients with newly diagnosed ovarian cancer for germline testing fulfils the international gold standard. Subsequent somatic homologous recombination deficiency analysis complements testing and identifies more patients who will benefit from PARP inhibitor maintenance therapy. Contrary to previous health cost model studies, the procedure does not increase testing costs in the Swiss population and does not delay maintenance therapy. Therefore, all patients should be offered a primary germline analysis. The challenge for the future will be to ensure sufficient resources for prompt genetic counselling and germline testing.</p>","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 immunity and reasons for non-vaccination among healthcare workers from eastern and northern Switzerland: results from a nested multicentre cross-sectional study.","authors":"Selina Albrecht, Fabian Grässli, Alexia Cusini, Angela Brucher, Stephan Goppel, Elsbeth Betschon, J Carsten Möller, Manuela Ortner, Markus Ruetti, Reto Stocker, Danielle Vuichard-Gysin, Ulrike Besold, Lorenz Risch, Matthias Von Kietzell, Matthias Schlegel, Pietro Vernazza, Stefan P Kuster, Christian R Kahlert, Philipp Kohler","doi":"10.57187/s.3734","DOIUrl":"10.57187/s.3734","url":null,"abstract":"<p><strong>Aims of the study: </strong>We aimed to assess the extent of SARS-CoV-2 humoral immunity elicited by previous infections and/or vaccination among healthcare workers, and to identify reasons why healthcare workers decided against vaccination.</p><p><strong>Methods: </strong>This nested cross-sectional study included volunteer healthcare workers from 14 healthcare institutions in German-speaking Switzerland. In January 2021, SARS-CoV-2 vaccines were available for healthcare workers. In May and June 2022, participants answered electronic questionnaires regarding baseline characteristics including SARS-CoV-2 vaccination status (with one or more vaccine doses defined as vaccinated) and previous SARS-CoV-2 infections. Unvaccinated participants indicated their reasons for non-vaccination. Participants underwent testing for SARS-CoV-2 anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibodies. Antibody prevalence was described across age groups. In addition, we performed multivariable logistic regression to identify baseline characteristics independently associated with non-vaccination and described reasons for non-vaccination.</p><p><strong>Results: </strong>Among 22,438 eligible employees, 3,436 (15%) participated; the median age was 43.7 years (range 16-73), 2,794 (81.3%) were female, and 1,407 (47.7%) identified as nurses; 3,414 (99.4%) underwent serology testing, among whom 3,383 (99.0%) had detectable anti-S (3,357, 98.3%) antibodies, anti-N (2,396, 70.1%) antibodies, or both (2,370, 69.4%). A total of 296 (8.6%) healthcare workers were unvaccinated, whereas 3,140 (91.4%) were vaccinated. In multivariable analysis, age (adjusted OR [aOR] 1.02 per year, 95% CI 1.01-1.03), being a physician (aOR 3.22, 95% CI 1.75-5.92) or administrator (aOR 1.88, 95% CI 1.27-2.80), and having higher education (aOR 2.23, 95% CI 1.09-4.57) were positively associated with vaccine uptake, whereas working in non-acute care (aOR 0.58, 95% CI 0.34-0.97), active smoking (aOR 0.68, 95% CI 0.51-0.91), and taking prophylactic home remedies against SARS-CoV-2 (aOR 0.42, 95% CI 0.31-0.56) were negatively associated. Important reasons for non-vaccination were a belief that the vaccine might not have long-lasting immunity (267/291, 92.1%) and a preference for gaining naturally acquired instead of vaccine-induced immunity (241/289, 83.4%).</p><p><strong>Conclusions: </strong>Almost all healthcare workers in our cohort had specific antibodies against SARS-CoV-2 from natural infection and/or from vaccination. Young healthcare workers and those working in non-acute settings were less likely to be vaccinated, whereas physicians and administrative staff showed higher vaccination uptake. Presumed ineffectiveness of the vaccine is an important reason for non-vaccination.</p>","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sickle cell disease today: a 75-year journey from \"first molecular disease\" to \"first gene-editing therapy\".","authors":"Marc Schapira, Mark J. Koury, Irene Roberts","doi":"10.57187/s.3829","DOIUrl":"https://doi.org/10.57187/s.3829","url":null,"abstract":"No abstract available.","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140719205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacometric in silico studies used to facilitate a national dose standardisation process in neonatology - application to amikacin.","authors":"V. Gotta, J. Bielicki, P. Paioni, Chantal Csajka, Dominic Stefan Bräm, Christoph Berger, Elisabeth Giger, Michael Buettcher, K. Posfay-Barbe, J. van den Anker, Marc Pfister","doi":"10.57187/s.3632","DOIUrl":"https://doi.org/10.57187/s.3632","url":null,"abstract":"BACKGROUND AND AIMS\u0000Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study.\u0000\u0000\u0000METHODS\u0000Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries. Clinical concerns have been raised for the subpopulation of neonates with a post-menstrual age of 30-35 weeks and a post-natal age of 0-14 days (\"subpopulation of clinical concern\"), as potentially oto-/nephrotoxic trough concentrations (Ctrough >5 mg/l) were observed with a once-daily dose of 15 mg/kg. We applied a two-compartmental population pharmacokinetic model (amikacin clearance depending on birth weight and post-natal age) to real-world demographic data from 1563 neonates receiving anti-infectives (median birth weight 2.3 kg, median post-natal age six days) and performed pharmacometric dose-exposure simulations to identify extended dosing intervals that would ensure non-toxic Ctrough (Ctrough <5 mg/l) dosages in most neonates.\u0000\u0000\u0000RESULTS\u0000In the subpopulation of clinical concern, Ctrough <5 mg/l was predicted in 59% versus 79-99% of cases in all other subpopulations following the current recommendations. Elevated Ctrough values were associated with a post-natal age of less than seven days. Simulations showed that extending the dosing interval to ≥36 h in the subpopulation of clinical concern increased the frequency of a desirable Ctrough below 5 mg/l to >80%.\u0000\u0000\u0000CONCLUSION\u0000Pharmacometric in silico studies using high-quality real-world demographic data can provide a scientific rationale for national paediatric dose optimisation. This may increase clinical acceptance of fine-tuned standardised dosing recommendations and support their implementation, including in vulnerable subpopulations.","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140731006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring viral aetiology in upper respiratory tract infections: insights from metagenomic next-generation sequencing in Swiss outpatients before and during the SARS-CoV-2 pandemic.","authors":"V. Kufner, Andrea C Frey, Sara H. Burkhard, S. Schmutz, Gabriela Ziltener, M. Zaheri, Caroline V Wiedmer, Andreas Plate, A. Trkola, Michael Huber, Nicolas J Mueller","doi":"10.57187/s.3797","DOIUrl":"https://doi.org/10.57187/s.3797","url":null,"abstract":"AIMS OF THE STUDY\u0000Upper respiratory tract infections are among the most common reasons for primary care consultations. They are diagnosed predominantly based on clinical assessment. Here, we investigated the benefit of viral metagenomic next-generation sequencing (mNGS) in an outpatient setting.\u0000\u0000\u0000METHODS\u0000This prospective cross-sectional study included immunocompetent patients with acute upper respiratory tract infections. General practitioners collected pharyngeal swabs and demographic and clinical data. Specimens were analysed using viral mNGS and conventional tests.\u0000\u0000\u0000RESULTS\u0000Two hundred seventy-seven patients were recruited by 21 general practitioners between 10/2019 and 12/2020, of which 91% had a suspected viral aetiology. For 138 patients (49.8%), mNGS identified one or more respiratory viruses. The mNGS showed a high overall agreement with conventional routine diagnostic tests. Rhinoviruses were the most frequently detected respiratory viruses (20.2% of patients). Viral mNGS reflected the influenza wave in early 2020 and the SARS-CoV-2 pandemic outbreak in Switzerland in March 2020. Notably, rhinoviruses continued to circulate despite non-pharmaceutical hygiene measures.\u0000\u0000\u0000CONCLUSIONS\u0000Viral mNGS allowed the initial diagnosis to be retrospectively re-evaluated. Assuming reduced turnaround times, mNGS has the potential to directly guide the treatment of upper respiratory tract infections. On an epidemiological level, our study highlights the utility of mNGS in respiratory infection surveillance, allowing early detection of epidemics and providing information crucial for prevention.","PeriodicalId":22111,"journal":{"name":"Swiss medical weekly","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140737338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}