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Heterozygous deletion of the NSDHL gene in an Appenzeller Mountain Dog with verrucous epidermal keratinocytic nevi.
Get PDFThe impact of continuity correction methods in Cochrane reviews with single-zero trials with rare events: A meta-epidemiological study.
Get PDFMeta-analyses examining dichotomous outcomes often include single-zero studies, where no events occur in intervention or control groups. These pose challenges, and several methods have been proposed to address them. A fixed continuity correction method has been shown to bias estimates, but it is frequently used because sometimes software (e.g., RevMan software in Cochrane reviews) uses it as a default. We aimed to empirically compare results using the continuity correction with those using alternative models that do not require correction. To this aim, we reanalyzed the original data from 885 meta-analyses in Cochrane reviews using the following methods: (i) Mantel-Haenszel model with a fixed continuity correction, (ii) random effects inverse variance model with a fixed continuity correction, (iii) Peto method (the three models available in RevMan), (iv) random effects inverse variance model with the treatment arm continuity correction, (v) Mantel-Haenszel model without correction, (vi) logistic regression, and (vii) a Bayesian random effects model with binominal likelihood. For each meta-analysis we calculated ratios of odds ratios between all methods, to assess how the choice of method may impact results. Ratios of odds ratios <0.8 or <1.25 were seen in ~30% of the existing meta-analyses when comparing results between Mantel-Haenszel model with a fixed continuity correction and either Mantel-Haenszel model without correction or logistic regression. We concluded that injudicious use of the fixed continuity correction in existing Cochrane reviews may have substantially influenced effect estimates in some cases. Future updates of RevMan should incorporate less biased statistical methods
Feasibility and cost-effectiveness of genetic counselling for all patients with newly diagnosed ovarian cancer: a single-centre retrospective study.
Get PDFBACKGROUND AND AIMS OF THE STUDY
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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
Physicians' emotion awareness and emotion regulation training during medical education: a systematic scoping review protocol.
Get PDFINTRODUCTION
The objective of this systematic scoping review is to identify what approaches have been implemented in medical education programmes to teach medical students the skills to identify and manage emotions that may be elicited in them during physician-patient interactions and in the clinical environment. Emotions of all involved in the clinical encounter are central to the process of clinical care. However, a gap remains addressing and teaching medical students about recognising and dealing with their own emotions.
METHODS AND ANALYSIS
This scoping review will follow the updated JBI (The Johanna Briggs Institute) methodology guidance for the conduct and reporting of systematic scoping reviews, and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. A search strategy was developed and applied to five databases. Terms used included medical education, medical curriculum, medical students, emotion (regulation), psychological well-being and mental health. Additionally, a grey literature and reference list search will be conducted. Two independent reviewers will first screen titles and abstracts followed by a second, full-text screening phase. Publications to be included will contain information and data about teaching approaches such as lectures, and other teaching material on physicians' emotion awareness and emotion regulation training in medical education.
ETHICS AND DISSEMINATION
This study will review existing literature on emotion awareness and emotion regulation training in medical education, and a systematic scoping review does not require ethical approval. The results of this scoping review will be submitted for publication to relevant peer-reviewed journals and will be used to inform the development and implementation of training programmes and research studies aimed at preparing medical students to identify and manage their own emotions in the clinical environment
Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.
Get PDFBACKGROUND
It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone.
METHODS
In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed.
FINDINGS
SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment.
INTERPRETATION
SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups.
FUNDING
Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim
The impact of motion on onboard MRI-guided pencil beam scanned proton therapy treatments.
Get PDFObjective.Online magnetic resonance imaging (MRI) guidance could be especially beneficial for pencil beam scanned (PBS) proton therapy of tumours affected by respiratory motion. For the first time to our knowledge, we investigate the dosimetric impact of respiratory motion on MRI-guided proton therapy compared to the scenario without magnetic field.Approach.A previously developed analytical proton dose calculation algorithm accounting for perpendicular magnetic fields was extended to enable 4D dose calculations. For two geometrical phantoms and three liver and two lung patient cases, static treatment plans were optimised with and without magnetic field (0, 0.5 and 1.5 T). Furthermore, plans were optimised using gantry angle corrections (0.5 T +5° and 1.5 T +15°) to reproduce similar beam trajectories compared to the 0 T reference plans. The effect of motion was then considered using 4D dose calculations without any motion mitigation and simulating 8-times volumetric rescanning, with motion for the patient cases provided by 4DCT(MRI) data sets. Each 4D dose calculation was performed for different starting phases and the CTV dose coverageV95%and homogeneityD5%-D95%were analysed.Main results.For the geometrical phantoms with rigid motion perpendicular to the beam and parallel to the magnetic field, a comparable dosimetric effect was observed independent of the magnetic field. Also for the five 4DCT(MRI) cases, the influence of motion was comparable for all magnetic field strengths with and without gantry angle correction. On average, the motion-induced decrease in CTVV95%from the static plan was 17.0% and 18.9% for 1.5 T and 0.5 T, respectively, and 19.9% without magnetic field.Significance.For the first time, this study investigates the combined impact of magnetic fields and respiratory motion on MR-guided proton therapy. The comparable dosimetric effects irrespective of magnetic field strength indicate that the effects of motion for future MR-guided proton therapy may not be worse than for conventional PBS proton therapy
Governing the reterritorialization of agricultural activities: An assessment of food planning policies in France
Get PDFDifferential reflectivity columns and hail-linking C-band radar-based estimated column characteristics to a uniquely large dataset of crowdsourced surface observations in Switzerland
Get PDFIt has been shown that differential reflectivity columns (ZDRC) are a radar signature that can be used to characterize the updrafts of severe convective storms. Consequently, various studies have attempted to link ZDRC characteristics to severe weather development, such as tornado formation, intense precipitation, and hail. Much of this work, specifically on hail, has been done on case studies with limited ground truth hail data and using S-band radar data. Here, we investigate the characteristics of ZDRC automatically detected on an operational C-band radar network and relate them to hail on the ground using 173’000 crowdsourced hail reports collected over a period of 3.5 years in Switzerland. The automated detection of ZDRC in the alpine region provides challenges regarding visibility and data quality due to effects such as ground clutter and the shielding of the radar beam by topography. Further, ZDR measurements are affected by the effects of differential attenuation and artefacts such as three-body scattering. To counteract these effects, we derive a 3D composite of ZDR using all five Swiss weather radars, two of which are located at an altitude of close to 3000m above sea level. This composite is then used to identify ZDRC by an adapted version of an established detection algorithm. The detected ZDRC areas and heights, as well as maximum measured ZDR values, are linked to reported hail size categories, and we attempt to determine thresholds to differentiate between storms producing hail of different sizes and non-hail-producing storms. Further, we investigate the potential of ZDRC to nowcast hail for possible warning applications. Switzerland is a unique location for this work due to the high frequency of hail, the good overlap of the radars, the scanning strategy with an exceptionally high spatial and temporal resolution and the large number of hail reports from the population
Convective environments in AI-models – What have Panguweather, Graphcast and Fourcastnet learned about atmospheric profiles?
Get PDFThe recently released suite of AI-based medium-range forecast models can produce multi-day
forecasts within seconds, with a skill on par with the IFS model of ECMWF. Traditional model
evaluation predominantly targets global scores on single levels. Specific prediction tasks, such
as severe convective environments, require much more precision on a local scale and with
the correct vertical gradients in between levels. With a focus on the North American and
European convective season of 2020, we assess the performance of Panguweather, Graphcast
and Fourcastnet for instability and bulk shear at lead times of up to 5 days. By advancing the
assessment of large AI-models towards process-based evaluations we lay the foundation for
hazard-driven applications of AI-weather-forecasts.
POSTE
CODE product series for the IGS-MGEX project
No full textCODE, the Center for Orbit Determination in Europe, is a joint venture of the following four institutions: Astronomical Institute, University of Bern (AIUB), Bern, Switzerland; Federal Office of Topography swisstopo, Wabern, Switzerland; Federal Agency of Cartography and Geodesy (BKG), Frankfurt a. M., Germany; Institut für Astronomische und Physikalische Geodäsie, Technische Universität München (IAPG, TUM), Munich, Germany.
It acts as a global analysis center of the International GNSS Service (IGS). The operational computations are performed at AIUB using the latest development version of the Bernese GNSS Software.
In this context a multi-GNSS solution is generated considering all active GPS, GLONASS, Galileo, BeiDou (expect for GEOs), and QZSS satellites as a contribution to the IGS-MGEX project. The results are published with a delay of about two weeks
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