Importation of Alpha and Delta variants during the SARS-CoV-2 epidemic in Switzerland: Phylogenetic analysis and intervention scenarios.

The SARS-CoV-2 pandemic has led to the emergence of various variants of concern (VoCs) that are associated with increased transmissibility, immune evasion, or differences in disease severity. The emergence of VoCs fueled interest in understanding the potential impact of travel restrictions and surveillance strategies to prevent or delay the early spread of VoCs. We performed phylogenetic analyses and mathematical modeling to study the importation and spread of the VoCs Alpha and Delta in Switzerland in 2020 and 2021. Using a phylogenetic approach, we estimated between 383-1,038 imports of Alpha and 455-1,347 imports of Delta into Switzerland. We then used the results from the phylogenetic analysis to parameterize a dynamic transmission model that accurately described the subsequent spread of Alpha and Delta. We modeled different counterfactual intervention scenarios to quantify the potential impact of border closures and surveillance of travelers on the spread of Alpha and Delta. We found that implementing border closures after the announcement of VoCs would have been of limited impact to mitigate the spread of VoCs. In contrast, increased surveillance of travelers could prove to be an effective measure for delaying the spread of VoCs in situations where their severity remains unclear. Our study shows how phylogenetic analysis in combination with dynamic transmission models can be used to estimate the number of imported SARS-CoV-2 variants and the potential impact of different intervention scenarios to inform the public health response during the pandemic

Social contacts and attitudes towards vaccination during the COVID-19 pandemic: Insights from the CoMix study.

During the coronavirus disease 2019 (COVID-19) pandemic, individuals adapted their patterns of social contact to avoid pathogen exposure and due to government restrictions that aimed to slow down disease transmission. Studying the changing social contact patterns during the pandemic can play an important role to improve future pandemic responses. Furthermore, a better understanding of COVID-19 vaccination uptake and attitudes towards vaccination in different age and socioeconomic groups can help inform vaccination strategies. CoMix is a social contact survey that follows households across Europe in real-time over the course of the COVID-19 pandemic. In Switzerland, we conducted the CoMix study over 24 survey waves from January 2021 to May 2022. Across all survey waves and participants, the average number of reported contacts was 4.8 per day. The number of contacts were highest in the age group of 0-18 year olds and lowest in people who are 65 or older. The survey captured the vaccination uptake in the general population well and participants provided detailed insights into their reasons to get vaccinated and to not get vaccinated. The CoMix study provides the first detailed data on social contact patterns in Switzerland. The results from the study can be used to improve pandemic preparedness, parameterize mathematical models of infectious disease transmission, and design future vaccination strategies

Impact of cross-border-associated cases on the SARS-CoV-2 epidemic in Switzerland during summer 2020 and 2021

During the summers of 2020 and 2021, the number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Switzerland remained at relatively low levels, but grew steadily over time. It remains unclear to what extent epidemic growth during these periods was a result of the relaxation of local control measures or increased traveling and subsequent importation of cases. A better understanding of the role of cross-border-associated cases (imports) on the local epidemic dynamics will help to inform future surveillance strategies. We analyzed routine surveillance data of confirmed cases of SARS-CoV-2 in Switzerland from 1 June to 30 September 2020 and 2021. We used a stochastic branching process model that accounts for superspreading of SARS-CoV-2 to simulate epidemic trajectories in absence and in presence of imports during summer 2020 and 2021. The Swiss Federal Office of Public Health reported 22,919 and 145,840 confirmed cases of SARS-CoV-2 from 1 June to 30 September 2020 and 2021, respectively. Among cases with known place of exposure, 27% (3,276 of 12,088) and 25% (1,110 of 4,368) reported an exposure abroad in 2020 and 2021, respectively. Without considering the impact of imported cases, the steady growth of confirmed cases during summer periods would be consistent with a value of that is significantly above the critical threshold of 1. In contrast, we estimated at 0.84 (95% credible interval, CrI: 0.78–0.90) in 2020 and 0.82 (95% CrI: 0.74–0.90) in 2021 when imported cases were taken into account, indicating that the local was below the critical threshold of 1 during summer. In Switzerland, cross-border-associated SARS-CoV-2 cases had a considerable impact on the local transmission dynamics and can explain the steady growth of the epidemic during the summers of 2020 and 2021

Socio-demographic characteristics associated with COVID-19 vaccination uptake in Switzerland: longitudinal analysis of the CoMix study.

BACKGROUND Vaccination is an effective strategy to reduce morbidity and mortality from coronavirus disease 2019 (COVID-19). However, the uptake of COVID-19 vaccination has varied across and within countries. Switzerland has had lower levels of COVID-19 vaccination uptake in the general population than many other high-income countries. Understanding the socio-demographic factors associated with vaccination uptake can help to inform future vaccination strategies to increase uptake. METHODS We conducted a longitudinal online survey in the Swiss population, consisting of six survey waves from June to September 2021. Participants provided information on socio-demographic characteristics, history of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), social contacts, willingness to be vaccinated, and vaccination status. We used a multivariable Poisson regression model to estimate the adjusted rate ratio (aRR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake. RESULTS We recorded 6,758 observations from 1,884 adults. For the regression analysis, we included 3,513 observations from 1,883 participants. By September 2021, 600 (75%) of 806 study participants had received at least one vaccine dose. Participants who were older, male, and students, had a higher educational level, household income, and number of social contacts, and lived in a household with a medically vulnerable person were more likely to have received at least one vaccine dose. Female participants, those who lived in rural areas and smaller households, and people who perceived COVID-19 measures as being too strict were less likely to be vaccinated. We found no significant association between previous SARS-CoV-2 infections and vaccination uptake. CONCLUSIONS Our results suggest that socio-demographic factors as well as individual behaviours and attitudes played an important role in COVID-19 vaccination uptake in Switzerland. Therefore, appropriate communication with the public is needed to ensure that public health interventions are accepted and implemented by the population. Tailored COVID-19 vaccination strategies in Switzerland that aim to improve uptake should target specific subgroups such as women, people from rural areas or people with lower socio-demographic status

A review of the use of high-flow nasal cannula oxygen therapy in hospitalised children at a regional hospital in the Cape Town Metro, South Africa

Background. High-flow nasal cannula (HFNC) oxygen is a non-invasive alternative to nasal continuous positive airway pressure (CPAP) therapy for infants and children requiring respiratory support. There is a paucity of data to support its use in children, with no published data from sub-Saharan Africa.Objectives. To describe the outcomes of and adverse events related to HFNC in the first year of its use in a level 2 (L2) general paediatric ward, and to compare these outcomes with those of a historical cohort when this intervention was unavailable.Methods. This retrospective descriptive study included children aged <13 years who received HFNC in the first 12 months after its introduction (HFNC-availability group, n=66). Demographic data, clinical characteristics and outcomes (death, treatment failure, length of HFNC and HFNC-related adverse events) were assessed. A comparative description of children who required transfer to level 3 (L3) for any form of respiratory support (other than the available standard low-flow oxygen) during the 12-month period prior to HFNC availability (pre-HFNC group, n=54) was made. All analyses were performed in the paediatric wards, New Somerset Hospital, Cape Town, South Africa. Outcomes were compared using standard descriptive and comparative statistics.Results. The median age of the cohort was 5 months (interquartile range (IQR) 1.9 - 14.6). Sixteen children (13.3%) were malnourished, 10 (8.3%) were HIV-infected, and 30 (25.0%) had been born prematurely. The most common diagnoses were pneumonia, bronchiolitis and asthma. Asthma, anaemia and cardiac abnormalities were the most prevalent underlying comorbidities. Two children died in each group. All 54 children in the pre-HFNC group were transferred to L3; 38 (70.4%) needed CPAP or invasive ventilation. In the HFNC-availability period, 85 children were assessed as needing more than standard low-flow oxygen therapy: of the 19 immediately transferred to L3, 17 (89.4%) received CPAP or invasive ventilation; of the 66 who received HFNC at L2, 16 (24.2%) subsequently required transfer to L3 for CPAP or invasive ventilation. The median duration of HFNC was 46.3 hours (IQR 19.5 - 93.5) overall, and it was 12 hours (IQR 4 - 28) and 58.5 hours (IQR 39.5 - 106) for those who failed or were successfully managed on HFNC, respectively. No HFNC-related serious adverse events were recorded.Conclusions. HFNC is a safe, effective, feasible option for non-invasive ventilation of children with respiratory illnesses in a resource-limited L2 setting. A greater proportion of children with lower respiratory tract infections in the HFNC-availability group than in the pre-HFNC group required support, but the intervention reduced the bed pressure on L3. Improved ways to identify HFNC failures would be beneficial

Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland.

Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland. We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy. Improvements were reported in 59 (66%) study participants. The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young. What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders. What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting. • The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions

Natural polymorphisms in mycobacterium tuberculosis conferring resistance to delamanid in drug-naïve patients.

Mutations in the genes of the F420 signaling pathway, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, of Mycobacterium tuberculosis (Mtb) complex can lead to delamanid resistance. We searched for such mutations among 129 Mtb strains from Asia, South-America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For ten strains with mutations, we determined the minimum inhibitory concentration (MIC) of delamanid. We found one strain from a delamanid-naïve patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical MIC to delamanid

Ultrastructure of the organ of Corti in harbor seals (Phoca vitulina)

Ultrastructural descriptions of the inner ear of highly sound-dependent mammalian species are lacking and needed to gain a better understanding of the hearing sense. Here, we present the first morphometric descriptions of the sensory cells of the inner ear in the harbor seal (Phoca vitulina), a mammal with broadly sensitive amphibious hearing. Scanning electron micrographs of the apical surface of the outer hair cells (OHCs) and inner hair cells (IHCs) within the organ of Corti were obtained from five individuals and analyzed by linear and geometric morphometrics. Measurements were taken at regular locations along the cochlea. The spiral shape of the seal cochlea contained two and a half turns. The organ of Corti had an average length of 27.7 mm with 12,628 OHCs (12,400-12,900). Six linear morphometric parameters showed significant patterns of change associated with their location within the cochlear spiral. Likewise, these trends were similarly expressed in cell configuration (cell blocks with 57 landmarks in 12 representative cells) revealed by geometric morphometry. Cell configuration varied predictably with position in the cochlea according to clustering analyses and Procrustes ANOVA (F= 25.936, p&lt;0001). Changes associated with OHCs were primarily responsible for observed changes in cell configuration. An integration trend in cell shape change was also observed in which IHCs and OHCs share features in their morphological variation by the two-block partial least squares analysis (CR=0.987, p&lt;0.001) and the modularity hypothesis (CV=0.99, p=0.05). These descriptive and quantitative findings provide a baseline for the morphology and morphometry of the sensory cells of the organ of Corti in harbor seals, allowing for comparisons between normal and pathological features. This initial morphological description should enable the correlation between position, morphometric features, and frequency coding along the spiral of the inner ear in this species, whose hearing ability is well studied

Inconsistency in aortic stenosis severity between CT and echocardiography: Prevalence and insights into mechanistic differences using computational fluid dynamics

© 2019 Author(s). Objectives The aims of this study were to evaluate the inconsistency of aortic stenosis (AS) severity between CT aortic valve area (CT-AVA) and echocardiographic Doppler parameters, and to investigate potential underlying mechanisms using computational fluid dynamics (CFD). Methods A total of 450 consecutive eligible patients undergoing transcatheter AV implantation assessment underwent CT cardiac angiography (CTCA) following echocardiography. CT-AVA derived by direct planimetry and echocardiographic parameters were used to assess severity. CFD simulation was performed in 46 CTCA cases to evaluate velocity profiles. Results A CT-AVA>1 cm 2 was present in 23% of patients with echocardiographic peak velocity≥4 m/s (r=-0.33) and in 15% patients with mean Doppler gradient≥40 mm Hg (r=-0.39). Patients with inconsistent severity grading between CT and echocardiography had higher stroke volume index (43 vs 38 mL/m 2, p1 cm 2 in up to a quarter of patients. CFD demonstrates that haemodynamic severity may be exaggerated on Doppler analysis due to high LVOT flow rates, with or without skewed velocity profiles, across the valve orifice. These factors should be considered before making a firm diagnosis of severe AS and evaluation with CT can be helpful

Availability and experiences of differentiated antiretroviral therapy delivery at HIV care facilities in rural Zimbabwe: a mixed-method study.

INTRODUCTION: Zimbabwe adopted differentiated HIV care policies in 2015 to promote client-centred care and relieve strain on health facilities. We examined the availability, experiences and perceptions of differentiated antiretroviral therapy (ART) delivery in rural Zimbabwe following the policy adoption. METHODS: We undertook a cross-sectional mixed methods study in all the 26 facilities providing HIV care in a rural district in Zimbabwe. We collected quantitative data about ART delivery and visit durations from 31 healthcare providers and a purposive stratified sample of 378 clients obtaining ART either through routine care or differentiated ART delivery models. We performed 26 semi-structured interviews among healthcare providers and seven focus group discussions (FGDs) among clients to elicit their perceptions and experiences of ART delivery. Data were collected in 2019, with one follow-up FGD in 2021. We analysed the transcripts thematically, with inductive coding, to identify emerging themes. RESULTS: Twenty facilities (77%) offered at least one differentiated ART delivery models, including community ART refill groups (CARGs; 13 facilities, 50%), fast-track refill (8, 31%), family refill (6, 23%) or club refill (1, 4%). Thirteen facilities (50%) offered only one model. The median visit duration was 28 minutes (interquartile range [IQR]: 16-62). Participants in fast-track had the shortest visit durations (18 minutes, IQR: 11-24). Confidentiality and disclosure of HIV status, travelling long distances, travel costs and waiting times were the main issues influencing clients' views on differentiated ART delivery. Fast-track refill was perceived as the preferred model of clients for its limited involuntary disclosure and efficiency. In contrast, group- and community-based refill models reduced travel costs but were felt to be associated with involuntary disclosure of HIV status, which could discourage clients. Healthcare providers also experienced an additional workload when offering facility-based group models, such as CARGs. CONCLUSIONS: Differentiated ART delivery models were widely available in this rural setting, but most facilities did not offer a choice of models to address clients' diverse preferences. A minority offered fast-track refills, although this model was often mentioned as desirable. Confidentiality, travel expenses and client waiting times are key elements to consider when planning and rolling out differentiated HIV care