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BackgroundInformal caregivers of people with dementia are at high risk of developing mental and physical distress because of the intensity of the care provided. iSupport is an evidence-based digital program developed by the World Health Organization to provide education and support for the informal everyday care of people living with dementia. ObjectiveOur study aims to describe in detail the cultural adaptation process of iSupport in Switzerland. We specifically focused on the participatory strategies we used to design a culturally adapted, Swiss version of iSupport that informed the development of the desktop version, mobile app, and printed manual. MethodsWe used a mixed methods design, with a community-based participatory approach. The adaptation of iSupport followed the World Health Organization adaptation guidelines and was developed in 4 phases: content translation, linguistic and cultural revision by the members of the community advisory board, validation with formal and informal caregivers, and refinement and final adaptation. ResultsThe findings from each phase showed and consolidated the adjustments needed for a culturally adapted, Swiss version of iSupport. We collected feedback and implemented changes related to the following areas: language register and expressions (eg, from “lesson” to “chapter” and from “suffering from” dementia to “affected by” dementia), resources (hyperlinks to local resources for dementia), contents (eg, from general nonfamiliar scenarios to local and verisimilar examples), graphics (eg, from generalized illustrations of objects to human illustrations), and extra features (eg, a glossary, a forum session, and a read-aloud option, as well as a navigation survey). ConclusionsOur study provides evidence on how to culturally adapt a digital program for informal caregivers of people living with dementia. Our results suggest that adopting a community-based participatory approach and collecting lived experiences from the final users and stakeholders is crucial to meet local needs and to inform the further development, testing, and implementation of digital interventions in a specific cultural context.

Objectives This study aimed to analyse the usability, content, readability and cultural appropriateness of alcohol and other drugs (AODs) resources for Aboriginal and Torres Strait Islander Peoples in New South Wales (NSW), Australia.Outcome measures The content of 30 AOD resources for Aboriginal and Torres Strait Islander Peoples was analysed according to the following criteria: general characteristics; elements of graphical design and written communication; thoroughness and content; readability (Flesch-Kincaid grade level (FKGL), Gunning Fog index (Fog), Simplified Measure of Gobbledygook and Flesch Reading Ease); and cultural appropriateness.Results Most resources displayed good usability, depicted by the use of headings and subheadings (n=27), superior writing style (n=19), relevant visuals (n=19) and use of colour support (n=30). However, some resources used at least one professional jargon (n=13), and many did not provide any peer-reviewed references (n=22). During content analysis, 12 resources were categorised into the alcohol group and 18 resources in the other drugs group. Impact of alcohol during pregnancy and breast feeding (n=12) was the most common included topics in the resources related to alcohol, while the physical impact of drugs (n=15) was the most discussed topics among the other drugs group. Based on the FKGL readability score, 83% of resources met the recommended reading grade level of 6–8 by NSW Health. Many resources (n=21) met at least half of the cultural appropriateness elements of interest. However, less than one-third were developed in collaboration with the local community (n=9), used local terms (n=5), targeted the local community (n=3), included an Aboriginal voice (n=2) and addressed the underlying cause (n=1).Conclusions Many AOD resources are developed specifically for Aboriginal and Torres Strait Islander Peoples, but their usability, content and readability differed, and they were not culturally appropriate for all communities. Development of a standardised protocol for resource development is suggested.

Abstract Background We aimed to determine whether living in a household with children is associated with SARS-CoV-2 seropositivity in adults and investigated interacting factors that may influence this association. Methods SARS-CoV-2 serology testing was performed in randomly selected individuals from the general population between end of October 2020 and February 2021 in 11 cantons in Switzerland. Data on sociodemographic and household characteristics, employment status, and health-related history was collected using questionnaires. Multivariable logistic regression was used to examine the association of living with children

Background Post COVID-19 condition (PCC) is an important complication of SARS-CoV-2 infection, affecting millions worldwide. This study aimed to evaluate the prevalence and severity of post COVID-19 condition (PCC) with novel SARS-CoV-2 variants and after prior vaccination. Methods We used pooled data from 1350 SARS-CoV-2-infected individuals from two representative population-based cohorts in Switzerland, diagnosed between Aug 5, 2020, and Feb 25, 2022. We descriptively analysed the prevalence and severity of PCC, defined as the presence and frequency of PCC-related symptoms six months after infection, among vaccinated and non-vaccinated individuals infected with Wildtype, Delta, and Omicron SARS-CoV-2. We used multivariable logistic regression models to assess the association and estimate the risk reduction of PCC after infection with newer variants and prior vaccination. We further assessed associations with the severity of PCC using multinomial logistic regression. To identify groups of individuals with similar symptom patterns and evaluate differences in the presentation of PCC across variants, we performed exploratory hierarchical cluster analyses. Results We found strong evidence that vaccinated individuals infected with Omicron had reduced odds of developing PCC compared to non-vaccinated Wildtype-infected individuals (odds ratio 0.42, 95% confidence interval 0.24–0.68). The odds among non-vaccinated individuals were similar after infection with Delta or Omicron compared to Wildtype SARS-CoV-2. We found no differences in PCC prevalence with respect to the number of received vaccine doses or timing of last vaccination. The prevalence of PCC-related symptoms among vaccinated, Omicron-infected individuals was lower across severity levels. In cluster analyses, we identified four clusters of diverse systemic, neurocognitive, cardiorespiratory, and musculoskeletal symptoms, with similar patterns across variants. Conclusion The risk of PCC appears to be lowered with infection by the Omicron variant and after prior vaccination. This evidence is crucial to guide future public health measures and vaccination strategies.

As infecções associadas aos Dispositivos Cardíacos Eletrônicos Implantáveis (DCEI) apresentam uma incidência de até 3,4% e notável impacto na morbidade e mortalidade dos pacientes. As bactérias Gram-positivas, especialmente do gênero Staphylococcus sp. representam 60-70% dos agentes isolados. Por sua vez, as Gram-negativas correspondem até 9% dos casos. Relatamos uma infecção de loja de gerador de Cardioversor-desfibrilador implantável (CDI) por uma Klebsiella sp. resistente aos carbapenêmicos, em um paciente masculino jovem, cujo desafiador diagnóstico de certeza desse caso somente foi possível após exploração cirúrgica e cultura do material da loja do CDI, haja vista a apresentação clínica oligossintomática. Embora já descritas, Klebsiella sp. são raras nesse contexto e em nosso conhecimento, esse é o primeiro relato de uma infecção de DCEI por uma enterobactéria resistente a carbapenêmico.

Introduction Drivers of lower vaccine efficacy and impaired vaccine-specific immune responses in low-income versus high-income countries, and in rural compared with urban settings, are not fully elucidated. Repeated exposure to and immunomodulation by parasite infections may be important. We focus on Plasmodium falciparum malaria, aiming to determine whether there are reversible effects of malaria infection on vaccine responses.Methods and analysis We have designed a randomised, double-blind, placebo-controlled, parallel group trial of intermittent preventive malaria treatment versus placebo, to determine effects on vaccine response outcomes among school-going adolescents (9 to 17 years) from malaria-endemic rural areas of Jinja district (Uganda). Vaccines to be studied comprise BCG vaccine on day ‘zero’; yellow fever, oral typhoid and human papilloma virus vaccines at week 4; and tetanus/diphtheria booster vaccine at week 28. Participants in the intermittent preventive malaria treatment arm will receive dihydroartemisinin/piperaquine (DP) dosed by weight, 1 month apart, prior to the first immunisation, followed by monthly treatment thereafter. We expect to enrol 640 adolescents. Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. In secondary analyses, we will determine effects of monthly DP treatment (versus placebo) on correlates of protective immunity, on vaccine response waning, on whether there are differential effects on priming versus boosting immunisations, and on malaria infection prevalence. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of the intervention on vaccine responses.Ethics and dissemination Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration number Current Controlled Trials identifier: ISRCTN62041885.

Introduction Vaccine-specific immune responses vary between populations and are often impaired in low income, rural settings. Drivers of these differences are not fully elucidated, hampering identification of strategies for optimising vaccine effectiveness. We hypothesise that urban–rural (and regional and international) differences in vaccine responses are mediated to an important extent by differential exposure to chronic infections, particularly parasitic infections.Methods and analysis Three related trials sharing core elements of study design and procedures (allowing comparison of outcomes across the trials) will test the effects of (1) individually randomised intervention against schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus Calmette-Guérin (BCG) revaccination (trial C), on a common set of vaccine responses. We will enrol adolescents from Ugandan schools in rural high-schistosomiasis (trial A) and rural high-malaria (trial B) settings and from an established urban birth cohort (trial C). All participants will receive BCG on day ‘0’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. Primary outcomes are BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine effects of interventions on correlates of protective immunity, vaccine response waning, priming versus boosting immunisations, and parasite infection status and intensity. Overarching analyses will compare outcomes between the three trial settings. Sample archives will offer opportunities for exploratory evaluation of the role of immunological and ‘trans-kingdom’ mediators in parasite modulation of vaccine-specific responses.Ethics and dissemination Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numbers ISRCTN60517191, ISRCTN62041885, ISRCTN10482904.

Introduction Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysis We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and dissemination Ethics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration number ISRCTN60517191.

IntroductionHigh participation in epidemiological studies is crucial for both external and internal validity. Because response rates have declined in recent years, there is an increasing need to understand the drivers and the barriers to research participation. This study aims to uncover the motivations in favour and against participation of older adults to an epidemiological study on health and dementia.MethodsTwenty-two older adults, who already took part to the preliminary phase of an epidemiological study in Switzerland, agreed to participate to semi-structured, face-to- face interviews. An experienced researcher carried out all interviews in a quiet place of choice of the interviewee either at their domicile or the university, between November 2019 and January 2020. The interviews were audio and video taped, transcribed verbatim, and thematically analysed by two independent researchers.ResultsWe identified three main themes for the motivations in favour of participation (i.e. personal, related to the outcomes of research, and altruistic motivations), and we highlighted subthemes for each theme (e.g. personal motivations: curiosity; civic engagement; interest in the topic; trust in science; everyone counts; openness; play the game). Motivations against participation reflected the first two themes, while there was no counterpart for altruistic motivations.ConclusionsOur thematic analysis revealed that older adults hold specular motivations in favour and against participation to research. Studying jointly motivations in favour and against provides information for recruitment strategies and to overcome barriers to participation, respectively. Participatory action research can inform the design and conduction of and should precede epidemiological studies in older adults, and can potentially contribute to attain high response rates.

We previously identified a guanidinium-based lead compound that inhibited BRAF through a hypothetic type-III allosteric mechanism. Considering the pharmacophore identified in this lead compound (i.e., “lipophilic group”, “di-substituted guanidine”, “phenylguanidine polar end”), several modifications were investigated to improve its cytotoxicity in different cancer cell lines. Thus, several lipophilic groups were explored, the di-substituted guanidine was replaced by a secondary amine and the phenyl ring in the polar end was substituted by a pyridine. In a structure-based design approach, four representative derivatives were docked into an in-house model of an active triphosphate-containing BRAF protein, and the interactions established were analysed. Based on these computational studies, a variety of derivatives was synthesized, and their predicted drug-like properties calculated. Next, the effect on cell viability of these compounds was assessed in cell line models of promyelocytic leukaemia and breast, cervical and colorectal carcinomas. The potential of a selection of these compounds as apoptotic agents was assessed by screening in the promyelocytic leukaemia cell line HL-60. The toxicity against non-tumorigenic epithelial MCF10A cells was also investigated. These studies allowed for several structure-activity relationships to be derived. Investigations on the mechanism of action of representative compounds suggest a divergent effect on inhibition of the MAPK/ERK signalling pathway.