Educational inequalities in multimorbidity at older ages: a multi-generational population-based study.

BACKGROUND: Social inequalities in multimorbidity may occur due to familial and/or individual factors and may differ between men and women. Using population-based multi-generational data, this study aimed to (1) assess the roles of parental and individual education in the risk of multimorbidity and (2) examine the potential effect modification by sex. METHODS: Data were analysed from 62 060 adults aged 50+ who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 European countries. Intergenerational educational trajectories (exposure) were High-High (reference), Low-High, High-Low and Low-Low, corresponding to parental-individual educational attainments. Multimorbidity (outcome) was ascertained between 2013 and 2020 as self-reported occurrence of ≥2 diagnosed chronic conditions. Inequalities were quantified as multimorbidity-free years lost (MFYL) between the ages of 50 and 90 and estimated via differences in the area under the standardized cumulative risk curves. Effect modification by sex was assessed via stratification. RESULTS: Low individual education was associated with higher multimorbidity risk regardless of parental education. Compared to the High-High trajectory, Low-High was associated with -0.2 MFYL (95% confidence intervals: -0.5 to 0.1), High-Low with 3.0 (2.4-3.5), and Low-Low with 2.6 (2.3-2.9) MFYL. This pattern was observed for both sexes, with a greater magnitude for women. This effect modification was not observed when only diseases diagnosed independently of healthcare-seeking behaviours were examined. CONCLUSIONS: Individual education was the main contributor to intergenerational inequalities in multimorbidity risk among older European adults. These findings support the importance of achieving a high education to mitigate multimorbidity risk.

Effect of dairy consumption on cognition in older adults: A population-based cohort study.

OBJECTIVE: We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy. DESIGN: Secondary analysis of a prospective population-based cohort study. PARTICIPANTS: We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland. MEASUREMENTS: The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes. METHODS: Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up. RESULTS: Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (-3% to 26.5%)] and eggs [18% (2.3%-33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes. CONCLUSION: We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results.

Residential relocation to assess impact of changes in the living environment on cardio-respiratory health: A narrative literature review with considerations for exposome research.

Residential relocation studies have become increasingly valuable tools for evaluating the effects of changing living environments on human health, but little is known about their application to multiple aspects of the living environment and the most appropriate methodology. This narrative review explores the utility of residential relocation as a natural experiment for studying the impact of changing urban exposures on cardio-metabolic health in high-income settings. It provides a comprehensive overview of the use of residential relocation studies, evaluates their methodological approaches, and synthesizes findings related to health behaviors and cardio-metabolic outcomes. Our search identified 43 relevant studies published between January 1995 and February 2023, from eight countries, predominantly the USA, Canada, and Australia. The majority of eligible studies were published between 2012 and 2021 and examined changes in various domains of the living environment, such as walkability, the built and social environments, but rarely combinations of exposures. Included studies displayed heterogeneity in design and outcomes, 25 involving only movers and 18 considering both movers and non-movers. To mitigate the issue of residential self-selection bias, most studies employed a "change-in-change" design and adjusted for baseline covariates but only a fraction of them accounted for time-varying confounding. Relocation causes simultaneous changes in various features of the living environment, which presents an opportunity for exposome research to establish causal relationships, using large datasets with increased statistical power and a wide range of health outcomes, behaviors and biomarkers. Residential relocation is not a random process. Thus, studies focusing on living environment characteristics need to carefully select time-varying covariates and reference group. Overall, this review informs future research by guiding choices in study design, data requirements, and statistical methodologies. Ultimately, it contributes to the advancement of the urban exposome field and enhances our understanding of the complex relationship between urban environments and human health.

Dairy Intake and Risk of Cognitive Decline and Dementia: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with >300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.

Factors Associated With COVID-19 Non-Vaccination in Switzerland: A Nationwide Study.

Objectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness.

Doença de Fabry e 18 meses de terapia de reposição enzimática: relato de caso / Fabry disease and 18 months of enzyme replacement therapy: case report

INTRODUÇÃO: Doença de Fabry (DF) é uma doença de depósito lisossomal causada pela mutação do gene GLA do cromossomo X, que codifica a enzima α-galactosidase A. Como consequência, há acúmulo progressivo de glicoesfingolipídeos em diversos tecidos, dentre eles pele, rins, coração, sistema nervoso e endotélio vascular. Descrevemos o caso clínico de um paciente (p) jovem com diagnóstico de DF e sua resposta terapêutica após18 meses de terapia de reposição enzimática (TRE). RELATO DE CASO: p masculino, 24 anos.Aos 8 anos de idade iniciou quadro de acroparestesia, hipoidrose e dores em queimação em ambos os pés, que se manifestavam ao praticar atividades físicas. Aos 10 anos de idade, as dores progrediram para as mãos e despertaram-se crises de dores, associadas à fadiga e sensação de hipertermia. Aos 15 anos, surgiram angioqueratomas difusos na cintura pélvica, mãos, braços, costas e joelhos. O diagnóstico de DF foi confirmado aos 22 anos de idade, com a positividade da variante patogênica c.334C>T no gene GLA. Ao diagnóstico, o eletrocardiograma constatou distúrbio de condução de ramo direito, ecocardiograma e ressonância magnética normais. Antes do início da TRE, o paciente apresentou dosagem do biomarcador liso Gb-3 de 25,7ng/ml (valor de referência: < 2,0ng/ml). Instituiu-se a TRE com infusões intravenosas quinzenais de 1mg/kg de beta-agalsidase.Após nove meses de terapia, nova dosagem do liso Gb-3 reduziu para 10,9 ng/ml.Após 18 meses do início da TRE, o p observou diminuição da intensidade das dores, fadiga e frequência das crises de fabry, com melhora da qualidade de vida.Todavia, mantém o avanço de angioqueratomas e microalbuminúria, em uso de inibidor de enzima conversora de angiotensina. CONCLUSÃO: relatamos um caso com retardo diagnóstico de 14 anos, apesar de consultas médicasfrequentes. Contudo, o diagnóstico e o início da TRE ocorreram antes da instalação de alterações cardíacas e renais bem estabelecidas. A TRE foi associada à importante melhora sintomática e à redução significativa do biomarcador liso Gb-3, de 25 para 10ng/ml. Apesar da melhora clínica, ainda continuam a ocorrer crises de dor, aparecimento de novos angioqueratomas e microalbuminúria. Com diagnóstico na infância, possivelmente os sintomas poderiam ter sido aliviados antecipadamente e a microalbuminúria provavelmente prevenida, o que reforça a importância do conhecimento da doença de Fabry para o sucesso terapêutico precoce.

Seroprevalence trends of anti-SARS-CoV-2 antibodies and associated risk factors: a population-based study.

PURPOSE: We aimed to assess the seroprevalence trends of SARS-CoV-2 antibodies in several Swiss cantons between May 2020 and September 2021 and investigate risk factors for seropositivity and their changes over time. METHODS: We conducted repeated population-based serological studies in different Swiss regions using a common methodology. We defined three study periods: May-October 2020 (period 1, prior to vaccination), November 2020-mid-May 2021 (period 2, first months of the vaccination campaign), and mid-May-September 2021 (period 3, a large share of the population vaccinated). We measured anti-spike IgG. Participants provided information on sociodemographic and socioeconomic characteristics, health status, and adherence to preventive measures. We estimated seroprevalence with a Bayesian logistic regression model and the association between risk factors and seropositivity with Poisson models. RESULTS: We included 13,291 participants aged 20 and older from 11 Swiss cantons. Seroprevalence was 3.7% (95% CI 2.1-4.9) in period 1, 16.2% (95% CI 14.4-17.5) in period 2, and 72.0% (95% CI 70.3-73.8) in period 3, with regional variations. In period 1, younger age (20-64) was the only factor associated with higher seropositivity. In period 3, being aged ≥ 65 years, with a high income, retired, overweight or obese or with other comorbidities, was associated with higher seropositivity. These associations disappeared after adjusting for vaccination status. Seropositivity was lower in participants with lower adherence to preventive measures, due to a lower vaccination uptake. CONCLUSIONS: Seroprevalence sharply increased over time, also thanks to vaccination, with some regional variations. After the vaccination campaign, no differences between subgroups were observed.

Changes in socioeconomic resources and mental health after the second COVID-19 wave (2020-2021): a longitudinal study in Switzerland.

BACKGROUND: During the 2020/2021 winter, the labour market was under the impact of the COVID-19 pandemic. Changes in socioeconomic resources during this period could have influenced individual mental health. This association may have been mitigated or exacerbated by subjective risk perceptions, such as perceived risk of getting infected with SARS-CoV-2 or perception of the national economic situation. Therefore, we aimed to determine if changes in financial resources and employment situation during and after the second COVID-19 wave were prospectively associated with depression, anxiety and stress, and whether perceptions of the national economic situation and of the risk of getting infected modified this association. METHODS: One thousand seven hundred fifty nine participants from a nation-wide population-based eCohort in Switzerland were followed between November 2020 and September 2021. Financial resources and employment status were assessed twice (Nov2020-Mar2021, May-Jul 2021). Mental health was assessed after the second measurement of financial resources and employment status, using the Depression, Anxiety and Stress Scale (DASS-21). We modelled DASS-21 scores with linear regression, adjusting for demographics, health status, social relationships and changes in workload, and tested interactions with subjective risk perceptions. RESULTS: We observed scores above thresholds for normal levels for 16% (95%CI = 15-18) of participants for depression, 8% (95%CI = 7-10) for anxiety, and 10% (95%CI = 9-12) for stress. Compared to continuously comfortable or sufficient financial resources, continuously precarious or insufficient resources were associated with worse scores for all outcomes. Increased financial resources were associated with higher anxiety. In the working-age group, shifting from full to part-time employment was associated with higher stress and anxiety. Perceiving the Swiss economic situation as worrisome was associated with higher anxiety in participants who lost financial resources or had continuously precarious or insufficient resources. CONCLUSION: This study confirms the association of economic stressors and mental health during the COVID-19 pandemic and highlights the exacerbating role of subjective risk perception on this association.

Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers.

BACKGROUND: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. METHODS: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. FINDINGS: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. INTERPRETATION: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. FUNDING: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.

Adult human neurogenesis: early studies clarify recent controversies and go further.

Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). However, findings published from 2018 rekindled controversies on adult human SGZ neurogenesis. We systematically reviewed studies published during the first decade of characterization of adult human neurogenesis (1994-2004) - when the two-neurogenic-niche concept in humans was consolidated - and compared with further studies. The synthesis of both periods is that adult human neurogenesis occurs in an intensity ranging from practically zero to a level comparable to adult mammalian neurogenesis in general, which is the prevailing conclusion. Nonetheless, Bernier and colleagues showed in 2000 intriguing indications of adult human neurogenesis in a broad area including the limbic system. Likewise, we later showed evidence that limbic and hypothalamic structures surrounding the circumventricular organs form a continuous zone expressing neurogenesis markers encompassing the SGZ and SVZ. The conclusion is that publications from 2018 on adult human neurogenesis did not bring novel findings on location of neurogenic niches. Rather, we expect that the search of neurogenesis beyond the canonical adult mammalian neurogenic niches will confirm our indications that adult human neurogenesis is orchestrated in a broad brain area. We predict that this approach may, for example, clarify that human hippocampal neurogenesis occurs mostly in the CA1-subiculum zone and that the previously identified human rostral migratory stream arising from the SVZ is indeed the column of the fornix expressing neurogenesis markers.

Reliability of Self-Reported Height and Weight in Children: A School-Based Cross-Sectional Study and a Review.

Since anthropometric measurements are not always feasible in large surveys, self-reported values are an alternative. Our objective was to assess the reliability of self-reported weight and height values compared to measured values in children with (1) a cross-sectional study in Switzerland and (2) a comprehensive review with a meta-analysis. We conducted a secondary analysis of data from a school-based study in Switzerland of 2616 children and a review of 63 published studies including 122,629 children. In the cross-sectional study, self-reported and measured values were highly correlated (weight: r = 0.96; height: r = 0.92; body mass index (BMI) r = 0.88), although self-reported values tended to underestimate measured values (weight: -1.4 kg; height: -0.9 cm; BMI: -0.4 kg/m2). Prevalence of underweight was overestimated and prevalence of overweight was underestimated using self-reported values. In the meta-analysis, high correlations were found between self-reported and measured values (weight: r = 0.94; height: r = 0.87; BMI: r = 0.88). Weight (-1.4 kg) and BMI (-0.7 kg/m2) were underestimated, and height was slightly overestimated (+0.1 cm) with self-reported values. Self-reported values tended to be more reliable in children above 11 years old. Self-reported weight and height in children can be a reliable alternative to measurements, but should be used with caution to estimate over- or underweight prevalence.

Riesgo biomecánico por sobrecarga estática y presencia de trastornos musculoesqueléticos en odontólogos durante su práctica clínica asistencial. Una revisión narrativa / Ergonomic risk by static overload and musculoskeletal disorders in dental practice: a review / Risco biomecânico devido a sobrecarga estática e presença de distúrbios musculosqueléticos em dentistas durante sua prática clínica de assistência. Uma revisão narrativa

Resumen Los trastornos musculoesqueléticos son lesiones que afectan el movimiento corporal, incluyendo músculos, tendones, ligamentos, entre otros. Estos trastornos son unos de los problemas más importantes en la práctica clínica odontológica, ocasionados en su mayoría por sobrecarga física tanto dinámica como estática, en particular para esta última, toma relevancia la postura mantenida en posición bípeda o sedente durante la realización de procedimientos extremadamente precisos en un espacio de trabajo tan pequeño como lo es la cavidad oral; por esto, se pretende con base en la literatura existente, describir el riesgo biomecánico por sobrecarga estática y los trastornos musculoesqueléticos en odontólogos. Con esta intención se realizó una revisión narrativa de la literatura científica al respecto en español e inglés de productos de investigación de los últimos diez años, utilizando descriptores DeCS y MeSH, en fuentes académicas y científicas de Pubmed, Medline, Scopus y Google académico en donde se seleccionaron 50 artículos teniendo como resultado principal que si existe una relación entre riesgo biomecánico y sobrecarga estática con la aparición de trastornos musculoesqueléticos.

Abstract Musculoskeletal disorders are injuries that affect body movement, including muscles, tendons, ligaments, among others. These disorders are one of the most important problems in dental clinical practice, caused mostly by static overload due to prolonged posture in a standing or sitting position when performing extremely precise procedures in a workspace as small as the oral cavity; For this reason, based on the existing literature, it is intended to describe the biomechanical risk due to static overload and musculoskeletal disorders in dentists. With this intention, a narrative review of the scientific literature on the matter in Spanish and English of research products of the last ten years was carried out using DeCS and MeSH descriptors, in academic and scientific sources of PubMed, Medline, Scopus and academic Google in where 50 articles were selected, the main result being that there is a relationship between biomechanics factors and static overload with the use appearance of musculoskeletal disorders.

Resumo As desordens musculoesqueléticas são lesões que afetam os movimentos do corpo, incluindo músculos, tendões, ligamentos, entre outros. Esses distúrbios constituem um dos problemas mais importantes na prática clínica odontológica, ocasionados principalmente pela sobrecarga física, tanto dinâmica quanto estática, em particular para esta última, torna-se relevante a postura mantida na posição bípede ou sentada durante procedimentos extremamente precisos. tão pequeno quanto a cavidade oral; Portanto, pretende-se, com base na literatura existente, descrever o risco biomecânico devido à sobrecarga estática e distúrbios musculoesqueléticos em dentistas. Com esse intuito, foi realizada uma revisão narrativa da produção científica sobre o assunto, em espanhol e inglês, de produtos de pesquisa dos últimos dez anos, utilizando os descritores DeCS e MeSH, em fontes acadêmicas e científicas do Pubmed, Medline, Scopus e Google acadêmico onde foram selecionados 50 artigos, sendo que o principal resultado é que existe uma relação entre o risco biomecânico e a sobrecarga estática com o aparecimento de distúrbios musculoesqueléticos.

Mutação "de novo" na doença de fabry: relato de caso / Mutação "de novo" na doença de fabry: relato de caso

INTRODUÇÃO: Doença de Fabry (DF) é uma patologia rara de depósito lisossomal causada por mutação do gene GALA na região Xq22.1 do cromossomo X que codifica a enzima α-galactosidase A (α-GAL). Trata-se de um erro inato do metabolismo que causa acúmulo progressivo de glicoesfingolipídeos não clivados principalmente em locais como pele, rins, coração, sistema nervoso, endotélio vascular e olhos. Descrevemos o caso de um paciente com a forma clássica da doença com investigação genética da família negativa. RELATO DE CASO: masculino, 22 anos, aos 8 anos de idade apresentou quadro de dores em queimação e pontada em região de metatarso bilateral, com intensidade 6/10 pela escala visual analógica (EVA), associado a acroparestesia, que surgia ao praticar exercícios físicos, e hipoidrose generalizada. Aos 10 anos de idade, as dores também acometiam as mãos, com intensidade maior (EVA 8/10), desencadeadas por febre, ansiedade e exposição ao calor. Nesse mesmo período, passaram a ocorrer crises episódicas de dores excruciantes, intensidade EVA 10/10, juntamente com acroparestesia intensificada, fadiga extrema, sensação de hipertermia em região abdominal, torácica e cervical, e extremidades frias, com duração de horas a dias. Aos 15 anos, apresentou alterações do hábito intestinal e angioqueratomas difusos na cintura pélvica, com progressão lenta para mãos, braços, tronco, costas, joelhos e mucosa oral. Seu diagnóstico só foi confirmado aos 22 anos de idade, com a atividade de α-GAL de 0 mcmol/L/h e presença de variante patogênica no gene GLA, c.334C>T. Mãe e única irmã do paciente não apresentaram esta variante. ECG, ECOTT e RNM de coração não evidenciaram alterações. CONCLUSÃO: Em todas as doenças raras, o diagnóstico tardio é a regra, pelo desconhecimento da doença. No caso relatado, apesar do diagnóstico ter sido feito após 14 anos do início dos sintomas, ainda não estavam presentes complicações bem estabelecidas, como comprometimento cardíaco e renal, favorecendo o sucesso do tratamento de reposição enzimática. A ausência da mesma variante patogênica em sua mãe faz o diagnóstico de uma mutação primária "de novo".

Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses.

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.

SARS-CoV-2 Seroprevalence and Antibody Kinetics Among Health Care Workers in a Spanish Hospital After 3 Months of Follow-up.

BACKGROUND: At the COVID-19 spring 2020 pandemic peak in Spain, prevalence of SARS-CoV-2 infection in a cohort of 578 randomly selected health care workers (HCWs) from Hospital Clínic de Barcelona was 11.2%. METHODS: A follow-up survey 1 month later (April-May 2020) measured infection by rRT-PCR and IgM, IgA, and IgG to the receptor-binding domain of the spike protein by Luminex. Antibody kinetics, including IgG subclasses, was assessed until month 3. RESULTS: At month 1, the prevalence of infection measured by rRT-PCR and serology was 14.9% (84/565) and seroprevalence 14.5% (82/565). We found 25 (5%) new infections in 501 participants without previous evidence of infection. IgM, IgG, and IgA levels declined in 3 months (antibody decay rates 0.15 [95% CI, .11-.19], 0.66 [95% CI, .54-.82], and 0.12 [95% CI, .09-.16], respectively), and 68.33% of HCWs had seroreverted for IgM, 3.08% for IgG, and 24.29% for IgA. The most frequent subclass responses were IgG1 (highest levels) and IgG2, followed by IgG3, and only IgA1 but no IgA2 was detected. CONCLUSIONS: Continuous and improved surveillance of SARS-CoV-2 infections in HCWs remains critical, particularly in high-risk groups. The observed fast decay of IgA and IgM levels has implications for seroprevalence studies using these isotypes.

Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital.

Health care workers (HCW) are a high-risk population to acquire SARS-CoV-2 infection from patients or other fellow HCW. This study aims at estimating the seroprevalence against SARS-CoV-2 in a random sample of HCW from a large hospital in Spain. Of the 578 participants recruited from 28 March to 9 April 2020, 54 (9.3%, 95% CI: 7.1-12.0) were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. The cumulative prevalence of SARS-CoV-2 infection (presence of antibodies or past or current positive rRT-PCR) was 11.2% (65/578, 95% CI: 8.8-14.1). Among those with evidence of past or current infection, 40.0% (26/65) had not been previously diagnosed with COVID-19. Here we report a relatively low seroprevalence of antibodies among HCW at the peak of the COVID-19 epidemic in Spain. A large proportion of HCW with past or present infection had not been previously diagnosed with COVID-19, which calls for active periodic rRT-PCR testing in hospital settings.

Association between Sense of Coherence Associated with Mental Health in Caregivers of Older Adults.

The purpose of this study was to analyze association between sense of coherence and perceived burden, anxiety, depression, and quality of life in caregivers of older adults. A cross-sectional study was carried out with a probabilistic sample of 132 caregivers of older relatives from the regions of Jaén, Spain. The measures assessed were sense of coherence (Life Orientation Questionnaire), subjective burden (Caregiver Strain Index of Robinson), anxiety and depression (Goldberg Scale), and quality of life (Health Questionnaire SF-12). The main analyses included bivariate analysis using Pearson's correlation coefficient and multivariate analysis through canonical correlation analysis. Our findings show that the sense of coherence explained 50.8% of the variance shared between subjective burden, anxiety, depression, and quality of life. We highlighted manageability as the variable within the dimensions of the sense of coherence with the greatest participation in the model. The sense of coherence may be an important protective factor for the mental health of the caregiver of dependent elderly relatives.

Coping strategies and psychological distress in family carers of frail older people: A longitudinal study.

BACKGROUND: Carers of dependent older people experience high levels of psychological distress. However, little is known about the effects of coping on carer distress over time. In this one year longitudinal study we investigated the relationship between distress, and coping strategies in a representative sample of family carers living in Spain. METHODS: Primary carers of older people were recruited (N = 200). We used probability sampling and collected data via individual interviews from 2013 to 2015. Variables investigated included psychological distress, coping, and levels of objective and subjective burden. Panel data analysis was used to test a model of association of psychological distress, and coping strategies controlling for key confounders. RESULTS: Acceptance and emotional support were the most frequently used strategies, whereas behavioural disengagement and humour were the least used. In the panel data regressions, positive reframing (B = -0.79, p < 0.001), self-distraction (B = -0.46, p = 0.034), substance use (B = 0.57, p < 0.001) and denial (B = 0.57, p = 0,049) were significantly related to psychological distress at one year follow-up. LIMITATIONS: Limitations include participant drop out and assessing substance use coping via a brief measure. CONCLUSIONS: Positive reframing and self-distraction were longitudinally associated with lower levels of carer psychological distress. Using denial and substance use coping increased distress long-term. Our results suggest that interventions that focus on positive reframing and assisting carers in decreasing dysfunctional coping may be useful therapeutic targets mitigating carer psychological morbidity.

Obligation and negative consequences in primary caregivers of dependent older relatives.

The purpose of this study was to analyse the multidimensional nature of obligation and the relations between each dimension of obligation and both anxiety and depression. A secondary analysis of data from two cross-sectional studies of primary home caregivers (N = 400; probabilistic sample) of older adult relatives in Spain was conducted. Data regarding obligation (four categories basing on beliefs of obligation and social pressure: low pressure and low beliefs, low pressure and high beliefs, high pressure and low beliefs and high pressure and high beliefs), stressors, anxiety and depression were collected by interview in 2013. The combination of high pressure and low beliefs had the highest levels of anxiety and depression, and the combination of low pressure and high beliefs had the lowest levels of anxiety and depression. When the relation of behavioural problems with anxiety and depression stratified by the previous four categories of obligation was analysed, behavioural problems were associated with anxiety and depression in the subgroups with low beliefs of obligation, whereas this association disappeared in the subgroups with high beliefs of obligation.

Eventos adversos: estratégias e incentivos para notificações hospitalares / Adverse events: strategies and incentive for hospital notifications

O presente trabalho é um relato de experiência sobre os incentivos e estratégias adotadas pelo Núcleo de Segurança do Paciente para promoção das notificações dos eventos adversos. Objetivou-se avaliar os resultados das estratégias adotadas para notificação de eventos adversos no Hospital Dr. Eulalino Ignácio de Andrade. Foram realizadas diversas ações a fim de promover a identificação de incidentes relacionados à segurança do paciente. A mais efetiva constitui-se na criação de um formulário simplificado e instalação de urnas em locais estratégicos. A partir dos resultados obtidos, verificou-se um aumento significativo das notificações, ampliação dos notificadores e diversificação dos eventos relacionados que interferem na qualidade da assistência. O advento destas novas informações possibilitam o (re)direcionamento de ações para melhoria da assistência e segurança do paciente.(AU)

The present work is an experience report on the incentives and strategies adopted by the Patient Safety Center to promote the reporting of adverse events. The objective of this study was to evaluate the results of strategies adopted to report adverse events at the Hospital Dr. Eulalino Ignácio de Andrade. Several actions were taken to promote the identification of incidents related to patient safety. The most effective one is the creation of a simplified form and installation of ballot boxes at strategic locations. From the results obtained, there was a significant increase in notifications, increase of notifiers, and diversification of related events that interfere in the quality of care. The advent of this new information allows (re)directing actions to improve patient care and safety.(AU)