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1.
JMIR Res Protoc ; 10(11): e28191, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751660

RESUMO

BACKGROUND: Crisis Resolution and Home Treatment (CRHT) teams represent a community-based mental health service offering a valid alternative to hospitalization. CRHT teams have been widely implemented in various mental health systems worldwide, and their goal is to provide care for people with severe acute mental disorders who would be considered for admission to acute psychiatric wards. The evaluation of several home-treatment experiences shows promising results; however, it remains unclear which specific elements and characteristics of CRHT are more effective and acceptable. OBJECTIVE: This study aims to assess the acceptability, effectiveness, and cost-effectiveness of a new CRHT intervention in Ticino, Southern Switzerland. METHODS: This study includes an interventional, nonrandomized, quasi-experimental study combined with a qualitative study and an economic evaluation to be conducted over a 48-month period. The quasi-experimental evaluation involves two groups: patients in the northern area of the region who were offered the CRHT service (ie, intervention group) and patients in the southern area of the region who received care as usual (ie, control group). Individual interviews will be conducted with patients receiving the home treatment intervention and their family members. CRHT members will also be asked to participate in a focus group. The economic evaluation will include a cost-effectiveness analysis. RESULTS: The project is funded by the Swiss National Science Foundation as part of the National Research Program NRP74 for a period of 48 months starting from January 2017. As of October 2021, data for the nonrandomized, quasi-experimental study and the qualitative study have been collected, and the results are expected to be published by the end of the year. Data are currently being collected for the economic evaluation. CONCLUSIONS: Compared to other Swiss CRHT experiences, the CRHT intervention in Ticino represents a unique case, as the introduction of the service is backed by the closing of one of its acute wards. The proposed study will address several areas where there are evidence gaps or contradictory findings relating to the home treatment of acute mental crisis. Findings from this study will allow local services to improve their effectiveness in a challenging domain of public health and contribute to improving access to more effective care for people with severe mental disorders. TRIAL REGISTRATION: ISRCTN registry ISRCTN38472626; https://www.isrctn.com/ISRCTN38472626. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28191.

3.
Front Public Health ; 9: 695231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395369

RESUMO

Aims: One of the major ethical challenges posed by the Covid-19 pandemic comes in the form of fair triage decisions for critically ill patients in situations where life-saving resources are limited. In Spring 2020, the Swiss Academy of Medical Sciences (SAMS) issued specific guidelines on triage for intensive-care treatment in the context of the Covid-19 pandemic. While evidence has shown that the capacities of intensive care medicine throughout Switzerland were sufficient to take care of all critically ill patients during the first wave of the outbreak, no evidence is available regarding the acceptance of these guidelines by ICU staff. The aim of this qualitative study was to explore the acceptance and perceived implementation of the SAMS guidelines among a sample of senior physicians involved in the care of Covid-19 patients in the Canton of Ticino. Specific objectives included capturing and describing physicians' attitudes toward the guidelines, any challenges experienced in their application, and any perceived factors that facilitated or would facilitate their application. Methods: We conducted face-to-face and telephone interviews with a purposive sample of nine senior physicians employed as either head of unity, deputy-head of unit, or medical director in either one of the two Covid-19 hospitals in the Canton of Ticino during the peak of the outbreak. Interviews were transcribed verbatim and thematically analyzed using an inductive approach. Results: We found that participants held different views regarding the nature of the guidelines, saw decisions on admission as a matter of collective responsibility, argued that decisions should be based on a medical futility principle rather than an age criterion, and found that difficulties to address end-of-life issues led to a comeback of paternalism. Conclusions: Results highlight the importance of clarifying the nature of the guidelines, establishing authority, and responsibility during triaging decisions, recognizing and addressing sources of interference with patients' autonomy, and the need of a cultural shift in timely and efficiently addressing end-of-life issues.


Assuntos
COVID-19 , Médicos , Humanos , Pandemias , SARS-CoV-2 , Triagem
4.
Vaccine X ; 8: 100108, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34308329

RESUMO

Background: The Covid-19 pandemic is causing unprecedented disruption and suffering to people across the globe, with a disproportionate toll on the elderly. The development and equitable distribution of a vaccine seems to be the most promising and sustainable route ahead. The goal of this study was to explore older adults' attitudes towards and beliefs regarding the Covid-19 vaccination in Southern Switzerland. Methods: We conducted a qualitative study employing telephone interviews to understand older adults' attitudes towards and beliefs about the Covid-19 vaccine. No Covid-19 vaccine had yet been approved at the moment of data collection. A convenience and snowball sample of 19 participants was recruited. Participants had to be at least 65 years old, without any hearing impairments, and be resident in the Canton of Ticino. Results: Most participants were women (n = 12), Swiss nationals (n = 14), retired (n = 18), resident in urban areas (n = 14), and had obtained a secondary school degree (n = 14). The average age was 75 (SD = 6.04; range = 64-85). We found that the majority of participants were in favor of the vaccination and highlighted its positive consequences, such as the abandonment of current freedom-limiting protective measures. Those participants who were against or unsure about the vaccination had concerns regarding the novelty of the vaccine and its impact on its safety and efficacy, stated they would prefer other protective measures rather than the vaccination, and identified contextual and individual drivers of their concerns. Conclusions: Independently from the outbreak's trajectory, efforts to foster vaccination acceptance should focus on the benefit of relapsing freedom-limiting protective measures. Vaccination strategies should be grounded in an evidence-based, participatory approach, ongoing community engagement, trust-building activities, and communication about vaccine developments and how the vaccine will be combined with other outbreak response measures.

5.
BMJ Open ; 11(6): e045867, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193490

RESUMO

OBJECTIVES: To determine the criterion and concurrent validity of the Italian version of the short 10/66 Dementia Diagnostic Schedule and algorithm in a sample of Italian native speakers, older adults. DESIGN: A cross-sectional, validation study. SETTING: The study was conducted with older adults living in the community and in nursing homes in the Canton of Ticino, Switzerland, and the Piedmont region in Italy between March and August 2019. PARTICIPANTS: A convenience sample of 229 participants (69% females) were recruited. The eligibility criteria were being ≥60 years old and having an informant. The final sample included 74 participants (32%) with a previous clinical diagnosis of dementia and 155 (68%) cognitively healthy older adults. PRIMARY AND SECONDARY OUTCOME MEASURES: The short version of 10/66 Dementia Diagnostic Schedule consists of the Community Screening Instrument for Dementia, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) 10-word list learning task with delayed recall and the depression scale, Euro-Depression (EURO-D) scale. Disability was measured using the WHO Disability Assessment Schedule (WHO-DAS II). RESULTS: The Italian version of the short 10/66 Dementia Diagnostic Schedule showed fair sensitivity (87%), specificity (61%) and agreement with the clinical diagnosis of dementia (kappa=0.40, area under the receiver operating characteristics curve=0.74). Older adults with dementia living in nursing homes had higher disability scores (WHO-DAS II mean=23.14, SE=1.29) than those living in the community (WHO-DAS II mean=7.08, SE=0.66). WHO-DAS II was positively correlated with the short version of the 10/66 dementia diagnosis (ß=5.23, 95% CI 2.05 to 8.41). CONCLUSIONS: In settings where lengthy diagnostic procedures are not feasible, the short 10/66 is a practical tool to identify dementia in older adults. Our findings extend evidence on the validity of the 10/66 dementia diagnostic algorithm to high-income countries, where epidemiological evidence on dementia and its impact is outdated.


Assuntos
Demência , Idoso , Estudos Transversais , Demência/diagnóstico , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Suíça
6.
Dementia (London) ; : 14713012211029105, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196585

RESUMO

Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22-49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process.

7.
PLoS One ; 16(6): e0252101, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161334

RESUMO

BACKGROUND AND AIM: Public health measures used to mitigate the COVID-19 epidemic may have unintended, detrimental consequences particularly on older adults, whose voices and perspectives are often silent or silenced. The aim of this study was to explore the lived experiences of individuals aged 64 or older during the first COVID-19 lockdown. METHODS: We conducted a qualitative study in a convenience sample of 19 older adults (aged 64+) living at home in the Italian-speaking region of Switzerland during the first COVID-19 lockdown, between April and May 2020. Participants varied in terms of gender, education, age, nationality, and socio-economic status. We conducted semi-structured phone interviews to elicit emotions, expectations and hopes in relation to the present situation, and the post-pandemic world. We inquired about opinions on the enforced public health measures, including those specifically targeting older adults, and on the societal portrayal of older adults. FINDINGS: We found that the epidemic and the public health response to it had both generated a variety of resentments and a high degree of ambivalence at the individual, micro-, meso- and macro-social levels. We also found that labelling older adults as an at-risk sub-population inevitably contributed to public and self-stigmatization. DISCUSSION: We conducted an in-depth qualitative investigation of lived experiences of older adults during the first wave of the COVID-19 pandemic in one of the most gravely hit region in Europe. Our findings on the complexity of unintended, detrimental consequences of outbreak responses on older adults have relevant implications for local adaptions of public health measures, and suggest that public health authorities should engage vulnerable sub-populations and promote bi-directional communication to inform and support communities.


Assuntos
COVID-19/prevenção & controle , COVID-19/psicologia , Idoso , Idoso de 80 Anos ou mais , Controle de Doenças Transmissíveis , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipamento de Proteção Individual , Isolamento Social , Fatores Socioeconômicos , Suíça
8.
Lancet Reg Health Eur ; 1: 100013, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34173621

RESUMO

Background: Hospital healthcare workers (HCW), in particular those involved in the clinical care of COVID-19 cases, are presumably exposed to a higher risk of acquiring the disease than the general population. Methods: Between April 16 and 30, 2020 we conducted a prospective, SARS-CoV-2 seroprevalence study in HCWs in Southern Switzerland. Participants were hospital personnel with varying COVID-19 exposure risk depending on job function and working site. They provided personal information (including age, sex, occupation, and medical history) and self-reported COVID-19 symptoms. Odds ratio (OR) of seropositivity to IgG antibodies was estimated by univariate and multivariate logistic regressions. Findings: Among 4726 participants, IgG antibodies to SARS-CoV-2 were detected in 9.6% of the HCWs. Seropositivity was higher among HCWs working on COVID-19 wards (14.1% (11.9-16.5)) compared to other hospital areas at medium (10.7% (7.6-14.6)) or low risk exposure (7.3% (6.4-8.3)). OR for high vs. medium wards risk exposure was 1.42 (0.91-2.22), P = 0.119, and 1.98 (1.55-2.53), P<0.001 for high vs. low wards risk exposure. The same was for true for doctors and nurses (10.1% (9.0-11.3)) compared to other employees at medium (7.1% (4.8-10.0)) or low risk exposure (6.6% (5.0-8.4)). OR for high vs. medium profession risk exposure was 1.37 (0.89-2.11), P = 0.149, and 1.75 (1.28-2.40), P = 0.001 for high vs. low profession risk exposure. Moreover, seropositivity was higher among HCWs who had household exposure to COVID-19 cases compared to those without (18.7% (15.3-22.5) vs. 7.7% (6.9-8.6), OR 2.80 (2.14-3.67), P<0.001). Interpretation: SARS-CoV-2 antibodies are detectable in up to 10% of HCWs from acute care hospitals in a region with high incidence of COVID-19 in the weeks preceding the study. HCWs with exposure to COVID-19 patients have only a slightly higher absolute risk of seropositivity compared to those without, suggesting that the use of PPE and other measures aiming at reducing nosocomial viral transmission are effective. Household contact with known COVID-19 cases represents the highest risk of seropositivity. Funding: Henry Krenter Foundation, Ente Ospedaliero Cantonale and Vir Biotechnology.

9.
Alzheimers Dement ; 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33984176

RESUMO

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

11.
Front Psychiatry ; 12: 656822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897504

RESUMO

Aim: In the absence of an effective treatment, informed participation in dementia research can hardly be underestimated. However, although informed consent is key in biomedical research, it may become a barrier to participation. Whether informed consent may cause confusion and contribute to unfair participant selection in dementia research is not known. In preparation of a future epidemiological study on the prevalence and impact of dementia in Switzerland, we aimed to conduct a qualitative study to explore participants' comprehension of the purpose of informed consent form and process shortly after participation in the pilot and validation study that preceded the large scale survey. Methods: We conducted a qualitative study with 22 participants of the validation phase of an epidemiological study on the prevalence and impact of dementia in Switzerland to capture their understanding of both the nature and the content of the informed consent form and process. Participants were older adults (65 years or more) eligible for a dementia epidemiological study and their informant (a person who could provide information on their health and cognition). None of the participants reported to be suffering from dementia at the time of the interview. Results: We found that participants held inaccurate and potentially trust-threatening beliefs regarding the scope of the informed consent. Participants identified contradictory contextual, formal and content needs that are difficult to be fulfilled, and misperceived the clinical and research settings in terms of informed consent procedures. Conclusions: Participants and their proxies should be informed about both the scope of the informed consent process, and the content of the informed consent document in a focused, age-appropriate manner, while dispelling confusion about the purpose of research.

12.
Eur J Nucl Med Mol Imaging ; 48(7): 2070-2085, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33688996

RESUMO

BACKGROUND: The 2017 Alzheimer's disease (AD) Strategic Biomarker Roadmap (SBR) structured the validation of AD diagnostic biomarkers into 5 phases, systematically assessing analytical validity (Phases 1-2), clinical validity (Phases 3-4), and clinical utility (Phase 5) through primary and secondary Aims. This framework allows to map knowledge gaps and research priorities, accelerating the route towards clinical implementation. Within an initiative aimed to assess the development of biomarkers of tau pathology, we revised this methodology consistently with progress in AD research. METHODS: We critically appraised the adequacy of the 2017 Biomarker Roadmap within current diagnostic frameworks, discussed updates at a workshop convening the Alzheimer's Association and 8 leading AD biomarker research groups, and detailed the methods to allow consistent assessment of aims achievement for tau and other AD diagnostic biomarkers. RESULTS: The 2020 update applies to all AD diagnostic biomarkers. In Phases 2-3, we admitted a greater variety of study designs (e.g., cross-sectional in addition to longitudinal) and reference standards (e.g., biomarker confirmation in addition to clinical progression) based on construct (in addition to criterion) validity. We structured a systematic data extraction to enable transparent and formal evidence assessment procedures. Finally, we have clarified issues that need to be addressed to generate data eligible to evidence-to-decision procedures. DISCUSSION: This revision allows for more versatile and precise assessment of existing evidence, keeps up with theoretical developments, and helps clinical researchers in producing evidence suitable for evidence-to-decision procedures. Compliance with this methodology is essential to implement AD biomarkers efficiently in clinical research and diagnostics.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Biomarcadores , Estudos Transversais , Progressão da Doença , Humanos , Padrões de Referência , Proteínas tau
13.
PLoS One ; 16(2): e0247141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33577607

RESUMO

INTRODUCTION: High 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. METHODS: Twenty-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. RESULTS: We 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. CONCLUSIONS: Our 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.


Assuntos
Demência/epidemiologia , Estudos Epidemiológicos , Motivação , Participação do Paciente/psicologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Demência/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suíça , Confiança
14.
Int J Geriatr Psychiatry ; 36(1): 207-214, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869397

RESUMO

OBJECTIVES: To explore prospective participants' preferences regarding the return of their individual-specific results from a dementia prevalence study (a probabilistic diagnosis of dementia). METHODS/DESIGN: We conducted a qualitative study with 22 individuals aged 45 to 86 and resident in the Canton of Ticino (Switzerland). Participants had previously joined the validation phase of an epidemiological study into dementia and its impact. RESULTS: We found that individuals welcome the return of their individual-specific results, provided these meet a number of validity, clinical, and personal utility criteria. They justify researchers' duty to return study findings with the principles of beneficence (eg, providing information that can help participants' medical decision-making) and justice (eg, acknowledging participants' efforts to help research by sharing their personal information). Furthermore, individuals anticipate societal benefits of the return of individual specific study findings, including improved interpersonal relationships among individuals and decreased dementia-related stigma. CONCLUSIONS: Our findings suggest that researchers should address the return of individual-specific study results early on during study design and involve prospective participants in identifying both the conditions under which results should be offered and the perceived individual and societal benefits returning can have.


Assuntos
Demência , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Demência/epidemiologia , Humanos , Estudos Prospectivos , Pesquisa Qualitativa , Suíça/epidemiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-33352883

RESUMO

As of 27 March 2020, 199 countries and territories and one international conveyance are affected by the COVID-19 pandemic. As of the same date, Italy represents the third country worldwide in total number of cases and the first one in total number of deaths. The purpose of this study is to analyse the Italian case and identify key problem questions and lessons learned from the Italian experience. The study initially provides a general overview of the country's characteristics and health care system, followed by a detailed description of the Italian epidemiological picture regarding COVID-19. Afterwards, all non-pharmaceutical measures adopted by the Government against COVID-19 are presented in chronological order. The study explores some estimations of the economic impact of the epidemic, as well as its implications for society, lifestyle, and social media reactions. Finally, the study refers to two types of mathematical models to predict the evolution of the spread of COVID-19 disease. Having considered all of the above-mentioned aspects, some significant issues can be raised, including the following: (1) the available epidemiological data presents some gaps and potential biases; (2) mathematical models always come with high levels of uncertainty; (3) the high number of deaths should be interpreted in light of the national demographic context; and (4) the long-term management of the epidemic remains an open question. In conclusion, the Italian experience definitely highlights the importance of preparedness and early action, effective interventions and risk communication.


Assuntos
COVID-19/epidemiologia , Pandemias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Adulto Jovem
16.
Int J Public Health ; 65(9): 1529-1548, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33098441

RESUMO

OBJECTIVES: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community. METHODS: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic. RESULTS: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far. CONCLUSIONS: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 .


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , SARS-CoV-2/isolamento & purificação , Estudos Soroepidemiológicos , Adolescente , Adulto , Idoso , Betacoronavirus/imunologia , Criança , Humanos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Projetos de Pesquisa , Suíça , Adulto Jovem
17.
Cell ; 183(4): 1024-1042.e21, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32991844

RESUMO

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.


Assuntos
Anticorpos Neutralizantes/imunologia , Mapeamento de Epitopos/métodos , Glicoproteína da Espícula de Coronavírus/imunologia , Enzima de Conversão de Angiotensina 2 , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/química , Anticorpos Antivirais/sangue , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Reações Antígeno-Anticorpo , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/metabolismo , Sítios de Ligação , COVID-19 , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Epitopos/química , Epitopos/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Cinética , Simulação de Dinâmica Molecular , Pandemias , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Ligação Proteica , Domínios Proteicos/imunologia , Estrutura Quaternária de Proteína , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
19.
Transcult Psychiatry ; 57(1): 108-123, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31237805

RESUMO

Health care should be informed by the physical, socioeconomic, mental, and emotional well-being of the person, and account for social circumstances and culture. Patient-generated outcome measures can contribute positively to mental health research in culturally diverse populations. In this study, we analysed qualitative responses to the Psychological Outcome Profiles (PSYCHLOPS) Questionnaire-a patient-generated outcome measure based on open-ended questions, and compared the qualitative responses gathered to conventional, nomothetic measures used alongside the PSYCHLOPS in two studies. Data were collected as part of outcome research on a psychological intervention in Pakistan (N = 346) and Kenya (N = 521). Two researchers coded the qualitative responses to the PSYCHLOPS and identified overarching themes. We compared the overarching themes identified to the items in the conventional, nomothetic outcome measures to investigate conceptual equivalence. Using the PSYCHLOPS, the most frequently reported problems in Kenya were financial constraints, poor health, and unemployment. In Pakistan, the most frequent problems were poor health and emotional problems. Most of the person-generated problem concepts were covered also in nomothetic measures that were part of the same study. However, there was no item equivalence in the nomothetic measures for the most frequent PSYCHLOPS problem cited in both countries. Response bias and measurement bias may not be excluded. More research on the use of PSYCHLOPS alongside conventional outcome measures is needed to further explore the extent to which it may bring added value. Use of a PSYCHLOPS semistructured interview schedule and efforts to minimise response biases should be considered.


Assuntos
Diversidade Cultural , Transtornos Mentais/psicologia , Avaliação de Resultados em Cuidados de Saúde , Autoimagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Quênia , Masculino , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Paquistão , Inquéritos e Questionários , Adulto Jovem
20.
Res Synth Methods ; 11(2): 227-236, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31733091

RESUMO

BACKGROUND: There is an agreement that the methodological quality of randomized trials should be assessed in systematic reviews, but there is a debate on how this should be done. We conducted a construct validation study of the Physiotherapy Evidence Database (PEDro) scale, which is widely used to assess the quality of trials in physical therapy and rehabilitation. METHODS: We analyzed 345 trials that were included in Cochrane reviews and for which a PEDro summary score was available. We used one- and two-parameter logistic item response theory (IRT) models to study the psychometric properties of the PEDro scale and assessed the items' difficulty and discrimination parameters. We ran goodness of fit post estimations and examined the IRT unidimensionality assumption with a multidimensional IRT (MIRT) model. RESULTS: Out of a maximum of 10, the mean PEDro summary score was 5.46 (SD = 1.51). The allocation concealment and intention-to-treat scale items contributed most of the information on the underlying construct (with discriminations of 1.79 and 2.05, respectively) at similar difficulties (0.63 and 0.65, respectively). The other items provided little additional information and did not distinguish trials of different quality. There was substantial evidence of departure from the unidimensionality assumption, suggesting that the PEDro items relate to more than one latent trait. CONCLUSIONS: Our findings question the construct validity of the PEDro scale to assess the methodological quality of clinical trials. PEDro summary scores should not be used; rather, the physiotherapy community should consider working with the individual items of the scale.


Assuntos
Análise Fatorial , Ensaios Clínicos Controlados Aleatórios como Assunto , Reabilitação/métodos , Reabilitação/normas , Algoritmos , Bases de Dados Factuais , Medicina Baseada em Evidências , Humanos , Análise de Intenção de Tratamento , Internet , Modalidades de Fisioterapia , Psicometria , Reprodutibilidade dos Testes , Pesquisa/normas , Revisões Sistemáticas como Assunto
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