Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort

Objective To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. Patients and methods Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE – Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). Results Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index – BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA. Conclusions Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores.Objetivo Analisar as características clínicas e epidemiológicas das espondiloartrites (EpA) de início juvenil (< 16 anos) e compará-las com um grupo de pacientes com EspA de início na vida adulta (≥ 16 anos). Pacientes e métodos Coorte prospectiva, observacional e multicêntrica com 1.424 pacientes com diagnóstico de EspA de acordo com o European Spondyloarthropathy Study Group (ESSG) submetidos a um protocolo comum de investigação e recrutados em 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE). Os pacientes foram divididos em dois grupos: idade no início<16 anos (grupo EspAiJ) e idade no início ≥ 16 anos. Resultados Entre os 1.424 pacientes, 235 manifestaram o início da doença antes dos 16 anos (16,5%). As variáveis clínicas e epidemiológicas associadas com a EspAiJ foram: gênero masculino (p<0,001), artrite em membro inferior (p=0,001), entesite (p=0,008), uveíte anterior (p=0,041) e HLA-B27 positivo (p=0,017), em associação com escores mais baixos de atividade da doença (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI; p=0,007) e de capacidade funcional (Bath Ankylosing Spondylitis Functional Index – BASFI; p=0,036). A psoríase cutânea (p<0,001), a doença inflamatória intestinal (p=0,023), a dactilite (p=0,024) e o envolvimento ungueal (p=0,004) foram mais frequentes em pacientes com EspA de início na vida adulta. Conclusões Nessa grande coorte brasileira, os pacientes com EspAiJ se caracterizavam predominantemente pelo gênero masculino, envolvimento periférico (artrite e entesite), HLA-B27 positivo e escores de doença mais baixos.Universidade Federal de PernambucoInsper Instituto de Educação e PesquisaUniversidade de São Paulo Faculdade de Medicina Divisão de ReumatologiaUniversidade de BrasíliaHospital Geral de GoiâniaUniversidade de CampinasUniversidade Federal do AmazonasPontifícia Universidade CatólicaHospital Evangélico de CuritibaUniversidade Federal do Rio de JaneiroUniversidade Estadual do Rio de JaneiroFaculdade de Medicina de São José do Rio PretoUniversidade Federal do ParanáHospital Geral de FortalezaSanta Casa do Rio de JaneiroSanta Casa de São PauloHospital de Base do Distrito FederalUniversidade Federal do Mato Grosso do SulUniversidade Federal do Rio Grande do SulFaculdade de Medicina Souza MarquesHospital do Servidor Público EstadualUniversidade de São Paulo Instituto de Ortopedia e TraumatologiaUniversidade Federal de Santa CatarinaUniversidade Federal de São Paulo (UNIFESP)Santa Casa de Belo HorizonteUniversidade Federal de Minas GeraisUniversidade Federal do CearáEscola de Medicina e Saúde PúblicaUniversidade Federal do ParáUniversidade Federal do Espírito SantoUNIFESPSciEL

Erratum of Enteropathic arthritis in Brazil: data from the Brazilian registry of spondyloarthritis

Universidade Federal de Minas GeraisInstituto Insper de Educação e PesquisaUniversidade de São Paulo Disciplina de ReumatologiaUniversidade de BrasíliaHospital Geral de GoiâniaUniversidade de CampinasUniversidade Federal do AmazonasPontifícia Universidade CatólicaFaculdade de Medicina de São José do Rio PretoHospital Evangélico de CuritibaUniversidade Federal do Rio de JaneiroUniversidade Federal do ParanáHospital Geral de FortalezaUniversidade Estadual do Rio de JaneiroSanta Casa do Rio de JaneiroSanta Casa de São PauloHospital de BaseUniversidade Federal do Mato Grosso do SulUniversidade Federal de PernambucoUniversidade Federal do Rio Grande do SulFaculdade de Medicina Souza MarquesHospital do Servidor Público EstadualUniversidade de São Paulo Instituto de Ortopedia e TraumatologiaUniversidade Federal de Santa CatarinaUniversidade Federal de São Paulo (UNIFESP)Santa Casa de Belo HorizonteUniversidade Federal do CearáEscola de Medicina e Saúde PúblicaUniversidade Federal do ParáUniversidade Federal do Espírito SantoUNIFESPSciEL

Enteropathic arthritis in Brazil: data from the brazilian registry of spondyloarthritis

Inflammatory bowel diseases (Crohn's disease and ulcerative rectocolitis) have extraintestinal manifestations 25% of the patients, with the most common one being the enteropathic arthritis. METHODS: Prospective, observational, multicenter study with patients from 29 reference centers participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the assessment of axial mobility, quality of life, enthesitic involvement, disease activity and functional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treatment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort. RESULTS: A total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spondylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with enteroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less non-steroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001). CONCLUSION: There were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.As doenças inflamatórias intestinais (doença de Crohn e retocolite ulcerativa) apresentam manifestações extraintestinais em um quarto dos pacientes, sendo a mais comum a artrite enteropática. MÉTODOS: Estudo prospectivo, observacional e multicêntrico, realizado com pacientes de 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE), que se incorpora ao grupo RESPONDIA (Registro Ibero-americano de Espondiloartrites). Dados demográficos e clínicos de 1472 pacientes foram colhidos, e aplicaram-se questionários padronizados de avaliação de mobilidade axial, de qualidade de vida, de envolvimento entesítico, de atividade de doença e de capacidade funcional. Exames laboratoriais e radiográficos foram realizados. Objetivamos, neste presente artigo, comparar as características clínicas, epidemiológicas, genéticas, imagenológicas, de tratamento e prognóstico de enteroartríticos com os outros espondiloartríticos nesta grande coorte brasileira. RESULTADOS: Foram classificados como enteroartrite 3,2% dos pacientes, sendo que 2,5% tinham espondilite e 0,7%, artrite (predomínio periférico). O subgrupo de indivíduos com enteroartrite apresentava maior prevalência de mulheres (P < 0,001), menor incidência de dor axial inflamatória (P < 0,001) e de entesite (P = 0,004). O HLA-B27 foi menos frequente no grupo de enteroartríticos (P = 0,001), mesmo se considerado apenas aqueles com a forma axial pura. Houve menor prevalência de sacroiliíte radiológica (P = 0,009) e também menor escore radiográfico (BASRI) (P = 0,006) quando comparado aos pacientes com as demais espondiloartrites. Também fizeram mais uso de corticosteroides (P < 0,001) e sulfassalasina (P < 0,001) e menor uso de anti-inflamatórios não hormonais (P < 0,001) e metotrexato (P = 0,001). CONCLUSÃO: Foram encontradas diferenças entre as enteroartrites e as demais espondiloartrites, principalmente maior prevalência do sexo feminino, menor frequência do HLA-B27, associados a uma menor gravidade do acometimento axial.Universidade Federal de Minas GeraisInstituto Insper de Educação e PesquisaUniversidade de São PauloUniversidade de BrasíliaHospital Geral de GoiâniaUniversidade de CampinasUniversidade Federal do AmazonasPontifícia Universidade CatólicaFaculdade de Medicina de São José do Rio PretoHospital Evangélico de CuritibaUniversidade Federal do Rio de JaneiroUniversidade Federal do ParanáHospital Geral de FortalezaUniversidade Estadual do Rio de JaneiroSanta Casa do Rio de JaneiroSanta Casa de São PauloHospital de BaseUniversidade Federal do Mato Grosso do SulUniversidade Federal de PernambucoUniversidade Federal do Rio Grande do SulFaculdade de Medicina Souza MarquesHospital do Servidor Público EstadualUniversidade de São Paulo Instituto de Ortopedia e TraumatologiaUniversidade Federal de Santa CatarinaUniversidade Federal de São Paulo (UNIFESP)Santa Casa de Belo HorizonteUniversidade Federal do CearáEscola de Medicina e Saúde PúblicaUniversidade Federal do ParáUniversidade Federal do Espírito SantoUNIFESPSciEL

Low prevalence of renal, cardiac, pulmonary, and neurological extra-articular clinical manifestations in spondyloarthritis: analysis of the Brazilian Registry of Spondyloarthritis

OBJECTIVE: To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients. MATERIALS AND METHODS: This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis). RESULTS: Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form. CONCLUSION: Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA.OBJETIVO: Descrever as manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas) geralmente não relacionadas às espondiloartrites (EpA) em uma grande coorte de pacientes brasileiros. MÉTODOS: Este estudo retrospectivo analisou 1.472 pacientes com o diagnóstico de EpA atendidos em 29 centros distribuídos pelas cinco principais regiões geográficas do Brasil, integrantes do Registro Brasileiro de Espondiloartrites. Todos os pacientes foram avaliados para a prevalência das principais manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas), divididas por diagnóstico [espondilite anquilosante (EA), artrite psoriásica (AP), artrite reativa (ARe), artrite associada a doença inflamatória intestinal (DII), EpA indiferenciada (EI) e EpA juvenil] e por forma clínica (axial, periférica, mista e entesítica). RESULTADOS: Dentre os pacientes avaliados com EpA, 963 apresentavam EA, 271 AP, 49 ARe, 48 artrite associada a DII, 98 EI e 43 EpA juvenil. Acometimento cardíaco foi observado em 44 pacientes (3,0%), seguido por acometimento pulmonar em 19 (1,3%), renal em 17 (1,2%) e neurológico em 13 pacientes (0,9%). A maioria dos casos de acometimento visceral ocorreu nos pacientes com EA ou AP e naqueles com forma clínica mista (axial e periférica) e/ou predominantemente axial. CONCLUSÃO: As manifestações extra-articulares cardíacas, renais, pulmonares e neurológicas são muito pouco frequentes nas EpA, variando de 0,9%-3% nesta grande coorte brasileira, estando mais associadas a EA e AP.37938

Brazilian consortium for the study on renal diseases associated with COVID-19 : a multicentric effort to understand SARS-CoV-2-related nephropathy

Kidney involvement appears to be frequent in coronavirus disease 2019 (COVID-19). Despite this, information concerning renal involvement in COVID-19 is still scarce. Several mechanisms appear to be involved in the complex relationship between the virus and the kidney. Also, different morphological patterns have been described in the kidneys of patients with COVID-19. For some authors, however, this association may be just a coincidence. To investigate this issue, we propose assessing renal morphology associated with COVID-19 at the renal pathology reference center of federal university hospitals in Brazil. Data will come from a consortium involving 17 federal university hospitals belonging to Empresa Brasileira de Serviços Hospitalares (EBSERH) network, as well as some state hospitals and an autopsy center. All biopsies will be sent to the referral center for renal pathology of the EBSERH network. The data will include patients who had coronavirus disease, both alive and deceased, with or without pre-existing kidney disease. Kidney biopsies will be analyzed by light, fluorescence, and electron microscopy. Furthermore, immunohistochemical (IHC) staining for various inflammatory cells (i.e., cells expressing CD3, CD20, CD4, CD8, CD138, CD68, and CD57) as well as angiotensin-converting enzyme 2 (ACE2) will be performed on paraffinized tissue sections. In addition to ultrastructural assays, in situ hybridization (ISH), IHC and reverse transcription-polymerase chain reaction (RT-PCR) will be used to detect Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in renal tissue. For the patients diagnosed with Collapsing Glomerulopathy, peripheral blood will be collected for apolipoprotein L-1 (APOL1) genotyping. For patients with thrombotic microangiopathy, thrombospondin type 1 motif, member 13 (ADAMTS13), antiphospholipid, and complement panel will be performed. The setting of this study is Brazil, which is second behind the United States in highest confirmed cases and deaths. With this complete approach, we hope to help define the spectrum and impact, whether immediate or long-term, of kidney injury caused by SARS-CoV-2

O perfil semiológico do paciente portador de hemorragia digestiva alta

OBJETIVO: O seguinte estudo objetivou descrever a semiologia do paciente portador de hemorragia digestiva alta, considerando como determinante na avaliação de potencias focos hemorrágicos. METODOLOGIA: Foram realizadas buscas nas plataformas do SciELO, LILACS, PubMed, Scopus e Google Scholar,utilizando os descritores gastrointestinal bleeding, peptic ulcerous disease e varicose hemorrhage, sendo identificados 35 estudos, dos quais foram incluídos 13 artigos completos. Desses estudos, 5 avaliaram as principais etiologias, 2 o surgimento de novos testes diagnósticos, 2 analisaram os aspectos epidemiológicos e 1 a sintomatologia apresentada pelo acometimento da hemorragia digestiva alta. Observou-se inicialmente a abundâncias de informações conceituais sobre o sangramento, como um transtorno clínico comum, acompanhada de inúmeras manifestações, considerando que o foco hemorrágico pode ocorrer em qualquer porção do trato gastrointestinal. Neste estudo, todas as publicações eleitas apresentaram o quadro semiológico composto por algia abdominal, indícios de choque hipovolêmico e taquicardia, alguns exibiram quedas abruptas da pressão arterial, odinofagia, êmese, náuseas e estado ictérico. Os pacientes implicados, cronicamente, já manifestaram ocorrências prévias, devido ao caráter recidivante torna-se essencial investigar a existência de varizes, fístula aorto-entérica, angiodisplasia e doença ulcerosa. CONCLUSÃO: Elucida-se que a hemorragia digestiva alta representa a principal causa de sangramento do trato gastrointestinal, majoritamente manifesta-se como hematêmese ou melena e cursam com o quadro sintomatológico que auxilia na avaliação da gravidade deste e o embasamento de potenciais focos de sangramento e que contribuam para disseminação de informações e intervenções futuras

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

IntroductionMannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.MethodsBlood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.ResultsThe frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p&lt; 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p&lt; 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p&lt; 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.DiscussionThe results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Quality of life in spondyloarthritis : analysis of a large Brazilian cohort

Objetivo: analisar as variáveis demográficas e clínicas associadas à diminuição da qualidade de vida em uma grande coorte brasileira de pacientes com espondiloartrite (EpA). Métodos: Foi aplicado um protocolo de pesquisa único a 1.465 pacientes brasileiros classificados como tendo EpA de acordo com os critérios do European Spondyloarthropaties Study Group (ESSG), atendidos em 29 centros de referência em reumatologia do Brasil. Foram registradas as variáveis clínicas e demográficas. A qualidade de vida foi analisada por meio do questionário Ankylosing Spondylitis Quality of Life (ASQoL). Resultados: A pontuação média do ASQoL foi de 7,74 (+ 5,39). Ao analisar doenças específicas no grupo de EpA, as pontuações do ASQoL não apresentaram diferença estatisticamente significativa. Os dados demográficos mostraram piores escores de ASQoL associados ao gênero feminino (p = 0,014) e etnia negra (p < 0,001). Quanto aos sintomas clínicos, a dor na região glútea (p = 0,032), a dor cervical (p < 0,001) e a dor no quadril (p = 0,001), estiveram estatisticamente associadas a piores escores no ASQoL. O uso contínuo de fármacos anti-inflamatórios não esteroides (p < 0,001) e agentes biológicos (p = 0,044) esteve associado a escores mais elevados de ASQoL, enquanto outros medicamentos não interferiram nos escores do ASQoL. Conclusão: Nesta grande série de pacientes com EpA, o sexo feminino e a etnia negra, bem como sintomas predominantemente axiais, estiveram associados a uma qualidade de vida reduzida.Objective: to analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (± 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African-Brazilian ethnicity (p < 0.001). Regarding clinical symptoms, buttock pain (p = 0.032), cervical pain (p < 0.001) and hip pain (p = 0.001), were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biologic agents (p = 0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores. Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life