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OBJECTIVE: Dyadic coping, the process of coping that transpires between couples challenged by one partner's illness, is an important predictor of disease adjustment and patient well-being. However, the extent of dyadic coping in rheumatoid arthritis (RA) remains unclear. This study examines the effect of dyadic coping on psychological distress and relationship quality from the perspectives of both participants with RA and their spouses. METHODS: Participants and their spouses were invited to participate in an online survey study if they were aged ≥ 18 years and had lived together for more than a year. The survey included the Chronic Pain Grade Scale, Dyadic Coping Inventory, Depression Anxiety Stress Scale, and Dyadic Adjustment Scale. Participants and spouses completed the survey independently. The actor-partner interdependence model was used to analyze the dyadic data. RESULTS: One hundred sixty-three couples participated. Our findings showed that participants who reported higher supportive dyadic coping reported lower depression, anxiety, and stress, and higher relationship quality, whereas participants who reported higher negative dyadic coping reported higher depression, anxiety, and stress, and lower relationship quality. Spouses who reported higher supportive dyadic coping reported higher relationship quality, but no effect on depression, anxiety, and stress was observed. In contrast, spouses who reported higher negative dyadic coping reported higher levels of depression, anxiety, and stress, and lower relationship quality. CONCLUSION: Participants' and spouses' perceptions of supportive and negative dyadic coping closely influenced their psychological distress and relationship quality. Further, having a partner with RA also seemed to affect the spouse, especially when there was a negative dyadic coping pattern.
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OBJECTIVES: To determine long-term (20 year) survival in RA patients enrolled in the Australian Rheumatology Association Database (ARAD). METHODS: ARAD patients with RA and data linkage consent who were diagnosed from 1995 onwards were included. Death data were obtained through linkage to the Australian National Death Index. Results were compared with age-, gender- and calendar year-matched Australian population mortality rates. Analysis included both the standardized mortality ratio (SMR) and relative survival models. Restricted mean survival time (RMST) at 20 years was calculated as a measure of life lost. Cause-specific SMRs (CS-SMRs) were estimated for International Classification of Diseases, Tenth Revision cause of death classifications. RESULTS: A total of 1895 RA patients were included; 74% were female, baseline median age 50 years (interquartile range 41-58), with 204 deaths. There was no increase in mortality over the first 10 years of follow up, but at 20 years the SMR was 1.49 (95% CI 1.30, 1.71) and the relative survival was 94% (95% CI 91, 97). The difference between observed (18.41 years) and expected (18.68 years) RMST was 4 months. Respiratory conditions were an important underlying cause of death in RA, primarily attributable to pneumonia [CS-SMR 5.2 (95% CI 2.3, 10.3)] and interstitial lung disease [CS-SMR 7.6 (95% CI 3.0, 14.7)], however, coronary heart disease [CS-SMR 0.82 (95% CI 0.42, 1.4)] and neoplasms [CS-SMR 1.2 (95% CI 0.89, 1.5)] were not. CONCLUSION: Mortality risk in this RA cohort accrues over time and is moderately increased at 20 years of follow-up. Respiratory diseases may have supplanted cardiovascular diseases as a major contributor to this mortality gap.
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Artrite Reumatoide , Doenças Cardiovasculares , Doenças Respiratórias , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Causas de Morte , Austrália/epidemiologiaRESUMO
OBJECTIVES: To determine COVID-19 vaccine hesitancy rates in inflammatory arthritis patients and identify factors associated with changing vaccine hesitancy over time. METHODS: This investigation was a prospective cohort study of inflammatory arthritis patients from community and public hospital outpatient rheumatology clinics enrolled in the Australian Rheumatology Association Database (ARAD). Two surveys were conducted, one immediately prior to (pre-pandemic) and another approximately 1 year after the start of the pandemic (follow-up). Coronavirus disease 2019 (COVID-19) vaccine hesitancy was measured at follow-up, and general vaccine hesitancy was inferred pre-pandemic; these were used to identify factors associated with fixed and changing vaccine beliefs, including sources of information and broader beliefs about medication. RESULTS: Of the 594 participants who completed both surveys, 74 (12%) were COVID-19 vaccine hesitant. This was associated with pre-pandemic beliefs about medications being harmful (P < 0.001) and overused (P = 0.002), with stronger beliefs resulting in vaccine hesitancy persistent over two time points (P = 0.008, P = 0.005). For those not vaccine hesitant pre-pandemic, the development of COVID-19 vaccine hesitancy was associated with a lower likelihood of seeking out vaccine information from health-care professionals (P < 0.001). COVID-19 vaccine hesitancy was not associated with new influenza vaccine hesitancy (P = 0.138). CONCLUSION: In this study of vaccine beliefs before and during the COVID-19 pandemic, factors associated with COVID-19 vaccine hesitancy in inflammatory arthritis patients varied, depending on vaccine attitudes immediately prior to the start of the pandemic. Fixed beliefs reflected broader views about medications, while fluid beliefs were highly influenced by whether they sought out information from health-care professionals, including rheumatologists.
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Artrite , COVID-19 , Humanos , Vacinas contra COVID-19/uso terapêutico , Pandemias , Estudos Prospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Austrália/epidemiologia , Artrite/tratamento farmacológico , VacinaçãoRESUMO
OBJECTIVE: The aim of this study was to describe treatment patterns in RA, including the frequency and reasons for switching or stopping biologic and targeted synthetic DMARDs (b/tsDMARDs). METHODS: The reasons for switching or stopping b/tsDMARDs were extracted from the Australian Rheumatology Association Database (ARAD) from 2003 to 2018 for RA participants. Switching patterns for each b/tsDMARD and time on first-, second- and third-line b/tsDMARDs were evaluated using Sankey diagrams and survival methods. RESULTS: A total of 2839 participants were included in the analysis. The first-line b/tsDMARDs were etanercept (n = 1414), adalimumab (n = 1024), infliximab (n = 155), golimumab (n = 98), abatacept (n = 66), certolizumab (n = 38), tocilizumab (n = 21) and tofacitinib (n = 23). Of those starting first-, second- and third-line biologic therapy, 24.0%, 31.8% and 24.4% switched to another b/tsDMARD within 12 months, respectively. Inefficacy or adverse effects were the most common reasons for stopping therapy, irrespective of line of treatment. Compared with first-line etanercept, participants were more likely to stop adalimumab [Hazard ratio (HR) 1.16, 95% CI: 1.04, 1.29] and infliximab (HR 1.77, 95% CI: 1.46, 2.16). No differences were seen for other b/tsDMARDs. For second-line therapies compared with etanercept, the risk of stopping was lower for tocilizumab (HR 0.41, 95% CI: 0.25, 0.70), rituximab (HR 0.51, 95% CI: 0.30, 0.85) and tofacitinib (HR 0.29, 95% CI: 0.15, 0.57). Participants taking rituximab, tocilizumab and tofacitinib were also less likely to stop third-line therapy in comparison with participants taking etanercept. CONCLUSIONS: Switching between b/tsDMARDs was common among ARAD participants with RA, most commonly due to inefficacy or adverse effects. Durability of exposure and reasons for switching varied between b/tsDMARDs.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Abatacepte/uso terapêutico , Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Austrália , Produtos Biológicos/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Infliximab/uso terapêutico , Rituximab/uso terapêuticoRESUMO
OBJECTIVES: To examine the association between DMARD use and subsequent risk of herpes zoster in a large, heterogeneous and prospective population-based cohort. METHODS: Using data from a cohort of adults (45 and Up Study) recruited between 2006 and 2009 and linked to pharmaceutical, hospital and death data (2004-2015), the effect of DMARD use on zoster risk was analysed using Cox proportional hazards models, adjusting for sociodemographic characteristics, comorbidities and corticosteroid use. RESULTS: Among 254 065 eligible participants, over 1 826 311 person-years follow-up, there were 6295 new DMARD users and 17 024 incident herpes zoster events. Compared with non-users, the risk of zoster was higher in those who used biologic (b)DMARDs, either alone or in combination with conventional synthetic (cs)DMARDs than in those who only used csDMARDs (adjusted hazard ratio [aHR] 2.53 [95% CI: 2.03, 3.16]) for bDMARDs vs 1.48 [95% CI: 1.33, 1.66] for csDMARDs, P-heterogeneity < 0.001; reference: non-users). Among users of csDMARDs, compared with non-users, zoster risks were highest in those using exclusively cyclophosphamide (aHR 2.69 [95% CI: 1.89, 3.83]), more moderate in those using azathioprine (aHR 1.57 [95% CI: 1.07, 2.30]) and hydroxychloroquine (aHR 1.43 [95%CI: 1.11, 1.83]) and not elevated in users of methotrexate (aHR 1.24 [95% CI: 0.98, 1.57]), sulfasalazine (aHR 1.00 [95% CI: 0.71, 1.42]) and leflunomide (aHR 0.41 [95% CI: 0.06, 2.88]). CONCLUSIONS: The risk of zoster was high among bDMARD and cyclophosphamide users. Also, the risk was increased in those using hydroxychloroquine alone and in combination with methotrexate but not methotrexate alone. Preventative strategies such as zoster vaccination or antiviral therapies should be considered in these populations if not contraindicated.
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Antirreumáticos/efeitos adversos , Herpes Zoster/induzido quimicamente , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Community restrictions due to COVID-19 have changed healthcare, including increased telehealth use. During the early pandemic phase, a cohort of Australian patients with inflammatory arthritis was surveyed. Self-reported access to healthcare was maintained and physical health was more likely to be self-rated poorly than mental health. There was a high level of support for telehealth during and after the pandemic.
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Artrite , COVID-19 , Telemedicina , Artrite/epidemiologia , Atitude , Austrália/epidemiologia , Humanos , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: Comorbid conditions are common and impact outcomes in people with rheumatoid arthritis (RA), but less data are available for psoriatic arthritis (PsA). AIMS: To describe baseline demographics and prevalence of comorbidities in participants with PsA in an Australian cohort using data from the Australian Rheumatology Association Database (ARAD) and to compare the prevalence of comorbidities in ARAD participants with PsA with those with RA. METHODS: ARAD is a voluntary national registry for inflammatory arthritis. Data, including demographic details, medication use, history of comorbid medical illnesses and patient-reported outcomes, all self-reported, were extracted from questionnaires completed at the time of database enrolment for participants with PsA and RA. Demographic information and prevalence of comorbidities were summarised using descriptive statistics. Prevalence of comorbidities in PsA and RA were compared using logistic regression, adjusting for age, gender, disease duration, education, employment and prednisone use. RESULTS: There were 490 participants with PsA, 59.2% female, mean (standard deviation (SD)) age 50.4 (21.1) years and disease duration 16.4 (9.7) years, and 57.8% reported having two or more comorbidities. Hypertension (38.2%) and depression (35.9%) were the most common. Compared with RA, participants with PsA had greater odds of depression (adjusted OR (95% CI): 2.1 (1.7-2.6)), hypertension (1.7 (1.4-2.1)), hyperlipidaemia (2.0 (1.6-2.5)), diabetes (2.2 (1.6-3.0)) and a history of ischaemic heart disease (2.0 (1.3-2.9)). CONCLUSIONS: High rates of comorbidity were found in ARAD participants with PsA. The prevalence of depression, cardiovascular risk factors and other comorbidities were higher in PsA than RA participants in our Australian cohort.
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Artrite Psoriásica/epidemiologia , Artrite Reumatoide/epidemiologia , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Austrália/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doença Crônica/epidemiologia , Comorbidade , Depressão/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Sistema de Registros , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The aim of this study was to examine the impact of smoking on health-related quality of life (HRQoL) among AS patients who were taking biologic DMARDS. METHODS: This is a longitudinal cohort study of AS patients with anti-TNF treatment in the Australian Rheumatology Association Database (2003-11). They were assessed using the 36-item Short Form Health Survey (SF-36), Assessment of Quality of Life (AQoL) and HAQ for spondylitis (HAQ-S) on a biannual basis. Linear mixed models were used to assess the impact of smoking on HRQoL outcomes over the first 2 years of treatment. RESULTS: Four hundred and twenty-two patients [73% male, mean age 44.9 years (s.d. 12.7) provided 1189 assessments for the study. Current smokers (n = 79) were slightly younger, more likely to be male, less likely to use or to have previously used prednisolone and had a slightly shorter disease duration than past smokers (n = 138) or non-smokers (n = 205). After adjusting for smoking, gender, age, education, employment, co-morbidities and medication use, including DMARDs, anti-inflammatories and analgesics, all the HRQoL measures improved significantly over the study period and the improvements were not modified by smoking status (all P-values >0.36). Current smokers tended to have a poorer HRQoL on the SF-36 physical score [-1.93 (95% CI -3.94, 0.09), P = 0.06] and the HAQ-S score [0.10 (95% CI -0.01, 0.20), P = 0.07] compared with non-smokers. CONCLUSION: Among AS patients, active smoking did not diminish or modify the improvements in HRQoL from anti-TNF treatment, even though current smokers compared with non-smokers tended to have poorer scores in some HRQoL measures.
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Antirreumáticos/uso terapêutico , Fatores Biológicos/uso terapêutico , Fumar/efeitos adversos , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Malignancy risk with tumour necrosis factor inhibitor (TNFi) therapy remains unclear. Our primary aim was to assess malignancy risk with TNFi therapy in a cohort of Australian patients with rheumatoid arthritis (RA). We also assessed risk in a biologic-naïve group. METHODS: Demographic data of all RA patients enrolled in the Australian Rheumatology Association Database before 25 October 2010 were matched to national cancer records in July 2010 (linkage complete to 2007). Verified self-reported malignancies occurring between 1 January 2008 and 25 October 2010 were also included in the analysis. Standardised incidence ratios (SIRs) were used to compare malignancy incidence in biologic-naïve and TNFi-exposed ARAD participants to the general population using site-, age- and sex-specific rates by calendar year. Rate ratios (RRs) were used to compare malignancy incidence in TNFi-exposed participants to biologic-naïve RA patients, and a composite RA cohort that included pre-TNFi person years, both adjusted for age, gender, smoking, methotrexate use and prior malignancy. RESULTS: Forty-four malignancies were reported after 5752 person-years in the TNFi-exposed group (N = 2145) and 32 malignancies were reported after 1682 person-years in the biologic-naïve group (N = 803). No overall increased risk of malignancy in TNFi-treated RA patients was found when compared with the general population or with biologic-naïve RA patients. Compared to the biologic naïve group, without the inclusion of pre-TNFi years in the comparator group, the relative risk of female breast cancer was reduced in TNFi-treated patients (RR 0.17 (95 % CI 0.03 to 0.95)). It was no longer significant when adding pre-TNFi years in the comparator group. The risk of melanoma was increased for both biologic naïve and TNFi-treated patients when compared with the general population (SIR 2.72 (95 % CI 1.13 to 6.53) and SIR 2.03 (95 % CI 1.09 to 3.78) respectively). The relative risk of melanoma was not increased in the TNFi-exposed group compared with biologic naïve patients (RR 0.54, 95 % CI 0.12, 2.40). Inclusion of pre-TNFi person years in the comparator group did not change these results. CONCLUSIONS: Malignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible.
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Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Neoplasias/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Austrália/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Prospectivos , Medição de RiscoRESUMO
OBJECTIVES: To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions. METHODS: The optimum case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010. RESULTS: The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs). CONCLUSIONS: RA continues to cause modest global disability, with severe consequences in the individuals affected.
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Artrite Reumatoide/epidemiologia , Efeitos Psicossociais da Doença , Saúde Global , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/mortalidade , Artrite Reumatoide/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Anos de Vida Ajustados por Qualidade de Vida , Análise de Regressão , Índice de Gravidade de Doença , Distribuição por Sexo , Adulto JovemRESUMO
OBJECTIVE: To determine distinct trajectories of self-reported pain-related health status in rheumatoid arthritis (RA), their relationship with sociodemographic factors and medication use. METHODS: 988 Australian Rheumatology Association Database participants with RA (71% female, mean age 54 years, mean disease duration 2.3 years) were included. Distinct multi-trajectories over 15-year follow-up for five different self-reported pain-related health outcome measures (Health Assessment Questionnaire Disability Index, visual analogue scores for pain, arthritis, global health and the Assessment of Quality of Life utility index) were identified using latent variable discrete mixture modelling. Random effects models were used to determine associations with medication use and biologic therapy modification during follow-up. RESULTS: Four, approximately equally sized, pain/health status groups were identified, ranging from 'better' to 'poorer', within which changes over time were relatively small. Important determinants of those with poorer pain/health status included female gender, obesity, smoking, socioeconomic indicators and comorbidities. While biologic therapy use was similar between groups during follow-up, biologic therapy modifications (plinear<0.001) and greater tendency of non-tumour necrosis factor inhibitor use (plinear<0.001) were observed in those with poorer pain/health status. Similarly, greater use of opioids, prednisolone and non-steroidal anti-inflammatory drugs was seen in those with poorer pain/health status. CONCLUSION: In the absence of disease activity information, distinct trajectories of varying pain/health status were seen from the outset and throughout the disease course in this RA cohort. More biologic therapy modifications and greater use in anti-inflammatories, opioids and prednisolone were seen in those with poorer pain/health status, reflecting undesirable lived experience of persistent pain in RA.
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Antirreumáticos , Artrite Reumatoide , Reumatologia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Autorrelato , Estudos Prospectivos , Qualidade de Vida , Analgésicos Opioides , Antirreumáticos/uso terapêutico , Austrália/epidemiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Dor/tratamento farmacológico , Dor/epidemiologia , Dor/etiologia , Prednisolona/uso terapêutico , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded.
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BACKGROUND: Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit. METHODS: We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3). RESULTS: In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure was an A grade surrogate endpoint for stroke prevention. In comparison, using the same stroke data sets, no STEs could be estimated for cardiovascular (CV) mortality or all-cause mortality reduction, although the STE for CV mortality approached 25 mmHg for systolic blood pressure. CONCLUSIONS: In this report we provide the first surrogate threshold effect (STE) values for systolic and diastolic blood pressure. We suggest the STEs have face and content validity, evidenced by the inclusivity of trial populations, subject populations and pharmacologic intervention populations in their calculation. We propose that the STE and STEP metrics offer another method of evaluating the evidence supporting surrogate endpoints. We demonstrate how surrogacy evaluations are strengthened if formally evaluated within specific-context evaluation frameworks using the Biomarker- Surrogate Evaluation Schema (BSES3), and we discuss the implications of our evaluation of blood pressure on other biomarkers and patient-reported instruments in relation to surrogacy metrics and trial design.
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Biomarcadores/análise , Pressão Sanguínea , Hipertensão/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Idoso , Biometria , Determinação de Ponto Final , Métodos Epidemiológicos , Feminino , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Análise de Regressão , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Níveis Máximos PermitidosRESUMO
Introduction: A key element in the big data revolution is large-scale biobanking and the associated development of high-quality data collections and supporting informatics solutions. As such, in establishing the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), we sought to establish a low-cost, nation-scale data management system capable of managing a multisite biobank registry with complex longitudinal sample and data requirements. Materials and Methods: We assessed several international commercial and nonprofit software platforms using standardized system requirement criteria and follow-up interviews. Vendor compliance scoring was prioritized to meet our project-critical requirements. Consumer/end-user codesign was integral to refining our system requirements for optimized adoption. Customization of the selected software solution was performed to optimize field auto-population between participant timepoints and forms, using modules that are transferable and that do not impact core code. Institutional and independent testing was used to ensure data security. Results: We selected the widely used research web application Research Electronic Data Capture (REDCap), which is "free" (under nonprofit license agreement terms), highly configurable, and customizable to a variety of biobank and registry needs and can be developed/maintained by biobank users with modest IT skill, time, and cost. We created a secure, comprehensive participant-centric biobank-registry database that includes: (1) best practice data security measures (incl. multisite access login using institutional user credentials), (2) permission-to-contact and dynamic itemized electronic consent, (3) a complete chain of custody from consent to longitudinal biospecimen data collection to publication, (4) complex longitudinal patient-reported surveys, (5) integration of record-level extracted/linked participant data, (6) significant form auto-population for streamlined data capture, and (7) native dashboards for operational visualizations. Conclusion: We recommend the versatile, reusable, and sustainable informatics model we have developed in REDCap for prospective chronic disease biobanks or registry biobanks (of local to national complexity) supporting holistic research into disease prediction, precision medicine, and prevention strategies.
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Bancos de Espécimes Biológicos , Austrália , Bases de Dados Factuais , Humanos , Estudos Prospectivos , Sistema de RegistrosRESUMO
OBJECTIVES: To describe changes in health-related quality of life (HRQoL) up to 60 months after commencing anti-TNF therapy for RA patients enrolled in the Australian Rheumatology Association Database (ARAD), and to determine the continuation rate and predictors of discontinuation of first-line anti-TNF therapy. METHODS: Responses to the HAQ, Assessment of Quality of Life, Medical Outcomes Study Short Form-36 (SF-36) and European Quality of Life-5 Dimensions (EQ-5D) were extracted from ARAD for patients commencing anti-TNF therapy and analysed in 6-monthly intervals from the start date. Predictors of discontinuation of therapy were assessed using Cox regression. RESULTS: Since September 2001, 2601 RA patients have enrolled in ARAD; 1801 have used anti-TNF therapy. Before starting the therapy, all HRQoL scores were below the population norms, but showed improvements in the first 6 months. From 12 to 60 months, HRQoL remained stable but below population means. Data to 60 months were available for 106 patients; 47% were still on first-line therapy at 5 years, all were using concurrent DMARDs and 55% were using concurrent prednisolone. Predictors of discontinuation of therapy were poorer HRQoL scores, a more recent therapy start date, concurrent prednisolone use and self-reported severe infection. Older patients and those with longer symptom duration were more likely to remain on therapy. CONCLUSIONS: In routine practice, HRQoL scores improve rapidly within 6 months of starting anti-TNFs and then remain stable for up to 60 months. Almost half remain on first-line therapy.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/psicologia , Produtos Biológicos/uso terapêutico , Qualidade de Vida , Inibidores do Fator de Necrose Tumoral , Idoso , Artrite Reumatoide/epidemiologia , Austrália/epidemiologia , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Índice de Gravidade de Doença , Estatística como Assunto , Fatores de Necrose Tumoral/uso terapêuticoRESUMO
BACKGROUND: Venous Thromboembolism (VTE) is a cause of hospital mortality and managing its morbidity is associated with significant expenditure. Uptake of evidenced based guideline recommendations intended to prevent VTE in hospital settings is sub-optimal. This study was conducted to explore clinicians' attitudes and the clinical environment in which they work to understand their reluctance to adopt VTE prophylaxis guidelines. METHODS: Between February and November 2009, 40 hospital employed doctors from 2 Australian metropolitan hospitals were interviewed in depth. Qualitative data were analysed according to thematic methodology. RESULTS: Analysis of interviews revealed that barriers to evidence based practice include i) the fragmented system of care delivery where multiple members of teams and multiple teams are responsible for each patient's care, and in the case of VTE, where everyone shares responsibility and no-one in particular is responsible; ii) the culture of practice where team practice is tailored to that of the team head, and where medicine is considered an 'art' in which guidelines should be adapted to each patient rather than applied universally. Interviewees recommend clear allocation of responsibility and reminders to counteract VTE risk assessment being overlooked. CONCLUSIONS: Senior clinicians are the key enablers for practice change. They will need to be convinced that guideline compliance adds value to their patient care. Then with the support of systems in the organisation designed to minimize the effects of care fragmentation, they will drive practice changes in their teams. We believe that evidence based practice is only possible with a coordinated program that addresses individual, cultural and organisational constraints.
Assuntos
Atitude do Pessoal de Saúde , Fidelidade a Diretrizes , Mortalidade Hospitalar/tendências , Guias de Prática Clínica como Assunto , Tromboembolia Venosa/prevenção & controle , Austrália , Estudos de Avaliação como Assunto , Medicina Baseada em Evidências/normas , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Corpo Clínico Hospitalar , Cultura Organizacional , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Medição de Risco , Tromboembolia Venosa/mortalidadeRESUMO
OBJECTIVE: To examine the relationship between corticosteroid use and herpes zoster risk. METHODS: With data from a large cohort of adults (the 45 and Up Study) recruited between 2006 and 2009 and linked to health data sets, the effect of corticosteroid use on zoster risk was analyzed by Cox proportional hazards models, adjusting for age, sex, and other characteristics. RESULTS: During 602,152 person-years (median, 7.36 years) of follow-up, there were 20,048 new systemic corticosteroid users and 6294 incident herpes zoster events among 94,677 participants (zoster incidence, 11.0 per 1000 person-years). Compared with nonusers, the risk of zoster was 59% higher in those using systemic corticosteroids (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.48 to 1.71) and greater with higher cumulative doses: aHR of 1.32 (95% CI, 1.17 to 1.48), 1.74 (95% CI, 1.55 to 1.95), and 1.80 (95% CI, 1.61 to 2.02) for use of less than 500 mg, 500 mg to less than 1000 mg, and 1000 mg or more prednisolone equivalents, respectively (P value for trend, <.001). Compared with nonusers, zoster risk increased significantly (aHR, 6.00; 95% CI, 4.85 to 7.42) in the month after a single prescription of systemic corticosteroids and returned to levels similar to those in nonusers by the third month after dispensing (aHR, 0.91; 95% CI, 0.49 to 1.69). CONCLUSION: Practitioners should be alert to the increased risk of zoster among patients taking systemic corticosteroids. Given the significant morbidity from zoster, particularly in older adults, these findings support judicious prescribing of corticosteroids, including using as low a dose and as short a course as possible.
Assuntos
Corticosteroides , Herpes Zoster , Prednisolona , Risco Ajustado/métodos , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Idoso , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Herpes Zoster/diagnóstico , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms).
Assuntos
Gota , Ácido Úrico , Biomarcadores , Supressores da Gota/uso terapêutico , Humanos , Avaliação de Resultados em Cuidados de Saúde , Resultado do TratamentoRESUMO
OBJECTIVE: To elicit patients' views on whether they could contribute to improvements in their care by carrying their own health information to clinician encounters; and to consider the implications for the development of a patient-held health file (PHF). BACKGROUND: Increasing rates of chronic disease lead to health care being delivered by multiple care providers often at distributed geographic locations. As a way of increasing the availability of patient information to care providers our project will trial a PHF. Patients carry these files to doctors' appointments where clinicians record data for other doctors or the patient. Increasing the availability of patient information is anticipated to enhance the safety and quality of care delivery and improve health outcomes. STUDY DESIGN: Qualitative semi-structured interviews were conducted with 10 patients. Participants were evenly distributed in terms of gender, aged 60 years or greater and visited at least two specialists and one general practitioner. FINDINGS: In this exploratory study, patients who were currently active in decision making about their own health already recorded some health information. They were receptive to carrying their information and thought they should take some responsibility for their health. Patients who were more passive in making decisions about their health did not perceive a need to carry their own information and felt that their doctors communicated adequately. CONCLUSION: Patient-held health files provide an opportunity for patients to access their health information. Such files have the potential to improve health outcomes for patients who adopt both active and passive roles in relation to their own health and engaging with their health information.