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BACKGROUND: Immunity to SARS-CoV-2 vaccination and infection differs considerably among individuals. We investigate the critical pathways that influence vaccine-induced cross-variant serological immunity among individuals at high-risk of COVID-19 complications. METHODS: Neutralizing antibodies to the wild-type SARS-CoV-2 virus and its variants (Beta, Gamma, Delta and Omicron) were analyzed in patients with autoimmune diseases, chronic comorbidities (multimorbidity), and healthy controls. Antibody levels were assessed at baseline and at different intervals up to 12-months following primary and booster vaccination with either BNT162b2 or mRNA-1273. Immunity induced by vaccination with and without infection (hybrid immunity) was compared with that of unvaccinated individuals with recent SARS-CoV-2 infection. Plasma cytokines were analyzed to investigate variations in antibody production following vaccination. RESULTS: Patients with autoimmune diseases (n=137) produced lesser antibodies to the wild-type SARS-CoV-2 virus and its variants compared with those in the multimorbidity (n=153) and healthy groups (n=229); antibody levels were significantly lower in patients with neuromyelitis optica and those on prednisolone, mycophenolate or rituximab treatment. Multivariate logistic regression analysis identified neuromyelitis optica (odds ratio 8.20, 95% CI 1.68-39.9) and mycophenolate (13.69, 3.78-49.5) as significant predictors of a poorer antibody response to vaccination (i.e, neutralizing antibody <40%). Infected participants exhibited antibody levels that were 28.7% higher (95% CI 24.7-32.7) compared to non-infected participants six months after receiving a booster vaccination. Individuals infected during the Delta outbreak generated cross-protective neutralizing antibodies against the Omicron variant in quantities comparable to those observed after infection with the Omicron variant itself. In contrast, unvaccinated individuals recently infected with the wild-type (n=2390) consistently displayed lower levels of neutralizing antibodies against both the wild-type virus and other variants. Pathway analyses suggested an inverse relationship between baseline T cell subsets and antibody production following vaccination. CONCLUSION: Hybrid immunity confers a robust protection against COVID-19 among immunocompromised individuals.
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OBJECTIVE: Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time. METHODS: We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score. RESULTS: At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up. CONCLUSION: The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines.
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Péptido Natriurético Encefálico , Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/mortalidad , Esclerodermia Sistémica/diagnóstico , Femenino , Masculino , Medición de Riesgo , Persona de Mediana Edad , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/mortalidad , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/sangre , Péptido Natriurético Encefálico/sangre , Anciano , Adulto , Factores de Riesgo , Prueba de Paso , Fragmentos de Péptidos/sangre , Incidencia , Europa (Continente)/epidemiología , Pronóstico , Valor Predictivo de las Pruebas , Sociedades Médicas , Biomarcadores/sangreRESUMEN
INTRODUCTION: Caregiver burden is a significant issue in the care of patients with advanced kidney disease. Its assessment is crucial for evaluating the needs of caregivers and for the development of interventions to support them. Several instruments have been developed to measure caregiver burden in these patients. However, the measurement properties of these instruments have not been systematically reviewed. METHODS AND ANALYSIS: This systematic review will include a comprehensive search of databases including PubMed, CINAHL, Embase, Cochrane Library, SCOPUS and Web of Science by using keywords and MeSH terms to identify relevant studies starting from each database inception to 1 January 2024 and covering papers in English. The search strategy will combine relevant keywords and database-specific subject headings related to the following concepts: (1) caregivers, (2) burden, stress, distress, (3) chronic kidney disease, end-stage kidney disease, dialysis. Reference lists of eligible articles will also be hand searched. We will include quantitative and qualitative studies evaluating measurement properties of instruments assessing caregiver burden in caregivers of adult patients (aged ≥18 years). Data will be extracted from the selected studies and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist as the study quality assessment tool. Subsequently, the van der Vleuten utility index will be used to critique and categorise the instruments. A narrative that synthesises the utility of all instruments will be presented along with recommendations for the selection of instruments depending on specific clinical contexts. This systematic review will provide an overview of the measurement properties of available instruments, including discussion on reliability, validity and responsiveness. Results from the review may give rise to the subsequent development of most appropriate instrument that could be applied to the assessment of caregiver burden in advanced kidney disease. ETHICS AND DISSEMINATION: Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023433906.
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Carga del Cuidador , Insuficiencia Renal Crónica , Humanos , Cuidadores/psicología , Calidad de Vida , Insuficiencia Renal Crónica/terapia , Proyectos de Investigación , Estrés Psicológico , Revisiones Sistemáticas como AsuntoRESUMEN
OBJECTIVE: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). METHODS: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. CONCLUSION: About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.
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Artritis Psoriásica , Artritis Reumatoide , COVID-19 , Espondiloartritis , Humanos , Artritis Psoriásica/epidemiología , Estudios de Cohortes , Prevalencia , COVID-19/epidemiología , COVID-19/prevención & control , Artritis Reumatoide/epidemiología , Espondiloartritis/epidemiología , VacunaciónRESUMEN
OBJECTIVE: Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We describe the clinical characteristics, treatment and survival outcomes of SLE patients with DAH in Singapore. METHODS: We conducted a retrospective review of the medical records of SLE patients with DAH hospitalised in 3 tertiary hospitals between January 2007 and October 2017. Patient demographics, clinical characteristics, laboratory, radiologic and bronchoscopic findings, as well as the treatments, were compared between survivors and non-survivors. Survival rates were analysed between the various treatment groups. RESULTS: A total of 35 patients with DAH were included in this study. Majority of them were female (71.4%) and of Chinese ethnicity (62.9%). Median age was 40.0 years (IQR: 25-54), with a median disease duration of 8.9 months (IQR: 0.13-102.4). Haemoptysis was the most common clinical presentation, and majority had concomitant cytopaenia and lupus nephritis. All patients received high dose glucocorticoids; 27 (77.1%), 16 (45.7%) and 23 (65.7%) received cyclophosphamide (CYP), rituximab (RTX), and plasmapheresis (PLEX), respectively. Twenty-two patients required mechanical ventilation with a median duration of 12 days. Overall mortality rate was 40%, with a median survival time of 162 days. Twenty-six patients (74.3%) achieved remission, with an overall median time to remission of 12 days (IQR: 6-46) after diagnosis of DAH. Patients on triple therapy (CYP, RTX and PLEX) had a median survival of 162 days as compared to 14 days in patients on PLEX alone (p = .0026). CONCLUSIONS: The overall mortality of DAH in SLE patients remained high. There were no significant differences in patient demographics or clinical characteristics between the survivors and non-survivors. However, better survival appears to be associated with treatment with cyclophosphamide.
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Enfermedades Pulmonares , Lupus Eritematoso Sistémico , Humanos , Femenino , Masculino , Adulto , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/diagnóstico , Estudios Retrospectivos , Singapur/epidemiología , Hemorragia/etiología , Hemorragia/terapia , Enfermedades Pulmonares/terapia , Enfermedades Pulmonares/complicaciones , Ciclofosfamida/uso terapéutico , Rituximab/uso terapéutico , Alveolos PulmonaresRESUMEN
OBJECTIVES: The association between gout and risk of cognitive impairment or dementia is not well established. We examined the relationship between having gout at midlife and the risk of developing cognitive impairment later on. METHODS: We used data of 16,948 participants from the population-based Singapore Chinese Health Study cohort. Participants were recruited from 1993 to 1998 at mean age of 53 years and re-contacted for three follow-up interviews: 1999 to 2004 for follow-up 1, 2006 to 2010 for follow-up 2, and 2014 to 2016 for follow-up 3. History of physician-diagnosed gout was self-reported at follow-up 1 and follow-up 2, while cognitive function was assessed with the Singapore modified Mini-Mental State Examination during follow-up 3, when participants had a mean age of 73.2 years. RESULTS: Gout was reported by 1281 (7.6%) participants at either follow-up 1 or 2, and 2243 (14.4%) had cognitive impairment at follow-up 3. A history of gout was associated with reduced risk of cognitive impairment (OR 0.78, 95% CI 0.65-0.93). This risk was reduced in a stepwise manner with either increased duration of gout or lower age at first diagnosis of gout (Ptrend <0.001). Compared to those without gout, those with gout for ≥20 years (OR 0.56, 95% CI 0.39-0.80) and those with age of onset of gout <50 years old (OR 0.59, 95% CI 0.37-0.94) had a lower risk of developing cognitive impairment. CONCLUSION: A young age of onset or a long history of gout was associated with reduced risk of cognitive impairment in late life.
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Disfunción Cognitiva , Gota , Humanos , Anciano , Factores de Riesgo , Estudios Prospectivos , Singapur/epidemiología , Disfunción Cognitiva/epidemiología , Gota/complicaciones , Gota/epidemiologíaRESUMEN
BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.
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Artritis Reumatoide , Enfermedades Autoinmunes , COVID-19 , Coronavirus , Lupus Eritematoso Sistémico , Fiebre Reumática , Humanos , Femenino , Persona de Mediana Edad , Niño , Masculino , Vacunas contra la COVID-19/uso terapéutico , Estudios Retrospectivos , Singapur/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Prednisolona/uso terapéutico , Vacunas Sintéticas/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Vacunación , Sistema de Registros , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/epidemiología , Vacunas de ARNmRESUMEN
Increasing workload and case complexity of a multimorbid ageing population have catalysed primary care transformation for general practitioners to meet these challenges. There is also a need to re-examine the role of hospital specialists as overly disease-centric, hospital-based specialist care is no longer sustainable. A new specialist-generalist model can maximise the potential of generalists and specialists to provide person-centred care, increase cost-effectiveness, improve appropriateness of referrals, decrease length of hospital stay and lower mortality.
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Atención Primaria de Salud , Especialización , Humanos , Atención Primaria de Salud/organización & administración , Rol del Médico , Atención Dirigida al Paciente/organización & administración , Médicos Generales , Derivación y ConsultaRESUMEN
Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.
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BACKGROUND: Patients with chronic diseases have seen unprecedented changes to healthcare practices since the emergence of COVID-19. Traditional 'on-site' clinics have had to innovate to continue services. Whether these changes are acceptable to patients and are effective for care continuation are largely unreported. METHODS: We evaluated the effectiveness of care provision at a re-structured chronic care clinic and elicited the patient experiences of care and self-management. We conducted a convergent, parallel, mixed-methods study. Adult patients attending a chronic care clinic were included. We extracted data from 4,849 clinic visits before and during the COVID-19 pandemic, including operational metrics and attendee profile. We also conducted fifteen interviews with patients from the same clinic using a semi-structured interview guide. RESULTS: Re-structuring the chronic clinic, including the introduction of teleconsultations, home-delivery of prescriptions and use of community-based phlebotomy services, served to maintain continuity of care while adhering to COVID-19 containment measures. Qualitatively, five themes emerged. Patients were able to adjust to healthcare practice changes and adapt their own lifestyles, although poor self-management practices were adopted. While most were apprehensive about attending the clinic, they valued ongoing care access and were reassured by the on-site containment measures. CONCLUSIONS: Continuation of routine services is desired by patients and can be achieved through the adoption of containment measures, by greater collaboration with community partners, and the use of technology. Patients adapted to service changes, but poor self-management was evident. To prevent chronic disease relapse, services must strive to innovate rather than suspend services during pandemics.
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COVID-19 , Pandemias , Adulto , Instituciones de Atención Ambulatoria , COVID-19/epidemiología , COVID-19/terapia , Humanos , Cuidados a Largo Plazo , Pandemias/prevención & controlRESUMEN
Chronic diseases typically require long-term management through healthy lifestyle practices and pharmacological intervention. Although efficacious treatments exist, disease control is often sub-optimal leading to chronic disease-related sequela. Poor disease control can partially be explained by the 'one size fits all' pharmacological approach. Precision medicine aims to tailor treatments to the individual. CURATE.AI is a dosing optimisation platform that considers individual factors to improve the precision of drug therapies. CURATE.AI has been validated in other therapeutic areas, such as cancer, but has yet to be applied in chronic disease care. We will evaluate the CURATE.AI system through a single-arm feasibility study (n = 20 hypertensives and n = 20 type II diabetics). Dosing decisions will be based on CURATE.AI recommendations. We will prospectively collect clinical and qualitative data and report on the clinical effect, implementation challenges, and acceptability of using CURATE.AI. In addition, we will explore how to enhance the algorithm further using retrospective patient data. For example, the inclusion of other variables, the simultaneous optimisation of multiple drugs, and the incorporation of other artificial intelligence algorithms. Overall, this project aims to understand the feasibility of using CURATE.AI in clinical practice. Barriers and enablers to CURATE.AI will be identified to inform the system's future development.
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Diabetes Mellitus Tipo 2 , Hipertensión , Algoritmos , Inteligencia Artificial , Enfermedad Crónica , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios de Factibilidad , Humanos , Hipertensión/tratamiento farmacológico , Estudios RetrospectivosAsunto(s)
Autoanticuerpos/inmunología , Dermatomiositis/diagnóstico , Helicasa Inducida por Interferón IFIH1/inmunología , Úlcera Cutánea/etiología , Anciano , Dermatomiositis/complicaciones , Dermatomiositis/inmunología , Dermatomiositis/patología , Diagnóstico Diferencial , Femenino , Mano , Humanos , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/patologíaRESUMEN
AIM: People with rheumatic diseases (PRD) remain vulnerable in the era of the COVID-19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS-CoV-2 in PRD. METHODS: Systematic literature reviews were performed to evaluate: (a) outcomes in PRD with COVID-19; (b) efficacy, immunogenicity and safety of COVID-19 vaccination; and (c) published guidelines/recommendations for non-live, non-COVID-19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: The consensus comprises 2 overarching principles and 7 recommendations. Vaccination against SARS-CoV-2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommend that eligible PRD and household contacts be vaccinated against SARS-CoV-2. We conditionally recommended that the COVID-19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommend that the COVID-19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post-vaccination antibody titers against SARS-CoV-2 need not be measured. Any of the approved COVID-19 vaccines may be used, with no particular preference. CONCLUSION: These recommendations provide guidance for COVID-19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low-level evidence.
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Vacunas contra la COVID-19/farmacología , COVID-19/epidemiología , Guías de Práctica Clínica como Asunto , Enfermedades Reumáticas/terapia , Reumatólogos , SARS-CoV-2/inmunología , Vacunación/métodos , COVID-19/prevención & control , Humanos , Pandemias , Enfermedades Reumáticas/epidemiología , Singapur/epidemiologíaRESUMEN
AIMS: Urate-lowering therapy (ULT) is effective in gout, but suboptimal management with wide variability in dose escalation remains widespread. We protocolized dose escalation of ULT to improve gout management. The aim was to reduce time to achieve target serum urate (SU) <360 µmol/L. METHODS: Process improvement tools were used to identify underlying causes of prolonged time to target SU. We designed a nurse-led telemedicine intervention for dose escalation of ULT. Patients with gout with SU ≥360 µmol/L meeting indications for ULT at a single institution were recruited. Exclusion criteria were estimated glomerular filtration rate <30 mL/min, pregnancy, cognitive impairment and poor mobility. A nurse-led telemedicine clinic was set up to perform patient education, monitoring of adverse events and drug escalation. We partnered with primary healthcare centers for routine blood tests. RESULTS: From July 2016 to December 2017, 127 patients were recruited. Median time to target SU was 19.0 weeks (interquartile range [IQR] 11.0-31.0). Median dose of allopurinol was 300 mg/d (IQR 200-400) in normal renal function and lower in renal impairment. Median telemedicine calls required to achieve target SU was 2 (IQR 1-3). No patient was hospitalized for gout flares. Two patients had adverse drug reactions, one required cessation of allopurinol for rash with eosinophilia, the other had self-resolving ulcers and allopurinol was continued. Lower baseline SU and number of gout flares were associated with attainment of target SU. CONCLUSION: A nurse-led telemedicine for gout care is effective and safe. Our results affirm the utility of telemedicine in increasing access to care and lower healthcare utilization.
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Alopurinol/uso terapéutico , Supresores de la Gota/uso terapéutico , Gota/tratamiento farmacológico , Gota/enfermería , Rol de la Enfermera , Reumatología , Telemedicina , Ácido Úrico/sangre , Adulto , Anciano , Alopurinol/efectos adversos , Biomarcadores/sangre , Regulación hacia Abajo , Femenino , Gota/sangre , Gota/diagnóstico , Supresores de la Gota/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente , Evaluación de Programas y Proyectos de Salud , Prueba de Estudio Conceptual , Reumatólogos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Aim: Concerns for fatal severe cutaneous adverse reactions (SCARs) hamper allopurinol use. Methods and material: We adopted a health system perspective to evaluate the cost-effectiveness of HLA-B*58:01 genotyping before allopurinol initiation. A decision tree compared three treatment strategies in gout patients with chronic kidney disease who have higher risk for SCAR. They were standard allopurinol treatment followed by febuxostat in nonresponders, test-positive patients receive febuxostat while test-negative receive allopurinol and universal use of febuxostat. Results: The first strategy was the most cost effective. Genotyping dominated universal febuxostat use. Time horizon and SCAR incidence were the most influential factors on the incremental cost-effectiveness ratio. Conclusion: HLA-B*58:01 genotyping compared with standard allopurinol-febuxostat sequential treatment does not provide good value for money in gout with chronic kidney disease.
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Alopurinol/uso terapéutico , Gota/tratamiento farmacológico , Gota/genética , Antígenos HLA-B/genética , Insuficiencia Renal Crónica/genética , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Femenino , Pruebas Genéticas , Genotipo , Supresores de la Gota/uso terapéutico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Approximately 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARDs). However, widespread use of biologic DMARDs (bDMARDs) and targeted-synthetic (tsDMARDs) is limited by cost. We formulated updated recommendations for eligibility criteria for government-assisted funding of bDMARDs/tsDMARDs for RA patients in Singapore. MATERIALS AND METHODS: Published guidelines regarding use of bDMARD and tsDMARDs were reviewed. We excluded those without a systematic literature review, formal consensus process or evidence grading. Separately, unpublished national reimbursement guidelines were included. RESULTS: Eleven recommendations regarding choice of disease activity measure, initiation, order of selection and continuation of bDMARD/tsDMARDs were formulated. A bDMARD/tsDMARD is indicated if a patient has: (a) at least moderately active RA with a Disease Activity Score in 28 joints/erythrocyte sedimentation rate (DAS28-ESR) score of ≥3.2; (b) failed ≥2 csDMARD strategies, 1 of which must be a combination; (c) received an adequate dose regimen of ≥3 months for each strategy. For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered. If a first-line TNFi fails, options include another TNFi, non-TNFi biologic or tsDMARDs. If a first-line non-TNFi biologic or tsDMARD fails, options include TNFi or another non-TNF biologic or tsDMARD. For continued bDMARD/tsDMARD subsidization, a patient must have a documented DAS28-ESR every 3 months and at least a moderate European League Against Rheumatism response by 6 months. CONCLUSION: These recommendations are useful for guiding funding decisions, making bDMARD/tsDMARDs usage accessible and equitable in RA patients who fail csDMARDs.
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Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Consenso , Determinación de la Elegibilidad/métodos , Programas de Gobierno , Reumatología , Sociedades Médicas , Humanos , SingapurRESUMEN
Gout has significant impact on the quality of life with over-utilisation of health resources. While lowering serum urate (SU) to ≤ 360 µmol/L improves clinical outcomes, this is usually not achieved. We describe the burden of gout and determine predictors of achieving SU target in gout patients in Singapore. This was a cross-sectional study of 282 gout patients from a Singapore hospital rheumatology service. Sociodemographic and lifestyle factors, co-existing medical conditions and medications, gout history and severity, SU levels and treatment were obtained. Patients with SU ≤ 360 µmol/L were compared with those > 360 µmol/L to determine factors associated with achieving SU target. Descriptive statistics and multivariate model were used. Severe disease was reported in 50%, with emergency attendances and hospitalisations in 33% and 19% respectively, and unemployment in 32%. Only 22% were at SU target and 67% on urate-lowering therapy (ULT) at recruitment. Hypertension, dyslipidaemia, chronic kidney disease and diabetes were prevalent in 56.7%, 48.2%, 32.3% and 18.8%, respectively. Malays had more comorbidities compared to Chinese participants. In multivariate analysis, ULT prescription and ≥ 2 comorbidities were associated with reaching SU target with odds ratios of 3.92 [95% confidence interval (CI) (1.75-8.71)] and 2.65 [95% CI (1.59-4.43)] respectively, independent of age, tophi, disease duration, body mass index, alcohol and diuretic use. Patients with gout have high disease burden resulting in significant healthcare utilisation. SU control is sub-optimal hence the use of ULT remains key in achieving SU target. Patients with other comorbidities are more likely to reach target than those with only gout as a single diagnosis.
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Supresores de la Gota/uso terapéutico , Gota/epidemiología , Hiperuricemia/epidemiología , Ácido Úrico/sangre , Adulto , Anciano , Alopurinol/uso terapéutico , Comorbilidad , Estudios Transversales , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Etnicidad , Febuxostat/uso terapéutico , Femenino , Gota/sangre , Gota/tratamiento farmacológico , Gota/fisiopatología , Hospitalización/estadística & datos numéricos , Humanos , Hipertensión/epidemiología , Hiperuricemia/sangre , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/fisiopatología , Masculino , Persona de Mediana Edad , Probenecid/uso terapéutico , Insuficiencia Renal Crónica/epidemiología , Índice de Severidad de la Enfermedad , Singapur/epidemiología , Resultado del TratamientoRESUMEN
AIM: There have been major advances in biologic treatment options for psoriatic arthritis (PsA) since the publication of the 2015 consensus recommendations by the Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore, for government-assisted funding, thus warranting a revision of this guideline. METHODS: Recent trials and nine published guidelines on the use of biologic therapy for PsA were reviewed. Based on the synthesized evidence, a task force panel (TFP), consisting of 10 practicing rheumatologists in Singapore, rated the statements pertaining to the use of biologic therapy, using a modified Delphi approach. Consensus was obtained if >70% agreed on a statement. RESULTS: The TFP agreed on 10 recommendations pertaining to the initiation, choice and continuation of biologic therapy. A biologic is indicated in patients with PsA: (a) with at least three swollen and tender joints, digits or entheses; and (b) who have failed at least two conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) strategies for a minimum of 3 months each. Any approved drug class including tumor necrosis factor inhibitors, interleukin-17 inhibitors (IL-17i), IL-12/23i or targeted synthetic DMARDs may be considered as first-line treatment, and continued only if a response is achieved by 6 months. CONCLUSION: These recommendations developed through a formal consensus method may be useful to guide funding considerations for appropriate and equitable use of biologic therapy for eligible patients with PsA.