Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

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.

Diffuse alveolar haemorrhage in systemic lupus erythematosus: A multicentre retrospective study in Singapore.

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.

Continuing chronic care services during a pandemic: results of a mixed-method study.

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.

Burden and management of gout in a multi-ethnic Asian cohort.

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.

Factors influencing medication adherence in patients with gout: A descriptive correlational study.

AIMS AND OBJECTIVES: To examine the factors influencing adherence to urate-lowering therapy in patients with gout in Singapore. BACKGROUND: Gout is the most common type of chronic inflammatory arthritis. Urate-lowering therapy is used to treat gout by reducing serum uric acid levels. However, adherence to urate-lowering therapy among patients remains poor. To date, there have been no available studies based on a conceptual framework that examined factors influencing medication adherence in patients with gout. DESIGN: Cross-sectional, descriptive correlational study. METHODS: A convenience sample of outpatients (n = 108) was recruited between October 2014-January 2015 from a tertiary hospital in Singapore. Outcomes were measured by relevant valid and reliable instruments. Descriptive statistics and parametric tests including multiple linear regression were used to analyse the data. RESULTS: Although 44.4% of the participants were high adherers to urate-lowering therapy, the mean adherence level was moderate. Significant differences in medication adherence scores were found among the subgroups of gender, ethnicity, marital status, employment status and presence of comorbidity. Medication adherence was positively significantly correlated with age, number of comorbidities and beliefs about medicines. Linear regression showed that higher level of beliefs about medicines, presence of comorbidity and being married were factors positively influencing medication adherence. CONCLUSIONS: This study revealed moderate adherence to urate-lowering therapy in patients with gout in Singapore, indicating the need for strategies to improve adherence by considering its main influencing factors. Future research should be conducted to develop interventions targeted at modifying patients' beliefs about medicines in order to improve medication adherence. RELEVANCE TO CLINICAL PRACTICE: Findings from this study allow healthcare providers to quickly and easily identify patients who may have low adherence. Nurses should take the lead in educating patients on the mechanism of urate-lowering therapy and highlight the importance of adhering to it.

A randomized controlled trial for improving patient self-assessment of synovitis in rheumatoid arthritis with education by ultrasonography: the RAEUS Study.

OBJECTIVE: Patients can potentially monitor disease activity of RA through self-assessed swollen joints (clinical synovitis), but reliability is poor. The objective is to evaluate the use of education by US feedback on the ability of patients to assess for clinical synovitis in RA. METHODS: We performed a 6 month, single-centre, randomized controlled trial on patients with established RA to study the effect of education on self-assessment of joints that included initial brief patient training on tender (TJC) and swollen (SJC) joint counts followed by US feedback every 3 months vs standard care without education. Patient and physician independently performed 28-joint counts at each visit. Outcome variables included the percentage of patients with good agreement with physician-derived swollen joints [prevalence-adjusted bias-adjusted kappa (PABAK) >0.6] as well as agreement in the SJC (Bland and Altman 95% limits of agreement), feasibility/patient satisfaction survey and disease activity at 6 months. RESULTS: Of the 101 randomized patients, 95 were included (51 in the education arm and 44 in the standard care arm). At 6 months there was a significant difference in the proportion of patients with swollen joint PABAK >0.6 in the education arm compared with standard care (98 vs 85%, P = 0.02). Limits of agreement for the SJC difference between physician and patients were reduced only in the education arm. The training method is considered feasible, with 94% of patients reporting it as useful. A trend of higher rates of disease remission (28-joint DAS <2.6) in the education arm vs standard care (47% vs 29%, P = 0.07) was seen. CONCLUSION: A short course of education with US feedback may be helpful in educating patients to assess for clinical synovitis. TRIAL REGISTRATION: Clinical trials.gov, https://clinicaltrials.gov, NCT02351401.

The NLRP3 inflammasome affects DNA damage responses after oxidative and genotoxic stress in dendritic cells.

The NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a cytoplasmic protein complex that mediates inflammatory responses to a broad array of danger signals. The inflammasome drives caspase-1 activation and promotes secretion of the pro-inflammatory cytokines IL-1ß and IL-18, and might also participate in other cellular processes. Here, we tried to identify new pathways regulated by the NLRP3 inflammasome in murine dendritic cells (DCs) in response to monosodium urate (MSU) crystals. Using a transcriptomic approach, we found that DCs from Nlrp3(-/-) mice responded to MSU with differential expression of genes involved in the DNA damage response and apoptosis. Upon exposure to MSU or other ROS-mobilizing stimuli (rotenone and γ-radiation), DNA fragmentation was markedly ameliorated in Nlrp3(-/-) and casp-1(-/-) DCs compared with WT DCs. Moreover, Nlrp3(-/-) DCs experienced significantly less oxidative DNA damage mediated by ROS. A significant decrease of the expression of several genes involved in double-strand and base-excision DNA repair was observed in WT DCs. Basal DNA repair capacity in WT DCs resulted in activation and stabilization of p53 in vitro and in vivo, which resulted in increased cell death compared with that in Nlrp3(-/-) DCs. These data provide the first evidence for the involvement of the NLRP3 inflammasome in DNA damage responses induced by cellular stress.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

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.

Predictive factors for interstitial lung disease progression in a Singapore systemic sclerosis cohort: a multicentre study.

INTRODUCTION: Interstitial lung disease (ILD) in systemic sclerosis (SSc) is heterogeneous with varied progression rate. This study aimed to identify the baseline clinical characteristics associated with ILD progression within 1, 3 and 5 years of the diagnosis of ILD. METHODS: This was a prospective, multicentre study - Systematic Sclerosis Cohort Singapore - conducted from January 2008 to February 2021, which included SSc patients with ILD diagnosed by high-resolution computed tomography. Progression of ILD was defined by forced vital capacity (FVC) decline ≥10% predicted or FVC decline 5%-9% predicted, with diffusing lung capacity of carbon monoxide decline ≥15% from the time of ILD diagnosis. Multivariable logistic and Cox regression analyses, adjusting for malignancy and treatment, were performed to determine independent risk factors of ILD progression. RESULTS: Of 124 SSc patients with ILD, 47.6% had limited cutaneous SSc, 33.9% had diffuse SSc and 18.5% had SSc-overlap. Progression of ILD was seen in 6%, 15% and 23% of patients within 1, 3 and 5 years, respectively. After adjusting for malignancy and treatment, anti-La was associated with ILD progression within 1 year (odds ratio [OR] 6.94, 95% confidence interval [CI]: 1.14-42.2; P = 0.04) and 3 years (OR 5.98, 95% CI: 1.31-27.4; P = 0.02), and anti-Scl-70 was associated with ILD progression within 5 years (OR 2.54, 95% CI: 1.05-6.12; P = 0.04). Analysing time to ILD progression as an outcome, anti-La was significantly associated with higher risk of ILD progression (hazard ratio 3.47, 95% CI: 1.18-10.2; P = 0.02). Time to ILD progression was 1.4 years in patients with anti-La versus 6.9 years in patients without anti-La (P = 0.02), and 4.7 years in patients with anti-Scl-70 versus 8.9 years in patients without anti-Scl-70 (P = 0.12). CONCLUSION: In this Asian cohort of SSc patients, autoantibodies may help to predict ILD progression rates.

Assessing caregiver burden in advanced kidney disease: protocol for a systematic review of the measurement properties of instruments and tools.

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.

Hybrid immunity augments cross-variant protection against COVID-19 among immunocompromised individuals.

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.

Re-examining the roles of generalists and specialists in healthcare.

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.

Association between gout at midlife and cognitive impairment at late life - The Singapore Chinese Health Study.

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.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study.

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.

Mortality due to coronary heart disease and kidney disease among middle-aged and elderly men and women with gout in the Singapore Chinese Health Study.

OBJECTIVES: Whether the link between gout and mortality is causal or confounded by lifestyle factors or comorbidities remains unclear. Studies in Asia are warranted due to the rapid modernisation of the locale and ageing of the population. METHODS: The association between gout and mortality was examined in a prospective cohort, the Singapore Chinese Health Study, comprising 63 257 Singapore Chinese individuals, aged 45-74 years during the enrolment period of 1993-8. All enrollees were interviewed in person on lifestyle factors, current diet and medical histories. All surviving cohort members were contacted by telephone during 1999-2004 to update selected exposure and medical histories (follow-up I interview), including the history of physician-diagnosed gout. Cause-specific mortality in the cohort was identified via record linkage with the nationwide death registry, up to 31 December 2009. RESULTS: Out of 52 322 participants in the follow-up I interview, 2117 (4.1%) self-reported a history of physician-diagnosed gout, with a mean age at diagnosis of 54.7 years. After a mean follow-up period of 8.1 years, there were 6660 deaths. Relative to non-gout subjects, subjects with gout had a higher risk of death (HR 1.18; 95% CI 1.06 to 1.32), and specifically from death due to coronary heart disease (CHD) (HR 1.38, 95% CI 1.10 to 1.73) and kidney disease (HR 5.81, 95% CI 3.61 to 9.37). All gout-mortality risk associations were present in both genders but the risk estimates appeared higher for women. CONCLUSION: Gout is an independent risk factor for mortality, and specifically for death due to CHD and kidney disease.

Neurosjögren: early therapy is associated with successful outcomes.

BACKGROUND: Primary Sjögren syndrome (PSS) is a systemic autoimmune condition with an estimated prevalence of 0.6%. The frequency of neurologic manifestations in PSS varies widely from 0% to 60%. METHODS: We report the characteristics of PSS patients with neurologic involvement seen at a single tertiary hospital in Singapore. Eight consecutive women (median age, 51 years [range, 38-67 years]) with neurologic manifestations of PSS seen between March 2009 to June 2011 were followed up for a mean duration of 19 months from the onset of neurologic manifestations. RESULTS: Six of 8 patients with neurosjögren had their neurologic manifestation at time of PSS diagnosis. The lag times of neurologic manifestations from PSS diagnosis for the remaining 2 patients were 9 and 30 years, respectively. Sicca symptoms were not readily volunteered as a presenting complaint in the majority of patients. All our patients received early aggressive therapy with pulse corticosteroids and intravenously administered cyclophosphamide. The mean duration from initial presentation to initiation of treatment was 11 days (1-26 days). All achieved good recovery regardless of the type or site of neurologic involvement, initial erythrocyte sedimentation rate, immunoglobulin and complement levels. CONCLUSIONS: Neurologic disease, when present, is a strong contributor to disease activity and damage. Confirmatory tests should be conducted early regardless of the presence of sicca symptoms. Vigilance for the development of new neurologic symptoms is imperative even in chronic, apparently stable patients. It is likely that early initiation of treatment contributed to good recovery in our patients.

Personalised Dosing Using the CURATE.AI Algorithm: Protocol for a Feasibility Study in Patients with Hypertension and Type II Diabetes Mellitus.

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.

Recommendations for COVID-19 vaccination in people with rheumatic disease: Developed by the Singapore Chapter of Rheumatologists.

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.