Objective
Cigarette smoking is shown to reduce serum urate. However, its impact on risk of gout is unknown. We prospectively examined the relationship between cigarette smoking and gout risk in this ...Asian cohort.
Methods
We analyzed the data from the Singapore Chinese Health Study, a cohort of 63,257 Chinese ages 45–74 years at recruitment in 1993–1998. Information on cigarette smoking and other lifestyle factors was collected through in‐person interviews at recruitment. This analysis included 53,213 participants who took part in either the first followup (1999–2004) and/or the second followup interviews (2006–2010). Cox proportional hazards models were used to assess the relationship between cigarette smoking and gout risk.
Results
A total of 2,244 incident cases of physician‐diagnosed gout were identified after a mean followup of 11.1 years. Among men, compared to never smokers, the risk of gout in current smokers was decreased by 27% (hazard ratio HR 0.73 95% confidence interval (95% CI) 0.63–0.84). This risk reduction was greater in lean male smokers (HR 0.69 95% CI 0.57–0.83) than overweight smokers (HR 0.87 95% CI 0.67–1.13) (P = 0.09 for interaction). This inverse association with smoking was rapidly attenuated to become null even in former smokers who had recently quit smoking. Conversely, there was no association between smoking and gout risk in women. In a companion cross‐sectional study, current smokers had significantly lower levels of serum urate than former and never smokers, and this observation was present in men and not women.
Conclusion
Current smoking is associated with lower risk of gout in men in this Asian cohort.
IntroductionCaregiver 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 analysisThis 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 disseminationEthics 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 numberCRD42023433906.
Abstract
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.
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.
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‐1β 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.
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.
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.
Allopurinol is an efficacious urate-lowering therapy (ULT), but is associated with rare serious adverse drug reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with ...higher risk among HLA-B*5801 carriers. We assessed the cost-effectiveness of HLA-B*5801 testing, an enhanced safety program or strategies with both components.
The analysis adopted a health systems perspective and considered Singaporean patients with chronic gout, over a lifetime horizon, using allopurinol or probenecid. The model incorporated SJS/TEN and gout treatment outcomes, allele frequencies, drug prices and other medical costs.
Based on cost-effectiveness threshold of US$50,000 per quality-adjusted life year, HLA-B*5801-guided ULT selection or enhanced safety program was not cost effective. Avoidance of ULTs was the least preferred strategy as uncontrolled gout leads to lower quality-adjusted life years and higher costs.
The analysis underscores the need for biomarkers with higher positive predictive value for SJS/TEN, less expensive genetic tests or safety programs, or more effective gout drugs. .
It has been hypothesized that the association between hypertension and gout is bidirectional, however, few studies have examined this in a prospective cohort. We analyzed data from the Singapore ...Chinese Health Study (SCHS) follow-up I (1999-2004) and II (2006-2010) interviews, when both physician-diagnosed hypertension and gout were self-reported. We included participants with data for both follow-up interviews and who were free of heart disease, stroke and cancer at follow-up I. The analysis of hypertension and risk of gout included 31,137 participants when prevalent gout cases were excluded, while the analysis of gout and risk of hypertension included 20,369 participants when prevalent hypertension cases were excluded. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The mean age at follow-up I was 60.1 (SD 7.3) years, and the average follow-up was 6.8 (SD 1.4) years. In the analysis of hypertension and risk of gout, 682 incident cases were identified. Compared to normotensive participants, hypertensive patients had an 88% increased risk of developing gout (HR 1.88; 95% CI 1.61-2.21). In the parallel analysis, 5,450 participants reported to have newly diagnosed hypertension during follow-up. Compared to participants without gout, those with gout had an 18% increased risk of developing hypertension (HR 1.18; 95% CI 1.02-1.37). The bidirectional association was stronger in normal weight adults compared to overweight/obese individuals (Pinteraction = 0.06 and 0.04, respectively). The hypertension to gout association was stronger in women compared to men (Pinteraction = 0.04), while the gout to hypertension association was evident in women but not in men (Pinteraction = 0.02). In conclusion, our results suggest that the hypertension-gout association is bidirectional in this cohort of Singapore Chinese adults. The potential interactions of the bidirectional association with obesity and sex deserve further investigations.
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