Objectives The relationship between disability and comorbidity on mortality is widely perceived as additive in clinical models of frailty. Design National data were retrospectively extracted from medical records of community hospital. Data Sources There were of 12,804 acutely-disabled patients admitted for inpatient rehabilitation in Singapore rehabilitation community hospitals from 1996 through 2005 were followed up for death till 31 December 2011. Outcome Measure Cox proportional-hazards regression to assess the interaction of comorbidity and disability at discharge on all-cause mortality. Results During a median follow-up of 10.9 years, there were 8,565 deaths (66.9%). The mean age was 73.0 (standard deviation: 11.5) years. Independent risk factors of mortality were higher comorbidity (p<0.001), severity of disability at discharge (p<0.001), being widowed (adjusted hazard ratio [aHR]: 1.38, 95% confidence interval [CI]:1.25–1.53), low socioeconomic status (aHR:1.40, 95%CI:1.29–1.53), discharge to nursing home (aHR:1.14, 95%CI:1.05–1.22) and re-admission into acute care (aHR:1.54, 95%CI:1.45–1.65). In the main effects model, those with high comorbidity had an aHR = 2.41 (95%CI:2.13–2.72) whereas those with total disability had an aHR = 2.28 (95%CI:2.12–2.46). In the interaction model, synergistic interaction existed between comorbidity and disability (p<0.001) where those with high comorbidity and total disability had much higher aHR = 6.57 (95%CI:5.15–8.37). Conclusions Patients with greater comorbidity and disability at discharge, discharge to nursing home or re-admission into acute care, lower socioeconomic status and being widowed had higher mortality risk. Our results identified predictive variables of mortality that map well onto the frailty cascade model. Increasing comorbidity and disability interacted synergistically to increase mortality risk.
Objective To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. Methods A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). Results There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III–IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III–IV developed within 2 years (range: 12.7–44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III–IV if they are negative for H. pylori . Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV. Conclusions We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.
Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD). While genome-wide association studies (GWAS) for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes) and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH) (peak P = 1.5×10−31) and age-related maculopathy susceptibility 2 (ARMS2) (P = 4.3×10−24) loci, and suggested Apolipoprotein E (ApoE) polymorphisms (rs2075650; P = 1.1×10−6) associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9×10−6) and upstream of GLI2 (rs6721654; P = 6.5×10−6), encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR) gene (rs621313; P = 3.5×10−6), involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.
Abstract Tuberculosis (TB) continues to be a leading cause of morbidity and mortality worldwide. Past genome-wide association studies (GWAS) have explored TB susceptibility across various ethnic groups, yet a significant portion of TB heritability remains unexplained. In this study, we conducted GWAS in the Singapore Chinese and Vietnamese, followed by a comprehensive meta-analysis incorporating independent East Asian data, and identified a novel pulmonary TB (PTB) susceptibility locus at 22q12.2 [rs6006426, OR(95%Cl)=1.097(1.066, 1.130), P meta =3.31×10 -10 ]. Our lead SNP was found to affect the expression of SF3A1 in various immune-related cells ( P ranging from 1.48×10 -9 to 6.17×10 - 18 ). Furthermore, a significant association was observed between rs6006426 and cigarette smoking ( P <0.044). When exploring the interplay between genetic marker, smoking and TB, our findings indicated that smoking status significantly mediated the effect of rs6006426 on PTB (β indirect-effect =-0.004, P indirect-effect =0.020). Our findings offer novel insights into the genetic factors underlying TB and reveals new avenues for understanding its etiology.
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