Impact of overactive bladder on quality of life and resource use: results from Korean Burden of Incontinence Study (KOBIS).

BACKGROUND: To evaluate the impact of overactive bladder (OAB) on quality of life (QOL), resource use and productivity loss in patients recruited from six hospitals in Korea. METHODS: This cross-sectional survey recruited 625 OAB patients between July to December 2013. Patients were categorised into four groups based on the average number of urinary incontinence (UI) episodes over the past three days (0, 1, 2-3 and ≥4 UI/day). QOL was measured using the Incontinence-Specific Quality of Life Instrument (I-QOL), the Overactive Bladder Questionnaire (OAB-q), and a generic health-related utility instrument (EQ-5D). Information on hospital and clinic visit frequency, and continence pads use were also collected. Work productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire. Between group differences were assessed using ANOVA. Multivariable regression analyses were performed to examine the independent effects of OAB symptoms on QOL. RESULTS: Severity of UI showed a significant linear relationship with QOL, with clinically meaningful differences between each UI severity category. Compared to the dry category, patients in the most severe category (≥4 UI/day) had significantly lower I-QOL scores (69.8 vs 42.6; p < 0.0001), greater symptom bother on the OAB-q (30.4 vs 64.6; p < 0.0001), and poorer EQ-5D utility (0.848 vs 0.742; p < 0.001). Multivariable analyses showed that UI severity, frequency, urgency, and nocturia are independently associated with poorer QOL. Incontinence severity is also significantly associated with cost of incontinence pads (p < 0.0001), and a greater interference with work and regular activities (p = 0.001), however, no significant difference in hospital and clinic visits were observed. CONCLUSION: Severity of UI is a key contributor to the disease burden of OAB in Korean patients, even after taking into account the impact of other symptoms associated with OAB.

Mapping of incontinence quality of life (I-QOL) scores to assessment of quality of life 8D (AQoL-8D) utilities in patients with idiopathic overactive bladder.

BACKGROUND: The Incontinence Quality of Life (I-QOL) questionnaire is a commonly used and validated incontinence specific QOL instrument. The objective of this study is to develop an algorithm to map I-QOL to the Assessment of Quality of Life (AQoL) 8D utility instrument in patients with idiopathic overactive bladder (iOAB). METHODS: I-QOL and AQoL-8D scores were collected in a survey of 177 Australian adults with urinary incontinence due to iOAB. Three statistical methods were used for estimation, namely ordinary least squares (OLS) regression, the robust MM-estimator, and the generalised linear models (GLM). Each included a range of explanatory variables. Model performance was assessed using key goodness-of-fit measures in the validation dataset. RESULTS: The I-QOL total score and AQoL-8D utility scores were positively correlated (r = 0.50, p < 0.0001). Similarly, the three sub-scales of the I-QOL were correlated with the eight dimensions and two super-dimensions of the AQoL-8D. The GLM estimator, with I-QOL total score as the explanatory variable exhibited the best precision (MAE = 0.15 and RMSE = 0.18) with a mapping function given by AQoL-8D = exp(-1.28666 + 1.011072*I-QOL/100). CONCLUSIONS: The mapping algorithm developed in this study allows the derivation of AQoL-8D utilities from I-QOL scores. The algorithm allows the calculation of preference-based QOL scores for use in cost-utility analyses to assess the impact of interventions in urinary incontinence.

Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.

BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

Changing epidemiology of invasive pneumococcal disease in Australian children after introduction of a 7-valent pneumococcal conjugate vaccine.

OBJECTIVE: To evaluate trends in the incidence and serotype profile of invasive pneumococcal disease (IPD) in Australian children under 2 years of age after the introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV). DESIGN AND SETTING: Analysis of incidence rates calculated using IPD surveillance data (including age, Indigenous status and serotype of the pneumococcal isolate) from 2002 to 2007 obtained from the National Notifiable Diseases Surveillance System and population estimates obtained from the Australian Bureau of Statistics. MAIN OUTCOME MEASURES: Trends in IPD incidence among Indigenous and non-Indigenous children between 2002 and 2007; change in the serotype profile of IPD in non-Indigenous children after the introduction of universal 7vPCV vaccination in 2005. RESULTS: Overall incidence of IPD decreased by 74% in all children < 2 years of age between 2002 and 2007 (P < 0.001). While the incidence of IPD caused by 7vPCV serotypes decreased significantly among both Indigenous and non-Indigenous children, the incidence of non-7vPCV serotype IPD increased significantly in non-Indigenous children (from 9.7 to 15.7 per 100 000, P < 0.001). Compared with a pre-vaccination period (2002-2004), the 2007 incidence of serotype 19A IPD in non-Indigenous children increased significantly (from 2.7 to 8.6 per 100 000, P < 0.001). In 2007, 19A was the predominant serotype causing IPD (37.7%) in all children aged < 2 years. CONCLUSIONS: The overall incidence of IPD decreased from 2002 to 2007, primarily driven by a reduction in IPD caused by 7vPCV serotypes. However, this was partially offset by a significant increase in the incidence of IPD caused by non-7vPCV serotypes, particularly 19A, in non-Indigenous children.

The epidemiology and cost of surgical site infections in Korea: a systematic review.

PURPOSE: To conduct a systematic literature review of the epidemiological and economic burden of surgical site infection (SSI) in Korea. METHODS: A search of the EMBASE, Medline and KoreaMed databases for English and Korean language publications was conducted. Searches for epidemiological and economic studies were conducted separately and limited to 1995 to 2010 to ensure the pertinence of the data. RESULTS: Twenty-six studies were included. The overall incidence of SSI in Korea was 2.0 to 9.7%. The National Nosocomial Infections Surveillance risk index was positively correlated with the risk of developing an SSI. Specific risk factors for SSI, identified through multivariate analyses included; diabetes, antibiotic prophylaxis and wound classification. SSIs were associated with increased hospitalisation cost, with each episode of SSI estimated to cost about an additional ₩2,000,000. A substantial portion of the increased cost was attributed to hospital room costs and the need for additional medication. Studies also found that post-operative stays for patients with SSIs were 5 to 20 days longer, while two studies reported that following cardiac surgery, patients with SSIs spent an additional 5 to 11 days in the intensive care unit, compared to patients without SSIs. CONCLUSION: Data from the included studies demonstrate that SSI represents a significant clinical and economic burden in Korea. Consequently, the identification of high-risk patient populations and the development of strategies aimed at reducing SSI may lead to cost-savings for the healthcare system.

Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore.

CONTEXT: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized. OBJECTIVE: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. DESIGN: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians. RESULTS: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry. CONCLUSIONS: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.

Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore.

OBJECTIVE: The potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) has been found through a genome-wide association study to be a strong candidate for conferring susceptibility to type 2 diabetes in East Asian and European populations. Our objective was to describe the association between polymorphisms at the KCNQ1 locus with insulin resistance, beta-cell function, and other type 2 diabetes-related traits in a sample of Chinese, Malays, and Asian Indians living in Singapore. RESEARCH DESIGN AND METHODS: We examined the associations between four previously reported KCNQ1 single-nucleotide polymorphisms (SNPs) with type 2 diabetes-related traits in 3,734 participants from the population-based 1998 Singapore National Health Survey cohort (2,520 Chinese, 693 Malay, and 521 Asian Indians). Insulin resistance was calculated from fasting insulin and glucose using the homeostasis model assessment method, whereas pancreatic beta-cell function was assessed using the corrected insulin response at 120 min (CIR(120)). RESULTS: SNPs rs2237897, rs2237892, and rs2283228 were significantly associated with type 2 diabetes (odds ratio [OR] 1.48, P = 3 x 10(-4); OR 1.38, P = 0.002; OR 1.31, P = 0.012, respectively). Within the Chinese population, the risk alleles for rs2237897, rs2237892, and rs2283228 were significantly associated with higher fasting glucose levels (P = 0.014, 0.011, and 0.034, respectively) and reduced CIR(120)(P = 0.007, 0.013, and 0.014, respectively). A similar trend was observed among the Malay and Asian Indian minority groups, although this did not reach statistical significance because of limited sample sizes. CONCLUSIONS: The increased risk for type 2 diabetes associated with KCNQ1 is likely to be caused by a reduction in insulin secretion. Further studies will be useful to replicate these findings and to fully delineate the role of KCNQ1 and its related pathways in disease pathogenesis.

Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population.

We conducted a cross-sectional study of Malay participants aged 40-80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values <0.007) and with increased risk of coronary heart disease and CVD [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.03-1.46; and OR 1.2, 95% CI 1.02-1.42, respectively] under an additive model of inheritance. In addition, using recessive models of inheritance, polymorphisms on chromosome 19 adjacent to the CILP2 and PBX4 loci (rs16996148) and on chromosome 1 at the GALNT2 locus (rs4846914) were associated with elevated HDL-C (P = 0.005) and lower LDL-C (P = 0.048), respectively. Although novel, the former is consistent with the association between this polymorphism and lower blood triglycerides observed in the initial studies conducted in populations of European ancestry. Neither showed statistically significant association with CVD. These observations should form the basis of further investigation to identify the causative polymorphisms at this locus, and also to understand the mechanistic roles that this protein may play in lipoprotein metabolism in Asians and other populations.

A family history of type 2 diabetes is associated with glucose intolerance and obesity-related traits with evidence of excess maternal transmission for obesity-related traits in a South East Asian population.

AIM: To evaluate family history (FH) of type 2 diabetes (T2DM) as a risk factor for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), T2DM and related metabolic traits in South East Asia and to compare the effects of a paternal versus maternal history. METHODS: We studied 4717 men and women (68% Chinese, 18% Malays and 14% Asian Indians) living in Singapore. FH was considered positive if at least one first degree relative had T2DM. Obesity, fasting lipids, glucose and insulin levels were measured for all subjects. Insulin resistance (IR) was estimated by homeostasis model assessment (HOMA). An oral glucose tolerance test was carried for all subjects except those on diabetes medication. RESULTS: A positive FH was associated with increased risk of IFG/IGT (OR=1.67, 95% CI=1.42-1.97) and T2DM (OR=2.95, 95% CI=2.36-3.70) as well as higher levels of obesity, HOMA-IR, fasting triglyceride (TG), and lower levels of high density lipoprotein (HDL) cholesterol and HOMA-beta. A maternal history of T2DM appeared to have a greater impact on obesity-related traits than a paternal history of T2DM. Compared to individuals with no FH of T2DM, a maternal history was associated with (i) greater body mass index (BMI) (24.15kg/m(2) vs. 23.42kg/m(2), p=0.016) and waist-to-hip ratio (WHR) (0.874 vs. 0.865, p=0.037) in men; and (ii) greater WHR (0.788 vs. 0.779, p=0.004), fasting triglyceride (1.23mmol/L vs. 1.09mmol/L, p<0.001), HOMA-IR (2.02 vs. 1.75, p<0.001), fasting plasma glucose (5.25mmol/L vs. 5.18mmol/L, p=0.005) and 2-h plasma glucose (6.01mmol/L vs. 5.78mmol/L, p=0.001) and lower HDL-C (1.41mmol/L vs. 1.47mmol/L, p=0.031) in women. CONCLUSION: T2DM appears to be heritable in South East Asians with excess maternal transmission of obesity, IR and dyslipidemia.

FTO variants are associated with obesity in the Chinese and Malay populations in Singapore.

OBJECTIVE: Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans. The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations. RESEARCH DESIGN AND METHODS: We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese, 785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore Malay Eye Study (SiMES). RESULTS: All nine SNPs exhibited strong linkage disequilibrium (r(2) = 0.6-0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging from 0.42 to 0.68 kg/m(2) (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m(2) (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m(2) (P < 0.0001) in SiMES Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17-1.22; P