Sex and ethnicity modified high 1-year mortality in patients in Singapore with newly diagnosed atrial fibrillation.

INTRODUCTION: We investigated sex and ethnic differences in the incidence, clinical characteristics and 1-year mortality of patients with newly diagnosed AF in a multi-ethnic population. METHOD: This retrospective cohort study of patients diagnosed with AF from 2008 to 2015 was based on medical claims, casemix and subvention data submitted to the Ministry of Health. Patients with AF were matched with controls without AF for age (3-year bands), sex and ethnicity, and categorised as middle-aged (45-64 years) or elderly (≥65 years) among major ethnic groups in Singapore (Chinese, Malay and Indian). RESULTS: Among 40,602 adults with AF (elderly 74%), Malays had the highest age-standardised incidence rate of AF, followed by Chinese and Indians; and the rate was higher in men. Despite having the worst cardiovascular risk profile, Indians had the lowest prevalence and incidence of AF. The 1-year mortality rate after newly diagnosed AF was 22-26 deaths per 100 people. Newly diagnosed AF was independently associated with increased 1-year all-cause mortality among middle-aged (adjusted odds ratio [AOR] 9.08, 95% confidence interval [CI] 7.36-11.20) and elderly adults (AOR 3.60, 95% CI 3.40-3.80) compared with those without AF. Sex differences in mortality among patients with AF were limited to elderly adults (men: AOR 1.17, 95% CI 1.11-1.24), while Indians were associated with a 30% increased odds of mortality compared with Chinese regardless of age (middle-aged: AOR 1.27, 95% CI 1.09-1.548 elderly: AOR 1.33, 95% CI 1.22-1.45). CONCLUSION: Variations in incidence, clinical profile and 1-year mortality of patients with AF in a nationwide cohort were influenced by sex and ethnicity. Newly diagnosed AF portends a worse prognosis and is a marker of high mortality within the first year.

Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg).

BACKGROUND: Biomarkers such as quantitative HBsAg (qHBsAg), quantitative hepatitis B virus (HBV) core-related antigen (qHBcrAg) and HBV RNA may be useful in predicting HBsAg loss in patients with chronic hepatitis B (CHB) undergoing antiviral therapy. AIM(S): Our study evaluated qHBsAg, HBV RNA and qHBcrAg as a posthoc analysis of a randomized clinical trial of peginterferon±NA to determine their utility in predicting HBsAg loss. METHODS: CHB patients who completed therapy with 48weeks peginterferon alpha2b ± nucleoside analogue therapy (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBsAg loss. The predictive ability of qHBsAg, qHBcrAg, HBV RNA and other variables were investigated by univariate and multivariate logistic models for HBeAg-negative patients by odds ratios, area under the curve (AUC), sensitivity, specificity, and positive and negative likelihood ratios (LR). RESULTS: HBsAg loss occurred in 15/114(13%) HBeAg-negative CHB patients who completed 48 weeks of peginterferon. At baseline, qHBsAg was superior to HBcrAg and HBV RNA with AUC 0.916, 0.649 and 0.542, respectively. Using multivariate analysis, the model comprising treatmentarm, age, gender, baseline qHBsAg, HBcrAg and HBV RNA, weeks 4 & 8 qHBsAg had the highest AUC(0.98), but the univariate model with week 8 qHBsAg <70 IU/mL had AUC 0.96. Hence, the contributions of variables other than qHBsAg were marginal. HBV RNA and qHBcrAg were weak predictors of HBsAg loss. Kinetics of the novel markers showed only qHBsAg had a good relationship with HBsAg loss while HBV RNA had a marginal relationship and HBcrAg did not change at all, and none had a good relationship with viral rebound. CONCLUSIONS: On-treatment biomarker predictors were better than baseline ones, and the best predictor of HBsAg loss at 72 weeks was week 8 qHBsAg <70 IU/mL.

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta-analysis.

Current therapies for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) and interferon (IFN), but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence, we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination. We searched PubMed, EMBASE and abstracts from EASL, Asia Pacific Association for study of the Liver and American Association for the Study of Liver Disease for randomized controlled trials of CHB patients, comparing NA, IFN or the combination. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, IFN dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata, and HBsAg loss was measured at the end-of-study (EOS), end-of-treatment (EOT) or end-of-follow-up (EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random-effects model. Forty-five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination vs IFN, RD = 1%, 95%CI-1%, 2%; combination vs NA, RD = 5%, 95%CI 3%,7%; IFN vs NA, RD = 3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose vs nonstandard; IFN duration ≥48 weeks vs <48 weeks, and loss of efficacy >2 years of follow-up. Similar findings were seen in HBsAg seroconversion, but only three studies reported HBsAg seroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48 weeks of therapy, although this effect faded over time.

Does Changing Inhaler Device Impact Real-Life Asthma Outcomes? Clinical and Economic Evaluation.

BACKGROUND: Inhaler usability and deposition differ between devices. Change of device may therefore have an impact on clinical and economic outcomes. OBJECTIVE: To characterize clinical and economic asthma outcomes surrounding the change from a dry powder inhaler (DPI) to a pressurized metered-dose inhaler (pMDI) for fixed-dose combination inhaled corticosteroid/long-acting ß agonist (FDC ICS/LABA) treatment. METHODS: Three retrospective cohort substudies using 2010 to 2015 data from the Korean Health Insurance and Review Assessment Service database were performed. Patients with asthma who received an FDC ICS/LABA pMDI for the first time after initially being on FDC ICS/LABA DPI were included. The following outcomes were assessed: (1) persistence of change to pMDI over 6 months, (2) clinical outcomes during the year after the change compared with the baseline year; and (3) noninferiority comparison of costs and effectiveness between patients changing to a pMDI and matched patients who continued their DPI. RESULTS: Patients who change inhalers seem to represent a more severe subpopulation. Fifty-eight percent of patients (95% CI, 56-60) persisted with the change. After the change in therapy, an increased proportion of patients (58.3%) remained free from severe exacerbations compared with the year before (47.4%; P < .001). Patients who changed to pMDIs had significantly less severe exacerbations, acute respiratory events, and lower short-acting ß agonist inhaler average daily dose, but higher average ICS daily dose (all P < .05), compared with matched patients remaining on a DPI. Total costs were similar between patients who changed to pMDI therapy compared with those remaining on a DPI. CONCLUSION: Changing from a DPI to a pMDI for FDC ICS/LABA asthma treatment can be as effective and cost-effective as remaining on a DPI.