METHODS: We report the establishment of an immunocompetent wild type strain 129 (wt-129) mouse model, which can be cross-species infected with human EV-A71 clinical isolates via an intraperitoneal route.
RESULTS: One intriguing disease phenotype of this new model is the development of characteristic "White-Jade" patches in the muscle, which lost sporadically the normal pink color of uninfected muscle. Viral VP1 protein and massive leukocyte infiltration were detected in muscles with or without white-jades. We demonstrated further that hypoxia is a general phenomenon associated with white-jades in both immunocompetent and immunodeficient mouse models. Therefore, hypoxia appears to be a feature intrinsic to EV-A71 infection, irrespective of its host's immunogenetic background. To date, no effective treatment for EV-A71 is available. Here, using this new wt-129 mouse model, we showed that timely treatment with compound R837 (a TLR7 immune modulator) via oral or intraperitoneal routes, rescued the hypoxia, limb paralysis, and death at a high therapeutic efficacy.
CONCLUSIONS: In this new immunocompetent mouse 129 model, we observed an unexpected white-jade phenotype and its associated hypoxia. The successful treatment with TLR7 immune modulators via an oral route, provide us a new research direction for EV-A71 basic science and translational research. It remains an open issue whether R837 or its related compounds, will be a promising drug candidate in clinical trials in EV-A71 endemic or epidemic areas in the future.
DESIGN: This was a qualitative study comprising semi-structured face-to-face interviews guided by 10 open-ended questions. Interviews were conducted until data saturation was achieved and no new ideas were formed. The interviews were audio-recorded, transcribed verbatim and analysed for themes. To derive themes, we employed directed content analysis of transcript data. Coding was completed using a combination of open, axial and selective coding.
SETTING: Four nursing homes in Singapore.
PARTICIPANTS: The study involved 17 participants (comprising 4 doctors, 4 pharmacists and 9 nurses).
RESULTS: Two key themes were identified, enablers and challenges. These were enablers and challenges faced by doctors, pharmacists and nurses towards deprescribing. The identified subthemes for enablers of deprescribing were: (1) awareness of medications that are unnecessary or could be targeted for deprescribing; (2) improving quality of life for patients with limited life expectancy; (3) improving communication between doctors, pharmacists and nurses; (4) systematic deprescribing practice and educational tools and (5) acknowledgement of possible benefits of deprescribing. The identified subthemes for challenges of deprescribing were: (1) symptoms not acknowledged as possibly drug-related; (2) lack of knowledge in patient's and family members' preferences; (3) lack of coordination between health professionals in hospitals and nursing homes and (4) limited tools for deprescribing. The development of a local guideline, mentoring nurses, case discussions, better shared decision-making and improving multidisciplinary communication, may help to support the process of deprescribing.
CONCLUSION: In conclusion, this study highlighted that deprescribing in the nursing homes is perceived by health professionals to be challenging and future research could assess how routine case studies, mentoring and better multidisciplinary communication could improve deprescribing knowledge and process in the nursing homes.
OBJECTIVE: This study aimed to investigate the validity of HR measures of a high-cost consumer-based tracker (Polar A370) and a low-cost tracker (Tempo HR) in the laboratory and free-living settings.
METHODS: Participants underwent a laboratory-based cycling protocol while wearing the two trackers and the chest-strapped Polar H10, which acted as criterion. Participants also wore the devices throughout the waking hours of the following day during which they were required to conduct at least one 10-min bout of moderate-to-vigorous physical activity (MVPA) to ensure variability in the HR signal. We extracted 10-second values from all devices and time-matched HR data from the trackers with those from the Polar H10. We calculated intraclass correlation coefficients (ICCs), mean absolute errors, and mean absolute percentage errors (MAPEs) between the criterion and the trackers. We constructed decile plots that compared HR data from Tempo HR and Polar A370 with criterion measures across intensity deciles. We investigated how many HR data points within the MVPA zone (≥64% of maximum HR) were detected by the trackers.
RESULTS: Of the 57 people screened, 55 joined the study (mean age 30.5 [SD 9.8] years). Tempo HR showed moderate agreement and large errors (laboratory: ICC 0.51 and MAPE 13.00%; free-living: ICC 0.71 and MAPE 10.20%). Polar A370 showed moderate-to-strong agreement and small errors (laboratory: ICC 0.73 and MAPE 6.40%; free-living: ICC 0.83 and MAPE 7.10%). Decile plots indicated increasing differences between Tempo HR and the criterion as HRs increased. Such trend was less pronounced when considering the Polar A370 HR data. Tempo HR identified 62.13% (1872/3013) and 54.27% (5717/10,535) of all MVPA time points in the laboratory phase and free-living phase, respectively. Polar A370 detected 81.09% (2273/2803) and 83.55% (9323/11,158) of all MVPA time points in the laboratory phase and free-living phase, respectively.
CONCLUSIONS: HR data from the examined wrist-worn trackers were reasonably accurate in both the settings, with the Polar A370 showing stronger agreement with the Polar H10 and smaller errors. Inaccuracies increased with increasing HRs; this was pronounced for Tempo HR.
METHODS: Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses.
RESULTS: The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively.
CONCLUSION: The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.
METHODS: The Dyslipidemia International Study (DYSIS) II was a multinational observational study of patients with stable CHD and hospitalised patients with an acute coronary syndrome (ACS). A full lipid profile and use of LLT were documented at baseline, and for the ACS cohort, at four months post-hospitalisation.
RESULTS: 325 patients were recruited from four sites in Singapore; 199 had stable CHD and 126 were hospitalised with an ACS. At baseline, 96.5% of the CHD cohort and 66.4% of the ACS cohort were being treated with LLT. In both cohorts, low-density lipoprotein cholesterol (LDL-C) levels were lower for the treated than the non-treated patients; accordingly, a higher proportion of patients met the LDL-C goal of < 70 mg/dL (CHD: 28.1% vs. 0%, p = 0.10; ACS: 20.2% vs. 0%, p < 0.01). By the four-month follow-up, a higher proportion of the ACS patients that were originally not treated with LLT had met the LDL-C goal (from 0% to 54.5%), correlating with the increased use of medication. However, there was negligible improvement in the patients who were treated prior to the ACS.
CONCLUSION: Dyslipidaemia is a significant concern in Singapore, with few patients with stable or acute CHD meeting the recommended European Society of Cardiology/European Atherosclerosis Society goal. LLT was widely used but not optimised, indicating considerable scope for improved management of these very-high-risk patients.
METHODS: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia.
RESULTS: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived.
CONCLUSIONS: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease.
PURPOSE: Information regarding mediators of differences in bone mineral density (BMD) among Asian ethnicities are limited. Since the majority of hip fractures are predicted to be from Asia, differences in BMD in Asian ethnicities require further exploration. We compared BMD among the Chinese, Malay, or Indian ethnicities in Singapore, aiming to identify potential mediators for the observed differences.
METHODS: BMD of 1201 women aged 45-69 years was measured by dual-energy X-ray absorptiometry. We examined the associations between ethnicity and BMD at both sites, before and after adjusting for potential mediators measured using standardized questionnaires and validated performance tests.
RESULTS: Chinese women had significantly lower femoral neck BMD than Malay and Indian women. Of the more than 20 variables examined, age, body mass index, and height accounted for almost all the observed ethnic differences in femoral neck BMD between Chinese and Malays. However, Indian women still retained 0.047 g/cm2 (95% CI, 0.024, 0.071) higher femoral neck BMD after adjustment, suggesting that additional factors may contribute to the increased BMD in Indians. Although no crude ethnic differences in lumbar spine BMD were observed, adjusted regression model unmasked ethnic differences, wherein Chinese women had 0.061(95% CI, - 0.095, 0.026) and 0.065 (95% CI, - 0.091, 0.038) g/cm2 higher lumbar spine BMD compared to Malay and Indian women, respectively.
CONCLUSION: BMD in middle-aged Asian women differ by ethnicity and site. Particular attention should be paid to underweight women of Chinese ethnic origin, who may be at highest risk of osteoporosis at the femoral neck and hence hip fractures.
Methods: A child-sized mannequin head was developed to measure light illuminance levels with and without sun-protective equipment, across a wide range of environments in Singapore, outdoors (open park, under a tree, street) and indoors (under a fluorescent illumination with window, under white LED-based lighting without window). A comparison was made between indoor and outdoor light levels that are experienced while children are involved in day-to-day activities.
Results: Outdoor light levels were much higher (11,080-18,176 lux) than indoors (112-156 lux). The higher lux levels protective of myopia (>1000 lux) were measured at the tree shade (5556-7876 lux) and with hat (4112-8156 lux). Sunglasses showed lux levels between 1792 and 6800 lux. Although with sunglasses readings were lower than tree shade and hat, light levels were still 11 to 43 times higher than indoors.
Conclusions: Recommendations on spending time outdoors for myopia prevention with adequate sun protection should be provided while partaking in outdoor activities, including protection under shaded areas, wearing a hat or sunglasses, sunscreen, and adequate hydration.
Translational Relevance: Light levels outdoors were higher than indoors and above the threshold illuminance for myopia prevention even with adequate sun-protective measures.
METHODS: This is a secondary analysis of the database of a multicentre study which recorded participants' basic demographical and clinical data in standardised format in 10 Asian countries and territories. The data were analysed using univariate and multivariate logistic regression analyses.
RESULTS: A total of 955 older adult psychiatric in- and outpatients were included in this study. The proportion of concurrent AP and AD use was 32.0%, ranging from 23.3% in Korea to 44.0% in Taiwan. Multivariate logistic regression analysis found that younger age, inpatient status and diagnosis of schizophrenia, anxiety and other mental disorders were significantly related to a higher proportion of concurrent use of APs and ADs.
CONCLUSION: Around a third of older adult psychiatric patients had concurrent AP and AD use in the Asian countries/regions surveyed. Considering the uncertain effectiveness and questionable safety of the AP and AD combination in this patient population, such should be cautiously used.