Protocol for a mixed-methods and multi-site assessment of the implementation process and outcomes of a new community-based frailty programme.

BACKGROUND: Frailty is increasing in prevalence internationally with population ageing. Frailty can be managed or even reversed through community-based interventions delivered by a multi-disciplinary team of professionals, but to varying degrees of success. However, many of these care models' implementation insights are contextual and may not be applicable in different cultural contexts. The Geriatric Service Hub (GSH) is a novel frailty care model in Singapore that focuses on identifying and managing frailty in the community. It includes key components of frailty care such as comprehensive geriatric assessments, care coordination and the assembly of a multi-disciplinary team. This study aims to gain insights into the factors influencing the development and implementation of the GSH. We also aim to determine the programme's effectiveness through patient-reported health-related outcomes. Finally, we will conduct a healthcare utilisation and cost analysis using a propensity score-matched comparator group. METHODS: We will adopt a mixed-methods approach that includes a qualitative evaluation among key stakeholders and participants in the programme, through in-depth interviews and focus group discussions. The main topics covered include factors that affected the development and implementation of each programme, operations and other contextual factors that influenced implementation outcomes. The quantitative evaluation monitors each programme's care process through quality indicators. It also includes a multiple-time point survey study to compare programme participants' pre- and post- outcomes on patient engagement, healthcare services experiences, health status and quality of life, caregiver burden and societal costs. A retrospective cohort study will compare healthcare and cost utilisation between participants of the programme and a propensity score-matched comparator group. DISCUSSION: The GSH sites share a common goal to increase the accessibility of essential services to frail older adults and provide comprehensive care. This evaluation study will provide invaluable insights into both the process and outcomes of the GSH and inform the design of similar programmes targeting frail older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04866316 . Date of Registration April 26, 2021. Retrospectively registered.

Aortic pulse wave velocity, central pulse pressure, augmentation index and chronic kidney disease progression in individuals with type 2 diabetes: a 3- year prospective study.

BACKGROUND: Pulse wave velocity (PWV), central pulse pressure and augmentation index are arterial stiffness- related hemodynamic parameters but their associations with renal outcome are still controversial. We hereby aim to study, 1) which hemodynamic parameter is independently associated with progressive chronic kidney disease (CKD), 2) the association of 3-year change in PWV with CKD progression and, 3) the additive predictive value of PWV for progressive CKD. METHODS: Carotid- femoral PWV, central pulse pressure and augmentation index were measured in 1444 participants with type 2 diabetes at baseline and 3 years apart. Progressive CKD was defined as confirmed eGFR decline 40% or greater. RESULTS: In the follow-up, 102 participants experienced progressive CKD. All 3 hemodynamic parameters were significantly associated with progressive CKD In univariable analysis. However, only PWV remained statistically significant after adjustment for known clinical risk factors and the other 2 hemodynamic parameters (OR 1.14 [95% CI 1.01-1.29] per m/s increment). One m/s regression (decrement) in PWV in the 3-year follow-up was associated with 26% lower adjusted- risk of progressive CKD (OR 0.74, 95% CI 0.56-0.97). Adding PWV onto traditional risk factor- based model significantly improved classification (net reclassification improvement 0.25, 95% CI 0.05-0.45, P = 0.01) and positive prediction rate (24.5 to 32.3%). CONCLUSIONS: Of 3 arterial stiffness- related hemodynamic parameters, only PWV is independently associated with progressive CKD. PWV may be a potential intervention target to mitigate risk of CKD progression and also a biomarker to improve risk-stratification of adverse renal outcome in individuals with type 2 diabetes.

Association of haptoglobin phenotype with incident acute myocardial infarction in Chinese patients with type 2 diabetes.

BACKGROUND: Haptoglobin (Hp) is an abundant plasma protein with anti-oxidant properties. Hp polymorphism is associated with cardio-metabolic dysfunction but the allele conferring risk of developing acute myocardial infarction (AMI) in type 2 diabetes (T2D) patients is unclear. This study aimed to investigate the association of Hp phenotype (Hp 1-1, 2-1 and 2-2) with incident AMI in Chinese T2D patients. METHODS: This prospective study included Chinese T2D participants from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) and Diabetic Nephropathy (DN) cohorts. Information on incidence of non-fatal AMI was collected by data linkage with the Singapore Myocardial Infarction Registry. Hp phenotype was determined using enzyme-linked immunosorbent assay. Cox proportional hazards regression models were used to evaluate the association of Hp phenotype with incident AMI, adjusted for traditional risk factors separately in two cohorts, then meta-analysed. RESULTS: In total, 2324 Chinese participants (SMART2D; N = 1034, mean age [SD] of 59 [11]) and (DN: N = 1290, mean age [SD] of 58 [12]) were included in this study. There were total of 30 (56 events per 10,000 patient-years) and 99 (128 events per 10,000 patient-years) AMI events in SMART2D and DN cohorts respectively. In meta-analysis, presence of Hp 1 allele conferred 43% (hazard ratio [HR] = 1.43 [95% CI 1.10-1.87], P = 0.008, Phet = 0.413) increased risk of incident AMI, independent of age, sex, smoking, body mass index, HbA1c, diabetes duration, lipids, hypertension, renal function and usage of insulin and RAS antagonist. In adjusted model, compared to Hp 2-2 groups, individuals with Hp 1-1 (HR = 2.18 [95% CI 1.19-3.76], P = 0.010, Phet = 0.193) and Hp 2-1 (HR = 1.45 [95% CI 0.98-2.14], P = 0.065, Phet = 0.576) were at a higher risk of incident AMI. Moreover, compared to Hp 2-2 groups, non-Hp 2-2 groups (Hp 1-1 and Hp 2-1) were at 55% increased risk of incident AMI (HR = 1.55 [95% CI 1.07-2.24], P = 0.021, Phet = 0.940). CONCLUSIONS: Hp 1-1 phenotype was associated with increased risk of incident AMI, independent of traditional risk factors, in Chinese patients with T2D. Hp phenotyping may allow for identification of T2D individuals at higher risk for onset of AMI. However, further studies are needed to understand the underlying mechanism between Hp alleles and risk for AMI.

Mapping modified Mini-Mental State Examination (MMSE) scores to dementia stages in a multi-ethnic Asian population.

ABSTRACTThe MMSE is used to screen for cognitive impairment and estimate dementia severity. In clinical settings, conventional cut-off scores have been used to distinguish between dementia stages. However, these scores have not been validated for different populations. This study maps scores from the modified version of the MMSE to dementia stages delineated by the Diagnostic and Statistical Manual of Mental Disorders-3rd revised edition (DSM-III-R), the Clinical Dementia Rating (CDR) and Functional Assessment Staging Test (FAST). We used cross-sectional data from a tertiary hospital memory clinic. Subjects were stratified into "primary education and below" (PE) or "secondary education and above" (SE). Receiving operating characteristic (ROC) analyses and Cohen's κ were performed to determine MMSE cut-off scores for dementia stages. Our derived cut-off scores were lower compared to the conventional scores. Scores also differed between subjects of different education levels. MMSE cut-off scores were 19, 15, and 9 for CDR stages 1, 2, and 3 respectively in PE subjects, and 23, 17, and 10 for SE subjects. Cut-off scores were comparable for staging by DSM-III-R Criteria and FAST. There is a need for locally derived stage-specific MMSE cut-off scores for the Asian population adjusted for education.

Caregiving burden in foreign domestic workers caring for frail older adults in Singapore.

ABSTRACTBackground:Although foreign domestic workers (FDWs) play a significant role in caring for frail seniors in Singapore and are vulnerable to caregiving burden, there has been little research conducted hitherto. We explored caregiver burden and its determinants in this study. METHODS: FDWs (N = 221, Mage = 32.3, SD = 6.23) recruited from a hospital geriatric unit completed the Zarit Burden Interview (ZBI) administered in English, Bahasa Melayu, or Burmese. Univariate and multivariate regression were employed to investigate factors influencing caregiving burden in FDWs. RESULTS: Majority were Indonesians (60.0%), married (57.5%) with children (62.4%), with secondary-level education (59.7%), and providing care for >1 year (79.9%). Importantly, 25.1% reported physical health problems and 23.1% encountered language difficulties with employers. Univariate analysis revealed three significant factors associated with caregiving burden: nationality (p < 0.001), lack of privacy (p = 0.029), and caring for persons with dementia (PWD) (p = 0.001). On multivariate regression, FDWs who cared for PWD were 5.47 times (p = 0.013) more likely to experience burden, while FDWs who encountered language difficulties were 5.46 times (p = 0.030) more likely to experience burden. Filipinos FDWs were 9.73 times more likely to express burden (p < 0.001) compared to their Indonesian and Burmese counterparts. CONCLUSION: The study highlights caregiver burden in FDWs and potential ways to alleviate it by empowering FDWs with dementia-specific caregiving skills, providing language training opportunities, and supporting particular FDW ethnic groups with more emotional and practical help.

Epigenetic state and expression of imprinted genes in umbilical cord correlates with growth parameters in human pregnancy.

BACKGROUND: Genomic imprinting is a process causing genes to be expressed according to parental origin. Imprinting acts to coordinate fetal and prenatal growth, as well as control postnatal adaptations. Studies on human imprinting are confounded by tissue availability, sampling variability and limitations posed by tissue-specific expression and cellular heterogeneity within tissues. The human umbilical cord is an easily available, embryonic-derived fetal tissue with the potential to overcome many of these limitations. METHODS: In a sensitive, gene-specific quantitative expression analysis, we show for the first time robust imprinted gene expression combined with methylation analysis in cords isolated from Asian Chinese full-term births. RESULTS: Linear regression analyses revealed an inverse correlation between expression of pleckstrin homology-like domain, family A, member 2 (PHLDA2) with birth weight (BW). Furthermore, we observed significant down-regulation of the paternally expressed gene 10 (PEG10) in low BW babies compared to optimum BW babies. This change in PEG10 gene expression was accompanied by concomitant methylation alterations at the PEG10 promoter. CONCLUSIONS: These data are the first to demonstrate relative expression of an imprinted gene associated with epigenetic changes in non-syndromic fetal growth restriction in babies. They show that perturbed expression in compromised fetal growth may be associated with in utero modulation of the epigenetic state at the imprinting control regions and implicate specific imprinted genes as new biomarkers of fetal growth.

Antibiotic utilisation and resistance over the first decade of nationally funded antimicrobial stewardship programmes in Singapore acute-care hospitals.

OBJECTIVE: The aim of this study was to describe the time series of broad-spectrum antibiotic utilisation and incidence of antibiotic-resistant organisms during the implementation of antimicrobial stewardship programmes (ASP) in Singapore. METHODS: An observational study was conducted using data from 2011 to 2020 in seven acute-care public hospitals. We applied joinpoint regressions to investigate changes in antibiotic utilisation rate and incidence density of antibiotic-resistant organisms. RESULTS: Across the seven hospitals, quarterly broad-spectrum antibiotic utilisation rate remained stable. Half-yearly incidence density of antibiotic-resistant organisms with two joinpoints at first half (H1) of 2012 and second half (H2) of 2014 decreased significantly in the second and third period with a half-yearly percentage change (HPC) of -2.9% and - 0.5%, respectively. Across the five hospitals with complete data, half-yearly broad-spectrum antibiotic utilisation rate with one joinpoint decreased significantly from H1 of 2011 to H2 of 2018 (HPC - 4.0%) and H2 of 2018 to H2 2020 (HPC - 0.5%). Incidence density of antibiotic-resistant organisms decreased significantly in the two joinpoint periods from H1 of 2012 to H2 of 2014 (HPC - 2.7%) and H2 of 2014 to H2 of 2020 (HPC - 1.0%). Ceftriaxone with one joinpoint decreased significantly from H1 of 2011 to H1 of 2014 (HPC - 6.0%) and H1 of 2014 to H2 of 2020 (HPC - 1.8%) and ceftriaxone-resistant E. coli and K. pneumoniae decreased significantly in later periods, from H2 of 2016 to H2 of 2020 (HPC - 2.5%) and H1 of 2012 to H2 of 2015 (HPC - 4.6%) respectively. Anti-pseudomonal antibiotics with one joinpoint decreased significantly from H1 of 2011 to H2 of 2014 (HPC - 4.5%) and H2 of 2014 to H2 of 2020 (HPC - 0.8%) and that of quinolones with one joinpoint at H1 of 2015 decreased significantly in the first period. C. difficile with one joinpoint increased significantly from H1 of 2011 to H1 of 2015 (HPC 3.9%) and decreased significantly from H1 of 2015 to H2 of 2020 (HPC - 4.9%). CONCLUSIONS: In the five hospitals with complete data, decrease in broad-spectrum antibiotic utilisation rate was followed by decrease in incidence density of antibiotic-resistant organisms. ASP should continue to be nationally funded as a key measure to combat antimicrobial resistance in acute care hospitals.

A Patient-Centred Medical Home Care Model for Community-Dwelling Older Adults in Singapore: A Mixed-Method Study on Patient's Care Experience.

Patient-Centred Medical Home (PCMH) is a strategy to enhance patient-centredness to improve care experience. We aimed to understand patient experience of an integrated PCMH model for complex community-dwelling older adults in Singapore. We used a mixed-method design with a prospective single-group pre-post quantitative component and a concurrent qualitative component. Participants were administered the validated Consumer Assessment of Health Providers and Systems Clinician & Group Survey (CG-CAHPS) at baseline (N = 184) and 6-month (N = 166) post-enrolment. We conducted focus group discussions (FGDs) on a purposive sample of 24 participants. Both methods suggest better care experience in PCMH relative to usual care. There were improvements in the CG-CAHPS measures on patient-provider communication, care coordination, office staff interactions, support for patients in caring for their own health, and provider rating in PCMH relative to usual care. In the FGDs, participants reported benefits of consolidated appointments and positive experience in sustained patient-provider relationship, shared-decision making, and family/caregiver engagement in PCMH. Participants may not fully comprehend the concept of integrated care, hindering both the effective communication of the intended care model and perceived benefits such as the provision of multidisciplinary team-based care.

National surgical antibiotic prophylaxis guideline in Singapore.

INTRODUCTION: Institutional surgical antibiotic prophylaxis (SAP) guidelines are in place at all public hospitals in Singapore, but variations exist and adherence to guidelines is not tracked consistently. A national point prevalence survey carried out in 2020 showed that about 60% of surgical prophylactic antibiotics were administered for more than 24 hours. This guideline aims to align best practices nationally and provides a framework for audit and surveillance. METHOD: This guideline was developed by the National Antimicrobial Stewardship Expert Panel's National Surgical Antibiotic Prophylaxis Guideline Development Workgroup Panel, which comprises infectious diseases physicians, pharmacists, surgeons and anaesthesiologists. The Workgroup adopted the ADAPTE methodology framework with modifications for the development of the guideline. The recommended duration of antibiotic prophylaxis was graded according to the strength of consolidated evidence based on the scoring system of the Singapore Ministry of Health Clinical Practice Guidelines. RESULTS: This National SAP Guideline provides evidence-based recommendations for the rational use of antibiotic prophylaxis. These include recommended agents, dose, timing and duration for patients undergoing common surgeries based on surgical disciplines. The Workgroup also provides antibiotic recommendations for special patient population groups (such as patients with ß-lactam allergy and patients colonised with methicillin-resistant Staphylococcus aureus), as well as for monitoring and surveillance of SAP. CONCLUSION: This evidence-based National SAP Guideline for hospitals in Singapore aims to align practices and optimise the use of antibiotics for surgical prophylaxis for the prevention of surgical site infections while reducing adverse events from prolonged durations of SAP.

Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid, and sweat during treatment of opioid-dependent pregnant women.

BACKGROUND: Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high-dose (14-20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. METHODS: Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 hours during gestation weeks 28 or 29 and 34, and 2 months after delivery. Time to maximum concentration was not affected by pregnancy; however, BUP and NBUP maximum concentration and area under the curve at 0 to 24 hours tended to be lower during pregnancy compared with postpartum levels. RESULTS: Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations and BUP/NBUP ratios in plasma and oral fluid. Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP oral fluid/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of oral fluid specimens. In sweat, BUP and NBUP were detected in only four of 25 (12 or 24 hours) specimens in low concentrations (less than 2.4 ng/patch). CONCLUSION: These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation.

Evaluation of the Implementation and Effectiveness of Community-Based Brain-Computer Interface Cognitive Group Training in Healthy Community-Dwelling Older Adults: Randomized Controlled Implementation Trial.

BACKGROUND: Cognitive training can improve cognition in healthy older adults. OBJECTIVE: The objectives are to evaluate the implementation of community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults. METHODS: A single-blind randomized controlled trial with baseline and follow-up assessments was conducted at two community centers in Singapore. Healthy community-dwelling adults aged 55 years and older participated in a 10-week CCT program with 2-hour instructor-led group classes twice a week. Participants used a mobile app to play games targeting attention, memory, decision making, visuospatial abilities, and cognitive flexibility. Implementation was assessed at the participant, provider, and community level (eg, reach, implementation, and facilitators and barriers). Effectiveness measures were the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Color Trails Test 2 (CTT-2), Berg Balance Scale, and GAITRite walkway measures (single and dual task gait speed, dual task cost, and single and dual task gait variability index [GVI]). RESULTS: A total of 94 healthy community-dwelling adults participated in the CCT program (mean age 68.8 [SD 6.3] years). Implementation measures revealed high reach (125/155, 80.6%) and moderate adherence but poor penetration of sedentary older adults (43/125, 34.4%). The effectiveness data were based on intention-to-treat (ITT) and per-protocol (PP) analysis. In the ITT analysis, single task GVI increased (b=2.32, P=.02, 95% CI [0.30 to 4.35]) and RBANS list recognition subtest deteriorated (b=-0.57, P=.01, 95% CI [-1.00 to -0.14]) in both groups. In the PP analysis, time taken to complete CTT-2 (b=-13.5, P=.01, 95% CI [-23.95 to -3.14]; Cohen d effect size = 0.285) was faster in the intervention group. Single task gait speed was not statistically significantly maintained in the intervention group (b=5.38, P=.06, 95% CI [-0.30 to 11.36]) and declined in the control group (Cohen d effect size = 0.414). PP analyses also showed interaction terms for RBANS list recall subtest (b=-0.36, P=.08, 95% CI [-0.75 to 0.04]) and visuospatial domain (b=0.46, P=.08, 95% CI [-0.05 to 0.96]) that were not statistically significant. CONCLUSIONS: CCT can be implemented in community settings to improve attention and executive function among healthy older adults. Findings help to identify suitable healthy aging programs that can be implemented on a larger scale within communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04439591; https://clinicaltrials.gov/ct2/show/NCT04439591.

Dietary factors, myopia, and axial dimensions in children.

PURPOSE: To evaluate the possible associations between dietary factors and myopia. DESIGN: Cross-sectional study. PARTICIPANTS: Eight hundred fifty-one Chinese schoolchildren from the Singapore Cohort Study of Risk Factors for Myopia. METHODS: Diet was assessed using a semiquantitative food-frequency questionnaire. Spherical equivalent (SE) refraction was assessed with an autorefractometer, and axial length (AL) by contact ultrasound A-scan biometry. MAIN OUTCOME MEASURES: Myopia was defined as SE< or =-0.5 diopters (D). Spherical equivalent and AL were analyzed by quartile groups. RESULTS: The mean age (+/-standard deviation) was 12.81+/-0.83 years, approximately half were male (422 children [49.6%]), and 653 (73.8%) children had myopia. In multivariate models, AL was longest in the highest quartile group of total cholesterol intake compared with the lowest (adjusted mean [95% confidence interval], 24.66 [24.62-24.71] mm vs. 24.32 [24.27-24.36] mm; P = 0.026, for trend) and was longest in the highest quartile group of saturated fat intake compared with the lowest (24.65 [24.60-24.70] vs. 24.36 [24.32-24.41] mm; P = 0.039, for trend). None of the nutrients was associated with SE or a diagnosis of myopia. CONCLUSIONS: Higher saturated fat and cholesterol intake are associated with longer AL in otherwise healthy Singapore Chinese schoolchildren.

Excretion of methadone in sweat of pregnant women throughout gestation after controlled methadone administration.

Sweat patches (n = 350) were collected throughout gestation from 29 opioid-dependent pregnant women participating in an outpatient methadone-assisted therapy program. Volunteers provided informed consent to participate in institutional review board-approved protocols. Methadone was eluted from sweat patches with sodium acetate buffer, followed by solid-phase extraction and quantification by gas chromatography mass spectrometry (limit of quantification > or = 10 ng/patch). Methadone was present in all weekly patches (n = 311) in concentrations ranging from 10.2 to 12,129.7 nanograms per patch and in 92.3% of short-term patches (n = 39, worn for 12 or 24 hours) in concentrations up to 3303.9 nanograms per patch. Correlation between patch concentrations and total amount of drug administered (r = 0.224), and concentrations and duration of patch wear (r = 0.129) were both weak. Although there were large intra- and intersubject variations in sweat drug concentrations, sweat testing was an effective alternative technique to qualitatively monitor illicit drug use and simultaneously document methadone medication-assisted treatment.

Maternal buprenorphine dose, placenta buprenorphine, and metabolite concentrations and neonatal outcomes.

Buprenorphine is approved as pharmacotherapy for opioid dependence in nonpregnant patients in multiple countries and is currently under investigation for pregnant women in the United States and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in five term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships among maternal buprenorphine dose, placenta concentrations, and neonatal outcomes after controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (coefficient of variation less than 27.5%, four locations), except for buprenorphine in three placentas. In two of these, buprenorphine was not detected in some locations and in the third placenta was totally absent. Median (range) concentrations were 1.6 ng/g buprenorphine (not detected to 3.2), 14.9 ng/g norbuprenorphine (6.2-24.2), 3 ng/g buprenorphine-glucuronide (1.3-5.0), and 14.7 ng/g norbuprenorphine-glucuronide (11.4-25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15- to 70-fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome onset and duration, for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum neonatal abstinence syndrome score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women.

Monitoring pregnant women's illicit opiate and cocaine use with sweat testing.

Dependence on illicit drugs during pregnancy is a major public health concern as there may be associated adverse maternal, fetal, and neonatal consequences. Sweat patches (n = 389) were collected from 39 pregnant volunteers who provided written informed consent for this Institutional Review Board-approved protocol and wore patches, replaced approximately weekly, from study entry until delivery. Patches were analyzed for opiates (heroin, 6-acetylmorphine, 6-acetylcodeine, morphine and codeine) and cocaine (cocaine, benzoylecgonine, ecgonine methyl ester, anhydroecgonine methyl ester) by solid phase extraction and gas chromatography mass spectrometry. Seventy-one percent (276) of collected sweat patches were > or =5 ng per patch (limit of quantification) for one or more analytes. Cocaine was present in 254 (65.3%) patches in concentrations ranging from 5.2 to 11,835 ng per patch with 154 of these high enough to satisfy the proposed Substance Abuse and Mental Health Services Administration guidelines for a confirmatory drug test (25 ng per patch). Interestingly, 6-acetylmorphine was the most prominent opiate analyte documented in 134 patches (34.4%) with 11.3% exceeding the proposed opiate Substance Abuse and Mental Health Services Administration cut-off (25 ng per patch). Heroin was identified in fewer patches (77), but in a similar concentration range (5.3-345.4 ng per patch). Polydrug use was evident by the presence of both cocaine and opiate metabolites in 136 (35.0%) patches. Sweat testing is an effective method for monitoring abstinence or illicit drug use relapse in this high-risk population of pregnant opiate- and/or cocaine-dependent women.

Association of Urine Haptoglobin With Risk of All-Cause and Cause-Specific Mortality in Individuals With Type 2 Diabetes: A Transethnic Collaborative Work.

OBJECTIVE: Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We employed a transethnic approach with a cohort of Asian origin (Singapore) (N = 2,061) and a cohort of European origin (France) (N = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality. RESULTS: A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5-12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3-10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02-2.11], 2.28 [1.62-3.21], and 4.64 [3.39-6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15-2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09-3.42] and adjusted HR 1.49 [1.14-1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor. CONCLUSIONS: Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.

Urinary excretion of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide in pregnant women receiving buprenorphine maintenance treatment.

BACKGROUND: Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum. METHODS: We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-mass spectrometry method with limits of quantification of 5 microg/L for BUP and BUP-Gluc and 25 microg/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy. RESULTS: NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy. CONCLUSIONS: These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation.

Cause-Specific Mortality in Multiethnic South East Asians With Type 2 Diabetes Mellitus.

Data on specific causes of mortality in South East Asians with type 2 diabetes mellitus (T2DM) remain scarce. We followed 2061 outpatients with T2DM (Chinese 63%, Malays 20%, and Asian Indians 17%) for an average of 5.5 (standard deviation = 2.9) years and identified 365 death events by data linkage with national death registry. Cardiovascular disease was the main cause of mortality (44%), followed by renal disease (17%), infection (17%), cancer (14%), and others causes (8%). Survival analyses revealed that risks for all-cause and cause-specific mortality vary greatly among ethnic groups. Presence of diabetic kidney disease was an independent risk factor for death attributable to cardiovascular disease, renal disease, and infection, while HbA1c level predicted all major causes of deaths even after accounting for multiple other risk factors. These data reinforce the importance of glycemic control and prevention of diabetic kidney disease for mitigation of mortality burden in multiethnic Asians with T2DM.

Will teenagers today live with and care for their aged parents tomorrow?

AIMS: Older adults who live alone are vulnerable physically, emotionally and socially. However, there is a trend towards children not living with their parents. We studied the willingness of teenagers today to live with and care for their aged parents tomorrow, and the reasons for their decision. METHODS: A convenient sample of 1405 teenage students (M age = 14.9 ± 1.30) in the north region of Singapore completed a purpose-designed questionnaire. Structural equation modeling was used to explore the relationships between teenagers' closeness to grandparents, challenges faced living with grandparents, positive and negative perceptions towards aging, and willingness to stay with aged parents in the future, stratified by sex. Thematic analysis was used to understand the reasons for their choice. RESULTS: The majority (85.6%) chose to live with their parents, and the significant predictors were "closeness to grandparents" (P = 0.034) and "positive perceptions towards aging" (P < 0.01), but not "challenges in living with grandparents" (P = 0.391) or "negative perceptions" (P = 0.302). Among teenagers with positive perceptions, boys were more likely to live with their parents (P < 0.01). Conversely, among teenagers with negative perceptions, girls were more likely to do so (P = 0.026). Primary reasons for willingness included: "desire to care," "expression of love," "sense of responsibility" and "prompted by moral values." CONCLUSIONS: Efforts should be undertaken to strengthen teenagers' relationships with grandparents, and promote positive perceptions towards aging to better sustain the family as a social safety net for aging and frail older adults. Geriatr Gerontol Int 2018; 18: 957-964.

Dysregulated homeostatic pathways in sarcopenia among frail older adults.

Sarcopenia, a core feature of the physical frailty syndrome, is characterized by multisystem physiological dysregulation. No study has explored qualitatively the hierarchical network of relationships among different dysregulated pathways involved in the pathogenesis of sarcopenia. We used 40 blood biomarkers belonging to community-dwelling prefrail and frail older persons to derive measures of multiple physiological pathways, and structural equation modeling to generate path network models of the multisystem physiological dysregulations associated with muscle mass and function (MMF). Insulin-leptin signaling and energy regulation, anabolic sex steroid regulation (testosterone, leptin), and tissue oxygenation (hemoglobin, red cell count) appear to be primary mediating factors exerting direct influences on MMF. There was additionally secondary mediatory involvement of myocyte- and adipocyte-derived cytokines, hypothalamic pituitary adrenal (HPA) stress hormones (cortisol, DHEAS), glomerular function, and immune cell regulatory and inflammatory cytokines and glycoproteins. We conclude that within a hierarchical network of multisystem physiological dysregulations in sarcopenia, dysregulated anabolic and catabolic pathways via sex steroids and insulin-leptin dual signaling and tissue hypoxemia are primary physiological dysregulations responsible for sarcopenia and frailty.