Bioactive glycans in a microbiome-directed food for children with malnutrition.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.

Evolution of IgA nephropathy in Singapore over four decades and a comparison of two cohorts from the first and fourth decade.

OBJECTIVE: In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1st decade and the 4th decade. MATERIALS AND METHODS: This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1st and the 4th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1st cohort of IgAN studied in the 1970s for the comparative study. RESULTS: The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores. CONCLUSION: The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.

Possible Bioenergetic Biomarker for Chronic Cancer-Related Fatigue.

BACKGROUND: Cancer-related fatigue (CRF) is a highly prevalent, debilitating, and persistent symptom experienced by patients receiving cancer treatments. Up to 71% of men with prostate cancer receiving radiation therapy experience acute and persistent CRF. There is neither an effective therapy nor a diagnostic biomarker for CRF. This pilot study aimed to discover potential biomarkers associated with chronic CRF in men with prostate cancer receiving radiation therapy. METHODS: We used a longitudinal repeated-measures research design. Twenty men with prostate cancer undergoing radiation therapy completed all study visits. CRF was evaluated by a well-established and validated questionnaire, the Patient-Reported Outcomes Measurement Information System for Fatigue (PROMIS-F) Short Form. In addition, peripheral blood mononuclear cells were harvested to quantify ribonucleic acid (RNA) gene expression of mitochondria-related genes. Data were collected before, during, on completion, and 24 months postradiation therapy and analyzed using paired t-tests and repeated-measures analysis of variance. RESULTS: The mean of the PROMIS-F T score was significantly increased over time in patients with prostate cancer, remaining elevated at 24 months postradiation therapy compared to baseline. A significant downregulated BC1 ubiquinol-cytochrome c reductase synthesis-like (BCS1L) was observed over time during radiation therapy and at 24 months postradiation therapy. An increased PROMIS-F score was trended with downregulated BCS1L in patients 24 months after completing radiation therapy. DISCUSSION: This is the first evidence to describe altered messenger RNA for BCS1L in chronic CRF using the PROMIS-F measure with men receiving radiation therapy for prostate cancer. CONCLUSION: Our results suggest that peripheral blood mononuclear cell messenger RNA for BCS1L is a potential biomarker and therapeutic target for radiation therapy-induced chronic CRF in this clinical population.

Changes in primary glomerulonephritis in Singapore over four decades
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This review of 3,289 native kidney biopsies over the past four decades in Singapore documents the changing pattern of biopsy-proven glomerulonephritis (GN)from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative GN was the most common form of primary GN, similar to the Asian region. In the 2nd decade, the percentage of mesangial proliferative GN decreased, but membranous GN became more common, as was seen in China and Thailand. In the 3rd decade, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy continued to rise, but it was only recently, in the 4th decade, that FSGS prevalence increased dramatically, although membranous nephropathy continues to increase in some Asian countries. In the last decade in Singapore, Malaysia, and Japan, prevalence of IgA nephritis has decreased but remains the most common GN. The percentage of FSGS continues to increase in many countries like in Italy, United States of America, United Kingdom, China, and Malaysia. We surmise that socioeconomic factors play significant roles in the evolution of the renal biopsy pattern.
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Enablers and inhibitors of the implementation of the Casalud Model, a Mexican innovative healthcare model for non-communicable disease prevention and control.

BACKGROUND: The Mexican healthcare system is under increasing strain due to the rising prevalence of non-communicable diseases (especially type 2 diabetes), mounting costs, and a reactive curative approach focused on treating existing diseases and their complications rather than preventing them. Casalud is a comprehensive primary healthcare model that enables proactive prevention and disease management throughout the continuum of care, using innovative technologies and a patient-centred approach. METHODS: Data were collected over a 2-year period in eight primary health clinics (PHCs) in two states in central Mexico to identify and assess enablers and inhibitors of the implementation process of Casalud. We used mixed quantitative and qualitative data collection tools: surveys, in-depth interviews, and participant and non-participant observations. Transcripts and field notes were analyzed and coded using Framework Analysis, focusing on defining and describing enablers and inhibitors of the implementation process. RESULTS: We identified seven recurring topics in the analyzed textual data. Four topics were categorized as enablers: political support for the Casalud model, alignment with current healthcare trends, ongoing technical improvements (to ease adoption and support), and capacity building. Three topics were categorized as inhibitors: administrative practices, health clinic human resources, and the lack of a shared vision of the model. CONCLUSIONS: Enablers are located at PHCs and across all levels of government, and include political support for, and the technological validity of, the model. The main inhibitor is the persistence of obsolete administrative practices at both state and PHC levels, which puts the administrative feasibility of the model's implementation in jeopardy. Constructing a shared vision around the model could facilitate the implementation of Casalud as well as circumvent administrative inhibitors. In order to overcome PHC-level barriers, it is crucial to have an efficient and straightforward adaptation and updating process for technological tools. One of the key lessons learned from the implementation of the Casalud model is that a degree of uncertainty must be tolerated when quickly scaling up a healthcare intervention. Similar patient-centred technology-based models must remain open to change and be able to quickly adapt to changing circumstances.

Predicting first-year mortality in incident dialysis patients with end-stage renal disease - the UREA5 study.

We aimed to develop a risk prediction model for first-year mortality (FYM) in incident dialysis patients with end-stage renal disease. We retrospectively examined patient comorbidities and biochemistry, prior to dialysis initiation, using a single-center, prospectively maintained database from 2005-2010, and analyzed these variables in relation to FYM. A total of 983 patients were studied. 22% had left ventricular ejection fraction (LVEF) <45%. FYM was 17%, and independent predictors included URate <500 or >600 µmol/l, LVEF <45% (higher odds ratio if <30%), Age >70 years, Arteriopathies (cerebrovascular and/or peripheral-vascular diseases), serum Albumin <30 g/l, and Alkaline phosphatase >80 U/l (p < 0.05, C-statistic 0.74), and these constitute the acronym UREA5. Using linear modeling, risk weightage/integer of 3 was assigned to LVEF <30%, 2 to age >70 years, and 1 to each remaining variable. Cumulative UREA5 scores of ≤ 1, 2, 3, 4, and ≥ 5 were associated with FYM of 6, 8, 22, 31, and 46%, respectively (p < 0.0001). Increasing UREA5 scores were strongly associated with stepwise worsening of FYM after dialysis initiation.

Glomerular filtration rates in healthy Asians without kidney disease.

AIM: The Chronic Kidney Disease Collaboration - Epidemiology (CKD-EPI) glomerular filtration rates (GFR) estimation equation is believed to estimate GFR more accurately in healthy people but this has not been validated in Asians. We studied the distribution of GFR in a multi-ethnic Asian population without CKD, and compared the performance of measures of GFR estimation, including the CKD-EPI equation, Cockroft-Gault equation, and 24-hour urine creatinine clearances. MATERIALS AND METHODS: A total of 103 healthy volunteers without a history of kidney disease, hypertension, or diabetes underwent GFR measurement using 3-sample plasma clearance of (99m) Tc-DTPA. Cockroft-Gault estimated GFR and 24-hour urine creatinine clearances were normalized to body surface area. RESULTS: The mean measured GFR was 101 ± 15.8 mL/min per 1.73 m(2) and was lowest in Indians (93 ± 12.3 mL/min per 1.73 m(2); P < 0.001). The CKD-EPI equation appears to be more accurate for healthy participants. Estimated GFR correlated with measured GFR (r = 0.57, P < 0.001), and the mean difference is 3.72 ± 14.43 mL/min per 1.73 m(2) (P < 0.001). However, estimating GFR using self-directed 24-hour urine creatinine clearances is poorer than using the CKD-EPI equation. CONCLUSIONS: GFR estimation using self-directed 24-hour urine collection for creatinine clearance is less accurate than using the CKD-EPI equation. A larger study is required to clarify GFR in healthy Asians, and the association of health outcomes of Asian kidney donors with lower GFR thresholds.

Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition.

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure-function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.

Spot urine tests in predicting 24-hour urine sodium excretion in Asian patients.

OBJECTIVE: The control of hypertension is often suboptimal, and it is frequently due to excessive sodium intake. Monitoring sodium intake is cumbersome and involves 24-hour collection of urine. We hypothesize that a spot urine test can accurately predict 24-hour urine sodium excretion in an Asian population. DESIGN: This is a prospective, observational study. We used stored urine specimens (n = 333) from the Asian Kidney Disease Study and Singapore Kidney Function Study Phase I. We measured spot urine tests and correlated these variables to the previously measured 24-hour urine sodium measurements. RESULTS: Age, gender, ethnicity, diastolic blood pressure, height, weight, body mass index, serum creatinine, spot urine sodium, spot urine chloride, and spot urine osmolality were associated with 24-hour urine sodium excretion. The final model for predicting 24-hour urine sodium less than 100 mmol included age, gender, ethnicity, weight, and spot urine sodium. CONCLUSION: Spot urine sodium can help monitor a patient's sodium intake when used in the derived 5-variable equation.

Laboratory diagnosis of tuberculosis in resource-poor countries: challenges and opportunities.

With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a country's national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each country's laboratory network.

Genotype and Clinical Characteristics of Patients with Wolfram Syndrome and WFS1-related Disorders.

Objective: Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity and prognosis of Wolfram syndrome more accurately. Approach: Patient data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and patient case reports were analyzed to select for patients with two recessive mutations in the WFS1 gene. Mutations were classified as being either nonsense/frameshift variants or missense/in-frame insertion/deletion variants and statistical analysis was performed using unpaired and paired t-tests and one- and two-way ANOVA with Tukey's or Dunnett's tests. Results: A greater number of genotype variants correlated with earlier onset and a more severe presentation of Wolfram syndrome. Secondly, non-sense and frameshift variants had more severe phenotypic presentations than missense variants, as evidenced by optic atrophy emerging significantly earlier in patients with 2 nonsense/frameshift alleles compared with 0 missense transmembrane variants. In addition, the number of transmembrane in-frame variants demonstrated a statistically significant dose-effect on age of onset of diabetes mellitus and optic atrophy. Summary / Conclusions: The results contribute to our current understanding of the genotype-phenotype relationship of Wolfram syndrome, suggesting that alterations in coding sequences result in significant changes in the presentation and severity of Wolfram. The impact of these findings is significant, as the results will aid clinicians in predicting more accurate prognoses and pave the way for personalized treatments for Wolfram syndrome.

Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders.

Objective: Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity and prognosis of Wolfram syndrome more accurately. Approach: Patient data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and patient case reports were analyzed to select for patients with two recessive mutations in the WFS1 gene. Mutations were classified as being either nonsense/frameshift variants or missense/in-frame insertion/deletion variants. Missense/in-frame variants were further classified as transmembrane or non-transmembrane based on whether they affected amino acid residues predicted to be in transmembrane domains of WFS1. Statistical analysis was performed using Wilcoxon rank-sum tests with multiple test adjustment applied via the Bonferonni correction. Results: A greater number of genotype variants correlated with earlier onset and a more severe presentation of Wolfram syndrome. Secondly, non-sense and frameshift variants had more severe phenotypic presentations than missense variants, as evidenced by diabetes mellitus and optic atrophy emerging significantly earlier in patients with two nonsense/frameshift variants compared with zero or one nonsense/frameshift variants. In addition, the number of transmembrane in-frame variants demonstrated a statistically significant dose-effect on age of onset of diabetes mellitus and optic atrophy among patients with either one or two in-frame variants. Summary/Conclusion: The results contribute to our current understanding of the genotype-phenotype relationship of Wolfram syndrome, suggesting that alterations in coding sequences result in significant changes in the presentation and severity of Wolfram. The impact of these findings is significant, as the results will aid clinicians in predicting more accurate prognoses and pave the way for personalized treatments for Wolfram syndrome.

Prevotella copri-related effects of a therapeutic food for malnutrition.

Preclinical and clinical studies are providing evidence that the healthy growth of infants and children reflects, in part, healthy development of their gut microbiomes1-5. This process of microbial community assembly and functional maturation is perturbed in children with acute malnutrition. Gnotobiotic animals, colonized with microbial communities from children with severe and moderate acute malnutrition, have been used to develop microbiome-directed complementary food (MDCF) formulations for repairing the microbiomes of these children during the weaning period5. Bangladeshi children with moderate acute malnutrition (MAM) participating in a previously reported 3-month-long randomized controlled clinical study of one such formulation, MDCF-2, exhibited significantly improved weight gain compared to a commonly used nutritional intervention despite the lower caloric density of the MDCF6. Characterizing the 'metagenome assembled genomes' (MAGs) of bacterial strains present in the microbiomes of study participants revealed a significant correlation between accelerated ponderal growth and the expression by two Prevotella copri MAGs of metabolic pathways involved in processing of MDCF-2 glycans1. To provide a direct test of these relationships, we have now performed 'reverse translation' experiments using a gnotobiotic mouse model of mother-to-offspring microbiome transmission. Mice were colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains cultured from Bangladeshi infants/children in the study population, with or without P. copri isolates resembling the MAGs. By combining analyses of microbial community assembly, gene expression and processing of glycan constituents of MDCF-2 with single nucleus RNA-Seq and mass spectrometric analyses of the intestine, we establish a principal role for P. copri in mediating metabolism of MDCF-2 glycans, characterize its interactions with other consortium members including Bifidobacterium longum subsp. infantis, and demonstrate the effects of P. copri-containing consortia in mediating weight gain and modulating the activities of metabolic pathways involved in lipid, amino acid, carbohydrate plus other facets of energy metabolism within epithelial cells positioned at different locations in intestinal crypts and villi. Together, the results provide insights into structure/function relationships between MDCF-2 and members of the gut communities of malnourished children; they also have implications for developing future prebiotic, probiotic and/or synbiotic therapeutics for microbiome restoration in children with already manifest malnutrition, or who are at risk for this pervasive health challenge.

Bioactive glycans in a microbiome-directed food for malnourished children.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Designing effective microbiome-directed therapeutic foods to repair these perturbations requires knowledge about how food components interact with the microbiome to alter its expressed functions. Here we use biospecimens from a randomized, controlled trial of a microbiome-directed complementary food prototype (MDCF-2) that produced superior rates of weight gain compared to a conventional ready-to-use supplementary food (RUSF) in 12-18-month-old Bangladeshi children with moderate acute malnutrition (MAM)4. We reconstructed 1000 bacterial genomes (metagenome-assembled genomes, MAGs) present in their fecal microbiomes, identified 75 whose abundances were positively associated with weight gain (change in weight-for-length Z score, WLZ), characterized gene expression changes in these MAGs as a function of treatment type and WLZ response, and used mass spectrometry to quantify carbohydrate structures in MDCF-2 and feces. The results reveal treatment-induced changes in expression of carbohydrate metabolic pathways in WLZ-associated MAGs. Comparing participants consuming MDCF-2 versus RUSF, and MDCF-2-treated children in the upper versus lower quartiles of WLZ responses revealed that two Prevotella copri MAGs positively associated with WLZ were principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilization of its component glycans. Moreover, the predicted specificities of carbohydrate active enzymes expressed by polysaccharide utilization loci (PULs) in these two MAGs correlate with the (i) in vitro growth of Bangladeshi P. copri strains, possessing differing degrees of PUL and overall genomic content similarity to these MAGs, cultured in defined medium containing different purified glycans representative of those in MDCF-2, and (ii) levels of carbohydrate structures identified in feces from clinical trial participants. In the accompanying paper5, we use a gnotobiotic mouse model colonized with age- and WLZ-associated bacterial taxa cultured from this study population, and fed diets resembling those consumed by study participants, to directly test the relationship between P. copri, MDCF-2 glycan metabolism, host ponderal growth responses, and intestinal gene expression and metabolism. The ability to identify bioactive glycan structures in MDCFs that are metabolized by growth-associated bacterial taxa will help guide recommendations about use of this MDCF for children with acute malnutrition representing different geographic locales and ages, as well as enable development of bioequivalent, or more efficacious, formulations composed of culturally acceptable and affordable ingredients.

Estimating glomerular filtration rates by use of both cystatin C and standardized serum creatinine avoids ethnicity coefficients in Asian patients with chronic kidney disease.

BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is most accurate for estimating glomerular filtration rate (GFR) but requires an adjustment for African-American patients. Estimation equations are also improved with the use of serum cystatin C combined with standardized creatinine. Combination equations have been derived by the CKD-EPI and Chinese investigators. We investigated whether these cystatin C-based equations improve estimation adequately, so that adjustments for ethnicity are not required in a multiethnic Asian population with chronic kidney disease (CKD). METHODS: This was a cross-sectional study of 232 stable CKD patients who underwent GFR measurements using 3-sample plasma clearances of (99m)Tc-DTPA, and for whom serum cystatin C and creatinine were quantified. RESULTS: For all patients, the median biases with cystatin C equations were generally greater than with the CKD-EPI equation, and precision and root mean square error (RMSE) were not significantly better. However, the combination serum creatinine and cystatin C equation improved the precision, RMSE, and percentage of estimated GFR to within 15% and 30% of the measured GFR (57.3% vs 50.0%, 88.4% vs 82.8%, respectively). The derived ethnicity coefficients for the combination equation were all >1 (1.009-1.082) but small, suggesting that coefficients are not required. The Chinese-specific equations were more biased and performed more poorly than the CKD-EPI equation. CONCLUSIONS: The use of a cystatin C and creatinine combination equation for estimating GFR in a multiethnic Asian population with CKD does not require ethnicity coefficients because the derived coefficients are very close to each other.

Comparative outcomes of primary autogenous fistulas in elderly, multiethnic Asian hemodialysis patients.

BACKGROUND: The number of elderly (≥65 years) end-stage renal disease (ESRD) patients on hemodialysis is rapidly increasing. Vascular access outcomes remain contradictory and understudied across different elderly populations. We hypothesized age might influence primary autogenous fistula use and outcomes in a predominantly diabetic multiethnic Asian ESRD population. METHODS: Demographic and clinical factors affecting fistula patency and maturation were retrospectively compared among patients with incident ESRD aged <65 and ≥65 years at a single center. Fistula patency was estimated by Kaplan-Meier curves with log-rank test comparison. RESULTS: We analyzed 280 primary fistulas (59% radiocephalic, 33% brachiocephalic, and 8% brachiobasilic) in this cohort consisting of 31.8% aged ≥65 years, 50% Chinese, 39% Malay, 42% women, and 70% diabetic. One- and 2-year primary and secondary patency in patients aged <65 vs ≥65 years were comparable: 41.3% vs 36.7% and 28.7% vs 24.4% (P = .547) and 57.7% vs 56.8% and 47.1% vs 47.2% (P = .990). On multivariate analysis, only non-Chinese, dialysis initiation with tunneled catheters, and surgical/endovascular interventions affected fistula survival hazard ratios (HR): 0.622 (95% confidence interval [CI], 0.43-1.00), 0.549 (95% CI, 0.297-0.841), and 2.503 (95% CI, 1.695-3.697), respectively. Nonmaturation and intervention rates were also similar at 56.7% vs 61.8% and 34% vs 32.2% at 3 and 6 months and 0.31 vs 0.36 per access year, respectively (P > .05). Females and tunneled catheters were the only risk factors for nonmaturation (HR, 1.568; 95% CI, 1.148-1.608, and HR, 1.623; 95% CI, 1.400-1.881, respectively). CONCLUSIONS: A primary fistula strategy in incident elderly ESRD is feasible and does not result in inferior outcomes. Age should therefore not be a determinant for primary fistula creation.

Malaria rapid diagnostic test transport and storage conditions in Burkina Faso, Senegal, Ethiopia and the Philippines.

BACKGROUND: As more point of care diagnostics become available, the need to transport and store perishable medical commodities to remote locations increases. As with other diagnostics, malaria rapid diagnostic tests (RDTs) must be highly reliable at point of use, but exposure to adverse environmental conditions during distribution has the potential to degrade tests and accuracy. In remote locations, poor quality diagnostics and drugs may have significant negative health impact that is not readily detectable by routine monitoring. This study assessed temperature and humidity throughout supply chains used to transport and store health commodities, such as RDTs. METHODS: Monitoring devices capable of recording temperature and humidity were deployed to Burkina Faso (8), Senegal (10), Ethiopia (13) and the Philippines (6) over a 13-month period. The devices travelled through government supply chains, usually alongside RDTs, to health facilities where RDTs are stored, distributed and used. The recording period spanned just over a year, in order to avoid any biases related to seasonal temperature variations. RESULTS: In the four countries, storage and transport temperatures regularly exceeded 30.0°C; maximum humidity level recorded was above 94% for the four countries. In three of the four countries, temperatures recorded at central storage facilities exceeded pharmaceutical storage standards for over 20% of the time, in another case for a majority of the time; and sometimes exceeded storage temperatures at peripheral sites. CONCLUSIONS: Malaria RDTs were regularly exposed to temperatures above recommended limits for many commercially-available RDTs and other medical commodities such as drugs, but rarely exceeded the recommended storage limits for particular products in use in these countries. The results underline the need to select RDTs, and other commodities, according to expected field conditions, actively manage the environmental conditions in supply chains in tropical and sub-tropical climates. This would benefit from a re-visit of current global standards on stability of medical commodities based in tropical and sub-tropical climatic zones.

Quantifying acute changes in volume and nutritional status during haemodialysis using bioimpedance analysis.

AIM: To determine the precision of multi-frequency bioimpedance analysis (MFBIA) in quantifying acute changes in volume and nutritional status during haemodialysis, in patients with end-stage renal disease (ESRD). METHODS: Using whole-body MFBIA, we prospectively studied changes in total body water (TBW), extracellular volume (ECV), intracellular volume (ICV), lean body mass (LBM), body cell mass (BCM) and fat mass (FM), pre- and post-haemodialysis and tested the agreement of volume changes with corresponding acute weight change and ultrafiltration volume (UF) using Bland-Altman analysis. RESULTS: Forty-four prevalent and 17 incident haemodialysis patients were studied (median age 55 years, 56% males). MFBIA-derived TBW, ECV, ICV, LBM and BCM were significantly reduced after haemodialysis (P < 0.001), but FM remained constant. TBW change estimated weight change with mean bias of -0.52 L, with 56/61 (91.8%) data points within limits of agreement (-2.74 L, 1.69 L). TBW change estimated UF with mean bias of -0.62 L, with 55/61 (90.2%) data points within limits of agreement (-2.68 L, 1.43 L). ECV change underestimated weight change and UF with mean bias of -1.17 L and -1.27 L respectively. Similarly, ICV change underestimated both clinical measures with corresponding mean bias of -1.34 L and -1.44 L. Comparing incidents versus prevalent haemodialysis patients, TBW change estimated weight change with smaller mean bias (-0.10 L vs-0.69 L, respectively) and narrower limits of agreement. CONCLUSION: Multi-frequency bioimpedance analysis-derived TBW chan e has the best agreement with acute clinical volume change during haemodialysis compared to ECV or ICV change alone, but overall degree of precision remains poor. Nutritional assessment using LBM and BCM measurements is significantly confounded by hydration status.

GFR estimating equations in a multiethnic Asian population.

BACKGROUND: Clinical practice guidelines recommend using equations for estimating glomerular filtration rate (GFR) in chronic kidney disease (CKD) management and research. The MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (CKD Epidemiology Collaboration) equations originally were derived from a North American population and had an ethnic coefficient adjustment for African Americans. A Chinese coefficient for the MDRD Study equation subsequently was determined, but this has not been externally validated. We compared the accuracy of the equations, evaluated the ethnic coefficients, and assessed the equations for disease staging in a multiethnic Asian population with CKD. STUDY DESIGN: A diagnostic test study comparing the Asian coefficient (and subgroups)-modified MDRD Study and CKD-EPI equations and a cross-sectional study assessing disease staging. SETTING & PARTICIPANTS: 232 outpatients (52% men; 40.5% Chinese, 32% Malay, and 27.5% Indian/other) with stable CKD. INDEX TEST: Asian and ethnicity-based modifications of the MDRD Study and CKD-EPI equations. REFERENCE TEST: Measured GFR using 3-sample plasma clearance of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA), calculated using the slope-intercept method, with body surface area normalization (du Bois) and Brochner-Mortensen correction. RESULTS: Overall, the CKD-EPI equation is more accurate than the MDRD Study equation throughout the GFR range, with improved bias (median difference of estimated GFR - measured GFR) and root mean square error (P <0.001). CKD-EPI versus MDRD Study equation: bias, 1.1 ± 13.8 vs -1.0 ± 15.2 mL/min/1.73 m(2); precision, 12.1 vs 12.2 mL/min/1.73 m(2). Ethnic coefficients did not improve estimates of GFR significantly. The correctness of staging was improved using the CKD-EPI equation. LIMITATIONS: All participants had CKD, but few were of European descent. The reference GFR technique was different from the original studies. CONCLUSIONS: The CKD-EPI is more accurate than the MDRD Study equation, particularly at higher GFRs. Therefore, we recommend adopting the CKD-EPI equation without ethnic adjustment for estimating GFR in multiethnic Asian patients with CKD.

Microbiology of tunnelled catheter-related infections in a multi-ethnic South-east Asian patient population.

INTRODUCTION: Clinical practice guidelines recommend empiric antibiotic therapy for suspected tunnelled haemodialysis catheter-related infections (CRI), and the choice of antibiotics should be adjusted according to the local microbiological profile and antimicrobial sensitivities. We aim to describe the microbiology, antibiotic sensitivities, and clinical outcomes of CRI with tunnelled haemodialysis catheters in a multi-ethnic South-East Asian population. METHODS: Using a prospective vascular access registry, we identified 99 patients who had catheters removed for suspected or confirmed CRI (50.5% male, mean age 56.9 years) from January 1, 2007, till May 2009. We retrospectively retrieved microbiology, mortality and echocardiography data from the hospital electronic databases. RESULTS: There were 115 removal-unique cultures that yielded 75.7% Gram-positive and 24.3% Gram-negative isolates (15 removals were polymicrobial). Organisms isolated were methicillin-resistant Staphylococcus aureus (MRSA) 28.6%, methicillin-sensitive S. aureus 26.5%, coagulase-negative staphylococci 21.4%, Pseudomonas aeruginosa 10.2%, and others. Out of 8 patients who died, 7 had MRSA. Risk factors associated with mortality were Chinese race (p = 0.03), MRSA infection (p < 0.001), and older age (p < 0.001). CONCLUSION: Gram-positive isolates accounted for most tunnelled CRI and MRSA was highly associated with death. In sick patients presenting with suspected CRI, the preferred empiric antibiotic regimen should include agents active against both MRSA and P. aeruginosa.