High-Target Hemodiafiltration Convective Dose Achieved in Most Patients in a 6-Month Intermediary Analysis of the CONVINCE Randomized Controlled Trial.

Introduction: High convection volumes in hemodiafiltration (HDF) result in improved survival; however, it remains unclear whether it is achievable in all patients. Methods: CONVINCE, a randomized controlled trial, randomized patients with end-stage kidney disease 1:1 to high-dose HDF versus high-flux hemodialysis (HD) continuation. We evaluated the proportion of patients achieving high-dose HDF target: convection volume per visit of ≥23 l (range ±1 l) at baseline, month 3, and month 6. We compared baseline characteristics in the following 2 ways: (i) patients on target for all 3 visits versus patients who missed target on ≥1 visits and (ii) patients on target for all 3 visits or missing it once versus patients who missed target on ≥2 visits. Results: A total of 653 patients were randomized to HDF. Their mean age was 62.2 (SD 13.5) years, 36% were female, 81% had fistula vascular access, and 33% had diabetes. Across the 3 visits, 75 patients (11%), 27 patients (4%), and 11 patients (2%) missed the convection volume target once, twice, and thrice, respectively. Apart from diabetes, there were no apparent differences in patient characteristics between patients who always achieved the high-dose target (83%) and those who missed the target either once or more (17%) or twice or more (6%). Conclusion: Achieving high-dose HDF is feasible for nearly all patients in CONVINCE and could be maintained during the 6-month follow-up period. Apart from diabetes, there were no other indications for confounding by indication on multivariable analyses that may explain the potential survival advantage for patients receiving high-dose HDF.

The effect of Candida famata and Lactobacillus plantarum on the number of coliforms and the antibiotic resistance and virulence of Escherichia coli in the gut of broilers.

This study was undertaken to determine the effect of a yeast (Candida famata) and a bacterium (Lactobacillus plantarum), administered alone or in combination in the drinking water, on the population of yeast, Lactobacillus sp. and coliforms, and the prevalence of antimicrobial resistance (AMR) and virulence genes in Escherichia coli (E. coli) isolated from digesta samples taken throughout the life of broiler chickens. Male (Ross 308) day-old chicks (220) were used. C. famata (isolated from a chicken) and L. plantarum (isolated from a pig) were administered via the drinking water. Water was provided either untreated or with C. famata (CF; 108/ml), L. plantarum (LP; 105-108/ml), or a combination of CF and LP (106-108/ml) in water hoppers on 2 days each week for 35 days. Administering probiotics did not affect the growth performance in broiler chickens. No significant interactions were observed between main effects, and neither CF nor LP had any effect on the population size of Lactobacillus sp. or coliforms. The administration of C. famata increased the population density of yeasts in the small intestine at these ages. The population density of coliforms, Lactobacillus sp. and yeast decreased with age (P < 0.001). There was no significant effect of probiotics on the prevalence of phenotypic AMR and virulence genes in these studies. The prevalence of E. coli that was resistant to ampicillin and tetracycline, as well as carrying ≥3 virulence-associated genes, was greatest at the end of the starter phase (around 8 days old), before declining through the grower and finisher phases. There was only limited evidence that administering either CF or LP affected either the AMR or the virulence of E. coli in the bird. However, tetracycline resistance in E. coli was associated (P < 0.001, P < 0.01, P < 0.05, and P < 0.05) with the carriage of the iron uptake systems of E. coli D, iron-repressible protein, increased serum survival and temperature-sensitive haemagglutinin genes respectively, suggesting that the accumulation of iron and the genetic element conferring tetracycline resistance may be intertwined.

[Elisha and the Shunammite child: a headache of biblical proportions]. / Eliseo y el hijo de la sunamita: una cefalea de proporciones bíblicas.

TITLE: Eliseo y el hijo de la sunamita: una cefalea de proporciones bíblicas.

Publisher Correction: Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China.

The original version of this article, published on 25 November 2019, unfortunately contained a mistake.

Self-rated health scores predict mortality among people with type 2 diabetes differently across three different country groupings: findings from the ADVANCE and ADVANCE-ON trials.

AIMS: To explore whether there is a different strength of association between self-rated health and all-cause mortality in people with type 2 diabetes across three country groupings: nine countries grouped together as 'established market economies'; Asia; and Eastern Europe. METHODS: The ADVANCE trial and its post-trial follow-up were used in this study, which included 11 140 people with type 2 diabetes from 20 countries, with a median follow-up of 9.9 years. Self-rated health was reported on a 0-100 visual analogue scale. Cox proportional hazard models were fitted to estimate the relationship between the visual analogue scale score and all-cause mortality, controlling for a range of demographic and clinical risk factors. Interaction terms were used to assess whether the association between the visual analogue scale score and mortality varied across country groupings. RESULTS: The visual analogue scale score had different strengths of association with mortality in the three country groupings. A 10-point increase in visual analogue scale score was associated with a 15% (95% CI 12-18) lower mortality hazard in the established market economies, a 25% (95% CI 21-28) lower hazard in Asia, and an 8% (95% CI 3-13) lower hazard in Eastern Europe. CONCLUSIONS: Self-rated health appears to predict 10-year all-cause mortality for people with type 2 diabetes worldwide, but this relationship varies across groups of countries.

Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China.

This prospective study of Chinese adults demonstrated an inverse J-shaped association of number of children with risk of hip fracture in both men and postmenopausal women aged 50 years or older. Women with 2 or 3 children and men with 4 children had the lowest risk of hip fracture. INTRODUCTION: Women have higher absolute risks of fracture than men, which is believed to reflect differences in oestrogen exposure. The aim of this study was to compare the associations of number of children with risk of hip fracture between men and women aged over 50 years. METHODS: The China Kadoorie Biobank (CKB) recruited 133,399 women and 110,296 men, aged 50 years or older between 2004 and 2008. During 10-year follow-up, 2068 participants (1394 women and 674 men) suffered a hip fracture. Cox regression analysis was used to estimate sex-specific adjusted hazard ratios (HRs) and 95% CI for incident hip fracture. RESULTS: Over 98% of both subsets of men and women aged 50 or older reported having children. Women who had 2 or 3 children had the lowest risks of hip fracture compared with other groups. Compared with nulliparous women, the adjusted HR for hip fracture were 0.89 (95% CI; 0.72, 1.10) for 1 child, 0.79 (0.70, 0.90) for 2 children, 0.79 (0.72, 0.87) for 3 children, 0.81 (0.72, 0.91) for 4 children, and 0.95 (0.83, 1.10) for those with 5 or more children. The associations of number of children with hip fracture were broadly consistent in men of a similar age. CONCLUSIONS: The concordant effects of the number of children with risk of hip fracture between men and women suggest that the lower risks in multiparous women are not due to differences in oestrogen exposure or other biological effects, but may reflect residual confounding by socioeconomic or lifestyle factors.

Antimicrobial in vitro activities of condensed tannin extracts on avian pathogenic Escherichia coli.

Condensed tannins (CTs), which extracted from yew leaves, tilia flower and black locust leaves, were examined for their antimicrobial in vitro activity against avian pathogenic Escherichia coli (APEC). Past research demonstrated that CTs which contain procyanidins and prodelphinidins that could inhibit the growth of a wide range of bacteria. However, there is no information on how these affect pathogenic bacteria from chickens such as APEC. The high concentration of extracts, 10, 5, 2·5 mg ml-1 , affected the growth curves of APEC, which gave different inhibition values for the three CT extracts. Furthermore, these CTs had significant effects (P ≤ 0·05) on APEC biofilm and motility depending on each CT concentration and composition. However, at low concentration (0·6 mg ml-1 ), the tilia flowers, a high molar percentage of procyanidins, enhanced bacterial cell attachment and improved the swimming motility of APEC. In contrast, yew, an equal molar percentage of procyanidins/prodelphinidins, and black locust, a high molar percentage of prodelphinidins, interrupted and blocked swarming and swimming motility. The data suggested that the antimicrobial activity of the CT extracts was elicited by a positive relationship between anti-biofilm formation and anti-motility capacities. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed that condensed tannins (CTs), which were a group of secondary metabolites of many plants and rich in prodelphinidins (PD), had greater antibacterial activity against avian pathogenic Escherichia coli (APEC) than CTs that were rich in procyanidins (PC). The mode of action of the CTs was to inhibit the swimming and swarming motility of APEC, and its ability to form biofilms. The significance of this finding is that the use of PD-rich CTs to control APEC should not encourage the development of antibiotic resistance by APEC because a different mechanism is used. If confirmed in vivo, this could provide the poultry industry with a valuable and novel means of controlling the antibiotic resistance.

Decreased medial entorhinal cortical thickness in olanzapine exposed female rats is not ameliorated by exercise.

Aerobic exercise has been associated with hippocampal plasticity, both in healthy adults and in psychosis patients, but its impact on cortical regions remains unclear. The entorhinal cortex serves as a critical gateway for the hippocampus, and recent studies suggest that this region may also be impacted following an exercise regime. In order to investigate the effects of antipsychotic medications and exercise on the entorhinal cortex, female rats were chronically administered either olanzapine or vehicle and were either sedentary or had access to a running wheel for 9 weeks. Olanzapine-treated rats had decreased medial entorhinal cortical thickness compared to vehicle-treated rats. A statistically significant interaction was observed for layer II of the entorhinal cortex, with exercising rats having significantly greater thickness compared to sedentary rats in the vehicle group, but not the olanzapine group. Greater total entorhinal and lateral entorhinal cortical thickness was associated with greater average activity. In exercising rats, decreasing glucose intolerance was associated with larger total entorhinal and layer II cortical thickness. Lower fasting insulin levels were associated with greater total entorhinal, lateral entorhinal, and layer II cortical thickness. The relationship between increased activity and greater entorhinal cortical thickness was mediated by reduced fasting insulin, indicating that regulation of metabolic risk factors may contribute to impact of aerobic exercise on the entorhinal cortex. Aerobic exercise may be helpful in counteracting metabolic side effects of antipsychotic medications and managing these side effects may be key to promoting entorhinal cortical plasticity in patients treated with second-generation antipsychotic drugs.

Long-term outcome of JJ stent insertion for primary obstructive megaureter in children.

BACKGROUND/AIM: Endoscopic stenting is an accepted treatment option for children with symptomatic or progressive primary obstructive megaureter (PROM). Here, long-term outcomes with endoscopic stenting are reviewed. METHODS: Patients with PROM treated surgically over a 12-year period were identified using a prospectively maintained departmental database. Data were analysed using Microsoft Excel 2013 and unpaired t-tests through GraphPad Software QuickCalcs. RESULTS: Fifty-seven patients with PROM were surgically managed in the study centre from 2005 to 2017. Twenty-nine of fifty-seven patients had the stent as the primary procedure, whereas the remainder had ureterostomy, re-implantation or nephrectomy. Six patients had bilateral PROM, giving a total of 35 renal units that were fully analysed. There was 7:1 male predominance, and 20 of 29 patients (69%) were diagnosed antenatally. The median age at stent insertion was 8 months (40 days-10 years); the median prestent ureteric diameter was 19 mm and the median pre-operative function on MAG3 was 44%. Cystoscopic stent insertion was feasible in all patients. The stent was left for a median of 183 days. In 9 of 35 (26%) renal units, the JJ stent was a successful sole long-term treatment, with median follow-up of 5 years and 8 months. The success rate was not different in children aged <1 year (8/22; 36%) in comparison to children aged >1 year (1/13; 8%), P = 0.1. The remaining 26 renal units required further surgical intervention: ureteric re-implantation in 25 and nephrectomy in one. Indications for further surgery were stent complications in 11 renal units and stent failure in 15 (Table 1). Complications related to the stent were noted in 14 renal units (41%), half being stent migration. Other complications included UTIs, stent encrustation and recurrent haematuria. There was no identifiable prestent parameter, whether clinical or radiological, that could predict which patients were likely to be successfully managed solely by stent insertion. Stent insertion was never successful as a definitive procedure when the distal ureteric diameter was >12 mm on the ultrasound after stent removal. DISCUSSION: Success rates with primary stenting as a sole treatment for PROM was 26%, which is less than that seen in other reports (50-66%). This may be attributed to the long-term follow-up in this study, together with the strict criteria for success. CONCLUSION: In the authors' experience, cystoscopically inserted JJ stents are of limited success as the sole treatment for PROM. In infants aged <1 year, stent insertion remains a reasonable temporising measure until the infant is old enough for a definitive procedure.

Genotypic and phenotypic diversity differences of presumptive commensal and avian pathogenic E. coli.

1. The objective of the experiment was to characterise the genotypic and phenotypic differences between presumptive commensal E. coli and avian pathogenic E. coli (APEC) of poultry. 2. DNA was extracted from 65 confirmed APEC E. coli from chicken, 100 presumptive commensal E. coli from healthy turkey and 35 from healthy chicken. Enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and virulence factors genotyping was performed to characterise genetic features. 3. Carbon source utilisation and antimicrobial susceptibility tests were performed to characterise phenotypic features of isolates. 4. The genetic divergence between E. coli strains tested by ERIC-PCR profiles and virulence-associated genes showed a clear genetic separation between E. coli APEC and turkey E. coli strains. 5. The carbon utilisation profile of turkey isolates was different from chicken and APEC strains; whereas antimicrobial susceptibility was highest for turkey isolates (53%), and lowest for APEC strains (33.8%). 6. The study showed a significant negative correlation between utilisation of arabitol and adonitol with different virulence determinants tested, which suggests that the ability to utilise some uncommon carbon sources may be used to discriminate between presumptive commensal E. coli and APEC.

Hippocampal volume and vasculature before and after exercise in treatment-resistant schizophrenia.

BACKGROUND: Schizophrenia is associated with poor cognitive function and elevated cardiometabolic disease risk. These health concerns may exacerbate neurocognitive dysfunction associated with hippocampal abnormalities, particularly hippocampal volume reductions. Regular exercise is thought to improve symptom severity, reduce depression, and improve cognition in schizophrenia, and may trigger exercise-mediated hippocampal growth. The potential for the benefits of exercise for treatment-resistant schizophrenia patients has not been clearly assessed. This study aims to assess the effect of exercise on hippocampal plasticity and clinical outcomes in chronic schizophrenia. METHODS: Seventeen DSM-IV criteria schizophrenia or schizoaffective disorder patients completed a customized moderate intensity 12-week aerobic or weight-bearing exercise program. Adherence rates were 83% ±â€¯9.4%) with 70% of participants completing the entire exercise program. Concomitant neuroimaging, clinical and cognitive assessments were obtained at baseline and 12-weeks. RESULTS: At follow-up, symptom severity scores (t(16) = -16.8, p. ≤ 0.0001) and social functioning (t(16) = 4.4, p. = 0.0004) improved. A trend for improved depression scores (t(16) = -2.0, p. = 0.06) with no change in anxiety, or extrapyramidal symptoms were seen. Hippocampal volume increased (t(16) = -2.54, p. = 0.02), specifically in the left CA-1 field (F(16) = -2.33, p. = 0.03). Hippocampal vascular volume was unchanged. Change in hippocampal volume and vascular volume was not significantly correlated with change in symptom severity or affect scores. CONCLUSIONS: Adjunct exercise may accelerate symptom improvement in treatment-resistant psychosis patients. While the underlying mechanism remains unclear, these results indicate that chronic schizophrenia patients experience hippocampal plasticity in response to exercise. STUDY REGISTRATION: Clinical Trials.govNCT01392885.

The association of the dietary approach to stop hypertension (DASH) diet with blood pressure, glucose and lipid profiles in Malaysian and Philippines populations.

BACKGROUND AND AIM: Despite a growing body of evidence from Western populations on the health benefits of Dietary Approaches to Stop Hypertension (DASH) diets, their applicability in South East Asian settings is not clear. We examined cross-sectional associations between DASH diet and cardio-metabolic risk factors among 1837 Malaysian and 2898 Philippines participants in a multi-national cohort. METHODS AND RESULTS: Blood pressures, fasting lipid profile and fasting glucose were measured, and DASH score was computed based on a 22-item food frequency questionnaire. Older individuals, women, those not consuming alcohol and those undertaking regular physical activity were more likely to have higher DASH scores. In the Malaysian cohort, while total DASH score was not significantly associated with cardio-metabolic risk factors after adjusting for confounders, significant associations were observed for intake of green vegetable [0.011, standard error (SE): 0.004], and red and processed meat (-0.009, SE: 0.004) with total cholesterol. In the Philippines cohort, a 5-unit increase in total DASH score was significantly and inversely associated with systolic blood pressure (-1.41, SE: 0.40), diastolic blood pressure (-1.09, SE: 0.28), total cholesterol (-0.015, SE: 0.005), low-density lipoprotein cholesterol (-0.025, SE: 0.008), and triglyceride (-0.034, SE: 0.012) after adjusting for socio-demographic and lifestyle groups. Intake of milk and dairy products, red and processed meat, and sugared drinks were found to significantly associated with most risk factors. CONCLUSIONS: Differential associations of DASH diet and dietary components with cardio-metabolic risk factors by country suggest the need for country-specific tailoring of dietary interventions to improve cardio-metabolic risk profiles.

Screening for vision-threatening diabetic retinopathy in South India: comparing portable non-mydriatic and standard fundus cameras and clinical exam.

PurposeTo evaluate the sensitivity and specificity of a portable non-mydriatic fundus camera to diagnose vision-threatening diabetic retinopathy (VTDR).Patients and methodsA prospective, single-site, comparative instrument validation study was undertaken at the Aravind Eye Care System. Overall, 155 subjects with and without diabetes were recruited. Images from 275 eyes were obtained with the (1) non-mydriatic Smartscope, (2) mydriatic Smartscope, and (3) mydriatic table-top camera of the macular, nasal, and superotemporal fields. A retina specialist performed a dilated fundus examination (DFE), (reference standard). Two masked retina specialists graded the images. Sensitivity and specificity to detect VTDR with the undilated Smartscope was calculated compared to DFE.ResultsGraders 1 and 2 had a sensitivity of 93% (95% confidence interval (CI): 87-97%) and 88% (95% CI: 81-93%) and a specificity of 84% (95% CI: 77-89%) and 90% (95% CI: 84-94%), respectively, in diagnosing VTDR with the undilated Smartscope compared to DFE. Compared with the dilated Topcon images, graders 1 and 2 had sensitivity of 88% (95% CI: 81-93%) and 82% (95% CI: 73-88%) and specificity of 99% (95% CI: 96-100%) and 99% (95% CI: 95-100%).ConclusionsRemote graders had high sensitivity and specificity in diagnosing VTDR with undilated Smartscope images, suggesting utility where portability is a necessity.

Concordance and acceptability of electric stimulation therapy: a randomised controlled trial.

OBJECTIVE: A pilot single-blinded randomised controlled trial (RCT) was conducted to examine concordance with and acceptability of electric stimulation therapy (EST) in patients with venous leg ulcers (VLUs) who had not tolerated moderate to high compression. METHOD: Participants were randomised to the intervention group (n=15) or a placebo control group (n=8) in which EST was used four times daily for 20 minutes per session. Participants were monitored for eight weeks during which time concordance with the treatment and perceptions of the treatment were assessed. RESULTS: Concordance with the total recommended treatment time was 71.4% for the intervention group and 82.9% for the control group; a difference that was not statistically significant. Participants rated EST as acceptable (84.6% intervention; 83.3% control), only two participants, both from the placebo control group, would not be willing to use EST again. The majority considered EST easier to use than compression (68.4%). CONCLUSION: EST was a practical and acceptable treatment among people who have been unable to tolerate moderate to high compression therapy.

The impact of level of education on vascular events and mortality in patients with type 2 diabetes mellitus: Results from the ADVANCE study.

AIMS: The relationship between educational level and the risk of all-cause mortality is well established, whereas the association with vascular events in individuals with type 2 diabetes is not well described. Any association may reflect a link with common cardiovascular or lifestyle-based risk factors. METHODS: The relationships between the highest level of educational attainment and major cardiovascular events, microvascular complications and all-cause mortality were explored in a cohort of 11,140 individuals with type 2 diabetes. Completion of formal education before the age of 16 was categorized as a low level of education. Regional differences between Asia, East Europe and Established Market Economies were also assessed. RESULTS: During a median of 5years of follow up, 1031 (9%) patients died, 1147 (10%) experienced a major cardiovascular event and 1136 (10%) a microvascular event. After adjustment for baseline characteristics and risk factors, individuals with lower education had an increased risk of cardiovascular events (hazard ratio (HR) 1.31, 95% CI 1.16-1.48, p<0.0001), microvascular events (HR 1.23, 95% CI 1.08-1.39, p=0.0013) and all-cause mortality (HR 1.34, 95% CI 1.18-1.52, p<0.0001). In regional analyses the increased risk of studied outcomes associated with lower education was weakest in Established Market Economies and strongest in East Europe. CONCLUSIONS: A low level of education is associated with an increased risk of vascular events and death in patients with type 2 diabetes, independently of common lifestyle associated cardiovascular risk factors. The effect size varies between geographical regions.

Venous leg ulcer healing with electric stimulation therapy: a pilot randomised controlled trial.

OBJECTIVE: Compression therapy is a gold standard treatment to promote venous leg ulcer (VLU) healing. Concordance with compression therapy is, however, often sub-optimal. The aim of this study was to evaluate the effectiveness of electric stimulation therapy (EST) to facilitate healing of VLUs among people who do not use moderate-to-high levels of compression (>25 mmHg). METHOD: A pilot multicentre, single-blinded randomised controlled trial was conducted. Participants were randomised (2:1) to the intervention group or a control group where EST or a sham device was used 4 times daily for 20 minutes per session. Participants were monitored fortnightly for eight weeks. The primary outcome measure was percentage of area (wound size) change. RESULTS: In the 23 patients recruited, an average redution in wound size of 23.15% (standard deviation [SD]: 61.23) was observed for the control group compared with 32.67 % (SD: 42.54) for the intervention. A moderate effect size favouring the intervention group was detected from univariate [F(1,18)=1.588, p=0.224, partial eta squared=0.081] and multivariate repeated measures [F(1,18)=2.053, p=0.169, partial eta squared=0.102] analyses. CONCLUSION: The pilot study was not powered to detect statistical significance, however, the difference in healing outcomes are encouraging. EST may be an effective adjunct treatment among patients who have experienced difficulty adhering to moderate-to-high levels of compression therapy.

Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance.

Anti-apoptotic genes, including those of the Bcl-2 family, have been shown to have dual functionality inasmuch as they inhibit cell death but also regulate inflammation. Several anti-apoptotic molecules have been associated with endothelial cell (EC) survival following transplantation; however, their exact role has yet to be elucidated in respect to controlling inflammation. In this study we created mice expressing murine A1 (Bfl-1), a Bcl-2 family member, under the control of the human intercellular adhesion molecule 2 (ICAM-2) promoter. Constitutive expression of A1 in murine vascular ECs conferred protection from cell death induced by the proinflammatory cytokine tumour necrosis factor (TNF)-α. Importantly, in a mouse model of heart allograft transplantation, expression of A1 in vascular endothelium increased survival in the absence of CD8+ T cells. Better graft outcome in mice receiving an A1 transgenic heart correlated with a reduced immune infiltration, which may be related to increased EC survival and reduced expression of adhesion molecules on ECs. In conclusion, constitutive expression of the anti-apoptotic molecule Bfl1 (A1) in murine vascular ECs leads to prolonged allograft survival due to modifying inflammation.

Dietary Supplement Use in Older People Attending Memory Clinics in Australia.

BACKGROUND: Dietary supplement use is common in older adults. There has been limited research in people attending memory clinics. OBJECTIVES: To explore the use of dietary supplements in older people attending Australian memory clinics. DESIGN: Cross-sectional analysis of baseline data from the Prospective Research In MEmory clinics (PRIME) study. PARTICIPANTS: Community-dwelling older people who attended nine memory clinics and had a diagnosis of mild cognitive impairment (MCI) or dementia. MEASUREMENTS: Dietary supplement was defined as a product that contains one or more: vitamin, mineral, herb or other botanical, amino acid or other dietary substance. Non-prescribed supplement was defined as a supplement that is not usually prescribed by a medical practitioner. Polypharmacy was defined as use of five or more medications. RESULTS: 964 patients, mean age 77.6 years, were included. Dietary supplements were used by 550 (57.1%) patients; 353 (36.6%) used two or more. Non-prescribed supplements were used by 364 (36.8%) patients. Supplement use was associated with older age (OR: 1.12, 95% CI: 1.03-1.21), lower education level (OR: 1.53, 95% CI: 1.01-2.32) and a diagnosis of MCI rather than dementia (OR: 1.52, 95% CI: 1.05-2.21). Potential drug-supplement interactions were identified in 107 (11.1%) patients. Supplement users had increased prevalence of polypharmacy compared to non-users (80.5% vs. 48.1%, p<0.001). CONCLUSIONS: Dietary supplements, including non-prescribed supplements, were commonly used by people attending memory clinics. Supplement use increased the prevalence of polypharmacy and resulted in potential supplement-drug interactions. Further research is required to assess the clinical outcomes of supplement use.

A cardiovascular disease policy model: part 2-preparing for economic evaluation and to assess health inequalities.

OBJECTIVES: This is the second of the two papers introducing a cardiovascular disease (CVD) policy model. The first paper described the structure and statistical underpinning of the state-transition model, demonstrating how life expectancy estimates are generated for individuals defined by ASSIGN risk factors. This second paper describes how the model is prepared to undertake economic evaluation. DESIGN: To generate quality-adjusted life expectancy (QALE), the Scottish Health Survey was used to estimate background morbidity (health utilities) and the impact of CVD events (utility decrements). The SF-6D algorithm generated utilities and decrements were modelled using ordinary least squares (OLS). To generate lifetime hospital costs, the Scottish Heart Health Extended Cohort (SHHEC) was linked to the Scottish morbidity and death records (SMR) to cost each continuous inpatient stay (CIS). OLS and restricted cubic splines estimated annual costs before and after each of the first four events. A Kaplan-Meier sample average (KMSA) estimator was then used to weight expected health-related quality of life and costs by the probability of survival. RESULTS: The policy model predicts the change in QALE and lifetime hospital costs as a result of an intervention(s) modifying risk factors. Cost-effectiveness analysis and a full uncertainty analysis can be undertaken, including probabilistic sensitivity analysis. Notably, the impacts according to socioeconomic deprivation status can be made. CONCLUSIONS: The policy model can conduct cost-effectiveness analysis and decision analysis to inform approaches to primary prevention, including individually targeted and population interventions, and to assess impacts on health inequalities.

Risk prediction of major complications in individuals with diabetes: the Atherosclerosis Risk in Communities Study.

AIMS: To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers. METHODS: We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics. RESULTS: Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [ß-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%). CONCLUSIONS: These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.