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Aim: To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups. Materials and Methods: A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end‐stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes. Secondary outcomes included: (i) cardiovascular death or heart failure (HF) hospitalization; (ii) cardiovascular death, myocardial infarction (MI) or stroke; (iii) HF hospitalization; (iv) doubling of the SCr level, ESKD or kidney death; (v) cardiovascular death; (vi) all‐cause death; and (vii) cardiovascular death, MI, stroke, or hospitalization for HF or for unstable angina. Results: The 4401 patients were divided into six geographic region subgroups: North America (n = 1182, 27%), Central and South America (n = 941, 21%), Eastern Europe (n = 947, 21%), Western Europe (n = 421, 10%), Asia (n = 749, 17%) and Other (n = 161, 4%). The analyses included four racial groups: White (n = 2931, 67%), Black or African American (n = 224, 5%), Asian (n = 877, 20%) and Other (n = 369, 8%). Canagliflozin reduced the relative risk of the primary composite outcome in the overall trial by 30% (hazard ratio 0.70, 95% confidence interval 0.59‐0.82; P = 0.00001). Across geographic regions and racial groups, canagliflozin consistently reduced the primary composite endpoint without evidence of heterogeneity (interaction P values of 0.39 and 0.91, respectively) or significant safety outcome differences. Conclusions: Canagliflozin reduces the risk of kidney and cardiovascular events similarly across geographic regions and racial groups. [ABSTRACT FROM AUTHOR]

Mixture analysis is an emerging statistical tool in epidemiological research that seeks to estimate the health effects associated with mixtures of several exposures. This approach acknowledges that individuals experience many simultaneous exposures and it can estimate the relative importance of components in the mixture. Health effects due to mixtures may vary over space driven by to political, demographic, environmental, or other differences. In such cases, estimating a global mixture effect without accounting for spatial variation would induce bias in effect estimates and potentially lower statistical power. To date, no methods have been developed to estimate spatially varying chemical mixture effects. We developed a Bayesian spatially varying mixture model that estimates spatially varying mixture effects and the importance weights of components in the mixture, while adjusting for covariates. We demonstrate the efficacy of the model through a simulation study that varies the number of mixtures (one and two) and spatial pattern (global, one‐dimensional, radial) and magnitude of mixture effects, showing that the model is able to accurately reproduce the spatial pattern of mixture effects across a diverse set of scenarios. Finally, we apply our model to a multi‐center case‐control study of non‐Hodgkin lymphoma (NHL) in Detroit, Iowa, Los Angeles, and Seattle. We identify significant spatially varying positive and inverse associations with NHL for two mixtures of pesticides in Iowa and do not find strong spatial effects at the other three centers. In conclusion, the Bayesian spatially varying mixture model represents a novel method for modeling spatial variation in mixture effects. [ABSTRACT FROM AUTHOR]

Aims: To describe treatment pathways for key glucose‐lowering therapies in individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D) using retrospective data from DISCOVER CKD (NCT04034992). Methods: Data were extracted from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics data (2008–2020) and the US integrated Limited Claims and Electronic Health Records Database (LCED; 2012–2019). Eligible individuals were aged ≥18 years with CKD, identified by two consecutive estimated glomerular filtration rate (eGFR) measures (15–<75 mL/min/1.73 m2; 90–730 days apart; index date was the second measurement) and T2D. Chronological treatment pathways for glucose‐lowering therapies prescribed on or after CKD index to end of follow‐up were computed. Median time and proportion of overall follow‐up time on treatment were described for each therapy by database and by eGFR and urinary albumin‐to‐creatinine ratio (UACR) categories. Results: Of 36,951 and 4339 eligible individuals in the CPRD and LCED, respectively, median baseline eGFR was 67.8 and 64.9 mL/min/1.73 m2; 64.2 and 63.9% received metformin prior to index; and median (interquartile range) time on metformin during follow‐up was 917 (390–1671) and 454 (192–850) days (accounting for ~75% of follow‐up time in both databases). The frequency of combination treatment increased over time. There were trends towards decreased metformin prescriptions with decreasing eGFR and increasing UACR within each eGFR category. Conclusions: Individuals with CKD and T2D had many combinations of therapies and substantial follow‐up time on therapy. These results highlight opportunities for improved CKD management. [ABSTRACT FROM AUTHOR]

Aim: In the CANVAS Program and CREDENCE trials, the sodium glucose co‐transporter 2 inhibitor canagliflozin reduced the risk of cardiovascular and kidney events in patients with type 2 diabetes. The current study analysed a pooled population to ascertain the kidney protection provided by canagliflozin across the full spectrum of kidney parameters. Methods: This post‐hoc pooled analysis of the CANVAS Program (N = 10 142) and CREDENCE trial (N = 4401), assessed the risk of the primary kidney composite (doubling of serum creatinine, end‐stage kidney disease, renal death), in all patients and subgroups defined by baseline estimated glomerular filtration rate (<30, 30 to <45, 45 to <60 and ≥60 ml/min/1.73 m2), albuminuria [<30, 30‐300, >300 mg/g (<3.39, 3.39‐33.9, >33.9 mg/mmol)] and 2012 Kidney Disease: Improving Global Outcomes (KDIGO) classification of chronic kidney disease (low/moderate, high and very high risk). Results: In the overall population, the risk for the primary kidney composite outcome was 37% lower in the canagliflozin group versus placebo (HR: 0.63; 95% CI: 0.53, 0.77; p <.001). There was no evidence of heterogeneity in the kidney protective effects of canagliflozin across a range of kidney risks when stratified by baseline estimated glomerular filtration rate, albuminuria or KDIGO risk category (all pinteraction >.05). A statistically significant risk reduction of the primary kidney composite outcome was sustained by approximately 18 months after randomization. Conclusions: These results emphasize a critical role of canagliflozin in kidney protection across a broad spectrum of participants with type 2 diabetes with varying levels of kidney function. [ABSTRACT FROM AUTHOR]

Aims: To assess whether the sodium‐glucose cotransporter‐2 (SGLT2) inhibitor canagliflozin affects risk of non‐genital skin and soft tissue infections (SSTIs). Materials and methods: We performed a post hoc pooled individual participant analysis of the CANVAS Program and CREDENCE trials that randomized people with type 2 diabetes at high cardiovascular risk and/or with chronic kidney disease to either canagliflozin or placebo. Investigator‐reported adverse events were assessed by two blinded authors following predetermined criteria for non‐genital SSTIs. Risks of non‐genital SSTIs, overall and within prespecified subgroups, and risk of non‐genital fungal SSTIs, were analysed using Cox regression models. Factors associated with non‐genital SSTIs were assessed using multivariable Cox regression models. Results: Overall, 903 of 14 531 participants (6%) experienced non‐genital SSTIs over a median follow‐up of 26 months. No difference was observed in non‐genital SSTI rates between canagliflozin and placebo (24.0 events/1000 person‐years vs. 23.9 events/1000 person‐years, respectively; hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.85‐1.11; P = 0.70), with consistent results across subgroups (all P interaction > 0.05). The risk of recurrent events and non‐genital fungal infection also did not differ significantly between canagliflozin and placebo (HR 1.06, 95% CI 0.94‐1.19 [P = 0.32] and HR 1.18, 95% CI 0.88‐1.60 [P = 0.27], respectively). Baseline factors independently associated with non‐genital SSTIs were younger age, male sex, higher body mass index, higher glycated haemoglobin, lower estimated glomerular filtration rate (eGFR), established peripheral vascular disease, and history of neuropathy. Conclusions: Canagliflozin did not affect risk of non‐genital SSTIs or non‐genital fungal SSTIs compared with placebo. These findings suggest that any SGLT2 inhibitor‐mediated change in skin microenvironment is unlikely to have meaningful clinical consequences. [ABSTRACT FROM AUTHOR]

In addition, generalizability of the results may be limited to individuals with previous CV events, high CV risk or nephropathy, similar to the patients enrolled in the CANVAS programme and CREDENCE trial. This post-hoc analysis assessed the effects of canagliflozin versus placebo on CV and kidney outcomes in patients with T2DM and high CV risk, and/or chronic kidney disease according to baseline treatment target achievement and risk factors. Keywords: canagliflozin; cardiovascular disease; diabetic nephropathy; type 2 diabetes EN canagliflozin cardiovascular disease diabetic nephropathy type 2 diabetes 2038 2042 5 06/06/23 20230701 NES 230701 BACKGROUND Management of type 2 diabetes mellitus (T2DM), a progressive metabolic disorder associated with substantial cardiovascular (CV) and kidney complications, includes risk factor optimization of glucose, blood pressure (BP) and lipids. [Extracted from the article]

Similarly, Barraclough et al. showed that canagliflozin consistently decreased the risk of major CV and kidney outcomes in patients with T2D, regardless of PAD status at baseline. The MACE benefit with canagliflozin in individuals with T2D, CKD and PAD translates into an ARR of -26.0 events/1000 patients over 2.5 years versus placebo. [Extracted from the article]

The exposome is an ideal in public health research that posits that individuals experience risk for adverse health outcomes from a wide variety of sources over their lifecourse. There have been increases in data collection in the various components of the exposome, but novel statistical methods are needed that capture multiple dimensions of risk at once. We introduce a Bayesian index low‐rank kriging (LRK) multiple membership model (MMM) to simultaneously estimate the health effects of one or more groups of exposures, the relative importance of exposure components, and cumulative spatial risk over time using residential histories. The model employs an MMM to consider all residential locations for subjects weighted by duration and LRK to increase computational efficiency. We demonstrate the performance of the Bayesian index LRK‐MMM through a simulation study, showing that the model accurately and consistently estimates the health effects of one or several group indices and has high power to identify a region of elevated spatial risk due to unmeasured environmental exposures. Finally, we apply our model to data from a multicenter case‐control study of non‐Hodgkin lymphoma (NHL), finding a significant positive association between one index of pesticides and risk for NHL in Iowa. Additionally, we find an area of significantly elevated spatial risk for NHL in Los Angeles. In conclusion, our Bayesian index LRK‐MMM represents a step forward toward bringing the ideals of the exposome into practice for environmental risk analyzes. [ABSTRACT FROM AUTHOR]

Many health outcomes result from accumulated exposures to one or more environmental factors. Accordingly, spatial risk studies have begun to consider multiple residential locations of participants, acknowledging that participants move and thus are exposed to environmental factors in several places. However, novel methods are needed to estimate cumulative spatial risk for disease while accounting for other risk factors. To this end, we propose a Bayesian model (LRK-MMM) that embeds a multiple membership model (MMM) into a low-rank kriging (LRK) model in order to estimate cumulative spatial risk at the point level while allowing for multiple residential locations per subject. The LRK approach offers a more computationally efficient means to analyze spatial risk in case-control study data at the point level compared with a Bayesian generalized additive model, and as increased precision in spatial risk estimates by analyzing point locations instead of administrative areas. Through a simulation study, we demonstrate the efficacy of the model and its improvement upon an existing multiple membership model that uses area-level spatial random effects to estimate risk. The results show that our proposed method provides greater spatial sensitivity (improvements ranging from 0.12 to 0.54) and power (improvements ranging from 0.02 to 0.94) to detect regions of elevated risk for disease across a range of exposure scenarios. Finally, we apply our model to case-control data from the New England bladder cancer study to estimate cumulative spatial risk while adjusting for many covariates. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of dapagliflozin in patients with chronic kidney disease (CKD) and albuminuria, with and without type 2 diabetes, stratified by the Quételet (body mass) index (BMI). Methods: We randomized 4304 adult patients with an estimated glomerular filtration rate (eGFR) of 25‐75 ml/min/1.73m2 and urinary albumin‐to‐creatinine ratio of 200‐5000 mg/g to dapagliflozin 10 mg/day or placebo. The primary outcome was a composite of sustained decline in eGFR of 50% or more, kidney failure, or death from kidney or cardiovascular causes. Secondary outcomes included kidney composite endpoint (primary composite endpoint without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure/ cardiovascular death), and all‐cause mortality. We categorized participants according to World Health Organization BMI criteria: lean/ideal (<25 kg/m2), overweight (25‐< 30 kg/m2), grade 1 obesity (30‐<35 kg/m2), and grade 2/3 obesity (≥35 kg/m2). Results: Of 4296 (99.8%) randomized participants, 888 (20.7%), 1491 (34.7%), 1136 (26.4%), and 781 (18.2%) were categorized as lean/ideal, overweight, grade 1 obesity, and grade 2/3 obesity, respectively. Median follow‐up was 2.4 years. Benefits of dapagliflozin were observed independent of baseline BMI for primary and secondary endpoints. Hazard ratios (95% CI) for dapagliflozin versus placebo for the primary composite endpoint were 0.60 (0.43, 0.85), 0.55 (0.40, 0.75), 0.71 (0.49, 1.04), and 0.57 (0.37, 0.87) among participants in the lean/ideal, overweight, grade 1 obesity, and grade 2/3 obesity groups (interaction P =.72). Conclusion: Among participants with CKD and albuminuria, with or without type 2 diabetes, kidney and cardiovascular benefits of dapagliflozin were evident and consistent across the BMI spectrum. [ABSTRACT FROM AUTHOR]

Aim: The management of blood pressure in patients requiring dialysis remains challenging and controversial. This study aimed to describe the perspectives of patients treated with peritoneal or haemodialysis regarding blood pressure, to inform patient‐centred management. Methods: We conducted a secondary thematic analysis of qualitative data from multiple data sets derived from the Standardised Outcomes in Nephrology (SONG) initiative. We extracted and analysed the responses of adult patients (aged 18 years or over) on haemodialysis and peritoneal dialysis, and their caregivers. Qualitative data were extracted from 26 focus groups, two international Delphi surveys and two consensus workshops completed as part of the SONG‐Haemodialysis and SONG‐Peritoneal dialysis projects. Results: Collectively, the studies involved 644 patients and caregivers from 86 countries. We identified four themes: helpless and incapacitated (including the subthemes of disabling and debilitating symptoms, limiting ability to work, fear of "crashes" – a sudden drop in blood pressure – forced to depend on others); dismissed and ignored (disregarded as a problem, lacking information, education and reassurance); escalating medication burden; and taking control for improved self‐management (determining thresholds in fluid management, establishing a routine for proactive monitoring). Conclusion: Blood pressure symptoms are debilitating for patients on dialysis and exacerbated by a perceived lack of information about how to understand and manage these symptoms. More patient‐centred management of blood pressure, particularly symptom‐causing blood pressure, in patients on dialysis is likely to substantially improve patient satisfaction and outcomes. SUMMARY AT A GLANCE: To describe the perspectives of patients and to inform patient‐centred blood pressure management among 644 peritoneal or haemodialysis patients and 86 caregivers, the study identified four themes – helpless and incapacitated; dismissed and ignored; escalating medication burden; and taking control for improved self‐management – and concluded that blood pressure symptoms in dialysis patients are exacerbated by a perceived lack of information on how to understand and manage them. [ABSTRACT FROM AUTHOR]

In many studies on the spatial risk of disease, investigators use geographic locations at the time of disease diagnosis in spatial models to search for individual areas of elevated risk. However, these studies often fail to find a significant spatial signal. This may be due to the misspecification of the timing and location of pertinent exposures. Environmental exposures related to cancer risk vary over space and time, and many cancers have long latencies. When these factors are considered in conjunction with a mobile population, it is likely that the spatial signal related to relevant historic environmental exposures is obscured. To investigate this hypothesis, we conducted simulation studies to characterize the effect of residential mobility on the ability of generalized additive models to detect areas of significantly elevated historic environmental exposure. We generated data based on the residential histories of participants in the National Cancer Institute Surveillance, Epidemiology, and End Results non-Hodgkin lymphoma study, and varied the duration and intensity of the environmental exposure. Results showed that the probability of detection, mean spatial sensitivity, and mean spatial specificity of models decreased steadily as the time since relevant exposure increased. This suggests that for diseases with long latencies, spatial areas of high risk due to high-intensity exposure of relatively short duration will be difficult to detect over time when using residential locations at the time of diagnosis in mobile study populations. [ABSTRACT FROM AUTHOR]

In many studies of environmental risk factors for disease, researchers use the location at diagnosis as a geographic reference for environmental exposures. However, many environmental pollutants change continuously over space and time. The dynamic characteristics of these pollutants coupled with population mobility in the United States suggest that for diseases with long latencies like cancer, historic exposures may be more relevant than exposure at the time of diagnosis. In this article, we evaluated to what extent the commonly used assumption of no population mobility results in increased bias in the estimates of the relationship between environmental exposures and long-latency health outcomes disease in a case-control study. We conducted a simulation study using the residential histories of a random sample from the National Institutes of Health-AARP (formerly American Association of Retired Persons) Diet and Health Study. We simulated case-control status based on subject exposure and true exposure effects that varied temporally. We compared estimates from models using only subject location at diagnosis to estimates where subjects were assumed to be mobile. Ignoring population mobility resulted in underestimates of subject exposure, with largest deviations observed at time points further away from study enrollment. In general, the effect of population mobility on the bias of the estimates of the relationship between the exposure and the outcome was more prominent with exposures that showed substantial spatial and temporal variability. Based on our results, we recommend using residential histories when environmental exposures and disease latencies span a long enough time period that mobility is important. [ABSTRACT FROM AUTHOR]

Background: Given the large proportion of mothers in the United States work force, understanding the implications of workplace support on breastfeeding outcomes is an important public health priority. The current study investigates if (a) workplace support directly influences the working mothers' breastfeeding intention, self‐efficacy, and duration, and (b) workplace support indirectly influences breastfeeding duration through the mediating effect of breastfeeding intention and self‐efficacy. Methods: Data from the longitudinal Infant Feeding Practices Survey II were analyzed. The main predictor variable, workplace support, was based on a Likert scale from "not at all supportive" to "very supportive." Both mediators, exclusive breastfeeding intention and self‐efficacy, were dichotomized (yes; no) while the study outcome, breastfeeding duration, was continuous. Structural equation modeling was used to obtain direct and indirect effects of breastfeeding intention and confidence in attaining breastfeeding goals. Results: After adjusting for confounders, there was a statistically significant direct effect between self‐efficacy, breastfeeding intention, and breastfeeding duration. A statistically significant indirect effect of workplace support on breastfeeding duration through self‐efficacy in attaining breastfeeding goals was also observed. The mediation ratios of the indirect effects showed that self‐efficacy in attaining breastfeeding goals accounted for 40.8% (P‐value=0.032) of the total effect; however, all other mediation ratios did not show statistical significance. Conclusions: Self‐efficacy is an important predictor for breastfeeding duration. Workplaces may help bolster women's self‐efficacy by providing environments that are supportive to breastfeeding working mothers. Future research is needed to identify breastfeeding policies that boost self‐efficacy. [ABSTRACT FROM AUTHOR]

Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events ( EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient. [ABSTRACT FROM AUTHOR]

Purpose The generalisability of randomised controlled trials (RCTs) may be limited by restrictive entry criteria or by their experimental nature. Observational research can provide complementary findings but is prone to bias. Employing propensity score matching, to reduce such bias, we compared the real-life effect of cinacalcet use on all-cause mortality (ACM) with findings from the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) RCT in chronic haemodialysis patients. Methods Incident adult haemodialysis patients receiving cinacalcet, recruited in a prospective observational cohort from 2007-2009 (AROii; n = 10,488), were matched to non-exposed patients regardless of future exposure status. The effect of treatment crossover was investigated with inverse probability of censoring weighted and lag-censored analyses. EVOLVE ACM data were analysed largely as described for the primary composite endpoint. Results AROii patients receiving cinacalcet (n = 532) were matched to 1790 non-exposed patients. The treatment effect of cinacalcet on ACM in themainAROii analysis (hazard ratio 1.03 [95%confidence interval (CI) 0.78-1.35]) was closer to the null than for the Intention to Treat (ITT) analysis of EVOLVE (0.94 [95%CI 0.85-1.04]). Adjusting for non-persistence by 0- and 6-month lag-censoring and by inverse probability of censoring weight, the hazard ratios in AROii (0.76 [95%CI 0.51-1.15], 0.84 [95%CI 0.60-1.18] and 0.79 [95%CI 0.56-1.11], respectively) were comparable with those of EVOLVE (0.82 [95%CI 0.67-1.01], 0.83 [95%CI 0.73-0.96] and 0.87 [95%CI 0.71-1.06], respectively). Conclusions Correcting for treatment crossover, we observed results in the 'real-life' setting of the AROii observational cohort that closely mirrored the results of the EVOLVE RCT. Persistence-corrected analyses revealed a trend towards reduced ACM in haemodialysis patients receiving cinacalcet therapy. [ABSTRACT FROM AUTHOR]

Associations between ultraviolet radiation (UVR) exposure and non-Hodgkin lymphoma (NHL) have been inconsistent, but few studies have examined these associations for specific subtypes or across race/ethnicities. We evaluated the relationship between ambient UVR exposure and subtype-specific NHL incidence for whites, Hispanics and blacks in the United States for years 2001-2010 ( n = 187,778 cases). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quintiles using Poisson regression. Incidence was lower for the highest UVR quintile for chronic/small lymphocytic/leukemia (CLL/SLL) (IRR = 0.87, 95% CI: 0.77-0.97), mantle cell (IRR = 0.82, 95% CI: 0.69-0.97), lymphoplasmacytic (IRR = 0.58, 95% CI: 0.42-0.80), mucosa-associated lymphoid tissue (MZLMALT) (IRR = 0.74, 95% CI: 0.60-0.90), follicular (FL) (IRR = 0.76, 95% CI: 0.68-0.86), diffuse large B-cell (IRR = 0.84, 95% CI: 0.76-0.94;), peripheral T-cell other (PTCL) (IRR = 0.76, 95% CI: 0.61-0.95) and PTCL not otherwise specified (PNOS) (IRR = 0.77, 95% CI: 0.61-0.98). Trends were significant for MZLMALT, FL, DLBCL, BNOS and PTCL, with FL and DLBCL still significant after Bonferroni correction. We found interaction by race/ethnicity for CLL/SLL, FL, Burkitt, PNOS and MF/SS, with CLL/SLL and FL still significant after Bonferroni correction. Some B-cell lymphomas (CLL/SLL, FL and Burkitt) suggested significant inverse relationships in whites and Hispanics, but not in blacks. Some T-cell lymphomas suggested the most reduced risk for the highest quintile of UVR among blacks (PNOS and MF/SS), though trends were not significant. These findings strengthen the case for an inverse association of UVR exposure, support modest heterogeneity between NHL subtypes and suggest some differences by race/ethnicity. [ABSTRACT FROM AUTHOR]

Two important objectives in hedonic price analysis are to predict sale prices and delineate submarkets based on geographical and functional considerations. In this paper, we applied Bayesian models with spatially varying coefficients in an analysis of housing sale prices in the city of Toronto, Ontario to address these objectives. We evaluated model performance and identified patterns of submarkets indicated by the spatial coefficient processes. Our results show that Bayesian spatial process models predict housing sale prices well, provide useful inference regarding heterogeneity in prices within a market, and may be specified to include expert market opinions. [ABSTRACT FROM AUTHOR]

The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single-center cohort, we examined the relationship between donor-, recipient-, and transplantation-associated factors and change in a morphometric index of chronic damage ( ICD) between protocol biopsies performed at implantation and at 2-3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0-8) and 2-3 months post-transplant (median 8% IQR:4-15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post-transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes. [ABSTRACT FROM AUTHOR]

Background Arterial calcification ( AC) is a major health problem associated with extreme morbidity and a shortened survival. It is currently without any effective treatment. ATP and the purinergic system in general are now emerging as being important in the pathogenesis of AC and potentially provide a new focus for novel therapies. Methods This review systematically analyses and discusses the current literature examining the relevance of the purinergic system to AC. Particular emphasis is given to the enzymes associated with ATP metabolism and their role in maintaining a balance between promotion and inhibition of arterial mineralization. Points of controversy are highlighted, and areas for future research are suggested. Conclusion The potential roles of ATP and the purinergic system in AC are beginning to be elucidated. While further work is necessary, current knowledge suggests that several components of the purinergic system could be targeted to develop new treatments for AC. [ABSTRACT FROM AUTHOR]

Ecologic studies have reported that solar ultraviolet radiation (UVR) exposure is associated with cancer; however, little evidence is available from prospective studies. We aimed to assess the association between an objective measure of ambient UVR exposure and risk of total and site-specific cancer in a large, regionally diverse cohort [450,934 white, non-Hispanic subjects (50-71 years) in the prospective National Institutes of Health (NIH)-AARP Diet and Health Study] after accounting for individual-level confounding risk factors. Estimated erythemal UVR exposure from satellite Total Ozone Mapping Spectrometer (TOMS) data from NASA was linked to the US Census Bureau 2000 census tract (centroid) of baseline residence for each subject. We used Cox proportional hazards models adjusted for multiple potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of UVR exposure. Restricted cubic splines examined nonlinear relationships. Over 9 years of follow-up, UVR exposure was inversely associated with total cancer risk ( N = 75,917; highest versus lowest quartile; HR = 0.97, 95% CI = 0.95-0.99; p-trend < 0.001). In site-specific cancer analyses, UVR exposure was associated with increased melanoma risk (highest versus lowest quartile; HR = 1.22, 95% CI = 1.13-1.32; p-trend < 0.001) and decreased risk of non-Hodgkin's lymphoma (HR = 0.82, 95% CI = 0.74-0.92) and colon (HR = 0.88, 95% CI = 0.82-0.96), squamous cell lung (HR = 0.86, 95% CI = 0.75-0.98), pleural (HR = 0.57, 95% CI = 0.38-0.84), prostate (HR = 0.91, 95% CI = 0.88-0.95), kidney (HR = 0.83, 95% CI = 0.73-0.94) and bladder (HR = 0.88, 95% CI = 0.81-0.96) cancers (all p-trend < 0.05). We also found nonlinear associations for some cancer sites, including the thyroid and pancreas. Our results add to mounting evidence for the influential role of UVR exposure on cancer. [ABSTRACT FROM AUTHOR]

The Centers for Disease Control and Prevention defined epilepsy as an emerging public health issue in a recent report and emphasized the importance of epilepsy studies in minorities and people of low socioeconomic status. Previous research has suggested that the incidence rate for epilepsy is positively associated with various measures of social and economic disadvantage. In response, we utilize hierarchical Bayesian models to analyze health disparities in epilepsy and seizure risks among multiple ethnicities in the city of Philadelphia, Pennsylvania. The goals of the analysis are to highlight any overall significant disparities in epilepsy risks between the populations of Caucasians, African Americans, and Hispanics in the study area during the years 2002-2004 and to visualize the spatial pattern of epilepsy risks by ethnicity to indicate where certain ethnic populations were most adversely affected by epilepsy within the study area. Results of the Bayesian model indicate that Hispanics have the highest epilepsy risk overall, followed by African Americans, and then Caucasians. There are significant increases in relative risk for both African Americans and Hispanics when compared with Caucasians, as indicated by the posterior mean estimates of 2.09 with a 95 per cent credible interval of (1.67, 2.62) for African Americans and 2.97 with a 95 per cent credible interval of (2.37, 3.71) for Hispanics. Results also demonstrate that using a Bayesian analysis in combination with geographic information system (GIS) technology can reveal spatial patterns in patient data and highlight areas of disparity in epilepsy risk among subgroups of the population. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Higher cholesterol is strongly associated with an increased risk of coronary heart disease (CHD) in nonrenal populations, so the lack of a clear positive association between total cholesterol and mortality among dialysis patients is unexpected. This review of prospective studies of the association between total cholesterol and mortality among dialysis patients suggests that there is a negative association at below average cholesterol levels and a flat or weakly positive association at higher levels. In nonrenal populations total cholesterol is not positively associated with vascular causes of death other than CHD, so the lack of a strongly positive association at above average cholesterol concentrations in dialysis patients may be explained by the high proportion of deaths due to non-CHD vascular causes. The observation of a negative association between total cholesterol and mortality at below average cholesterol concentrations in some studies is consistent with confounding by both vascular and nonvascular morbidity (i.e., reverse causality). We argue that evaluating the importance of cholesterol for vascular disease risk in dialysis patients can only be achieved through the eradication of confounding by randomization, and that ongoing trials of cholesterol-lowering therapy will provide a definitive answer to this question. [ABSTRACT FROM AUTHOR]

The number of published randomized controlled trials in nephrology is fewer than in most other specialties in internal medicine. As a consequence, current clinical practice guidelines are based largely on expert opinion, which may prove to be incorrect. Enthusiasm for trials involving hemodialysis patients has been dampened by a series of high profile studies in which a range of different interventions have failed to improve outcomes. Despite these disappointments, recent experience suggests that nephrologists remain willing to participate in clinical studies that address important questions. Previous, ongoing and future trials involving hemodialysis patients are discussed. [ABSTRACT FROM AUTHOR]

Calcification of the cardiovascular system is well recognized in patients with chronic kidney disease receiving dialysis, persists following successful kidney transplantation, and is associated with a poor prognosis. Whether deposition of calcium in the arteries of such individuals contributes to excess cardiovascular morbidity and mortality remains uncertain as do the clinical advantages of slowing this process. However, detecting vascular calcification using simple imaging techniques such as plain radiographs or ultrasound can provide valuable information as to the nature of bone disease in patients receiving dialysis and may help to guide therapeutic strategies aimed at preventing the development of secondary hyperparathyroidism. Further advances in our understanding of arterial calcification and its relationship to bone disease are likely to help in the future development of therapies for these interrelated conditions. [ABSTRACT FROM AUTHOR]

Over the last 15 years, numerous clinical practice guidelines have been developed by clinicians driven by national societies and funders of healthcare services. Writing and publication of guidelines have been refined such that a transparent and robust process has evolved. The main purpose of clinical practice guidelines is to provide healthcare professionals with evidence-based recommendations to assist clinical decision-making and reduce variability in clinical practice: this benefits patients and the healthcare system. When evidence is abundant and robust, guideline development is relatively straightforward. However, in areas where evidence is lacking, there is a tension between providing advice based on expert opinion while maintaining a clinical equipoise that will facilitate the design and execution of clinical trials, so that new information is gained, and that will ultimately inform care . In this commentary, we explore these problems and suggest an alternative approach to the development of clinical guidance in areas where evidence is lacking. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the proposed Kidney Disease Improving Global Outcomes guidelines for the management of bone and mineral disorders in patients having chronic kidney disease-mineral bone disease (CKD-MBD).

Aim Method Results Conclusion The co‐existence of diabetes and CKD poses significant challenges to healthcare systems, current frameworks often inadequately address the complex needs of individuals with both conditions. Recognising these gaps, we introduced a new diabetes care model for people with advanced CKD in renal satellite units.This paper aims to evaluate this new diabetes model care.We conducted a prospective audit of a new integrated diabetes kidney care model. Data were presented as mean ± SD or counts/percentages, and pre‐ and post‐intervention differences were assessed using paired samples t‐tests.A total of 291 individuals with diabetes and advanced CKD stages 4 or 5, or undergoing haemodialysis, were included. The mean age was 68.5 (±13.0) years, 58.4% were males. Nearly half of the cohort had four or more long‐term conditions, while two‐thirds experienced mild/severe frailty. Only 6% were receiving ongoing diabetes care from secondary care diabetes specialist services. For patients with CKD not receiving dialysis, comparing pre‐ and post‐intervention, there were improvements in HbA1c (−13.0 mmol/mol, p < 0.001), SBP (−13.7 mm Hg, p < 0.0001), and weight (−2.9 kg, p < 0.0001). Furthermore, there was an increase in guideline‐directed therapies, with notable usage of SGLT2i (62.9%) and GLP1‐RA (28.4%), while access to diabetes technology increased to 89%.This new model of care resulted in improved metabolic outcomes, increased utilisation of guideline‐directed therapies, and enhanced access to diabetes technologies. However, the model also revealed significant unmet clinical needs in areas such as access to diabetes care, diabetes eye screening and foot surveillance. [ABSTRACT FROM AUTHOR]

Background The sodium-glucose cotransporter 2 inhibitor canagliflozin reduced the risk of first cardiovascular composite events in the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. In this post hoc analysis, we evaluated the effect of canagliflozin on total (first and recurrent) cardiovascular events. Methods and Results The CREDENCE trial compared canagliflozin or matching placebo in 4401 patients with type 2 diabetes, albuminuria, and estimated glomerular filtration rate of 30 to <90 mL/min per 1.73 m 2 , over a median of 2.6 years. The primary outcome was analyzed as a composite of any cardiovascular event including myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular death. Negative binomial regression models were used to assess the effect of canagliflozin on the net burden of cardiovascular events. During the trial, 634 patients had 883 cardiovascular events, of whom 472 (74%) had just 1 cardiovascular event and 162 (26%) had multiple cardiovascular events. Canagliflozin reduced first cardiovascular events by 26% (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P <0.001) and total cardiovascular events by 29% (incidence rate ratio, 0.71 [95% CI, 0.59-0.86]; P <0.001). The absolute risk difference per 1000 patients treated over 2.5 years was -44 (95% CI, -67 to -21) first cardiovascular events and -73 (95% CI, -114 to -33) total events. Conclusions Canagliflozin reduced cardiovascular events, with a larger absolute benefit for total cardiovascular than first cardiovascular events. These findings provide further support for the benefit of continuing canagliflozin therapy after an initial event to prevent recurrent cardiovascular events. Registration Information URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02065791.

Background: Given the large proportion of mothers in the United States work force, understanding the implications of workplace support on breastfeeding outcomes is an important public health priority. The current study investigates if (a) workplace support directly influences the working mothers' breastfeeding intention, self-efficacy, and duration, and (b) workplace support indirectly influences breastfeeding duration through the mediating effect of breastfeeding intention and self-efficacy., Methods: Data from the longitudinal Infant Feeding Practices Survey II were analyzed. The main predictor variable, workplace support, was based on a Likert scale from "not at all supportive" to "very supportive." Both mediators, exclusive breastfeeding intention and self-efficacy, were dichotomized (yes; no) while the study outcome, breastfeeding duration, was continuous. Structural equation modeling was used to obtain direct and indirect effects of breastfeeding intention and confidence in attaining breastfeeding goals., Results: After adjusting for confounders, there was a statistically significant direct effect between self-efficacy, breastfeeding intention, and breastfeeding duration. A statistically significant indirect effect of workplace support on breastfeeding duration through self-efficacy in attaining breastfeeding goals was also observed. The mediation ratios of the indirect effects showed that self-efficacy in attaining breastfeeding goals accounted for 40.8% (P-value=0.032) of the total effect; however, all other mediation ratios did not show statistical significance., Conclusions: Self-efficacy is an important predictor for breastfeeding duration. Workplaces may help bolster women's self-efficacy by providing environments that are supportive to breastfeeding working mothers. Future research is needed to identify breastfeeding policies that boost self-efficacy., (© 2018 Wiley Periodicals, Inc.)