Axial heterogeneity and filtered-load dependence of proximal bicarbonate reabsorption

A theoretical model was developed to examine the role of physical and chemical factors in the control of bicarbonate reabsorption in the renal proximal tubule. Included in the model were axial and radial variations in the concentrations of HCO3-, CO2 and related chemical species in the tubule lumen and epithelial cells. Relations between these concentrations and the solute fluxes across the brush border and basolateral membranes were also included, as were reaction rate and equilibrium expressions to describe the various buffering processes in the lumen and cells. The two most critical membrane parameters, the rate constant for H+ secretion at the brush border and the effective permeability of HCO3- at the basolateral membrane, were evaluated by comparing model predictions with available free-flow micropuncture data in the rat. It was found that the experimental observations could be explained only by decreasing one or both of these membrane parameters with axial position, suggesting a progressive decrease in HCO3- reabsorptive capacity along the tubule. For single nephron filtered loads of HCO3- up to about 1,400 pmol/min, absolute bicarbonate reabsorption was predicted to increase nearly in proportion to filtered load, whereas it was calculated to be relatively constant at higher filtered loads, irrespective of how filtered load was assumed to be varied. These predictions are in excellent agreement with most of the available micropuncture data in rats, as is the prediction that HCO3- reabsorption should change in parallel with CO2 partial pressure in the filtrate, at a given filtered load of HCO3–. Certain discrepancies between the model predictions and experimental observations are evident at very high filtered loads, and the implications of these are discussed in terms of possible adaptive responses of the tubule

Adherence to insulin pump treatment declines with increasing age in adolescents with type 1 diabetes mellitus

Aim This study assessed the impact of illness perceptions, emotional responses to the disease and its management, and patient characteristics on the adherence to optimal insulin pump management in adolescents with type 1 diabetes mellitus. Methods From May to December 2013 and May 2015 to September 2016, we investigated 90 adolescents (50% boys), 12-18 years with type 1 diabetes. We analysed the association of optimal adherence to insulin pump therapy to age, gender, diabetes duration, results of questionnaires relating to fear and problems of self-testing, illness perceptions, emotional distress and family conflicts. Optimal adherence was defined as bolusing insulin on average >= 2.5/3 main meals/d. Results Adolescents with suboptimal adherence were on average 1.8 years older (95% Confidence Interval 1.09-2.50 years, P <.001) than those with optimal adherence. After adjustment for age, no other patient or parent factors were related to optimal adherence. Conclusion Adherence to insulin pump self-management in adolescents with type 1 diabetes declined with increasing age, illustrating the challenges of transition of self-management from parents to the adolescent patient themselves

Healthcare reimbursement costs of children with type 1 diabetes in the Netherlands, a observational nationwide study (Young Dudes-4)

Background: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children. Studies on costs related to T1DM are scarce and focused primarily on the costs directly related to diabetes. We aimed to investigate both the overall healthcare costs and the more specific costs related to the management of diabetes.Methods: This is a retrospective and observational, nationwide cohort study of all Dutch children (aged 0-18 years) with T1DM. Data were collected from the national registry for healthcare reimbursement, in which all Dutch insurance companies combine their reimbursement data. In the Netherlands for all Dutch citizens health care is covered by law and all children are treated by hospital-based paediatricians.Results: We analysed 6710 children distributed over 81 hospitals: 475 children in 6 university hospitals and 6235 children in 75 general hospitals. Total reimbursement for all children with T1DM over the period 2009 to 2011 was (sic) 167,494,732 corresponding to an annual mean of (sic) 55,831,577 of total costs and (sic) 8326 euros per child. When comparing small (between 26 and 54 patients), medium (57-84 patients) and large (88-248 patients) general hospitals, costs per patient were highest in the hospitals with the highest number of T1DM patients. The costs for devices, secondary care and pharmaceutics had most impact on total expenditures. Over the study period, there was a slight decrease in per person costs.Conclusion: The overall health expenditure of a child with T1DM is more than (sic) 8000 per patient per annum. Given the move towards more device-intensive multidisciplinary care for these patients, the costs of treating T1DM in children are likely to increase further in the coming years.</p

Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes: ZODIAC-16

OBJECTIVE - Several Studies have suggested an association between specific diabetes treatment and cancer mortality. We studied the association between metformin use and cancer mortality in a prospectively followed cohort. RESEARCH DESIGN AND METHODS - in 1998 and 1999,1,353 patients With type 2 diabetes were enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care 0 (ZODIAC) study in the Netherlands. Vital status was assessed in January 2009. Cancer mortality rate was evaluated using Standardized Mortality ratios (SMRs), and the association between metformin use and cancer mortality was evaluated with a Cox proportional hazards model, taking possible confounders into account. RESULTS - Median follow-up time was 9.6 years, average age at baseline was 68 years, and average A1C was 7.5%. Of the patients, 570 died, of which 122 died of malignancies. The SMR for cancer mortality was 1.47 (95% CI 1.22-1.76). In patients taking metformin compared with patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95% Cl 0.23-0.80), and the HR With every increase of I g of metformin was 0.58 (95% CI 0.36-093), CONCLUSIONS - in general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality compared with nonuse of metformin. Although the design cannot provide a conclusion about causality, our results suggest a protective effect of metformin on cancer mortality

Selection tools and student diversity in health professions education:a multi-site study

Student diversity in health professions education (HPE) can be affected by selection procedures. Little is known about how different selection tools impact student diversity across programs using different combinations of traditional and broadened selection criteria. The present multi-site study examined the chances in selection of subgroups of applicants to HPE undergraduate programs with distinctive selection procedures, and their performance on corresponding selection tools. Probability of selection of subgroups (based on gender, migration background, prior education, parental education) of applicants (N = 1935) to five selection procedures of corresponding Dutch HPE undergraduate programs was estimated using multilevel logistic regression. Multilevel linear regression was used to analyze performance on four tools: prior-education grade point average (pe-GPA), biomedical knowledge test, curriculum-sampling test, and curriculum vitae (CV). First-generation Western immigrants and applicants with a foreign education background were significantly less likely to be selected than applicants without a migration background and with pre-university education. These effects did not vary across programs. More variability in effects was found between different selection tools. Compared to women, men performed significantly poorer on CVs, while they had higher scores on biomedical knowledge tests. Applicants with a non-Western migration background scored lower on curriculum-sampling tests. First-generation Western immigrants had lower CV-scores. First-generation university applicants had significantly lower pe-GPAs. There was a variety in effects for applicants with different alternative forms of prior education. For curriculum-sampling tests and CVs, effects varied across programs. Our findings highlight the need for continuous evaluation, identifying best practices within existing tools, and applying alternative tools.</p