On Generalizations of Network Design Problems with Degree Bounds

Iterative rounding and relaxation have arguably become the method of choice in dealing with unconstrained and constrained network design problems. In this paper we extend the scope of the iterative relaxation method in two directions: (1) by handling more complex degree constraints in the minimum spanning tree problem (namely, laminar crossing spanning tree), and (2) by incorporating `degree bounds' in other combinatorial optimization problems such as matroid intersection and lattice polyhedra. We give new or improved approximation algorithms, hardness results, and integrality gaps for these problems.Comment: v2, 24 pages, 4 figure

Health related quality of life in patients with type I diabetes mellitus:generic & disease-specific measurement

Background & objectives: An ideal instrument for the assessment of health related quality of life (HRQOL) in patients with diabetes mellitus type I (T1DM) should incorporate the benefits of both generic and disease-specific instruments. The objective of this study was to investigate the responsiveness and the ability to provide information about diabetes-specific associations with HRQOL, of two generic instruments, in comparison with two diabetes-specific instruments, in patients with T1DM. Methods: In a Dutch cohort of 234 patients with T1DM we longitudinally assessed HRQOL using both generic and diabetes-specific instruments. We investigated the responsiveness, the associations with diabetes-specific variables and the Identification of specific patients by the Instruments used. Results: The generic RAND-36 was able to detect statistically significant and clinically relevant changes in HRQOL over time. Moreover, the RAND-36 was associated with (changes In) diabetes. specific variables. The generic and diabetes-specific Instruments partly Identified different patients with lowest HRQOL. Interpretation & conclusion: The RAND-36 was highly responsive to changes in HRQOL in patients with T1DM and revealed diabetes-specific associations with HRQOL. A low correlation between the generic and diabetes-specific instruments and partly different identification of patients with lower HRQOL support the complementary use of these instruments In patients with T1DM

One in Five Laboratories Using Various Hemoglobin A(1c) Methods Do Not Meet the Criteria for Optimal Diabetes Care Management

Background: We assessed the reference change value (RCV) of currently available hemoglobin A(1c) (HbA(1c)) laboratory assays, which is defined as the critical difference between two consecutive HbA(1c) measurements representing a significant change in health status. Methods: We examined the individual laboratory coefficients of variation (CVs) in the Dutch/Belgian quality scheme based on 24 lyophilized samples and calculated the RCV per laboratory (n-220) and per assay method. In addition, two pooled whole blood samples were sent to the participating laboratories. The individual laboratory results were compared to the assigned value +/- an allowable total error (TEa) of 6%. Results: At HbA(1c) values of 41.0 mmol/mol (5.9%-Diabetes Control and Complications Trial [DCCT]) and 61.8 mmol/mol (7.8%-DCCT), 99% and 98%, respectively, of the laboratories reported a value within a TEa limit of 6%. The analytical CV of the HbA(1c) method used in 78% of the laboratories is Conclusions: The analytical performance of the majority of laboratory HbA(1c) methods is within the clinical requirements. However, based on the calculated RCV, 21.8% of the laboratories using different HbA(1c) methods are not able to distinguish an HbA(1c) result of 59 mmol/mol (7.5%-DCCT) from a previous HbA(1c) result of 53 mmol/mol (7.0%-DCCT). It can be presumed that differences in HbA(1c) results of 5 mmol/mol (0.5%-DCCT) do influence treatment decisions

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

World allergy organization guidelines for the assessment and management of anaphylaxis

The illustrated World Allergy Organization (WAO) Anaphylaxis Guidelines were created in response to absence of global guidelines for anaphylaxis. Uniquely, before they were developed, lack of worldwide availability of essentials for the diagnosis and treatment of anaphylaxis was documented. They incorporate contributions from more than 100 allergy/immunology specialists on 6 continents. Recommendations are based on the best evidence available, supported by references published to the end of December 2010. The Guidelines review patient risk factors for severe or fatal anaphylaxis, co-factors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, including pregnant women, infants, the elderly, and those with cardiovascular disease. They focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment. This involves having a written emergency protocol and rehearsing it regularly; then, as soon as anaphylaxis is diagnosed, promptly and simultaneously calling for help, injecting epinephrine (adrenaline) intramuscularly, and placing the patient on the back or in a position of comfort with the lower extremities elevated. When indicated, additional critically important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions. Vital signs and cardiorespiratory status should be monitored frequently and regularly (preferably, continuously). The Guidelines briefly review management of anaphylaxis refractory to basic initial treatment. They also emphasize preparation of the patient for self-treatment of anaphylaxis recurrences in the community, confirmation of anaphylaxis triggers, and prevention of recurrences through trigger avoidance and immunomodulation. Novel strategies for dissemination and implementation are summarized. A global agenda for anaphylaxis research is proposed

Glucose and potassium derangements by glucose-insulin-potassium infusion in acute myocardial infarction

Background. High-dose glucose-insulin-potassium infusion (GIK) has been suggested to be beneficial in acute myocardial infarction (MI). Recently new large trials have shown no effect of GIK on mortality. To investigate whether metabolic derangement could have negated the potential beneficial effect, we studied the relation between systemic glucose and potassium levels and outcome. Methods. Patients with signs and symptoms of ST-segment-elevation MI and treated with primary percutaneous coronary intervention (PCI) were randomised to no infusion or high-dose GIK, i.e. 80 mmol potassium chloride in 500 ml 20% glucose at a rate of 3 ml/kg/hour and 50 units short-acting insulin in 50 ml 0.9% sodium chloride for 12 hours. Results. A total of 6991 glucose values and 7198 potassium values were obtained in 476 GIK patients and 464 controls. Mean serum glucose was significantly higher in the GIK group (9.3±4.5 mmol/l vs. 8.4±2.9 mmol/l, p&lt;0.001). Mean potassium level was significantly higher in the GIK group (4.2±0.5 mmol/l vs. 3.9±0.4 mmol/l, p&lt;0.001). Incidence of hyperglycaemia (glucose &gt;11.0 mmol/l) occurred in 70.8% of GIK patients and 33.8% of controls (p&lt;0.001). Hypokalaemia was less common in the GIK group (23.5 vs. 41.2%, p&lt;0.001). Incidence of hyperkalaemia and hypoglycaemia did not differ significantly between the two groups. In multivariate analysis age, previous cardiovascular disease, Killip class &gt;1, unsuccessful PCI and mean glucose after admission were associated with increased one-year mortality. Conclusion. In ST-segment-elevation MI patients treated with primary PCI, high-dose GIK induced hyperglycaemia and prevented hypokalaemia. Derangement of the glucose metabolism was related to one-year mortality.</p