The burden of severe hypoglycemia in type 1 diabetes

Aims: Approximately 1.25 million people in the US have type 1 diabetes mellitus (T1DM), a chronic metabolic disease that develops from the body’s inability to produce insulin, and requires life-long insulin therapy. Poor insulin adherence may cause severe hypoglycemia (SHO), leading to hospitalization and long-term complications; these, in turn, drive up costs of SHO and T1DM overall. This study’s objective was to estimate the prevalence and costs of SHO-related hospitalizations and their additional longer-term impacts on patients with T1DM using basal-bolus insulin.

Methods: Using Truven MarketScan claims, we identified adult T1DM patients using basal-bolus insulin regimens who were hospitalized for SHO (inpatient SHO patients) during 2010–2015. Two comparison groups were defined: those with outpatient SHO-related encounters only, including emergency department (ED) visits without hospitalization (outpatient SHO patients), and those with no SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay and SHO-related hospitalization costs were estimated and propensity score and inverse probability weighting methods were used to adjust for baseline differences across the groups to evaluate longer-term impacts.

Results: We identified 8,734 patients, of which 4.2% experienced at least one SHO-related hospitalization. Among those who experienced SHO (i.e. of those in the inpatient and outpatient SHO groups), 31% experienced at least one SHO-related hospitalization, while 9% were treated in the ED without subsequent hospitalization. Approximately 79% of patients were admitted directly to the hospital; the remainder were first assessed or treated in the ED. The inpatient SHO patients stayed in the hospital, including time in the ED, for 1.7 days and incurred $3551 in costs. About one-third of patients were hospitalized again for SHO. Inpatient SHO patients incurred significantly higher monthly costs after their initial SHO-related hospitalization than patients in the two other groups ($2084 vs $1313 and $1372), corresponding to 59% or 52% higher monthly costs for inpatient SHO patients.

Limitations: These analyses excluded patients who did not seek ED or hospital care when faced with SHO; events may have been miscoded; and we were not able to account for clinical characteristics associated with SHO, such as insulin dose and duration of diabetes, or unmeasured confounders.

Conclusions: The burden associated with SHO is not negligible. About 4% of T1DM patients using basal-bolus insulin regimens are hospitalized at least once due to SHO. Not only did those patients incur the costs of their SHO hospitalization, but they also incur red at least $712 (52%) more in costs per month after their hospitalization than outpatient SHO or comparison patients. Reducing SHO events can help decrease the burden associated with SHO among patients with T1DM.     

The Effect of Increasing the Amount of Indium Alloying Material on the Efficiency of Sacrificial Aluminium Anodes

Al-Zn-In alloys having 4.2% zinc content and various indium content in the range of 0.02–0.2% were tested with respect to the most important electrochemical properties of sacrificial anodes in a cathodic protection, i.e., the current capacity and potential of the operating anode. The distribution of In and Zn in the tested alloys was mapped by means of the EDX technique, which demonstrated that these elements dissolve well in the alloy matrix and are evenly distributed within it. The current capacity of such alloys was determined by means of the method of determining the mass loss during the dissolution by a current of known charge. The results obtained demonstrate that the current capacity of Al-Zn-In alloy decreases with the increase in the In content, which results in an increased consumption of anode material and shorter lifetime of anodes. With 0.02% In content, the capacity amounted to approx. 2500 Ah/kg, whereas the alloy with 0.2% In had as much as 30% lower capacity amounting to approx. 1750 Ah/kg. Microscopic examination for the morphology and surface profile of the samples after their exposure demonstrated that a higher indium content in the alloy results in a more uneven general corrosion pattern during the dissolution of such alloy, and the cavities (pits) appearing on the alloy surface are larger and deeper. As the indium content is increased from 0.02% to 0.05%, the Al-Zn-In alloy potential decreases by about 50 mV to −1100 mV vs. Ag/AgCl electrode, which is advantageous in terms of using this alloy as a sacrificial anode. When the indium content is further increased from 0.05% to 0.2%, the potential of the alloy is no longer changed to a more negative one. The results obtained from all these tests demonstrate that alloys containing up to 0.05% of In additive are practically applicable for cathodic protection.     

Surface Roughness Evaluation in Thin EN AW-6086-T6 Alloy Plates after Face Milling Process with Different Strategies

Lightweight alloys made from aluminium are used to manufacture cars, trains and planes. The main parts most often manufactured from thin sheets requiring the use of milling in the manufacturing process are front panels for control systems, housing parts for electrical and electronic components. As a result of the final phase of the manufacturing process, cold rolling, residual stresses remain in the surface layers, which can influence the cutting processes carried out on these materials. The main aim of this study was to verify whether the strategy of removing the outer material layers of aluminium alloy sheets affects the surface roughness after the face milling process. EN AW-6082-T6 aluminium alloy thin plates with three different thicknesses and with two directions relative to the cold rolling process direction (longitudinal and transverse) were analysed. Three different strategies for removing the outer layers of the material by face milling were considered. Noticeable differences in surface roughness 2D and 3D parameters were found among all machining strategies and for both rolling directions, but these differences were not statistically significant. The lowest values of Ra = 0.34 µm were measured for the S#3 strategy, which asymmetrically removed material from both sides of the plate (main and back), for an 8-mm-thick plate in the transverse rolling direction. The highest values of Ra = 0.48 µm were measured for a 6-mm-thick plate milled with the S#2 strategy, which symmetrically removed material from both sides of the plate, in the longitudinal rolling direction. However, the position of the face cutter axis during the machining process was observed to have a significant effect on the surface roughness. A higher surface roughness was measured in the areas of the tool point transition from the up-milling direction to the down-milling direction (tool axis path) for all analysed strategies (Ra = 0.63–0.68 µm). The best values were obtained for the up-milling direction, but in the area of the smooth execution of the process (Ra = 0.26–0.29 µm), not in the area of the blade entry into the material. A similar relationship was obtained for analysed medians of the arithmetic mean height (Sa) and the root-mean-square height (Sq). However, in the case of the S#3 strategy, the spreads of results were the lowest.     

Expression of serum vascular endothelial growth factor correlates with clinical outcome in multiple myeloma

A total of 34 multiple myeloma (MM) patients (17 recently diagnosed and 17 in progression of the disease) treated at the Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation Medical University in Wroc?aw were studied. Among the 19 females and 15 males, aged 31-72 years, there were 17 IgG, 9 IgA and 1 IgM, one with plasma cell leukaemia and 6 with light chain disease. Staging according to Durie and Salmon disclosed: 7--IIA stage, 15--IIIA and 12--IIIB. Blood hyperviscosity symptoms (HS) developed in 9 patients, and precomatic state or coma was observed in four of them. Control group was constituted of 14 healthy subjects--10 women and 4 men aged 32-51 years. Vascular endothelial growth factor (VEGF) serum concentration in MM patients varied from 0 pg/ml to 760 pg/ml, mean 148.75 pg/ml, SD = 204.4 and in controls 0 pg/ml--164 pg/ml, mean 31.5, SD = 23.3; p < 0.05. The mean VEGF level in recently diagnosed patients was higher than in progression of the disease, mean 188.6 pg/ml, SD = 230.6 and mean 110.9 pg/ml, SD = 177.9; respectively, but the difference was not statistically significant. The patients with stage III had significantly (p < 0.05) higher VEGF level than those in stage II (mean 303.1 pg/ml, SD = 302.2 and mean 89.0 pg/ml SD = 121.6) respectively. The group of MM patients with renal failure (creatinine level > 2 mg%) had higher VEGF level than those with normal renal function: mean 199.9 pg/ml, SD = 235, and mean 46.9 SD = 47 respectively, p < 0.01. Elevated VEGF level was also present in comatic and precomatic patients when compared with hyperviscosity patients without these symptoms (p < 0.05). In multiple myeloma patients no correlation was found between the serum VEGF level and percentage of bone marrow plasma cells, serum beta-2-m and monoclonal Ig levels, levels of Hb, albumine and LDH. Median survival time (M-ST) of patients with VEGF higher than 71, 0 pg/ml was 32 months, M-ST of patients with VEGF below 71 pg/ml was 52 months. In summary: serum level of VEGF in advanced state of multiple myeloma was elevated and correlated with clinical state. An elevated serum level of VEGF is associated with a poor prognosis.     

Mortality among different occupational groups of workers with pneumoconiosis: Results from a register-based cohort study

A mortality cohort study was carried out on 11,224 men with pneumoconiosis diagnosed during the period 1970–1985. The cohort was selected from among subjects entered into the National Register of Occupational Diseases and included 7,065 coal miners, 924 employees of underground work enterprises, 1,796 workers of the metallurgical industry and iron and nonferrous foundries, as well as 1,439 refractory materials, china, ceramics, and quarry workers. The cohort was traced up to the end of 1991. The mortality of all groups enrolled in the study, as compared with that of the general male population of Poland, showed a statistically significant excess of overall mortality (SMRs ranging from 105; 95% confidence interval [CI]: 100–110 to 136; CI: 121–153) as well as a great excess of deaths from diseases of the respiratory system (SMRs from 383; 95% CI: 345–424 to 588; 95% CI: 457–744). In workers of the metallurgical industry, foundries, and those from refractory materials, china, and ceramics manufacturing plants as well as quarries, a statistically significant excess of deaths from infectious diseases (mostly tuberculosis) was found (SMRs: 503; 95% CI: 364–677 and 286; 95% CI: 177–437, respectively). Mortality from lung cancer as significantly elevated only in the group of metallurgical industry and iron and nonferrous foundry workers (SMR: 159; 95% CI: 124–201). In the remaining subcohorts, no significant excess of deaths from lung cancer was noted. The study does not support the hypothesis on the role of exposure to crystalline silica in the induction of lung cancer. Significantly lower mortality was seen for diseases of the circulatory system (SMR: 89; 95% CI: 82–96), hypertensive disease (SMR: 63; 95% CI: 38–98), cerebrovascular disease (SMR: 79; 95% CI: 62–99), atherosclerosis (SMR: 79: 95% CI: 66–93), and injuries and poisonings (SMR: 50; 95% CI: 38–64) in coal miners. In addition, lower mortality was noted for cerebrovascular disease (SMR: 56; 95% CI: 32–91) and injuries and poisonings (SMR: 34; 95% CI: 17–61) in metallurgical industry and iron and nonferrous foundry workers. © 1996 Wiley-Liss, Inc.     

Expression of p16INK4a,p15INK4b,p21WAF1/Clip1 cell cycle inhibitors on blastic cells in patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL)

Cyclin-dependent kinases (cdk) play the important role in neoplastic transformation. Their activity depends on interaction with proteins called inhibitors. There are two groups of inhibitors: INK4 (p16INK4a, p15INK4b, p18INK4c, p19INK4d) and proteins p21WAF1/Clip1, p27Kip1, p57Kip2. Alteration of inhibitors expression was assessed in acute lymphoblastic leukemia (ALL) and in acute myeloblastic leukemia (AML), but the results are not clear. The aim of our study was to estimate p16INK4a, p15INK-4b, p21WAF1/Clip1 expression in blast cells in patients with AML and ALL by cytochemistry method and to compare with the result of treatment. Forty-two patients were included in the study, 23 with AML and 19 with ALL. Expression of inhibitors was considered as positive when detected in > 5% of blast cells. Complete remission (CR) rate in patients with positive expression p16INK4a and p15INK4b was statistically significantly higher than in patients with negative expression: for p16INK4a chi 2 = 7.78, p < 0.01, for p15INK4b, chi 2 with Yates' modification = 3.94, p < 0.05. There was no difference in CR rate in patients with positive and negative p21WAF1/Clip1 expression. Moreover the patients with simultaneous expression of three inhibitors reached CR more often than the others: chi 2 = 7.43, p = 0.01 for AML and chi 2 = 6.74, p < 0.01 for ALL. Our study indicates that estimation of p16INK4a, p15INK4b, p21WAF1/Clip1 expression in blast cells can be used as prognostic factor in acute leukemia.     

Assessing Roadside Hybrid Energy Absorbers Using the Example of SafeEnd

A combination of crash cushion and end-terminal, hybrid energy absorbing devices have been in use worldwide for a few years already. They include SafeEnd, a system Poland has recently introduced. Some road authorities have raised concerns as regards the operating conditions of the devices and how they work together with safety barriers. The objective of this research is to clarify the concerns and answer the following questions: (1) Can SafeEnd devices be used as hybrid devices and combine the roles of end-terminal and crash cushion placed before an obstacle? (2) What should be the rules for installing crash cushions at diverging roads and at the start of an off-ramp? The article presents characteristics of SafeEnd devices, defines the doubts raised by road safety auditors, discusses the results of field and numerical tests of the devices and explains the design principles for interchange ramps where crash cushions are required. The study results have helped to answer the research questions: SafeEnd devices fulfil the role of end-terminal and crash cushion, it is possible to make them more visible and principles have been defined for how the devices should be used at road interchanges. Further research should help to define general principles of deploying road restraint systems such as crashworthy terminals, crash cushions or hybrid devices.     

Tubulointerstitial nephritis with uveitis: clinico-pathological and immunological study

A 10-year-old boy was evaluated for fever, weight loss, uveitis, normocytic, normochromic anemia, renal insufficiency, and hypergammaglobulinemia of 8 weeks' duration. Infectious and neoplastic causes of fever were excluded. A renal biopsy performed in the 4th week of disease revealed diffuse plasmocytic interstitial nephritis. No treatment was prescribed and the patient was transferred to another hospital. Because clinical symptoms and renal insufficiency were still present, in the 8th week of disease a second biopsy was performed, which showed lympho-monocytic interstitial nephritis. At the same time, phenotypic analysis of peripheral blood mononuclear cells was carried out, revealing a significantly decreased number of CD3(+), CD4(+), and CD3(+)/CD8(+) cells, increased non-T CD3(-)/CD8(+) and CD56(+) NK cells, and decreased "na?ve" (CD45RA(+)/CD4(+)) and memory (CD45RO(+)/CD8(+)) T lymphocytes. A 6-month course of oral prednisone was prescribed. Clinical symptoms and laboratory findings quickly returned to normal values. After 13 days of corticosteroid therapy, a second phenotypic analysis of peripheral blood mononuclear cells was performed, which revealed normalization of CD3(+), CD4(+), and CD3(+)/CD8(+) cells as well as proportions of non-T CD8(+) and CD56(+) NK lymphocytes, "na?ve" and memory cells. This case shows spontaneous evolution of tubulointerstitial infiltrates from plasmacytic to lympho-monocytic, profound disturbances of the immunological system, and the beneficial effect of corticosteroids on both the clinical course and immunological disturbances.     

Life insurance and its effect on estate taxation

Estate tax laws are subject to constant changes and revisions. Fortunately for most physicians, this ultimate liability has been drastically reduced, but it also has become much more complex. The key is to plan proactively with an understanding of the most current estate tax savings strategies.