Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

Clinical presentation and management of patients with primary hyperparathyroidism of the Swiss Primary Hyperparathyroidism Cohort: a focus on neuro-behavioral and cognitive symptoms.

PURPOSE: To describe the clinical and biochemical profile of patients with primary hyperparathyroidism (PHPT) of the Swiss Hyperparathyroidism Cohort, with a focus on neurobehavioral and cognitive symptoms and on their changes in response to parathyroidectomy. METHODS: From June 2007 to September 2012, 332 patients were enrolled in the Swiss PHPT Cohort Study, a nationwide prospective and non-interventional project collecting clinical, biochemical, and outcome data in newly diagnosed patients. Neuro-behavioral and cognitive status were evaluated annually using the Mini-Mental State Examination, the Hospital Anxiety and Depression Scale, and the Clock Drawing tests. Follow-up data were recorded every 6 months. Patients with parathyroidectomy had one follow-up visit 3-6 months' postoperatively. RESULTS: Symptomatic PHPT was present in 43 % of patients. Among asymptomatic patients, 69 % (131/189) had at least one of the US National Institutes for Health criteria for surgery, leaving thus a small number of patients with cognitive dysfunction or neuropsychological symptoms, but without any other indication for surgery. At baseline, a large proportion showed elevated depression and anxiety scores and cognitive dysfunction, but with no association between biochemical manifestations of the disease and test scores. In the 153 (46 %) patients who underwent parathyroidectomy, we observed an improvement in the Mini-Mental State Examination (P = 0.01), anxiety (P = 0.05) and depression (P = 0.05) scores. CONCLUSION: PHPT patients often present elevated depression and anxiety scores and cognitive dysfunction, but rarely as isolated manifestations. These alterations may be relieved upon treatment by parathyroidectomy.

Excessively high soluble Klotho in patients with acromegaly.

OBJECTIVES: Klotho-deficient mice develop a syndrome resembling accelerated ageing, and genetic variants of Klotho have been associated with human ageing. In humans, serum levels of soluble Klotho decrease with age and with chronic renal failure. The aim of our study was to examine the relationship between excess growth hormone (GH) and serum levels of Klotho in patients with acromegaly, a disease usually caused by a pituitary adenoma, which is associated with high phosphate levels and reduced life expectancy. PATIENTS AND DESIGN: We determined the levels of soluble Klotho, GH and insulin-like growth factor 1 (IGF-1) in serum samples from 24 consecutive patients with acromegaly (nine women/15 men, age 28-76 years) before and after transsphenoidal surgery. RESULTS: Soluble Klotho levels were excessively high at baseline (mean ± SEM, 4.2 ± 0.7 ng mL(-1) ) and correlated with GH (r = 0.64), IGF-1 (r = 0.57) and tumour size (r = 0.5). In multiple regression analysis, soluble Klotho was associated with GH after correction for age, gender and levels of creatinine and phosphate (P = 0.029). After surgery, GH and IGF-1 levels decreased in all patients (from 26.3 ± 5.2 to 2.6 ± 0.6 µg L(-1) , P <0.0001, and from 588 ± 35 to 193 ± 12 µg L(-1) , P < 0.001, 0.0001, respectively). Creatinine increased from 71 ± 3 to 80 ± 3 µmol L(-1) (P < 0.001), and phosphate decreased from 1.37 ± 0.04 to 1.06 ± 0.02 mmol L(-1) (P < 0.001). The markedly increased preoperative levels of soluble Klotho returned towards normal after surgery (0.7 ± 0.1 ng mL(-1) , P < 0.0001). CONCLUSIONS: This is the first study to show dramatically increased soluble Klotho levels in an acquired disease in humans. Reversal following tumour removal suggests a causal relation between the GH-producing adenoma and high serum Klotho concentration in acromegaly.

Cost-effectiveness of insulin glargine versus NPH insulin for the treatment of Type 2 diabetes mellitus, modeling the interaction between hypoglycemia and glycemic control in Switzerland.

OBJECTIVE: The objective of this study was to evaluate the short-term and long-term clinical and economic outcomes associated with insulin glargine or NPH insulin in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with oral anti-diabetic drugs in Switzerland, modeling the interaction between hypoglycemia and glycemic control (HbA1c). METHODS: A validated discrete event simulation model for T2DM was used to predict incidence of short-term complications (symptomatic, nocturnal and severe hypoglycemic events) and long-term complications (microvascular and macrovascular events), life expectancy, quality-adjusted life years (QALYs) and direct medical costs in patients treated with insulin glargine or NPH insulin. The model was populated with published Swiss patient characteristics with T2DM. Baseline risks of hypoglycemic events, utility decrements of diabetes-related long-term complications and the hypoglycemia fear score were derived from the literature. Relative risk reductions of hypoglycemia adjusted for HbA1c using insulin glargine compared with NPH insulin were based on a published negative binomial meta-regression analysis. Costs of severe hypoglycemia, micro- and macrovascular events were analyzed from literature whenever possible otherwise guideline-projected resource-use estimations were valued with Swiss official prices or tariffs in 2006 CHF. Simulations were run with 1,000 patients per cohort over a time horizon of 40 years. Incremental cost effectiveness ratios (ICERs) were presented as cost per QALY and per life year gained (LYG). Future costs and clinical benefits were discounted at 3.5%. Wide-range one-way sensitivity analyses were performed. RESULTS: Insulin glargine was associated with an improvement in quality of life (0.098 QALYs per patient) and additional life expectancy (0.05 life years gained per patient) compared to NPH insulin. Incremental costs of CHF 2,578 resulted in an ICER of CHF 26,271 per QALY and CHF 51,100 per LYG. The cost per QALY was most sensitive to changes in costs, utility decrements and relative risk reductions of hypoglycemia. CONCLUSIONS: This study evaluated, for the first time, the cost effectiveness of insulin glargine versus NPH insulin for the treatment of T2DM considering the interaction between glycemic control and hypoglycemia in Switzerland. The base case and sensitivity analyses demonstrated that insulin glargine proved to be cost-effective with respect to accepted willingness to pay thresholds and therefore represents good value for money.

Randomized controlled trial of bilateral superficial cervical plexus block versus placebo in thyroid surgery.

BACKGROUND: Bilateral superficial cervical block during thyroid surgery can reduce postoperative pain but its value is unclear. This randomized clinical trial assessed the efficacy of such regional anaesthesia on postoperative pain after thyroid surgery performed under general anaesthesia. METHODS: Patients undergoing thyroid surgery were randomized to one of four groups in a double-blind fashion. Patients received a cervical block with placebo or bupivacaine at the start or end of surgery. Postoperative pain, analgesic use and length of hospital stay were assessed. RESULTS: There were 159 patients eligible for analysis. The bupivacaine group had significantly less pain than the placebo group (P = 0.016). The timing of bupivacaine administration did not significantly influence pain (preoperative versus postoperative, P = 0.723). There was no difference between groups in the amount of analgesic used. Length of hospital stay was the same in the bupivacaine and placebo groups (P = 0.925) and when bupivacaine was administered at the beginning or end of surgery (P = 0.087). CONCLUSION: Bilateral superficial cervical block with bupivacaine combined with general anaesthesia significantly reduced postoperative pain after thyroid surgery. REGISTRATION NUMBER: NCT00472446 (http://www.clinicaltrials.gov).

Pleistocene phylogeography and phylogenetic concordance in cold-adapted spring snails (Bythinella spp.).

Previous studies on Pleistocene phylogeography of European taxa are biased towards (i) vertebrates, (ii) terrestrial taxa, (iii) single species, and (iv) taxa that survived the Pleistocene in southern refugia. Relatively little is known about whether evolutionary patterns of vertebrate and terrestrial taxa are also applicable to freshwater invertebrates, whether cold-adapted freshwater species could survive in extensive permafrost areas without retreating into refugia, and whether Pleistocene phylogeographical patterns are influenced by phylogeny. Here, the widespread and species-rich European spring snail genus Bythinella Moquin-Tandon, 1856 is utilized in an attempt to mitigate this bias. These strongly cold-adapted freshwater animals mostly occur in springs--highly isolated habitats that are relatively unaffected by anthropogenic influences. Phylogenetic and phylogeographical analyses based on mitochondrial DNA and nuclear DNA sequence data were conducted in 458 specimens from 142 populations occurring throughout Europe. The study provides evidence that most Bythinella spp. survived the Pleistocene in restricted northern glacial refugia that largely correspond to refugia previously recognized for other European biota. However, survival of Bythinella spp. in extensive permafrost areas outside of refugia can likely be rejected. Low dispersal ability and the isolation and fragmentation of spring habitats, as well as the distribution of perennial springs within permafrost regions, may account for this result. Tests involving a total of 29 nominal species showed that phylogenetically closely related Bythinella species did not occupy similar refugia. This lack of phylogenetic concordance could possibly be explained by the stochasticity of survival and dispersal in spring snails.

Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU).

AIM: To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n >or= 228) or placebo (n = 114) with glimepiride (2-4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes. METHODS: In total, 1041 adults (mean +/- sd), age 56 +/- 10 years, weight 82 +/- 17 kg and glycated haemoglobin (HbA(1c)) 8.4 +/- 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose-lowering mono : combination therapies (30 : 70%) to participate in a five-arm, 26-week, double-dummy, randomized study. RESULTS: Liraglutide (1.2 or 1.8 mg) produced greater reductions in HbA(1c) from baseline, (-1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (-0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (-0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [-2.5 to -2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (-0.4 mmol/l, P < 0.0001, baseline 12.7 mmol/l) or rosiglitazone (-1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (-0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (-0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (< 11%), vomiting (< 5%) and diarrhoea (< 8%). CONCLUSIONS: Liraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.

Exenatide versus insulin glargine: a cost-effectiveness evaluation in patients with Type 2 diabetes in Switzerland.

OBJECTIVES: To investigate the long-term clinical and economic outcomes associated with exenatide versus insulin glargine as "add-on" treatments to oral therapy in individuals with Type 2 diabetes inadequately controlled with combination oral agents in the Swiss setting. METHODS: A computer simulation model of diabetes was used to project complications, life expectancy, quality-adjusted life expectancy and direct medical costs over a 35-year time horizon. Cohort characteristics and treatment effect data were derived from a 26-week randomized clinical trial comparing exenatide and insulin glargine. Modeled treatment effects included reductions in glycosylated hemoglobin (HbA1c) by -0.99% and -1.07% and in body mass index (BMI) by -0.80 and +0.55 kg/m2 with exenatide and insulin glargine respectively. Changes in systolic blood pressure and serum lipid levels were also captured. Simulations incorporated published quality of life utilities and Swiss costs from 2006. Extensive sensitivity analyses were conducted to assess the robustness of projected outcomes. Future clinical and economic outcomes were discounted at 2.5% per annum. RESULTS: In the base-case analysis exenatide was associated with comparable life expectancy (11,549 years versus 11,468 years) and an improvement in quality-adjusted life expectancy of 0.43 quality-adjusted life years (QALYs) versus insulin glargine over a 35-year time horizon. Exenatide was associated with a reduced cumulative incidence of most diabetes-related complications including an absolute reduction in myocardial infarction by 0.28%. Assuming an annual treatment cost of CHF 2,797.74 for exenatide, direct costs increased by CHF 8,378 per patient over the 35-year time horizon compared to insulin glargine. The resultant incremental cost-effectiveness ratio was CHF 19,450 per QALY gained for exenatide versus insulin glargine. CONCLUSIONS: Exenatide was associated with comparable life expectancy and an improvement in quality-adjusted life expectancy versus insulin glargine over a 35-year time horizon. Based on current standards exenatide would be a cost-effective treatment alternative to insulin glargine in Switzerland for Type 2 diabetes patients inadequately controlled on oral therapy.

Shallow phylogeographic structuring of Vimba vimba across Europe suggests two distinct refugia during the last glaciation.

Genetic variation and geographical structuring of vimba Vimba vimba were analysed across 26 sites (80 individuals) by means of mtDNA sequences (cyt b gene, mitochondrial control region) to localize hypothesized glacial refugia and to reconstruct postglacial recoloniation routes. Although genetic diversity among sequenced individuals was low, a combined analysis of the two sequenced fragments revealed a western (central and northern Europe: Danube, Elbe and lakes of Sweden) and an eastern clade (eastern Europe: Dnieper-South Bug, Don, Neman). Furthermore, a number of divergent ancestral haplotypes distributed around the Black and Caspian Seas became apparent. Mismatch analyses supported a sudden expansion model for the populations of the western clade between 50 and 10 000 bp. Overall, the study provides strong evidence for a northward and westward expansion of V. vimba from two refugial regions located in the Danubian drainage and the northern Pontic regions respectively.

[New insights into diagnosis and management of gestational diabetes mellitus: recommendations of the Swiss Society for Endocrinology and Diabetes]. / Neue Erkenntnisse zur Diagnostik und Management des Gestationsdiabetes. Empfehlungen der Schweizerischen Gesellschaft für Endokrinologie und Diabetologie (SGED).

Physiology and current knowledge about gestational diabetes which led to the adoption of new diagnostic criterias and blood glucose target levels during pregnancy by the Swiss Society for Endocrinology and Diabetes are reviewed. The 6th International Workshop Conference on Gestational Diabetes mellitus in Pasedena (2008) defined new diagnostic criteria based on the results of the HAPO-Trial. These criteria were during the ADA congress in New Orleans in 2009 presented. According to the new criteria there is no need for screening, but all pregnant women have to be tested with a 75 g oral glucose tolerance test between the 24th and 28th week of pregnancy. The new diagnostic values are very similar to the ones previously adopted by the ADA with the exception that only one out of three values has to be elevated in order to make the diagnosis of gestational diabetes. Due to this important difference it is very likely that gestational diabetes will be diagnosed more frequently in the future. The diagnostic criteria are: Fasting plasma glucose > or = 5.1 mmol/l, 1-hour value > or = 10.0 mmol/l or 2-hour value > or = 8.5 mmol/l. Based on current knowledge and randomized trials it is much more difficult to define glucose target levels during pregnancy. This difficulty has led to many different recommendations issued by diabetes societies. The Swiss Society of Endocrinology and Diabetes follows the arguments of the International Diabetes Federation (IDF) that self-blood glucose monitoring itself lacks precision and that there are very few randomized trials. Therefore, the target levels have to be easy to remember and might be slightly different in mmol/l or mg/dl. The Swiss Society for Endocrinology and Diabetes adopts the tentative target values of the IDF with fasting plasma glucose values < 5.3 mM and 1- and 2-hour postprandial (after the end of the meal) values of < 8.0 and 7.0 mmol/l, respectively. The last part of these recommendations deals with the therapeutic options during pregnancy (nutrition, physical exercise and pharmaceutical treatment). If despite lifestyle changes the target values are not met, approximately 25 % of patients have to be treated pharmaceutically. Insulin therapy is still the preferred treatment option, but metformin (and as an exception glibenclamide) can be used, if there are major hurdles for the initiation of insulin therapy.

A patient with a "good nose".

We report on a 33-year-old man who underwent an odyssey of doctors for investigation of dysphagia. Eventually, a nasopharyngeal mass was found by several otorhinolaryngologists who repeatedly recommended biopsy or excision, because a polyp or fibroma was assumed on nasal endoscopy and MR imaging. However, we finally diagnosed the nasopharyngeal mass to be an ectopic pituitary gland after thorough clinical (cleft lip and palate) and radiological re-examination. Literally, the patient had a "good nose", since he refused manipulations on the nasopharyngeal tumour and assumably prevented inadvertent hypopituitarism. We conclude that biopsy or excision of nasopharyngeal masses should always be considered carefully, especially in patients with facial anomalies.

Cost-effectiveness and cost-utility of insulin glargine compared with NPH insulin based on a 10-year simulation of long-term complications with the Diabetes Mellitus Model in patients with type 2 diabetes in Switzerland.

OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness of insulin glargine compared with NPH insulin in patients with type 2 diabetes and in whom OAD (oral anti-diabetics) had failed in Switzerland. METHODS: Long-term diabetes outcomes were simulated with the Diabetes Mellitus Model (DMM) over a period of 10 years. The incidences of long-term complications (micro- and macrovascular events) were simulated for 10,000 patients over 10 years for six different scenarios. The scenarios were based on HbA1c reductions observed in clinical trials. For insulin glargine, HbA1c reductions of 0.96% (pessimistic case) and 1.24% (optimistic case) were simulated for three different HbA1c baseline values (10, 9 and 8%). For NPH insulin the HbA1c reduction was assumed to be 0.84%. A cost model and a utility model were developed in order to use the cumulated incidences of the simulations for the calculation of cost and QALYs (quality-adjusted life years). The unit costs of micro- and macrovascular events were assessed on the basis of published literature and guideline-projected resource-use estimations for Switzerland. Disutility values of diabetes-related long-term complications were derived from the literature. Total direct medical costs or QALYs were assessed by a combination of cumulated incidences of each event up to 10 years with the corresponding unit cost per event (in addition to the acquisition cost) or with disutility values per event, respectively. Events, total cost, and QALYs were discounted at 3%. In scenarios where no savings could be shown for insulin glargine, incremental cost-effectiveness ratios were calculated as the incremental cost per event prevented and the cost per QALY gained. RESULTS: Cost comparison demonstrated that insulin glargine is the dominant strategy for the optimistic case scenario starting at a baseline HbA1c value of 10% as savings in the management of complications exceeded the difference in acquisition costs after 8 years of treatment. Optimistic case scenarios for baseline HbA1c values of 9 and 8% achieved costs per QALY gained amounting to CHF 2,853 and CHF 5,711 and costs per event prevented amounting to CHF 2,054 and CHF 4,899, respectively. Pessimistic case scenarios for baseline HbA1c values of 10, 9 and 8% resulted in costs per QALY gained amounting to CHF 40,441, CHF 45,701 and CHF 49,468 and costs per event prevented amounting to CHF 27,742, CHF 32,451 and CHF 41,620, respectively. CONCLUSIONS: This study investigated the long-term health-economic implications of treating type 2 diabetes patients, in whom OAD had failed, with insulin glargine versus NPH insulin in Switzerland. The 10-year simulations demonstrated that the deltaHbA1c reductions of 0.4 and 0.12% achieved with insulin glargine led to a reduction of long-term complications, mortality and associated costs as well as to an improved quality of life. Insulin glargine proved to be cost-effective and represents good to excellent value for money compared to NPH insulin.

National survey on the management of primary hyperparathyroidism by Swiss endocrinologists.

BACKGROUND: From the endocrine surgeon's perspective, it is important to know how endocrinologists manage patients with primary hyperparathyroidism (pHPT). The aim of this survey was to evaluate the preoperative diagnostic workup and referral pattern for parathyroidectomy by Swiss endocrinologists. MATERIALS AND METHODS: The survey was conducted by mailing a questionnaire to all members of the Swiss Society for Endocrinology and Diabetes in spring 2005. RESULTS: The questionnaire was sent back by 68 of 124 endocrinologists (55%). The median annual case volume of patients with pHPT was 6 (range 1-50). The mean fraction of these patients referred for surgery was 59 +/- 24%. This fraction was significantly higher in the German-speaking part of Switzerland than in the French-speaking part (67 +/- 21% vs 51 +/- 27%). When considering surgery for asymptomatic pHPT, 62% of the endocrinologists rely routinely on the recommendations of the NIH consensus conference and 86% on the subsequent guidelines of the workshop in 2002. Sixty-seven percent of the endocrinologists routinely perform localization studies before possible referral for surgical exploration. Typically, they consisted of an ultrasonography of the neck (93%) and a (99m)Tc-MIBI scintigraphy (80%). The impact of the availability of a minimally invasive surgical procedure on the number of patients referred for surgery seems to be considerable. Sixty-one percent of the participants would expand the indication for surgery if the operation could be done by a limited surgical approach. CONCLUSIONS: In a relevant fraction of patients with pHPT, endocrinologists still do not regard curative therapy as mandatory. Surprisingly, there are significant cultural differences concerning referral patterns to surgery between the German-speaking and the French-speaking parts of Switzerland. Minimally invasive procedures seem to lower the threshold for referral for surgical therapy.

Impact of environmental temperature on skin thickness and microvascular blood flow in subjects with and without diabetes.

BACKGROUND: Glucose measurement from different skin areas might be influenced by changes in skin texture due to several environmental confounders. Our study was performed to investigate the effect of changes in ambient temperature on skin thickness and microvascular skin blood flow in subjects with and without diabetes at the lower forearm. METHODS: Thirteen subjects with diabetes and seven without diabetes participated in the study. The investigations were performed in a temperature- and humidity-controlled climatic chamber (EMPA, St. Gallen, Switzerland). Starting at 25 degrees C, the environmental temperature was changed in 4 degrees C steps every 40 min. Skin thickness was measured by an ultrasonic reflection technique, and microcirculation was measured by laser Doppler fluxmetry at the lower forearm. Study participants underwent the entire procedure on up to four separate study trials. RESULTS: Our study revealed a significantly reduced skin thickness (P<0.05) and microvascular blood flow (P<0.05) in patients with diabetes mellitus compared with controls without diabetes during the entire investigation. During declining ambient temperature a significant reduction in skin thickness (with diabetes, -0.09+/-0.13 mm; without diabetes, -0.06+/-0.11 mm; P<0.05) and microvascular blood flow (with diabetes, -41+/-49 arbitrary units; without diabetes, -46+/-51 arbitrary units; P<0.05) could be observed in both groups without significant differences between the two. CONCLUSIONS: Although skin thickness and microvascular skin blood flow at the lower forearm were found to be reduced in patients with diabetes compared with controls without diabetes, both groups revealed comparable dynamics in skin thickness and microvascular blood flow during changes in environmental temperature.

Severe hypernatraemia due to nephrogenic diabetes insipidus - a life-threatening side effect of chronic lithium therapy.

Renal toxicity of long-term lithium therapy is a common problem. Nephrogenic diabetes insipidus is the most frequently encountered complication, but often remains unrecognised because of the rather benign symptoms. We present a patient with long-term lithium therapy who developed life-threatening hypernatraemia due to insufficient oral fluid intake after elective spinal surgery. Careful daily substitution of up to 25 l of hypotonic fluids led to full recovery within 9 days. Nephrogenic diabetes insipidus should always be considered in lithium-treated patients undergoing elective surgery in order to avoid severe hypernatraemia.

Inaccurate self-monitoring of blood glucose readings in patients on chronic ambulatory peritoneal dialysis with icodextrin.

Patients on chronic ambulant peritoneal dialysis (CAPD) are increasingly likely to be treated with a new solution of corn starch-derived glucose polymers called icodextrin. This solution involves a very low carbohydrate absorption leading to a better glycemic control in diabetic patients. However these glucose polymers pass to the blood and are metabolized to oligosaccharids which interfere with blood glucose in distinct capillary glucose analyzers leading to overestimation of glycemia. We assessed the accuracy of glucose measurements with the three most commonly used glucose analyzers compared to venous plasma glucose measurement at our institution in 8 patients (4 patients with type 2 diabetes) on CAPD using icodextrin. Glycemia was measured simultaneously in plasma of venous blood using a reference laboratory method and in capillary blood using Accu-Chek sensor (Rotkreuz, Switzerland) (glucose dehydrogenase method), Glucotrend 2 (Rotkreuz, Switzerland) (glucose-dye-oxyreductase method) and Ascensia elite (Zurich, Switzerland) (glucose oxidase method) glucose analyzers. Only glucose readings with Ascensia elite correspond correctly with venous plasma glucose results (+0.3 mmol/l; n. s.), whereas glycemia was significantly overestimated by Accu-Chek sensor (+4.3 mmol/l; p<0.0001) and Glucotrend 2 glucose analyzers (+3.7 mmol/l; p<0.0001). Thus we conclude that distinct glucose analyzers overestimate real blood glucose concentration and are not suitable for monitoring glycemia in patients on CAPD with icodextrin. On the basis of our results, these patients should use glucose analyzers using glucose oxidase methods. All glucose analyzers should be cross-checked with a laboratory reference method before the application in patients on CAPD with icodextrin is recommended.

Thyrotoxicosis and the cardiovascular system.

Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. Palpitations, caused by sinus tachycardia and occasionally by atrial fibrillation, are the most frequent cardiovascular symptom. As atrial fibrillation may be the only manifestation of thyrotoxicosis, thyroid hormone excess should routinely be excluded in patients with this rhythm disturbance. Heart failure occurs mostly in the presence of underlying heart disease or tachycardia-induced cardiomyopathy in patients with long-standing atrial fibrillation. On occasion, long-standing hyperthyroidism may lead to heart failure even in the absence of concomitant cardiac conditions. Beta-blockers offer symptomatic relief and at the same time slow the ventricular response in patients with atrial fibrillation. Amiodarone, and occasionally iodinated contrast agents, may cause iodine-induced thyrotoxicosis. Clinical suspicion is essential in the diagnosis of amiodarone-induced thyrotoxicosis (AIT), because the antiadrenergic effect of the drug may conceal symptoms. AIT should be considered in any patient on amiodarone in the presence of new-onset or recurrent atrial arrhythmias or unexplained weight loss. Beyond discontinuation of amiodarone, treatment options include propylthiouracil or methimazole, potassium perchlorate, steroids, lithium and, if pharmacological treatment fails, surgery. Amiodarone may potentially be used less frequently in the future since recent studies have shown that this drug is inferior to implantable cardioverter defibrillators in prevention of sudden cardiac death in patients with severe heart failure. In addition, non-iodinated amiodarone analogues are currently in advanced phase of clinical testing.

Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNA(LEU(UUR)) gene mutation.

OBJECTIVE: The effects of glucose, arginine, and glucagon on beta-cell function as well as alpha-cell response to arginine were studied in a family with mitochondrial diabetes. RESEARCH DESIGN AND METHODS: The function of alpha- and beta-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test. RESULTS: The glucose disappearance constant (K(g)) value (mean +/- SEM 0.61 +/- 0.04 vs. 1.1 +/- 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0-10 min, 77.7 +/- 50.7 vs. 1,352.3 +/- 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 +/- 111.4 vs. 1,526.7 +/- 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 +/- 710.8 vs. 1,083.2 +/- 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 +/- 47.5 vs. 90.0 +/- 21.1 pmol/l, P = 0.099). CONCLUSIONS: This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.

Is the current standard of care leading to cost-effective outcomes for patients with type 2 diabetes requiring insulin? A long-term health economic analysis for the UK.

AIMS: The aim of the analysis was to investigate whether insulin intensification, based on the use of intensive insulin regimens as recommended by the current standard of care in routine clinical practice, would be cost-effective for patients with type 2 diabetes in the UK. METHODS: Clinical data were derived from a retrospective analysis of 3185 patients with type 2 diabetes on basal insulin in The Health Improvement Network (THIN) general practice database. In total, 48% (614 patients) intensified insulin therapy, defined by adding bolus or premix insulin to a basal regimen, which was associated with a reduction in HbA1c and an increase in body mass index. Projections of clinical outcomes and costs (2011 GBP) over patients' lifetimes were made using a recently validated type 2 diabetes model. RESULTS: Immediate insulin intensification was associated with improvements in life expectancy, quality-adjusted life expectancy and time to onset of complications versus no intensification or delaying intensification by 2, 4, 6, or 8 years. Direct costs were higher with the insulin intensification strategy (due to the acquisition costs of insulin). Incremental cost-effectiveness ratios for insulin intensification were GBP 32,560, GBP 35,187, GBP 40,006, GBP 48,187 and GBP 55,431 per QALY gained versus delaying intensification 2, 4, 6 and 8 years, and no intensification, respectively. CONCLUSIONS: Although associated with improved clinical outcomes, insulin intensification as practiced in the UK has a relatively high cost per QALY and may not lead to cost-effective outcomes for patients with type 2 diabetes as currently defined by UK cost-effectiveness thresholds.

Acute alcohol administration stimulates baroreceptor discharge in the dog.

It has been shown that alcohol administration causes baroreceptor reflex inhibition. The site of action of alcohol could reside anywhere within the baroreceptor reflex arc. Therefore, the goal of this study was to determine the effects of acute administration of alcohol on carotid sinus baroreceptor discharge characteristics. In pentobarbital-anesthetized dogs, the carotid sinus was isolated and perfused. Single unit baroreceptor discharge was recorded from the carotid sinus nerve along with carotid sinus diameter using sonomicrometry. Carotid sinus pressure-baroreceptor discharge and carotid sinus pressure-diameter curves were constructed. Perfusion of the carotid sinus with alcohol (100 mmol/L) significantly decreased the pressure threshold from 91.1 +/- 2.8 to 86.4 +/- 2.9 mm Hg (p < 0.05) and increased the peak discharge rate from 45.8 +/- 3.4 to 52.8 +/- 3.6 spikes per second (p < 0.01). The same phenomenon was seen during perfusion of the carotid sinus with acetaldehyde (2.5 mmol/L) but was not seen during perfusion with acetate (2.5 mmol/L). During perfusion of the carotid sinus with alcohol, the carotid sinus pressure-carotid sinus diameter relation did not change. The baroreceptor sensitization induced by alcohol is not an endothelium-dependent mechanism, because endothelial denudation did not block this alcohol-induced effect. Measurement of the duration of postexcitatory depression of carotid sinus baroreceptors, which is related to Na+,K(+)-ATPase activity, showed that perfusion of the carotid sinus with alcohol or acetaldehyde significantly reduced the duration of postexcitatory depression, indicating that the alcohol- and acetaldehyde-induced effect on baroreceptor discharge is most likely mediated by an inhibition of Na+,K(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)