Mobile health (mHealth) based medication adherence measurement - a pilot trial using electronic blisters in diabetes patients.

AIMS: The aim of the present study was to evaluate a mobile health (mHealth) based remote medication adherence measurement system (mAMS) in elderly patients with increased cardiovascular risk treated for diabetes, high cholesterol and hypertension. Cardiovascular risk was defined as the presence of at least two out of the three risk factors: type 2 diabetes, hypercholesterolaemia and hypertension. METHODS: For treatment of diabetes, hypercholesterolaemia and hypertension, four predefined routinely used drugs were selected. Drug adherence was investigated in a controlled randomized doctor blinded study with crossover design. The mAMS was used to measure and improve objectively the adherence by means of closed-loop interactions. RESULTS: The mean age of the 53 patients (30 female) was 69.4 ± 4.8 years. A total of 1654 electronic blisters were handed out. A statistically significant difference (P = 0.04) between the monitoring and the control phase was observed for the diabetes medication only. In a post-study questionnaire twenty-nine patients appreciated that their physician knew if and when they had taken their medications and 13 asked for more or automated communication with their physicians. Only one subject withdrew from the study because of technical complexity. CONCLUSIONS: The results indicate that mHealth based adherence management is feasible and well accepted by patients with increased cardiovascular risk. It may help to increase adherence, even in patients with high baseline adherence and, subsequently, lead to improved control of indicators including blood pressure and cholesterol concentrations. Electronic blisters can be used in a multi-medication regimen but need to be carefully designed for day-to-day application.

Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS).

BACKGROUND: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes.Review questions;1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes?2. Can the data from each study be adjusted for a consistent set of adjustment factors?3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? METHODS: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained.We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. DISCUSSION: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines.

CobraPLUS and Cookgas air-Q versus Fastrach for blind endotracheal intubation: a randomised controlled trial.

BACKGROUND AND OBJECTIVE: CobraPLUS and Cookgas air-Q are supraglottic airways expected to allow safe ventilation as well as reliable blind intubation. In a prospective, controlled trial, we hypothesised that quality of ventilation and success rate of blind endotracheal intubation of these new devices would be superior to the Fastrach intubating laryngeal mask airway (ILMA). When blind intubation failed the quality of fibrescope-guided intubation was investigated. To allow identification of those patients in whom blind intubation would be difficult, we investigated the predictive value of currently used predictors for ease of endotracheal intubation. METHODS: One hundred and eighty adult patients with documented BMI, Mallampati score, Cormack-Lehane classification, interincisor gap and thyromental distance were randomised into three groups according to the device used. Ventilation conditions were rated as excellent, good or difficult. When blind intubation failed, fibrescope-guided intubation conditions were rated as well. Statistical analysis was performed by a χ-test. RESULTS: The quality of ventilation was excellent for all devices. Three patients in the CobraPLUS group and two patients in the ILMA and the Cookgas groups needed a slight reposition. Blind intubation through the CPLA was successful in 47%, through the Cookgas in 57%, whereas the Fastrach group had a success rate of 95%. Fibreoptic intubation was possible in all but one patient. None of the registered scores and measures allowed prediction of difficult blind intubation. CONCLUSION: All devices appeared to be safe airways. The Fastrach ILMA proved to be a reliable facilitator for blind intubation. CobraPLUS and Cookgas air-Q allowed an easy fibrescopic intubation. Failed blind intubations could not be predicted by the used parameters.

Adipokines in type 1 diabetes after successful pancreas transplantation: normal visfatin and retinol-binding-protein-4, but increased total adiponectin fasting concentrations.

OBJECTIVE: In type 1 diabetes mellitus (T1DM), the release of many hormones, not only from beta-cells, but also from adipocytes (adipokines) may be altered. After successful pancreas-kidney-transplantation (PKTx), T1DM patients can revert to a nondiabetic metabolism, but it is unclear whether alterations of adipokines are still present after PKTx. DESIGN, PATIENTS AND MEASUREMENTS: Concentrations of adipokines [visfatin, retinol-binding protein-4 (RBP-4), adiponectin, high molecular weight (HMW) adiponectin] were measured at fasting in 10 PKTx and in 19 T1DM. Nondiabetic healthy controls (CON, n = 9) and six nondiabetic patients after kidney transplantation (KTx) were examined as control groups. In PKTx, KTx and CON, indices of insulin sensitivity (OGIS) and beta cell function (adaptation index, AI) were calculated from 75 g oral glucose tolerance test (OGTT) data. RESULTS: Fasting serum visfatin (T1DM: 56 +/- 4 microg/l, PKTx: 42 +/- 6 microg/l, KTx: 39 +/- 3 microg/l, CON: 40 +/- 3 microg/l) and RBP-4 (T1DM: 490 +/- 26 microg/l, PKTx: 346 +/- 39 microg/l, KTx: 401 +/- 13 microg/l, CON: 359 +/- 36 microg/l) was increased by 40% and 36%, respectively (each P < 0.03) in T1DM only. Levels were positively correlated with HbA1c in all subjects (visfatin: r = 0.43, P < 0.004; RBP-4: r = 0.46, P < 0.03). Fasting plasma adiponectin was 80% higher in T1DM and in PKTx (T1DM: 18 +/- 2 mg/l, PKTx: 18 +/- 3 mg/l, KTx: 12 +/- 3 mg/l, CON: 10 +/- 1 mg/l; P < 0.04) and was positively correlated with diabetes duration (r = 0.37, P < 0.02). HMW/total adiponectin ratio was increased in T1DM (P < 0.02). PKTx displayed a normoglycaemic metabolism as insulin sensitive as CON, but AI was lower than in CON and KT (P < 0.01). CONCLUSIONS: T1DM after successful PKTx show normal fasting visfatin and RBP-4 levels and HMW-adiponectin/adiponectin-ratio, which are elevated in T1DM, whereas total adiponectin levels are similarly increased in T1DM and PKTx patients.

[Detection of adverse events using IHI Global Trigger Tool during the adoption of a risk management system: A retrospective study over three years at a department for cardiovascular surgery in Vienna]. / Detektion unerwünschter Ereignisse mittels IHI Global Trigger Tool im Kontext der Einführung eines Risikomanagement-Systems: Eine retrospektive Studie über einen Zeitraum von 3 Jahren an der Herz- und Gefäßchirurgischen Abteilung eines Wiener Schwerpunktkrankenhauses.

BACKGROUND: Several studies point in the direction that the Global Trigger Tool for Measuring Adverse Events (GTT) published by the Institute for Healthcare Improvement (IHI) is an appropriate method to detect adverse events with high specificity, sufficient sensitivity and adequate interrater and intrarater reliability. After passing a certain training period, rating teams in healthcare institutions can successfully detect and reliably compare adverse event rates on local and national levels. To date there exist no published relevant data specifically for departments of cardiovascular surgery. METHODS: In this single-center, retrospective study adverse event rates were detected using GTT for a department of cardiovascular surgery in a Viennese hospital. Having begun to establish a risk management system in the year 2008, 120 case histories were rated by a trained team for the years 2009 and 2012 each (240 in total). RESULTS: From 2009 to 2012 the detection rate for adverse events improved significantly from 21.1 to 42.8 events per 1,000 patient days. This change was in agreement with an improvement in the detection rate of adverse events per 100 hospital admissions (from 43.7 to 80.0) as well as an improvement in the detection rate of the proportion of patients suffering from adverse events (from 24.4 % to 42.5 %). CONCLUSION: In the course of the introduction and continuous optimization of a risk management system, the detection rate of adverse events, as measured with GTT, could be brought up to international standards. Thus, the utility of GTT as a possible instrument to help increase patient safety and improve quality could also be established at a department of cardiovascular surgery.

Increased plasma amylin in type 1 diabetic patients after kidney and pancreas transplantation: A sign of impaired beta-cell function?

OBJECTIVE: In response to hyperglycemia, beta-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all beta-cell hormones. RESEARCH DESIGN AND METHODS: Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, beta-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 +/- 1 kg/m2, 47 +/- 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 +/- 1 kg/m2, 50 +/- 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 +/- 1 kg/m2, 47 +/- 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT). RESULTS: PKT patients had higher fasting amylin (19 +/- 3 vs. control subjects: 7 +/- 1 pmol/l) and insulin (20 +/- 2 vs. control subjects: 10 +/- 1 microU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9-31% higher (P < 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P < 0.05). OGIS was not significantly different between groups. beta-Cell sensitivity to glucose was reduced in PKT patients (-64%, P < 0.009). Fasting plasma amylin was inversely associated with beta-cell sensitivity to glucose (r = -0.543, P < 0.004). CONCLUSIONS: After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired beta-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired beta-cell function in type 1 diabetic patients after PKT.

The prevalence of symptoms of sensorimotor and autonomic neuropathy in Type 1 and Type 2 diabetic subjects.

The aim of this study was to analyze the prevalence and severity of sensorimotor and autonomic neuropathic symptoms within an outpatients diabetic population. A total of 350 consecutive Type 1 (26.9%) and Type 2 diabetic subjects were investigated using the Michigan Neuropathy Screening Instrument (MNSI). The original questionnaire was extended with questions on autonomic neuropathy and to include a six-point scale to rate the severity of symptoms, which were recorded accurately in order to avoid overrating. More than one half of Type 2 and nearly a third of Type 1 diabetic subjects suffer from at least one neuropathic symptom; the former suffered significantly more often from paresthesia (P<.05) and burning pain (P=.05). Less than 10% of the study population had autonomic symptoms. The prevalence of symptomatic polyneuropathy (PNP), diagnosed by an abnormal MNSI together with the presence of any symptom, was 16.0% in Type 1 and 37.5% (P<.001) in Type 2 diabetic subjects. Subjects with an abnormal ankle reflex (54.6%) had in 48.2% any sensorimotor, in 35.1% any autonomic, and in 25.7% any sensorimotor plus autonomic symptoms. The corresponding percentages for subjects with an abnormal vibration perception threshold (VPT; 28.9%) were 59.4%, 46.5%, and 34.7%, respectively. An abnormal ankle reflex was significantly correlated to numbness, and to the the sum of sensorimotor and autonomic symptoms. An abnormal vibration perception was significantly correlated to numbness, to paresthesia pain, and to the sum of sensorimotor and autonomic symptoms. A higher percentage of Type 2 diabetic subjects had symptoms of neuropathy and the most frequent symptoms were numbness, muscle cramps and postural hypotension.

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans.

Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 +/- 2 yr, BMI = 25.5 +/- 0.9 kg/m(2)) and low (IR; n = 18, 12 females and 6 males, age 45 +/- 2 yr, P = 0.49, BMI = 27.5 +/- 1.1 kg/m(2), P = 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU.min(-1).m(-2)) isoglycemic clamp tests. M(100-120 min) was higher in IS (10.7 +/- 0.7) than in IR (4.4 +/- 0.2 mg.min(-1).kg(-1), P < 10(-9)), whereas insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71 +/- 6% vs. IS: 82 +/- 5%, P < 0.02). In both groups, plasma ghrelin concentrations were comparable at fasting and similarly reduced by 24-28% during insulin infusion. IR had lower fasting plasma obestatin levels (383 +/- 26 pg/ml vs. IS: 469 +/- 23 pg/ml, P < 0.02). Clamp insulin infusion reduced plasma obestatin to approximately 81% of basal values in IS (P < 0.00002), but not in IR. Fasting plasma obestatin was correlated positively with M (r = 0.34, P = 0.04), HDL cholesterol (r = 0.45, P = 0.01), and plasma ghrelin concentrations (r = 0.80, P < 0.000001) and negatively with measures of adiposity, plasma FFA during clamp (r = -0.42, P < 0.01), and systolic blood pressure (r = -0.33, P < 0.05). In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance and are positively associated with whole body insulin sensitivity in nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulin-resistant persons.

Crucial aspects of smoking in wound healing after breast reduction surgery.

BACKGROUND: The aim of this study was to investigate the influence of cigarette smoking on wound-healing in patients undergoing breast reduction. METHODS: In our prospective study, 50 patients (25 smokers, 25 nonsmokers) scheduled for breast reduction have been evaluated. Urine cotinine levels were measured to analyse perioperative smoking habits. Urine samples were taken preoperatively and on the fourth postoperative day. Cotinine as a metabolite of nicotine allows precise evaluation of nicotine exposure. To assess the progress of woundhealing we classified secreting, instable, inflamed or necrotic wound conditions, which required a dressing after the tenth postoperative day as impaired wound healing. For statistical analysis non-parametrical tests for independent and dependent data were used. RESULTS: Ten of 25 smokers presented impaired wound healing compared to 4 of 25 nonsmokers. The median cotinine level of smokers was 1964 (783/3963)ng/cc preoperatively and 432 (148/1695)ng/cc postoperatively. Nonsmokers had a preoperative cotinine level of 18 (7/37)ng/cc and 15 (4/34)ng/cc postoperatively. Smokers who developed impaired wound-healing showed higher levels of cotinine pre- (2117 ng/cc) and especially postoperatively (485 ng/cc) compared to smokers with regular woundhealing (1614 ng/cc and 389 ng/cc). Both differences in cotinine levels were statistically significant (p=0.03 and p=0.02). CONCLUSIONS: The data of the present study confirm the negative effect of smoking on wound healing in patients undergoing breast reduction.

The Clamp-Like Index: a novel and highly sensitive insulin sensitivity index to calculate hyperinsulinemic clamp glucose infusion rates from oral glucose tolerance tests in nondiabetic subjects.

OBJECTIVE: Insulin resistance, the underlying pathophysiological mechanism of the metabolic syndrome, can not only predict type 2 diabetes development but also cardiovascular disease. Thus, precise insulin resistance measurement in individuals at risk for metabolic diseases would support clinical risk stratification. However, the gold standard for measuring insulin resistance, the hyperinsulinemic clamp test, is too labor intensive to be performed in large clinical studies/settings. RESEARCH DESIGN AND METHODS: Using plasma glucose and C-peptide concentrations from oral glucose tolerance tests (OGTTs), we developed the novel "clamp-like index" (CLIX) for insulin sensitivity calculation and compared CLIX to clamp glucose infusion rates (GIR) (100-120 min). We evaluated CLIX in 89 nondiabetic subjects (58 female and 31 male, aged 45 +/- 1 years, BMI 27.5 +/- 0.8 kg/m(2)) who underwent frequently sampled 3-h 75-g OGTTs and 2-h hyperinsulinemic-isoglycemic clamp (40 mU/min per m(2)) tests. RESULTS: CLIX, calculated as serum creatinine (x0.85 if male)/(mean AUC(glucose) x mean AUC(C-peptide)) x 6,600, was highly correlated (r = 0.670, P < 10(-12)) with and comparable to clamp GIRs(100-120 min). In subgroup analyses, GIRs(100-120 min) were lower (P < 0.005) in type 2 diabetic offspring (6.2 +/- 0.7 mg x min(-1) x kg(-1)) than in sex-, age-, and BMI-matched subjects without a family history of type 2 diabetes (8.6 +/- 0.5 mg x min(-1) x kg(-1)), which was also reflected by CLIX (insulin-resistant offspring 6.4 +/- 0.6 vs. those without a family history of type 2 diabetes 9.0 +/- 0.5; P < 0.002). When compared with normal-weight subjects (GIR 8.8 +/- 0.4 mg x min(-1) x kg(-1); CLIX 9.0 +/- 0.5), both GIRs(100-120 min) and CLIX of obese (5.2 +/- 0.9 mg x min (-1) x kg(-1); 5.7 +/- 0.9) and morbidly obese (2.4 +/- 0.4 mg x min (-1) x kg(-1); 3.3 +/- 0.5) humans were lower (each P < 0.02). CONCLUSIONS: CLIX, a novel index obtained from plasma OGTT glucose and C-peptide levels and serum creatinine, without inclusion of anthropometrical measures to calculate insulin sensitivity in nondiabetic humans, highly correlates with clamp GIRs and reveals even slight insulin sensitivity alterations over a broad BMI range and is as sensitive as the hyperinsulinemic clamp test.

[Diabetic foot syndrome]. / Das diabetische Fusssyndrom.

The diabetic foot syndrome (DFS) is an important diabetic complication. The typical lesion is a neuropathic plantar foot ulcer which heals well when treated properly. However, complications resulting from deep infections of soft tissue or bone, together with a reduced peripheral blood flow, may necessitate amputation of the lower limbs. In general, diabetic patients have a 10-fold higher risk for amputation than non-diabetic subjects and also a poorer long-time prognosis than the latter. The target of a 50% reduction of lower limb amputations in diabetic patients, given by the St. Vincent Declaration for Europe in 1990, has not been achieved. The prevention as well as treatment of DFS have to be improved in order to achieve this target. The feet of diabetic patients must be inspected regularly and the patients must be educated appropriately. Detailed information on avoidable risk factors and the availability of protective footwear are essential for the prevention of DFS. An increasing number of ischemic diabetic subjects undergo vascular reconstruction, which yields good results. On account of the multifactorial etiology of DFS, a multidisciplinary approach is required to resolve the problem. In addition to a diabetologist, the team should include a plastic and vascular surgeon, a neurologist, a radiologist and an orthopedist.