Comparison of the three-level and the five-level versions of the EQ-5D

The European Journal of Health Economics - EQ-5D is a generic instrument to measure health-related quality of life. In 2009, a new version, EQ-5D-5L, was introduced as an attempt to reduce ceiling...     

Airway management by paramedics using endotracheal intubation with a laryngoscope versus the oesophageal tracheal Combitube and EasyTube on manikins: a randomised experimental trial

INTRODUCTION: The EasyTube, which is constructed in a similar way to the Combitube, is a recently introduced alternative to tracheal intubation for airway management in emergency medicine. OBJECTIVE: To determine if there is a difference in rate of, and time to, successful airway placement and ventilation using tracheal intubation, Combitube and EasyTube. METHODS: Twenty-six paramedics, trained in tracheal intubation received additional training in the use of the Combitube and the EasyTube. Each participant performed all three methods twice in random order on a manikin. Time to successful ventilation (presented as mean and standard deviation) and success rate were recorded. RESULTS: Mean time to successful ventilation was significantly longer for tracheal intubation (45.2 s (S.D.=15.8)) than for the Combitube (36.0 s (S.D. = 8.6)) p = 0.002 and the EasyTube (38.0 s (S.D.=15.3)) p = 0.023 with no difference between the latter (p = 1.000). Success rate for the Combitube and EasyTube combined (103/104) was significantly higher than for tracheal intubation (45/52) with odds ratio 16.0 (95% CI: 1.9-134); p = 0.002. CONCLUSION: For paramedics tested on manikins placement success rate was higher with less time required for the Combitube and Easytube than for tracheal intubation with no differences between the Combitube and EasyTube.     

Use of sedation for routine diagnostic upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members

BACKGROUND/AIMS: Sedation rates may vary among countries, depending on patients' and endoscopists' preferences. The aim of this survey was to investigate the rate of using premedication for routine diagnostic upper gastrointestinal (UGI) endoscopy in endoscopy societies, members of the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We evaluated a multiple-choice questionnaire which was e-mailed to representatives of national endoscopy societies, which are members of the ESGE. The questionnaire had 14 items referring to endoscopy practices in each country and the representatives' endoscopy units. RESULTS: The response rate was 76% (34/45). In 47% of the countries, less than 25% of patients undergo routine diagnostic UGI endoscopy with conscious sedation. In 62% of the responders' endoscopy units, patients are not asked their preference for sedation and do not sign a consent form (59%). Common sedatives in use are midazolam (82%), diazepam (38%) or propofol (47%). Monitoring equipment is not available 'in most of the endoscopy units' in 46% (13/28) of the countries. Though they were available in 91% of the national representatives' endoscopy units, they are rarely (21%) used to monitor unsedated routine diagnostic UGI endoscopy. CONCLUSIONS: In about 50% of ESGE-related countries, less than 25% of patients are sedated for routine diagnostic UGI endoscopy. Major issues to improve include availability of monitoring equipment and the use of a consent form.     

Differential effects of age on large artery stiffness and minimal vascular resistance in normotensive and mildly hypertensive individuals

Large artery stiffness and small artery structural changes are both cardiovascular risk factors. Arterial stiffness increases with age and blood pressure (BP), but it is unclear in which way large artery pulse wave velocity (PWV) and peripheral vascular resistance are related and whether age has any influence. In a cross‐sectional study, PWV and forearm minimum vascular resistance (R_min) was compared with emphasis on the impact of age. Normotensive (n = 53) and untreated hypertensive (n = 23) subjects were included based on 24‐h BP measurements. Age ranged from 21 to 79 years with an even distribution from each age decade. PWV was assessed using tonometry. Forearm R_min was measured by venous occlusion plethysmography at maximal vasodilatation induced by 10 min of ischaemia in combination with skin heating and hand grip exercise. In both normotensive and hypertensive subjects, PWV correlated significantly with age and BP. Based on median age, both groups were assigned into two equally large subgroups. Normotensive older (66 ± 7 years) and younger (35 ± 10 years) persons had different carotid‐femoral PWV (7·9 ± 1·8 versus 5·7 ± 0·9 m/s, P<0·01), but similar R_min values (3·7 ± 0·9 versus 3·6 ± 1·2 mmHg/ml/min/100 ml). Hypertensive older (63 ± 6 years) and younger (40 ± 10 years) also had different PWV (8·0 ± 1·5 versus 6·7 ± 1·1 m/s, P<0·05), but the older had lower R_min (3·1 ± 0·8 versus 4·7 ± 2·2 mmHg/ml/min/100 ml, P<0·05). In a regression analysis adjusting for age, BP, gender and heart rate, no correlation was seen between PWV and R_min. The data suggest that age differentially affects PWV and R_min and that BP can increase in older persons without affecting R_min.     

Urinary excretion of alpha-GST and albumin in rheumatoid arthritis patients treated with methotrexate or other DMARDs alone or in combination with NSAIDs

OBJECTIVE: To evaluate the effect of methotrexate (MTX) and other disease-modifying anti-rheumatic drugs (DMARDs) alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the urinary excretion of alpha-glutathione S-transferase (alpha-GST) and albumin in rheumatoid arthritis (RA) patients. METHODS: Nineteen RA patients starting treatment with MTX were followed for 1 year with measurements of urinary alpha-GST, urinary albumin, and urinary and plasma creatinine at the start of treatment, and after 16, 28, and 52 weeks. A larger group of RA patients (n = 72) undergoing long-term treatment with different DMARDs was compared with 79 healthy controls regarding urinary alpha-GST and albumin. alpha-GST was quantified by an enzyme immunoassay. Urine albumin was measured turbidimetrically. RESULTS: The urine-alpha-GST/urine-creatinine ratio and the urine-albumin/urine-creatinine ratio did not change during 52 weeks of treatment with MTX. The long-term DMARD-treated RA patients and the healthy controls were comparable with regard to the urine-alpha-GST/urine-creatinine ratio and the urine-albumin/urine-creatinine ratio. All patients had preserved renal function as assessed by plasma creatinine, and none had proteinuria using urine dipstick methods. CONCLUSION: DMARD-treated RA patients with normal serum creatinine had no detectable renal injuries assessed by the urinary excretions of alpha-GST and albumin.     

Widespread dispersion of adeno-associated virus serotype 1 and adeno-associated virus serotype 6 vectors in the rat central nervous system and in human glioblastoma multiforme xenografts

The transduction patterns of recombinant adeno-associated virus serotype 1 (AAV1) and serotype 6 (AAV6) vectors were assessed in human glioblastoma multiforme (GBM) cell lines, in human GBM biopsy spheroids, and in tumor xenografts growing in nude rat brains. All the cell lines tested (A172, D37, GaMg, HF66, and U373Mg) were found to be permissive to both AAV1 and AAV6 vectors, and thus displayed a transduction pattern similar to AAV2 vectors. For every cell line tested, the transduction efficiency displayed by AAV2 vectors was better than by isogenic and isopromoter AAV1 vectors. Transduction efficiency was dependent on the viral particle number used, suggesting that the receptors for these vectors are widely distributed in GBM tissues. Interestingly, AAV1, AAV2, and AAV6 vectors were able to infect and transduce the same cells when added simultaneously to monolayer cultures. Infection of human GBM biopsy spheroids with AAV1 and AAV6 vectors resulted in transgene expression both at the surface layers and in the core of the spheroids. Following injection of AAV1 and AAV6 vectors into human GBM biopsy xenografts growing in nude rat brains, reporter gene expression was seen both in the periphery as well as in the central regions of the tumors. When injected into the normal rat brain, both AAV1 and AAV6 vectors were found to transduce several central nervous system (CNS) regions. The presented results suggest a potential therapeutic role for AAV1 and AAV6 vectors in gene therapy for GBM and also for other CNS malignancies.     

Diabetic ketoacidosis in Denmark Incidence and mortality estimated from public health registries

The aims of this study were to estimate incidence of diabetic ketoacidosis and mortality from diabetic ketoacidosis using data from public health registries. Four thousand eight hundred and seven admissions in the period 1996-2002 and 137 deaths in the period 1996-2000 with a diagnosis of diabetic ketoacidosis were identified from the Danish National Patient Registry and Danish Cause of Death Registry, respectively. Annual incidence of diabetic ketoacidosis in the general population was estimated to 12.9 per 100,000, being higher in males than in females (14.4 versus 11.4 per 100,000, p<0.0001). Twelve percent of all patients were classified as Type 2 diabetes, predominantly in patients >50 years. Overall mortality was 4%, being higher in patients >70 years than in patients < or =70 years (15% versus 2%, p<0.0001). One or more additional somatic diagnoses were stated on 77% of the death certificates, most often a diagnosis of cardiovascular (47%) or infectious (30%) diseases. Compared to previous studies, the incidence in the general population seems to have remained unaltered the past 25 years, but may have decreased in younger patients. Older patients with diabetic ketoacidosis differed from younger patients in having a higher mortality and a larger proportion of patients classified as Type 2 diabetes.     

Valine pyrrolidide preserves intact glucose-dependent insulinotropic peptide and improves abnormal glucose tolerance in minipigs with reduced beta-cell mass

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation. However, both incretin hormones are rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV). The concept of DPPIV inhibition as a treatment for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced beta-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)-treated minipig, using the DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg). VP did not significantly affect levels of intact GLP-1 but increased levels of intact GIP (from 4543 +/- 1880 to 9208 +/- 3267 pM x min; P <.01), thus improving glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 +/- 480 to 1582 +/- 353 mM x min; P =.05). VP did not increase insulin levels during the oral glucose tolerance test (OGTT) but increased the insulinogenic index in normal animals (from 83 +/- 42 to 192 +/- 108; P <.05), but not after NIA + STZ, possibly because of less residual insulin secretory capacity in these animals. GIP seems to contribute to the antihyperglycemic effect of VP in this model; however, additional mechanisms for the effect of DPPIV inhibition cannot be excluded. The authors conclude that DPPIV inhibitors may be useful to treat type 2 diabetes, even when this is due to reduced beta-cell mass.     

Gene therapy-mediated delivery of targeted cytotoxins for glioma therapeutics

Restricting the cytotoxicity of anticancer agents by targeting receptors exclusively expressed on tumor cells is critical when treating infiltrative brain tumors such as glioblastoma multiforme (GBM). GBMs express an IL-13 receptor (IL13Rα2) that differs from the physiological IL4R/IL13R receptor. We developed a regulatable adenoviral vector (Ad.mhIL-4.TRE.mhIL-13-PE) encoding a mutated human IL-13 fused to Pseudomonas exotoxin (mhIL-13-PE) that specifically binds to IL13Rα2 to provide sustained expression, effective anti-GBM cytotoxicity, and minimal neurotoxicity. The therapeutic Ad also encodes mutated human IL-4 that binds to the physiological IL4R/IL13R without interacting with IL13Rα2, thus inhibiting potential binding of mhIL-13-PE to normal brain cells. Using intracranial GBM xenografts and syngeneic mouse models, we tested the Ad.mhIL-4.TRE.mhIL-13-PE and two protein formulations, hIL-13-PE used in clinical trials (Cintredekin Besudotox) and a second-generation mhIL-13-PE. Cintredekin Besudotox doubled median survival without eliciting long-term survival and caused severe neurotoxicity; mhIL-13-PE led to ～40% long-term survival, eliciting severe neurological toxicity at the high dose tested. In contrast, Ad-mediated delivery of mhIL-13-PE led to tumor regression and long-term survival in over 70% of the animals, without causing apparent neurotoxicity. Although Cintredekin Besudotox was originally developed to target GBM, when tested in a phase III trial it failed to achieve clinical endpoints and revealed neurotoxicity. Limitations of Cintredekin Besudotox include its short half-life, which demanded frequent or continued administration, and binding to IL4R/IL13R, present in normal brain cells. These shortcomings were overcome by our therapeutic Ad, thus representing a significant advance in the development of targeted therapeutics for GBM.