A randomised crossover trial of minimising medical terminology in secondary care correspondence in patients with chronic health conditions: impact on understanding and patient reported outcomes.

BACKGROUND: There is little existing research on the role that secondary care letters have in ensuring patient understanding of chronic health conditions. AIM: To determine whether minimising the use of medical terminology in medical correspondence improved patient understanding and anxiety/depression scores. METHODS: A single-centre, non-blinded, randomised crossover design assessed health literacy, EQ-5D scores and the impact of the 'translated' letter on the doctor's professionalism, the patient's relationship with their general practitioner (GP) and their perceived impact on chronic disease management. Patients were crossed over between their 'translated' and original letter. RESULTS: Sixty patients were recruited. Use of a 'translated' letter reduced mean terms not understood from 7.78 to 1.76 (t(58) = 4.706, P < 0.001). Most patients (78.0%) preferred the 'translated' letter, with 69.5% patients perceiving an enhancement in their doctor's professionalism (z = 2.864, P = 0.004), 69.0% reporting a positive influence on relationship with their GP (z = 2.943, P = 0.003) and 79.7% reporting an increase in perceived ability to manage their chronic health condition with the 'translated' letter (z = 4.601, P < 0.001). There was no effect on EQ-5D depression/anxiety scores. CONCLUSION: Minimising the use of medical terminology in medical correspondence significantly improved patient understanding and perception of their ability to manage their chronic health condition. Although there was no impact on EQ-5D depression/anxiety scores, overwhelming patient preference for the 'translated' letter indicates a need for minimisation of medical terminology in medical correspondence for patients with chronic health conditions.

A unified gene catalog for the laboratory mouse reference genome.

We report here a semi-automated process by which mouse genome feature predictions and curated annotations (i.e., genes, pseudogenes, functional RNAs, etc.) from Ensembl, NCBI and Vertebrate Genome Annotation database (Vega) are reconciled with the genome features in the Mouse Genome Informatics (MGI) database (http://www.informatics.jax.org) into a comprehensive and non-redundant catalog. Our gene unification method employs an algorithm (fjoin--feature join) for efficient detection of genome coordinate overlaps among features represented in two annotation data sets. Following the analysis with fjoin, genome features are binned into six possible categories (1:1, 1:0, 0:1, 1:n, n:1, n:m) based on coordinate overlaps. These categories are subsequently prioritized for assessment of annotation equivalencies and differences. The version of the unified catalog reported here contains more than 59,000 entries, including 22,599 protein-coding coding genes, 12,455 pseudogenes, and 24,007 other feature types (e.g., microRNAs, lincRNAs, etc.). More than 23,000 of the entries in the MGI gene catalog have equivalent gene models in the annotation files obtained from NCBI, Vega, and Ensembl. 12,719 of the features are unique to NCBI relative to Ensembl/Vega; 11,957 are unique to Ensembl/Vega relative to NCBI, and 3095 are unique to MGI. More than 4000 genome features fall into categories that require manual inspection to resolve structural differences in the gene models from different annotation sources. Using the MGI unified gene catalog, researchers can easily generate a comprehensive report of mouse genome features from a single source and compare the details of gene and transcript structure using MGI's mouse genome browser.

20 THz broadband generation using semi-insulating GaAs interdigitated photoconductive antennas.

We demonstrate broadband (20 THz), high electric field, terahertz generation using large area interdigitated antennas fabricated on semi-insulating GaAs. The bandwidth is characterized as a function of incident pulse duration (15-35 fs) and pump energy (2-30 nJ). Broadband spectroscopy of PTFE is shown. Numerical Drude-Lorentz simulations of the generated THz pulses are performed as a function of the excitation pulse duration, showing good agreement with the experimental data.

Dietary fatty acid enrichment increases egg size and quality of yellow seahorse Hippocampus kuda.

Seahorses populations in the wild have been declining and to restore them a better knowledge of seahorse reproduction is required. This study examines the effect of dietary quality on seahorse fecundity and egg quality. Two different diets were tested with Hippocampus kuda females: frozen mysis (control) and frozen mysis enriched with a liposome spray containing essential fatty acids. Diets were given to females (two groups of five) over a seven week period. After this period, males (fed the control diet) and females were paired and the eggs dropped by the females were collected. Fatty acid profile were analysed and eggs were counted and measured. Results showed that females fed on enriched mysis had larger eggs and that these had a higher content of total polyunsaturated fatty acids. The size of the egg was especially affected in the first spawn, where egg size for females fed the enriched diet was significantly higher than the egg size from control females. This effect was reduced in the following spawning where no significant differences were found. Egg size is an important quality descriptor as seahorse juveniles originating from smaller eggs and/or eggs of poor quality will have less chances of overcoming adverse conditions in the wild and consequently have lower survival and growth rates. This study shows that enriching frozen mysis with polyunsaturated fatty acids increases egg size and egg quality of H. kuda.

Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study.

OBJECTIVE: Liraglutide, a once-daily human glucagon-like peptide-1 analog, induced clinically meaningful weight loss in a phase 2 study in obese individuals without diabetes. The present randomized phase 3 trial assessed the efficacy of liraglutide in maintaining weight loss achieved with a low-calorie diet (LCD). METHODS: Obese/overweight participants (≥18 years, body mass index ≥30 kg m(-2) or ≥27 kg m(-2) with comorbidities) who lost ≥5% of initial weight during a LCD run-in were randomly assigned to liraglutide 3.0 mg per day or placebo (subcutaneous administration) for 56 weeks. Diet and exercise counseling were provided throughout the trial. Co-primary end points were percentage weight change from randomization, the proportion of participants that maintained the initial ≥5% weight loss, and the proportion that lost ≥5% of randomization weight (intention-to-treat analysis). ClinicalTrials.gov identifier: NCT00781937. RESULTS: Participants (n=422) lost a mean 6.0% (s.d. 0.9) of screening weight during run-in. From randomization to week 56, weight decreased an additional mean 6.2% (s.d. 7.3) with liraglutide and 0.2% (s.d. 7.0) with placebo (estimated difference -6.1% (95% class intervals -7.5 to -4.6), P<0.0001). More participants receiving liraglutide (81.4%) maintained the ≥5% run-in weight loss, compared with those receiving placebo (48.9%) (estimated odds ratio 4.8 (3.0; 7.7), P<0.0001), and 50.5% versus 21.8% of participants lost ≥5% of randomization weight (estimated odds ratio 3.9 (2.4; 6.1), P<0.0001). Liraglutide produced small but statistically significant improvements in several cardiometabolic risk factors compared with placebo. Gastrointestinal (GI) disorders were reported more frequently with liraglutide than placebo, but most events were transient, and mild or moderate in severity. CONCLUSION: Liraglutide, with diet and exercise, maintained weight loss achieved by caloric restriction and induced further weight loss over 56 weeks. Improvements in some cardiovascular disease-risk factors were also observed. Liraglutide, prescribed as 3.0 mg per day, holds promise for improving the maintenance of lost weight.

Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes.

AIMS: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years. METHODS: Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia. RESULTS: For patients completing 2 years of therapy, HbA1c reductions were -0.6% with glimepiride versus -0.9% with liraglutide 1.2 mg (difference: -0.37, 95% CI: -0.71 to -0.02; p = 0.0376) and -1.1% with liraglutide 1.8 mg (difference: -0.55, 95% CI: -0.88 to -0.21; p = 0.0016). In the ITT population, HbA1c reductions were -0.3% with glimepiride versus -0.6% with liraglutide 1.2 mg (difference: -0.31, 95% CI: -0.54 to -0.08; p = 0.0076) and -0.9% with liraglutide 1.8 mg (difference: -0.60, 95% CI: -0.83 to -0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001). CONCLUSION: Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.

Outcomes from chemoradiotherapy for patients with esophageal cancer.

Chemoradiotherapy is a widely used alternative treatment to surgical resection in certain patient groups with early esophageal cancer. The aim of this study was to retrospectively assess toxicity and outcome of patients treated with definitive chemoradiotherapy for early esophageal cancer at one institution. A retrospective analysis of all patients treated with chemoradiotherapy between February 2000 and December 2008 at a single tertiary center was performed with documentation of treatment given, toxicities recorded, and follow-up and outcome data. Sixty-two patients received chemoradiotherapy for esophageal cancer. There were 20 males and 42 female patients with an average age of 68 years. Histology revealed adenocarcinoma in 28 patients and squamous cell carcinoma in 34 patients. All patients were staged with a computerized tomography scan, endoscopic ultrasound and positron emission tomography scan. Selection criteria for chemoradiotherapy were unfit for surgery, upper esophageal squamous carcinoma, unresectable primary tumor, or patient choice. The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 55 Gy in 25 fractions of radiotherapy. Grade 3 toxicities were recorded in 11% of the patients. Eleven patients suffered from local recurrence and a stent was required in nine patients. Radiation strictures occurred in 10 patients requiring dilation in four. Five patients required a radiologically inserted feeding gastrostomy. The median overall survival was 21 months. Patients with adenocarcinomas and those with squamous cell carcinoma had a similar median survival. Overall survival was 70% at 1 year, 48% at 2 years, and 26% at 3 years. This case series of patients treated with chemoradiation for localized esophageal cancer suggest a generally well-tolerated treatment with survival rates after chemoradiotherapy comparable with those seen with surgery.

Coherent nonlinear optical response of graphene.

We investigate the nonlinear optical properties of graphene flakes using four-wave mixing. The corresponding third-order optical susceptibility is found to be remarkably large and only weakly dependent on the wavelength in the near-infrared frequency range. The magnitude of the response is in good agreement with our calculations based on the nonlinear quantum response theory.

Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes.

AIM: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well-being and overall quality of life in type 2 diabetes, we investigated whether liraglutide treatment could improve these factors. METHODS: Seven hundred and thirty-two patients with type 2 diabetes completed a 77-item questionnaire during a randomized, 52-week, double-blind study with liraglutide 1.2 mg (n = 245) or 1.8 mg (n = 242) compared with glimepiride 8 mg (n = 245). RESULTS: Mean (SE) decreases in glycated haemoglobin levels were greater with liraglutide 1.2 mg [-0.84 (0.08)%] and 1.8 mg [-1.14 (0.08)%] than glimepiride [-0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on liraglutide [1.2 mg: -2.05 (0.28) kg; 1.8 mg: -2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331-0.696]. Mean (SE) weight concerns were less with liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41-0.73). Mean (SE) mental and emotional health and general perceived health improved more with liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively]. CONCLUSIONS: Improved glycaemic control and decreased weight with liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well-being and health perceptions by reducing anxiety and worry associated with weight gain.

Evaluation of a local optometric diabetic retinopathy screening service.

AIMS: To determine the sensitivity and specificity for sight-threatening eye disease (STED) of the diabetic retinopathy screening scheme for Stockport during the period 1 April 2000 to 31 March 2001. METHODS: A random sample of screen-negative patients was recalled for further assessment by consultant ophthalmologists. Screen-positive patients, who were referred, were tracked through the hospital system to determine the outcome. RESULTS: In a 12-month period, 3510 individuals with diabetes were screened, which is 1.2% of the district population. Sensitivity for STED was 75.8%[95% confidence interval (CI) 49.3, 99.99] and specificity for STED was 99.0% (95% CI 98.6, 99.3). CONCLUSIONS: The current screening arrangements in Stockport are satisfactory in terms of sensitivity and specificity. Population coverage was 1.2% over 12 months and 1.5% over 15 months and needs to be improved. An integrated computerized register requires further development.

Combination therapy for type 2 diabetes: repaglinide plus rosiglitazone.

AIMS: This 24-week, randomized, multicentre, open-label, parallel-group clinical trial compared efficacy and safety of repaglinide monotherapy, rosiglitazone monotherapy, and combination therapy (repaglinide plus rosiglitazone) in Type 2 diabetes after unsatisfactory response to sulphonylurea or metformin monotherapy. METHODS: Enrolled patients (n = 252) were adults having Type 2 diabetes for at least 1 year, with HbA(1c) values > 7.0% after previous monotherapy (sulphonylurea or metformin, >/= 50% maximal dose). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, rosiglitazone, or repaglinide/rosiglitazone. Study treatments were initiated with a 12-week dose optimization period (doses optimized according to labelling), followed by a 12-week maintenance period. Efficacy endpoints were changes in HbA(1c) values (primary) or fasting plasma glucose values (secondary). RESULTS: Baseline HbA(1c) values were comparable (9.3% for repaglinide, 9.0% for rosiglitazone, 9.1% for combination). Mean changes in HbA(1c) values at the end of treatment were greater for repaglinide/rosiglitazone therapy (-1.43%) than for repaglinide (-0.17%) or rosiglitazone (-0.56%) monotherapy. Reductions of fasting plasma glucose values were also greater for combination therapy (-5.2 mmol/l, -94 mg/dl) than for repaglinide monotherapy (-3.0 mmol/l, -54 mg/dl) or rosiglitazone monotherapy (-3.7 mmol/l, -67 mg/dl). Minor hypoglycaemic events occurred in 9% of combination therapy patients, vs. 6% for repaglinide and 2% for rosiglitazone. Individual weight gains for combination therapy were correlated to HbA(1c) response. CONCLUSIONS: The combination therapy regimen was well tolerated. In patients previously showing unsatisfactory response to oral monotherapy, glycaemic reductions were greater for the repaglinide/rosiglitazone combination regimen than for use of either repaglinide or rosiglitazone alone.

The proteasome participates in degradation of mutant alpha 1-antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes.

Because retention of mutant alpha(1)-antitrypsin (alpha(1)-AT) Z in the endoplasmic reticulum (ER) is associated with liver disease in alpha(1)-AT-deficient individuals, the mechanism by which this aggregated glycoprotein is degraded has received considerable attention. In previous studies using stable transfected human fibroblast cell lines and a cell-free microsomal translocation system, we found evidence for involvement of the proteasome in degradation of alpha(1)-ATZ (Qu, D., Teckman, J. H., Omura, S., and Perlmutter, D. H. (1996) J. Biol. Chem. 271, 22791-22795). In more recent studies, Cabral et al. (Cabral, C. M., Choudhury, P., Liu, Y., and Sifers, R. N. (2000) J. Biol. Chem. 275, 25015-25022) found that degradation of alpha(1)-ATZ in a stable transfected murine hepatoma cell line was inhibited by tyrosine phosphatase inhibitors, but not by the proteasomal inhibitor lactacystin and concluded that the proteasome was only involved in ER degradation of alpha(1)-ATZ in nonhepatocytic cell types or in cell types with levels of alpha(1)-AT expression that are substantial lower than that which occurs in hepatocytes. To examine this important issue in further detail, in this study we established rat and murine hepatoma cell lines with constitutive and inducible expression of alpha(1)-ATZ. In each of these cell lines degradation of alpha(1)-ATZ was inhibited by lactacystin, MG132, epoxomicin, and clasto-lactacystin beta-lactone. Using the inducible expression system to regulate the relative level of alpha(1)-ATZ expression, we found that lactacystin had a similar inhibitory effect on degradation of alpha(1)-ATZ at high and low levels of alpha(1)-AT expression. Although there is substantial evidence that other mechanisms contribute to ER degradation of alpha(1)-ATZ, the data reported here indicate that the proteasome plays an important role in many cell types including hepatocytes.

Assessment of growth by primary health care providers.

INTRODUCTION: Precise measurements of children are critical for accurate growth assessment. Many children are referred to endocrine practices in error because heights are obtained but plotted on length growth charts, giving the appearance that growth has decelerated. METHOD: In an attempt to evaluate growth assessment in primary care practices (PCPs), we instituted a telephone survey to gather the following data: (a) how often children are measured, (b) the criteria for whether children are measured standing or lying, (c) the methods for measuring children, and (d) whether measurements are plotted on growth charts and by whom. RESULTS: In PCPs, children were reported to be measured at every visit or only at well child visits. The criteria most frequently used to determine when children should be measured standing was "if they can stand, they are measured standing." Significantly more pediatric practices than family practices measured children standing at the correct age. Heights were most often obtained on a scale with a floppy arm. All but 4 practices reported that measurements on growth charts were plotted by the nurse or physician. DISCUSSION: Many practices had an incorrect policy related to obtaining measurements of length versus height. Children are measured with the correct equipment in only 22% of PCPs for height and 12% of PCPs for length. Most PCPs are diligent about plotting growth data. Clearly, education of personnel in PCPs is crucial so that accurate growth measurements can be obtained, necessary referrals can be made, and unnecessary referrals can be avoided.

Risk factors for cardiovascular disease in children with Type I diabetes.

BACKGROUND: The major cause of morbidity and mortality in individuals with Type I insulin-dependent diabetes mellitus (IDDM) is premature and extensive atherosclerotic cardiovascular disease (CVD). OBJECTIVES: To determine the prevalence and predictors of hypercholesterolemia and to examine the distribution and interrelationship of risk factors for CVD. METHODS: This observational (mixed-longitudinal) study, guided by an epidemiologic framework, assessed a sample of 140 children with IDDM. Total cholesterol (TC) and diabetes control were measured in the total sample. Standard CVD risk factors were measured in a subsample of 67 children. RESULTS: Observed frequency of TC greater than the 75th percentile and greater than the 95th percentile was significantly more than expected (p < 0.01 and p < 0.0001, respectively). In the total sample, TC-CVD risk factor associations were not observed. However, diabetes control and physical activity were correlated with TC in the risk sample of children at highest risk, as demonstrated by hypercholesterolemia. CONCLUSIONS: Results demonstrate the importance of assessing the lipid profile in children with IDDM and monitoring CVD risk factors in hyperlipidemic children with IDDM. Future research should focus on prospective longitudinal studies in population-based multiethnic samples of children with IDDM.