Mentor Support Provisions Scale: Measure dimensionality, measurement invariance, and associations with adolescent school functioning.

Mentoring relationships can have important effects on adolescents' psychosocial and academic outcomes; however, the transactions within mentoring relationships that may account for impact on psychosocial and academic outcomes are not well understood. This study investigated the psychometric properties of the Mentor Support Provisions Scale (MSPS), a tool for assessing the types of support that mentors provide. Exploratory factor analyses and confirmatory factor analyses were used to determine measure dimensionality. Findings indicated acceptable fit with a three-factor structure: Academic Support, Intimacy, and Warmth. The MSPS was found to have scalar invariance; thus, factor loadings and intercepts are the same across student sex and ethnic groups (e.g., White, Hispanic, and Black). In structural equation modeling analyses, the three latent factors predicted academic engagement and reading and math achievement, above baseline scores. Research and practical uses of the MSPS are discussed.

Advancing Stage 2 Research on Measures for Monitoring Kindergarten Reading Progress.

Although several measures exist for frequently monitoring early reading progress, little research has specifically investigated their technical properties when administered on a frequent basis with kindergarten students. In this study, kindergarten students ( N = 137) of whom the majority was receiving supplemental intervention for reading skills were monitored using Letter Sound Fluency, Phoneme Segmentation Fluency, Word Reading Fluency, Nonsense Word Fluency, Highly Decodable Passages, and Spelling on a biweekly basis between February and May. Acceptable reliability was observed for all measures. Analyses of slope validity using latent growth models, latent change score models, and slope differences according to level of year-end achievement indicated that the relation of slope to overall reading skills varied across the measures. A suggested approach to kindergarten students' reading progress is offered that includes Letter Sound Fluency and a measure of word-reading skills to provide a comprehensive picture of student growth toward important year-end reading outcomes.

Multi-walled carbon nanotube induced frustrated phagocytosis, cytotoxicity and pro-inflammatory conditions in macrophages are length dependent and greater than that of asbestos.

The potential toxicity of carbon nanotubes (CNTs) has been compared to pathogenic fibres such as asbestos. It is important to test this hypothesis to ascertain safe methods for CNT production, handling and disposal. In this study aspects reported to contribute to CNT toxicity were assessed: length, aspect ratio, iron content and crystallinity; with responses compared to industrially produced MWCNTs and toxicologically relevant materials such as asbestos. The impacts of these particles on a range of macrophage models in vitro were assessed due to the key role of macrophages in particle clearance and particle/fibre-induced disease. Industrially produced and long MWCNTs were cytotoxic to cells, and were potent in inducing pro-inflammatory and pro-fibrotic immune responses. Short CNTs did not induce any cytotoxicity. Frustrated phagocytosis was most evident in response to long CNTs, as was respiratory burst and reduction in phagocytic ability. Short CNTs, metal content and crystallinity had less or no influence on these endpoints, suggesting that many responses were fibre-length dependent. This study demonstrates that CNTs are potentially pathogenic, as they were routinely found to induce detrimental responses in macrophages greater than those induced by asbestos at the same mass-based dose.

Distance learning improves attainment of professional milestones in the early years of surgical training.

OBJECTIVES: To assess the impact of a surgical sciences e-learning programme in supporting the academic development of surgical trainees during their preparation for professional examination. BACKGROUND: In 2007, a 3-year online part-time Master of Surgical Sciences (MSc) degree programme was launched, utilizing an innovative platform with virtual case scenarios based on common surgical conditions addressed by the curriculum relating to the Membership Examination of the Royal Colleges of Surgeons (MRCS). Multiple-choice questions with feedback and discussion boards facilitated by expert clinical tutors provided formative assessment. Summative assessment comprised written examination at the end of each of the first 2 years (equivalent to MRCS level), culminating in submission of a research dissertation in year 3 toward an MSc. METHODS: Students' age, gender, and level at entry to the programme were documented. Anonymized student feedback from 2008 to 2012 was examined using online questionnaires, and performance in the MSc programme was compared to MRCS examination outcomes for students who had consented to release of their results. RESULTS: A total of 517 surgical trainees from 40 countries were recruited over the 6-year period, and 116 MSc students have graduated to date. Of 368 students, 279 (76%) were foundation doctors (interns) and had not commenced formal surgical training on enrolling in the MSc programme. However, level at entry did not influence performance (P > 0.05 across all 3 years). Average pass rates since the programme launched, for those students completing all of the required assessments, were 84% ± 11% in year 1, 85% ± 10% in year 2, and 88% ± 7% in year 3 of the MSc programme. MSc students had significantly higher MRCS pass rates than nonenrolled trainees (67% vs 51%, P < 0.01, n = 352). There was a significant correlation between MRCS examination performance and overall performance in the MSc (R = 58%; P < 0.01, n = 37). Of 248 respondents, 202 (81%) considered that the MSc would improve their chances of gaining a surgical training post, and 224 (90%) would recommend the programme to their peers. CONCLUSIONS: The online MSc programme supports academic development of trainees in the early years of surgical training, is well received by students, and is associated with improved success in their professional examination.

Economic outcomes of exenatide vs liraglutide in type 2 diabetes patients in the United States: results from a retrospective claims database analysis.

OBJECTIVE: The safety and efficacy of the GLP-1 receptor agonists exenatide BID (exenatide) and liraglutide for treating type 2 diabetes mellitus (T2DM) have been established in clinical trials. Effective treatments may lower overall treatment costs. This study examined cost offsets and medication adherence for exenatide vs liraglutide in a large, managed care population in the US. METHODS: This was a retrospective cohort analysis comprising adult patients with T2DM who initiated exenatide or liraglutide between 1/1/2010 and 6/30/2010 and had 6 months pre-index and post-index continuous eligibility. Patients were propensity score-matched to controls for baseline differences. Medication adherence was measured by proportion of days covered (PDC). Paired t-test and McNemar's test were used to compare outcomes. RESULTS: Matched exenatide and liraglutide cohorts (n=1347 pairs) had similar average total 6-month follow-up costs ($6688 vs $7346). However, exenatide patients had significantly lower mean pharmacy costs ($2925 vs $3272, p<0.001). Among liraglutide patients, patients receiving the 1.8 mg dose had significantly higher average total costs compared to those receiving the 1.2 mg dose ($8031 vs $6536, p=0.026), with higher mean pharmacy costs in the 1.8 mg cohort ($3935 vs $3146, p<0.001). There were no significant differences in inpatient or outpatient costs or medication adherence between groups (mean PDC: exenatide 56% vs liraglutide 57%, p=0.088). LIMITATIONS: The study assumed that all information needed for case classification and matching of cohorts was present and not differential across cohorts. The study did not control for covariates that were unavailable, such as HbA1c and duration of diabetes. CONCLUSIONS: Patients initiating exenatide vs liraglutide for T2DM had similar medication adherence and total healthcare costs; however, exenatide patients had significantly lower total pharmacy costs. Patients prescribed 1.8 mg liraglutide had significantly higher costs compared to those on 1.2 mg.

One-year treatment persistence and potential adverse events among patients with atrial fibrillation treated with amiodarone or sotalol: a retrospective claims database analysis.

BACKGROUND: The risk-benefit profile of antiarrhythmic drugs (AADs) affects the choice of pharmacotherapy for maintenance of sinus rhythm. Adverse events (AEs) associated with AADs may influence patient compliance and compromise the management of atrial fibrillation (AF). There are limited data on the incidence of AEs or persistence with AADs outside the clinical trial environment. OBJECTIVE: This study provides treatment persistence and AE data for patients with AF receiving treatment with amiodarone or sotalol, 2 of the most widely used AADs in the United States. METHODS: In this retrospective cohort study, patients satisfying the following criteria were identified from the US MarketScan claims databases: (1) age ≥18 years with a pharmacy claim for oral amiodarone or sotalol between 2004 and 2007; (2) ≥1 inpatient/outpatient medical claim with an AF diagnosis <90 days before the earliest (index) pharmacy claim; and (3) ≥12 months' continuous enrollment before and after the index pharmacy claim. Prespecified AE rates were compared between treatment cohorts during active treatment. RESULTS: Among 77,093 AF patients with ≥1 claim for amiodarone or sotalol, 3459 met all inclusion criteria (mean age, 70.8 years; 61.6% male; mean Charlson Comorbidity Index [CCI], 1.58), of whom 2392 received amiodarone (mean age, 72.2 years; 62.5% male; mean CCI, 1.8) and 1067 received sotalol (mean age, 67.5 years; 59.7% male; mean CCI, 1.1). Persistence was higher among the sotalol cohort than the amiodarone cohort (53.2% vs 30.6% at 12 months; P < 0.001). Postindex versus preindex comparisons revealed increases in cardiovascular AE rates in both cohorts. Intercohort comparisons showed higher rates of cardiovascular AEs (594 vs 339 patients/1000 patient-years; P < 0.001) and pulmonary AEs (128 vs 61 patients/1000 patient-years; P < 0.001) during active amiodarone treatment. CONCLUSIONS: Among the population analyzed, patients with AF receiving amiodarone versus sotalol therapy had differing clinical characteristics. Patients experienced frequent AEs (particularly cardiovascular events) with amiodarone and sotalol, and many discontinued treatment during the first year.

Aerobic fitness is associated with lower proportions of senescent blood T-cells in man.

Senescent T-cells accumulate with age, lowering the naïve T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness (VO(2max)) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61 yr) were analyzed for KLRG1, CD57, CD28, CD45RA, CD45RO surface expression on CD4+ and CD8+ T-cells by 4-color flow cytometry. Advancing age (yr) was positively associated with the proportion (%) of senescent (KLRG1+/CD57+; KLRG1+/CD28-) CD4+ (B=1.00; 1.02) and CD8+ (B=0.429; 1.02) T-cells and inversely associated with naïve (KLRG1-/CD28+) CD4+ (B=-1.000) and CD8+ (B=-0.993) T-cells. VO(2max) was inversely associated with senescent CD4+ (B=-0.97) and CD8+ (B=-0.240). Strikingly, age was no longer associated with the proportions of senescent or naïve T-cells after adjusting for VO(2max), while the association between VO(2max) and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted VO(2max) revealed that the highest tertile had 17% more naïve CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. VO(2max) was not associated with latent cytomegalovirus (CMV), Epstein-Barr virus (EBV) or herpes simplex virus-1 (HSV-1) infection, indicating that the moderating associations of VO(2max) were not confounded by persistent viral infections. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system.

Can adherence to antihypertensive therapy be used to promote adherence to statin therapy?

OBJECTIVE: To compare adherence with statin therapy in patients switching to single-pill amlodipine besylate/atorvastatin calcium with patients adding a separate statin to their amlodipine regimen. METHODS: We identified hypertensive patients prescribed amlodipine who switched to amlodipine/atorvastatin (switch) or added a statin to their amlodipine regimen (add-on) from July 2004 to June 2007. Propensity score matching (1 switch:3 add-on) was applied based on 'nearest neighbor' approach. The primary adherence measure was patients with proportion of days covered (PDC) >/=0.80 at 180 days; secondary measures included mean PDC and persistence. A sensitivity analysis was performed, accounting for total statin/amlodipine exposure. RESULTS: Among 4556 matched patients (n = 1139 switch; n = 3417 add-on), mean age was 53.9 years and 52.1% were male. After 180 days, adherence with statin therapy was higher for the switch vs add-on cohort (50.8% vs 44.3%; P < 0.001). After adjusting for pre-index amlodipine adherence, the switch cohort was more likely to be adherent than the add-on cohort (odds ratio: 1.64 [95% confidence interval: 1.42 to 1.89]). Persistence was higher in the switch than the add-on cohort (127.6 vs 117 days; P < 0.001). CONCLUSION: Hypertensive patients taking amlodipine who initiated statin therapy via single-pill amlodipine/atorvastatin were more likely to remain adherent to their statin than patients adding a separate statin to their antihypertensive regimen.

Cannabinoid CB(1) receptor activation stimulates neurite outgrowth and inhibits capsaicin-induced Ca(2+) influx in an in vitro model of diabetic neuropathy.

Cannabinoid CB(1) receptors mediate, in part, the neuroprotectant properties of endocannabinoids, and altered signalling via the CB(1) receptor may contribute to the pathogenesis of diabetic neuropathy. We investigated CB(1) receptor function in PC12 cells differentiated into a neuronal phenotype with nerve growth factor (NGF, 50 ng/ml) in 5.5 and 50 mM concentrations of glucose. High glucose was associated with impaired NGF-induced neurite outgrowth (P < 0.01; n = 185-218) and reduced expression of CB(1) receptor mRNA (P < 0.01; n = 6) on day 6 of culture. Whilst treatment of hyperglycemic cells with HU210 (0.03-3 microM) increased neurite length in a concentration-dependent manner (P < 0.01; n = 136-218), CB(1) receptor expression was not significantly altered by chronic agonist stimulation (P = 0.32; n = 6 per group). Application of the CB(1) agonist HU210 (1 microM) inhibited capsaicin-induced calcium transients to a similar degree in cells cultured in high glucose (40%) versus normal (43%) (P < 0.05; n = 33-50). HU210-mediated rescue of neurite outgrowth and inhibition of calcium influx was blocked by the selective CB(1) antagonist AM251 (1 microM), but not by the selective CB(2) antagonist AM630 (1 microM), confirming the role of CB(1) receptors. High glucose treatment did not significantly elevate endocannabinoid levels. These results suggest that high glucose concentrations are associated with decreased expression, but preserved function of CB(1) receptors in nerve cells.

Direct medical costs for type 2 diabetes mellitus complications in the US commercial payer setting: a resource for economic research.

BACKGROUND: Medical complications are the key drivers of the direct medical costs of treating patients with type 2 diabetes mellitus. However, the published literature shows great variability across studies in the number and type of sources from which these costs for diabetes are obtained. OBJECTIVE: To provide to researchers a set of costs for type 2 diabetes complications, originally developed for input into an established diabetes model, that are empirically based, clearly and consistently defined and applicable to a large segment of managed care patients in the US. METHODS: Patients with 1 of 24 diabetes-related complications between 1 January 2003 and 31 December 2004 and with evidence of type 2 diabetes were identified using a nationally representative US commercial insurance claims database. Therapy utilization and complication cost data were extracted for all patients for the 12 months following the first identified complication; data for months 13-24 were obtained for a subset of patients with at least 24 months of follow-up enrollment. Medical costs included both the amounts charged by medical providers and the health plan contracted allowed amounts. Costs were expressed as $US, year 2007 values. RESULTS: A total of 44 021 patients with a minimum of 12 months of continuous follow-up enrollment were identified, with a mean age of 56 years; a subset of 32 991 patients with at least 24 months of continuous health-plan enrollment was also identified. Among the aggregate sample, 74% of patients were receiving oral antidiabetics, 26% were receiving insulin, 43% were receiving ACE inhibitors and 50% were receiving antihyperlipidaemics/HMG-CoA reductase inhibitors (statins) during the first 12 months following the index complication. The majority of patients had at least one physician office visit (99.8%), laboratory diagnostic test (96.2%) and other outpatient visit (97.5%). Six complications (angina pectoris, heart failure, peripheral vascular disease, renal disease, nonproliferative retinopathy and neuropathy) had a prevalence of at least 10%. Allowed amounts for most complications were 30-45% of charges. Myocardial infarction, heart failure and renal disease had the greatest fiscal impact because of the total number of patients experiencing them (7.2%, 14.0% and 11.0%, respectively) and their associated costs; 12-month mean allowed amounts were $US 14,853, $US 11,257 and $US 13,876, respectively, and 12-month mean charged amounts were $US 41,695, $US 30, 066 and $US 34,987, respectively. Similarly, in the subset of 32 991 patients, these three complications had higher allowed and charged amounts over months 13-24 compared with the majority of other complications of interest. CONCLUSION: These costing results provide an important resource for economic modelling and other types of costing research related to treating diabetes-related complications within the US managed care system.

Expression of cannabinoid CB1 receptors in models of diabetic neuropathy.

A clearer understanding of the mechanisms underlying the development and progression of diabetic neuropathy is likely to indicate new directions for the treatment of this complication of diabetes. In the present study we investigated the expression of cannabinoid CB(1) receptors in models of diabetic neuropathy. PC12 cells were differentiated into a neuronal phenotype with nerve growth factor (NGF) (50 ng/ml) in varying concentrations of glucose (5.5-50 mM). CB(1) receptor expression was studied at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR) and at the protein level via immunohistochemical and Western blot analysis. CB(1) expression was also compared in dorsal root ganglia (DRG) removed from streptozotocin-induced diabetic rats versus control animals. Total neurite length induced by NGF was reduced in cells cultured in 20 to 50 mM glucose at day 6 (P < 0.01 versus 5.5 mM; n = 6). Cell viability assays conducted in parallel on day 6 confirmed that the total cell numbers were not significantly different among the various glucose concentrations (P = 0.86; n = 12). RT-PCR, immunohistochemical, and Western blot analysis all revealed down-regulation of the CB(1) receptor in cells treated with high glucose (P < 0.05; n = 4-5 for each), and in DRG removed from diabetic rats compared with controls (P < 0.01; n = 5 for immunohistochemistry, and n = 3 for Western blot). These results suggest that high glucose concentrations are associated with decreased expression of CB(1) receptors in nerve cells. Given the neuroprotective effect of cannabinoids, a decline in CB(1) receptor expression may contribute to the neurodegenerative process observed in diabetes.

Perivascular nerves induce cardiorespiratory reflexes in response to algogens in anaesthetised rats.

In the present study we measured cardiovascular and respiratory reflexes evoked by administration of bradykinin and capsaicin into the hindlimb vasculature of anaesthetised rats, whilst simultaneously recording activity of sensory afferents on the adventitial surface of femoral arteries and veins. Bradykinin (0.9 nmol) and capsaicin (0.3 nmol) caused a rapid reflex fall in mean arterial pressure (delta mmHg: -37 +/- 8 and -28 +/- 3, respectively; P < 0.01) and an increase in respiratory minute volume (delta ml min(-1): 180.0 +/- 39.2 and 156.1 +/- 24.5, respectively; P < 0.01), associated with an increase in neural discharge in arterial afferents (from basal 0.4 +/- 0.3 to 8.5 +/- 2.9 impulses s(-1) following intra-arterial administration of bradykinin, P < 0.05, n = 7; from basal 0.2 +/- 0.1 to 7.5 +/- 3.7 impulses s(-1) with capsaicin, P < 0.01, n = 18). The antagonists FR173657 and capsazepine confirmed bradykinin B2 and vanilloid VR1 receptors mediated the responses to bradykinin and capsaicin, respectively. Topical administration of algogen to the vessel surface, and electrical stimulation of the adventitia also evoked cardiovascular and respiratory responses. These data support the hypothesis that stimulation of sensory nerve endings within the hindlimb vasculature contributes to systemic cardiorespiratory reflexes in the rat.

Cannabidiol lacks the vanilloid VR1-mediated vasorespiratory effects of capsaicin and anandamide in anaesthetised rats.

The results of vasorespiratory studies in rats anaesthetised with pentobarbital show that (+/-) cannabidiol, a cannabinoid that lacks psychotropic actions and is inactive at cannabinoid (CB) receptors, does not affect respiration or blood pressure when injected (1-2000 microg; 3.2-6360 nmol i.a.). Cannabidiol in doses up to 2 mg (6360 nmol) i.a. or i.v. did not affect the fall in mean blood pressure or the increase in ventilation (respiratory minute volume) caused by capsaicin and high doses of anandamide, responses that are mediated by activation of vanilloid VR1 (TRPV1) receptors in this species. Similar results were obtained with (-) cannabidiol (30-100 microg i.a.; 95-318 nmol). It has previously been shown using human embryonic kidney (HEK) cells over-expressing vanilloid human VR1 (hVR1) receptors that cannabidiol is a full agonist at vanilloid VR1 receptors in vitro. However, in the intact rat cannabidiol lacked vanilloid VR1 receptor agonist effects. We conclude that there are substantial functional differences between human and rat vanilloid VR1 receptors with respect to the actions of cannabidiol as an agonist at vanilloid VR1 receptors. Studies in vivo show that cannabidiol lacks any significant effect on mean blood pressure or respiratory minute volume when injected i.a. or i.v., and that this cannabinoid does not modulate the vanilloid VR1 receptor-mediated cardiovascular and ventilatory changes reflexly evoked by capsaicin or anandamide in rats anaesthetised with pentobarbital.