The new COSMIN guidelines confront traditional concepts of responsiveness

The recently published "COSMIN" guidelines aim to rate properties of outcome instruments and state two issues with regard to responsiveness which is the instrument's ability to detect change over time. These issues are comparison of score changes with change of an external criterion using correlations and the judgement of traditional methods as inappropriate. The latter are the "transition" concept, a global rating of change, and parametric measures of responsiveness, for example, effect sizes. It can be shown that the methodology proposed by the guidelines has important weaknesses and that denunciation of traditional methods is not appropriate. Some claims of the guidelines about responsiveness do not match the demands of clinical reality and confront findings of numerous epidemiological studies

Effects of canagliflozin on myocardial infarction:a post hoc analysis of the CANVAS Program and CREDENCE trial

AIMS: Given the benefits of sodium glucose co-transporter 2 inhibition (SGLT2i) in protecting against heart failure in diabetic patients, we sought to explore the potential impact of SGLT2i on the clinical features of patients presenting with myocardial infarction (MI) through a post-hoc analysis of CANVAS Program and CREDENCE trial.METHODS AND RESULTS: Individuals with type 2 diabetes and history or high risk of cardiovascular disease (CANVAS Program) or type 2 diabetes and chronic kidney disease (CREDENCE) were included. The intervention was Canagliflozin 100 or 300 mg (combined in the analysis) or placebo. MI events were adjudicated as ST-elevation myocardial infarction (STEMI), non-STEMI as well as type 1 MI or type 2 MI. 421 first MI events in the CANVAS Program and 178 first MI events in the CREDENCE trial were recorded (83 fatal, 128 STEMI, 431 non-STEMI, and 40 unknown). No benefit of canagliflozin compared with placebo on time to first MI event was observed (HR 0.89; 95% CI 0.75, 1.05). Canagliflozin was associated with lower risk for non-STEMI (HR 0.78; 95% CI 0.65, 0.95) but suggested a possible increase in STEMI (HR 1.55; 95% CI 1.06, 2.27), with no difference in risk of type 1 or type 2 MI. There was no change in fatal MI (HR 1.22, 95% CI 0.78, 1.93).CONCLUSIONS: Canagliflozin was not associated with a reduction in overall MI in the pooled CANVAS Program and CREDENCE trial population. The possible differential effect on STEMI and Non-STEMI observed in the CANVAS cohort warrants further investigation.</p

On the Lx-L6micron ratio as a diagnostic for Compton-thick AGN

As the mid-IR luminosity represents a good isotropic proxy of the AGN power, a low X-ray to mid-IR luminosity ratio is often claimed to be a reliable indicator for selecting Compton-thick (CT) AGN. We assess the efficiency of this diagnostic by examining the 12mu IRAS AGN sample for which high signal-to-noise XMM observations have been recently become available. We find that the vast majority (10/11) of the AGN that have been classified as CT on the basis the X-ray spectroscopy by Brightman & Nandra present a low Lx/L6 luminosity ratio, i.e. lower than a few percent of the average AGN ratio which is typical of reflection-dominated CT sources. At low Lx/L6 ratios we also find a comparable number of AGN, most of which are heavily absorbed but not CT. This implies that although most Compton-thick AGN present low Lx/L6 ratios, at least in the local, Universe, the opposite is not necessarily true. Next, we extend our analysis to higher redshifts. We perform the same analysis in the CDFS where excellent quality chandra (4 Ms) and xmm (3 Ms) X-ray spectra are available. We derive accurate X-ray luminosities for chandra sources using X-ray spectral fits, as well as 6mu luminosities from SED fits. We find 8 AGN with low Lx/L6 ratios in total, after excluding one source where the 6mu emission primarily comes from star-formation. One of these sources has been already demonstrated to host a CT nucleus, while for another one at a redshift of z=1.22 we argue it is most likely CT on the basis of its combined chandra and xmm spectrum. We find a large number of non CT contaminant with low Lx/L6 ratios. The above suggest that a low Lx/L6 ratio alone cannot ascertain the presence of a CT AGN, albeit the majority of low Lx/L6 AGN are heavily obscured. The two most reliable CT AGN in the high redshift Universe have high Lx/L6 ratios, showing that this method cannot provide complete CT AGN samples.Comment: 11 pages, to appear to A&

Osteoid osteoma of the femur in a 7-month-old infant treated with radiofrequency ablation

Osteoid osteoma occurs most commonly in children, adolescents, and young adults between the ages of 5 and 30 years. In the preschool age group, it is quite uncommon, accounting for only 3–8% of all osteoid osteoma cases. We report a case of osteoid osteoma in a 7-month-old infant, who presented with decreased use of the right lower extremity due to pain. Magnetic resonance imaging (MRI) showed an atypical appearance. A biopsy of the lesion, with histopathological examination, confirmed the diagnosis of osteoid osteoma. Radiofrequency ablation (RFA) of the nidus under computed tomography (CT) guidance was performed. The patient developed a recurrence after 3 months, which was treated with a second RFA. On subsequent follow-up, the infant did not show signs of pain after 1 month. In summary, this case report shows that osteoid osteoma can present in early infancy and can be successfully treated with RFA at this age, however, recurrence after the procedure can occur and close follow-up is recommended

Longitudinal study of the diagnosis of components of the metabolic syndrome in individuals with binge-eating disorder

Background: Binge-eating disorder may represent a risk factor for the metabolic syndrome

Synergistic inhibition of prostate cancer cell lines by a 19- nor hexafluoride vitamin D3 analogue and anti-activator protein 1 retinoid

The secosteroid hormones, all- trans- and 9- cis -retinoic acid and vitamin D3, have demonstrated significant capacity to control proliferation in itro of many solid tumour cell lines. Cooperative synergistic effects by these two ligands have been reported, and it is, therefore, possible that greater therapeutic effects could be achieved if these compounds were administered together. The role of retinoid-dependent anti-activator protein 1 (anti-AP-1) effects in controlling cancer cell proliferation appears significant. We have utilized an anti- AP-1 retinoid [2-(4,4-dimethyl-3,4-dihydro-2H-1 benzopyran-6-yl)carbonyl-2-(4-carboxyphenyl)-1,3,-dithiane; SR11238], which does not transactivate through a retinoic acid response element (RARE), and a potent vitamin D3analogue [1α,25(OH)2-16-ene-23-yne-26,27-F6-19-nor -D3, code name LH] together at low, physiologically safer doses against a panel of prostate cancer cell lines that represent progressively more transformed phenotypes. The LNCaP (least transformed) and PC-3 (intermediately transformed) cell lines were synergistically inhibited in their clonal growth by the combination of LH and SR11238, whereas SR11238 alone was essentially inactive. DU-145 cells (most transformed) were completely insensitive to these analogues. LNCaP cells, but neither PC-3 nor DU-145, underwent apoptosis in the presence of LH and SR11238. Transactivation of the human osteocalcin vitamin D response element (VDRE) by LH was not enhanced in the presence of SR11238, although the expression of E-cadherin in these cells was additively up-regulated in the presence of both compounds. These data suggest the anti-AP-1 retinoid and the vitamin D3 analogue may naturally act synergistically to control cell proliferation, a process that is interrupted during transformation, and that this combination may form the basis for treatment of some androgen-independent prostate cancer. © 1999 Cancer Research Campaig

System Dynamics to Model the Unintended Consequences of Denying Payment for Venous Thromboembolism after Total Knee Arthroplasty

Background: The Hospital Acquired Condition Strategy (HACS) denies payment for venous thromboembolism (VTE) after total knee arthroplasty (TKA). The intention is to reduce complications and associated costs, while improving the quality of care by mandating VTE prophylaxis. We applied a system dynamics model to estimate the impact of HACS on VTE rates, and potential unintended consequences such as increased rates of bleeding and infection and decreased access for patients who might benefit from TKA. Methods and Findings: The system dynamics model uses a series of patient stocks including the number needing TKA, deemed ineligible, receiving TKA, and harmed due to surgical complication. The flow of patients between stocks is determined by a series of causal elements such as rates of exclusion, surgery and complications. The number of patients harmed due to VTE, bleeding or exclusion were modeled by year by comparing patient stocks that results in scenarios with and without HACS. The percentage of TKA patients experiencing VTE decreased approximately 3-fold with HACS. This decrease in VTE was offset by an increased rate of bleeding and infection. Moreover, results from the model suggest HACS could exclude 1.5% or half a million patients who might benefit from knee replacement through 2020. Conclusion: System dynamics modeling indicates HACS will have the intended consequence of reducing VTE rates. However, an unintended consequence of the policy might be increased potential harm resulting from over administration of prophylaxis, as well as exclusion of a large population of patients who might benefit from TKA

Improving hypertension management through pharmacist prescribing; the rural alberta clinical trial in optimizing hypertension (Rural RxACTION): trial design and methods

<p>Abstract</p> <p>Background</p> <p>Patients with hypertension continue to have less than optimal blood pressure control, with nearly one in five Canadian adults having hypertension. Pharmacist prescribing is gaining favor as a potential clinically efficacious and cost-effective means to improve both access and quality of care. With Alberta being the first province in Canada to have independent prescribing by pharmacists, it offers a unique opportunity to evaluate outcomes in patients who are prescribed antihypertensive therapy by pharmacists.</p> <p>Methods</p> <p>The study is a randomized controlled trial of enhanced pharmacist care, with the unit of randomization being the patient. Participants will be randomized to enhanced pharmacist care (patient identification, assessment, education, close follow-up, and prescribing/titration of antihypertensive medications) or usual care. Participants are patients in rural Alberta with undiagnosed/uncontrolled blood pressure, as defined by the Canadian Hypertension Education Program. The primary outcome is the change in systolic blood pressure between baseline and 24 weeks in the enhanced-care versus usual-care arms. There are also three substudies running in conjunction with the project examining different remuneration models, investigating patient knowledge, and assessing health-resource utilization amongst patients in each group.</p> <p>Discussion</p> <p>To date, one-third of the required sample size has been recruited. There are 15 communities and 17 pharmacists actively screening, recruiting, and following patients. This study will provide high-level evidence regarding pharmacist prescribing.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00878566">NCT00878566</a>.</p

Meta-Analysis of the Reasoned Action Approach (RAA) to Understanding Health Behaviors

YesBackground: Reasoned action approach (RAA) includes subcomponents of attitude (experiential/instrumental), perceived norm (injunctive/descriptive), and perceived behavioral control (capacity/autonomy) to predict intention and behavior. Purpose: To provide a meta-analysis of the RAA for health behaviors focusing on comparing the pairs of RAA subcomponents and differences between health protection and health-risk behaviors. Methods: The present research reports a meta-analysis of correlational tests of RAA subcomponents, examination of moderators, and combined effects of subcomponents on intention and behavior. Regressions were used to predict intention and behavior based on data from studies measuring all variables. Results: Capacity and experiential attitude had large, and other constructs had small-medium-sized correlations with intention; all constructs except autonomy were significant independent predictors of intention in regressions. Intention, capacity, and experiential attitude had medium-large, and other constructs had small-medium-sized correlations with behavior; intention, capacity, experiential attitude, and descriptive norm were significant independent predictors of behavior in regressions. Conclusions: The RAA subcomponents have utility in predicting and understanding health behaviors

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin