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Mohammadhossein Hajiebrahimi,1,2 Marie Linder,1 David Hägg,1 Ina Anveden Berglind,1 Sean McElligott,3 Valgard Sverrir Valgardsson,4 Reginald Villacorta,3 Anders Sundström1 1Center for Pharmacoepidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 2Statistics and Epidemiology Unit, Health Faculty, Golestan University of Medical Sciences, Gorgan, Iran; 3Janssen Research and Development, LLC, Horsham, PA, USA; 4Janssen-Cilag AS, Oslo, Norway Background: Association between psoriasis severity and cerebro- and cardiovascular comorbidities has rarely been investigated. Aim: We aimed to investigate differences in cerebro- and cardiovascular comorbidities by psoriasis severity. Materials and methods: Using Swedish nationwide health-care registers, new adult users of anti-psoriatic drugs (2007–2013) with a recorded diagnosis of psoriasis/psoriatic arthritis or a filled prescription for calcipotriol were included. Psoriasis severity was based on the type of anti-psoriatic treatment (topical/mild, non-biologic systemic/moderate-to-severe, and biologics/severe). Age standardized prevalence rates of cerebro- and cardiovascular comorbidities and their risk factors were compared between the groups. Results: We found that severe psoriasis patients (N=2147) were younger than moderate-to-severe (N=11,919) or mild (N=70,796) patients (median 44, 52, and 55 years). Prevalence of hypertension was 29.9%, 32.6%, and 36.5%, myocardial infarction was 2.5%, 2.3%, and 1.8%, and stroke was 2.4%, 2.2%, and 1.1% in mild, moderate-to-severe, and severe psoriasis patients, respectively. Diabetes prevalence was 7.6% in mild, 8.0% in moderate-to-severe, and 10.7% in severe psoriasis. Conclusion: Myocardial infarction and stroke were less common in patients with severe psoriasis while, despite being younger, they had a higher prevalence of diabetes and hypertension. Keywords: psoriasis, severity, cardiovascular, cerebrovascular, prevalence

An evaluation is presented of the precision of sea-water composition analysis, focusing on the use of spectrophotometric pH(T) measurements. Different methodologies and the results they produce are discussed.

Background: Prior studies of the Medicare Part D coverage gap are limited in generalizability and scope. Objective: To determine the effect of the coverage gap on drugs used for asymptomatic (antihypertensive and lipid-lowering drugs) and symptomatic (pain relievers, acid suppressants, and antidepressants) conditions in elderly patients with hypertension and hyperlipidemia. Design: Quasi-experimental study using pre-post design and contemporaneous control group. Setting: Medicare claims files from 2005 and 2006 for 5% random sample of Medicare beneficiaries. Patients: Part D plan enrollees with hypertension or hyperlipidemia aged 65 years or older who had no coverage, generic-only coverage, or both brand-name and generic coverage during the gap in 2006. Patients who were fully eligible for the low-income subsidy served as the control group. Measurements: Monthly 30-day supply prescriptions available, medication adherence, and continuous medication gaps of 30 days or more for antihypertensive or lipid-lowering drugs; monthly 30-day supply prescriptions available for pain relievers, acid suppressants, or antidepressants before and after coverage gap entry. Results: Patients with no gap coverage had a decrease in monthly antihypertensive and lipid-lowering drug prescriptions during the coverage gap. Nonadherence also increased in this group (antihypertensives: odds ratio [OR], 1.60 [95% CI, 1.50 to 1.71]; lipid-lowering drugs: OR, 1.59 [CI, 1.50 to 1.68]). The proportion of patients with no gap coverage who had continuous medication gaps in lipid-lowering medication use and antihypertensive use increased by an absolute 7.3% (OR, 1.38 [CI, 1.29 to 1.46]) and 3.2% (OR, 1.35 [CI, 1.25 to 1.45]), respectively, because of the coverage gap. Decreases in use were smaller for pain relievers and antidepressants and larger for acid suppressants in patients with no gap coverage. Patients with generic-only coverage had decreased use of cardiovascular medications but no change in use of drugs for symptomatic conditions. No measures changed in the brand-name and generic coverage groups. Results of sensitivity analyses were consistent with the main findings. Limitation: Because this study was nonrandomized, unobserved differences may still exist between study groups. Conclusion: The Part D coverage gap was associated with decreased use of medications for hypertension and hyperlipidemia in patients with no gap coverage and generic-only gap coverage. The proposed phasing out of the gap by 2020 will benefit such patients; however, use of low-value medications may also increase. Primary Funding Source: Penn-Pfizer Alliance and American Heart Association. [ABSTRACT FROM AUTHOR]

Background: The evidence for the benefits of branded levalbuterol over generic albuterol in patients with chronic obstructive pulmonary disease (COPD) is inconclusive. However, there are significant cost differences between these products. Objectives: This study examined use and spending on albuterol and levalbuterol in a nationally representative sample of Medicare beneficiaries with COPD enrolled in Part D in 2006. It also examined differences in patient characteristics and use of other COPD drugs among recipients of these 2 short-acting [beta]-agonists. Methods: Data were obtained from the 5% Medicare files for 2005-2006 linked to the 2006 Medicare Part D files. The sample consisted of all fee-for-service beneficiaries with COPD enrolled in stand-alone Part D plans in 2006. Patient characteristics and other COPD medication use were compared across albuterol-only users, levalbuterolonly users, and users of both albuterol and levalbuterol. Multinomial logistic regressions were used to identify factors independently associated with levalbuterol use. Results: There were 5.5 times more albuterol users than levalbuterol users in 2006; however, mean annual spending on levalbuterol was 18.6 times higher per user in 2006 than spending on albuterol ($1876 vs $101 per user, respectively). Levalbuterol-only users were more likely to be older than albuterol-only users (mean age: 71.5 vs 68.7 years; P < 0.05), as well as sicker (mean prescription drug hierarchical condition category score: 1.72 vs 1.55; P < 0.05) and residing in the South (67.9% vs 41.6%; P < 0.05). Levalbuterol-only users were more likely to use nebulizer forms covered under Part B than inhaler forms covered under Part D (78.6% vs 26.8%, respectively; P < 0.05), whereas albuterol-only users were more likely to use inhaler forms covered under Part D than nebulizer forms covered under Part B (82.2% vs 33.0%, respectively; P < 0.05). Conclusions: In this sample of Medicare beneficiaries with COPD enrolled in Part D, mean annual spending in 2006 was significantly higher for levalbuterol than for albuterol. The differences between levalbuterol and albuterol users in terms of patient characteristics, geographic region, and drug formulation/device type, coupled with the inconclusive evidence for efficacy differences in the literature, highlight the need for further comparative clinical and cost-effectiveness studies of these agents. [ABSTRACT FROM AUTHOR]

The article presents a research study on the signal transduction and activator of transcription 6's (STAT6) DNA interaction using JNJ7777120 (JNJ), and JNJ10191584 (VUF 6002). It states the measurement of the DNA-binding by electrophoretic mobility shift assay (EMSA). It states that STAT1/STAT6 balance should be considered for being adjusted by antihistamines.

Objective: To develop a minimally invasive, reproducible model of chronic severe mitral regurgitation (MR) that replicates the clinical phenotype of left atrial (LA) and left ventricular dilation and susceptibility to atrial fibrillation., Methods: Under transesophageal echocardiographic guidance, chordae tendinae were avulsed using endovascular forceps until the ratio of regurgitant jet area to LA area was ≥70%. Animals survived for an average of 8.6 ± 1.6 months (standard deviation) and imaged with monthly transthoracic echocardiography (TTE). Animals underwent baseline and preterminal magnetic resonance imaging. Terminal studies included TTE, transesophageal echocardiography, and rapid atrial pacing to test inducibility of atrial tachyarrhythmias., Results: Eight dogs underwent creation of severe MR and interval monitoring. Two were excluded-one died from acute heart failure, and the other had resolution of MR. Six dogs underwent the full experimental protocol; only one required medical management of clinical heart failure. MR remained severe over time, with a mean terminal regurgitant jet area to LA area of 71 ± 14% (standard deviation) and regurgitant fraction of 52 ± 11%. Mean LA volume increased over 130% (TTE: 163 ± 147%, P  = .039; magnetic resonance imaging: 132 ± 54%, P  = .011). Mean left ventricular end-diastolic volume increased by 38 ± 21% ( P  = .008). Inducible atrial tachyarrhythmias were seen in 4 of 6 animals at terminal surgery, and none at baseline., Conclusions: Within the 6 dogs that successfully completed the full experimental protocol, this model replicated the clinical phenotype of severe MR, which led to marked structural and electrophysiologic cardiac remodeling. This model allowed for precise measurements at repeated time points and will facilitate future studies to elucidate the mechanisms of atrial and ventricular remodeling secondary to MR and the pathophysiology of valvular atrial fibrillation., (© 2023 The Author(s).)

Objective: Expert consensus guidelines recommend surgical ablation (SA) for patients with symptomatic atrial fibrillation (AF), but less than half of patients with AF undergoing cardiac procedures receive concomitant SA. Complete isolation of the left atrial posterior wall (LAPW) has been shown to be the most critical part of the Cox maze procedure. The purpose of this study was to investigate the performance of a novel radiofrequency (RF) bipolar device, EnCompass™ (AtriCure, Inc., Mason, OH, USA), designed to isolate the LAPW in a single application., Methods: Five adult pigs underwent SA in a beating heart model. After a single ablation, the heart was arrested, explanted, and stained with triphenyl-tetrazolium-chloride for histological assessment. Each lesion was sectioned, and the ablation depth, muscle, and fat thickness were determined. The lesion width, energy delivery, and ablation times were compared with those from a reference RF clamp (Synergy™, AtriCure)., Results: Transmurality was documented in 100% of lesions (5 of 5) and cross sections (160 of 160). Electrical isolation was documented in every instance. There was no evidence of clot, charring, or pulmonary vein stenosis. Compared with the reference clamp, the lesions created by the EnCompass™ clamp were 1.5 times wider on average. The average energy delivered was 5 times higher over a duration that was 4.5 times longer due to the increased volume of tissue ablated., Conclusions: The EnCompass™ clamp reproducibly created transmural isolation of the LAPW with a single application. This may allow for simplification of the SA strategy and increased adoption of AF treatment during concomitant surgery.

Primary sensory cortex is thought to process incoming sensory information, while decision variables important for driving behavior are assumed to arise downstream in the processing hierarchy. Here, we used population two-photon calcium imaging and targeted two-photon optogenetic stimulation of neurons in layer 2/3 of mouse primary somatosensory cortex (S1) during a texture discrimination task to test for the presence of decision signals and probe their behavioral relevance. Small but distinct populations of neurons carried information about the stimulus irrespective of the behavioral outcome (stimulus neurons), or about the choice irrespective of the presented stimulus (decision neurons). Decision neurons show categorical coding that develops during learning, and lack a conclusive decision signal in Miss trials. All-optical photostimulation of decision neurons during behavior improves behavioral performance, establishing a causal role in driving behavior. The fact that stimulus and decision neurons are intermingled challenges the idea of S1 as a purely sensory area, and causal perturbation suggests a direct involvement of S1 decision neurons in the decision-making process., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: To evaluate the impact of guselkumab on work productivity, including absenteeism and presenteeism, in psoriasis patients with and without depression/anxiety. Methods: VOYAGE 2 is a randomized, double-blind, placebo-controlled, and comparator-controlled, phase 3 trial that compared guselkumab with adalimumab in patients with moderate-to-severe psoriasis. Absenteeism was evaluated among patients who reported that their skin prevented work/study based on the Dermatology Life Quality Index (DLQI) work/study domain (score = 3) at baseline. Presenteeism was assessed by summarizing mean changes in four Work Limitations Questionnaire (WLQ) domain scores at week 24. Analyses were compared between treatments and stratified by depression/anxiety status at baseline. Results: At week 24, 82.1% and 50.0% in the guselkumab and adalimumab groups, respectively, reported a DLQI work/study score = 0 (no effect of skin on work/study) ( p  < .001). Mean changes (improvements) were greater in guselkumab-treated versus adalimumab-treated patients in the work limitations domains of Physical Demands (-6.9 vs. -3.3, p  < .05), Mental-Interpersonal (-6.3 vs. -3.2, p  < .06), and Output Demands (-6.2 vs. -2.2, p  < .05). Improvements were consistent in patients with and without depression/anxiety. Conclusions: Psoriasis patients treated with guselkumab had significantly better improvements in absenteeism and presenteeism compared with those treated with adalimumab, regardless of depression/anxiety status.

Background: Guselkumab is an interleukin-23 inhibitor indicated for the treatment of moderate-to-severe plaque psoriasis in adults. Guselkumab has demonstrated additional benefit in patients with early inadequate response to ustekinumab. Long-term efficacy comparisons of guselkumab and ustekinumab are currently lacking among ustekinumab-naive patients., Objectives: To assess the relative efficacy of guselkumab and ustekinumab for maintenance therapy of moderate-to-severe plaque psoriasis, using individual patient data (IPD) from randomized controlled trials., Methods: IPD for guselkumab from the VOYAGE 1 and 2 trials were pooled and compared with IPD for ustekinumab from the NAVIGATE trial. Multivariable logistic regression analyses compared guselkumab 100 mg and ustekinumab 45 mg or 90 mg for the achievement and maintenance of Psoriasis Area and Severity Index (PASI) 90, 75 and 100 responses up to 40 weeks. The regression models accounted for a range of clinically relevant covariates (e.g. age, sex, psoriasis duration). Relative efficacy was expressed using odds ratios (ORs) and predicted probability of treatment response associated with each intervention., Results: Patients receiving guselkumab had significantly higher probabilities of achieving a PASI 90 response than patients receiving ustekinumab, at both week 16 [70·4% vs. 46·0%, OR 2·79, 95% confidence interval (CI) 2·22-3·45] and week 40 (74·2% vs. 54·5%, OR 2·40, 95% CI 1·89-3·13]. Guselkumab was also associated with a significantly increased likelihood of achieving both PASI 75 and PASI 100 responses at weeks 16 and 40, compared with ustekinumab., Conclusions: Adjusted analyses leveraging IPD demonstrate that guselkumab has a significantly higher probability of achieving and maintaining PASI treatment responses through week 40 than ustekinumab does., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction: Accidents during sporting activities are a common cause of head injury, particularly in children and young adults. Whilst most sporting head injuries are minor, there remains a proportion which is associated with high morbidity and mortality. The epidemiology of sports associated head injuries is variable based on geographical region so the aim of this study was to review the management and outcomes of sporting head injuries managed by a single neurosurgical unit in the South of England. Method: A retrospective review of the Trauma Audit and Research Network database was conducted for all patients admitted to a tertiary neurosurgical centre over a six-year period (January 2011-December 2016). Case notes were reviewed for demographics, mechanism of injury, injury severity score, intensive care admission, surgical interventions and Glasgow Outcome Score at discharge. Results: Seventy-six patients (mean age: 37.6 ± 18.4 years, male gender n  = 43; 56.6%) were eligible for inclusion in this series. Horse riding accidents were identified as the most common cause of head injury ( n  = 31; 40.8%). Fifteen patients (19.7%) in this series had a severe head injury (GCS 3-8 on admission). Twenty-eight (36.8%) patients required admission to an intensive care unit and 26 (34.2%) patients underwent neurosurgical intervention. At discharge, 68 (89.5%) patients had a Glasgow Outcome Score 4-5. Conclusion: The majority of patients with head injuries admitted to a neurosurgical unit can expect a good functional outcome despite the need for intensive care or neurosurgical intervention. The range of sports resulting in head injury is likely influenced by geographic location; however, further national study is required for wider comparison.

We recently identified Secernin-1 (SCRN1) as a novel amyloid plaque associated protein using localized proteomics. Immunohistochemistry studies confirmed that SCRN1 was present in plaque-associated dystrophic neurites and also revealed distinct and abundant co-localization with neurofibrillary tangles (NFTs). Little is known about the physiological function of SCRN1 and its role in Alzheimer's disease (AD) and other neurodegenerative diseases has not been studied. Therefore, we performed a comprehensive study of SCRN1 distribution in neurodegenerative diseases. Immunohistochemistry was used to map SCRN1 accumulation throughout the progression of AD in a cohort of 58 patients with a range of NFT pathology (Abundant NFT, n = 21; Moderate NFT, n = 22; Low/No NFT, n = 15), who were clinically diagnosed as having AD, mild cognitive impairment or normal cognition. SCRN1 accumulation was also examined in two cases with both Frontotemporal Lobar Degeneration (FTLD)-Tau and AD-related neuropathology, cases of Down Syndrome (DS) with AD (n = 5), one case of hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) and other non-AD tauopathies including: primary age-related tauopathy (PART, [n = 5]), Corticobasal Degeneration (CBD, [n = 5]), Progressive Supranuclear Palsy (PSP, [n = 5]) and Pick's disease (PiD, [n = 4]). Immunohistochemistry showed that SCRN1 was a neuronal protein that abundantly accumulated in NFTs and plaque-associated dystrophic neurites throughout the progression of AD. Quantification of SCRN1 immunohistochemistry confirmed that SCRN1 preferentially accumulated in NFTs in comparison to surrounding non-tangle containing neurons at both early and late stages of AD. Similar results were observed in DS with AD and PART. However, SCRN1 did not co-localize with phosphorylated tau inclusions in CBD, PSP or PiD. Co-immunoprecipitation revealed that SCRN1 interacted with phosphorylated tau in human AD brain tissue. Together, these results suggest that SCRN1 is uniquely associated with tau pathology in AD, DS and PART. As such, SCRN1 has potential as a novel therapeutic target and could serve as a useful biomarker to distinguish AD from other tauopathies.

Cryoablation is a safe and effective nonsurgical treatment for breast fibroadenomas (FAs). The treatment response is inversely related to the tumor size, with lesions less than 2 cm showing an optimal response. Ultrasound (US) imaging follow-up of the ablated tumor is recommended at 6-month intervals for 2 years at our institution. Although a decrease in the size of the FA clinically and on US imaging is the expected treatment response, variations can be seen. Knowledge of typical US changes over time is imperative to prevent unnecessary rebiopsy or excision in patients who have undergone cryoablation. We will review the initial patient selection criteria, cryoablation technique, and US findings at regular follow-up intervals after cryoablation of FAs through a series of cases treated at our institution., (© 2019 by the American Institute of Ultrasound in Medicine.)

Aim: The importance of adjusting for cross-study heterogeneity when conducting network meta-analyses (NMAs) was demonstrated using a case study of biologic therapies for moderate-to-severe plaque psoriasis., Methods: Bayesian NMAs were conducted for Psoriasis Area and Severity Index 90 response. Several covariates were considered to account for cross-trial differences: baseline risk (i.e., placebo response), prior biologic use, body weight, psoriasis duration, age, race and baseline Psoriasis Area and Severity Index score. Model fit was evaluated., Results: The baseline risk-adjusted NMA, which adjusts for multiple observed and unobserved effect modifiers, was associated with the best model fit. Lack of adjustment for cross-trial differences led to different clinical interpretations of findings., Conclusion: Failure to adjust for cross-trial differences in NMA can have important implications for clinical interpretations when studying the comparative efficacy of healthcare interventions.

Background: Near-peer teaching is used in anatomy education because of its benefits to the learner, teacher and faculty members. Despite the range of reports focusing on the learner, the advantages for the teacher, which are thought to include communication skills, subject knowledge and employability, are only beginning to be explored., Method: A questionnaire was distributed to the teachers involved in anatomy near-peer teaching at the University of Southampton and Brighton and Sussex Medical School (BSMS). This questionnaire was designed using a rating scale of 0-10 to assess teacher perspectives on their level of knowledge, teaching skills and enjoyment of teaching. Free-text responses determined the teachers' motivation and perceived benefits from the teaching., Results: Twenty-eight questionnaires were gathered (54.9% response rate), including 20 from Southampton and eight from BSMS. Long-term knowledge retention and better understanding of the material were rated 8.1 and 7.9 out of 10, respectively. Eight responses were from currently practising doctors, who rated how much they now use their teaching skills as doctors as 8.9 out of 10. Of the eight doctors, seven gained points for their foundation programme applications as a direct result of near-peer teaching. The most common motivator for engaging in teaching was to improve subject matter knowledge and the most common benefit was improved communication skills. There are numerous advantages to being a near-peer teacher in medical school DISCUSSION: There are numerous advantages to being a near-peer teacher in medical school, which include knowledge improvement, transferrable professional skills and employability. These initial results support the hypothesised benefits to the teachers and provide a foundation for further longitudinal studies., (© 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Telangiectasia macularis eruptiva perstans (TMEP) is a rare, heterogeneous disease of mast cell proliferation. The variable clinical presentation of TMEP, coupled with its rarity, makes the recognition and diagnosis of this disease difficult and challenging for clinicians. The histopathologic findings with hematoxylin and eosin staining that distinguish TMEP from a normal skin biopsy can be so subtle that confirmation of the diagnosis with additional special stains (c-Kit, Giemsa, toluidine blue) is strongly recommended. We describe three cases that highlight the variable clinical presentation of TMEP. One patient experienced only a localized skin manifestation, another an aggressive clinical course with systemic involvement, and a third diffuse skin involvement with mild fatigue, muscle pain, and weight gain.

The Patient-Centered Outcomes Research Institute, known as PCORI, was established by Congress as part of the Affordable Care Act (ACA) to promote evidence-based treatment. Provisions of the ACA prohibit the use of a cost-effectiveness analysis threshold and quality-adjusted life-years (QALYs) in PCORI comparative effectiveness studies, which has been understood as a prohibition on support for PCORI's conducting conventional cost-effectiveness analyses. This constraint complicates evidence-based choices where incremental improvements in outcomes are achieved at increased costs of care. How frequently this limitation inhibits efficient cost containment, also a goal of the ACA, depends on how often more effective treatment is not cost-effective relative to less effective treatment. We examined the largest database of studies of comparisons of effectiveness and cost-effectiveness to see how often there is disagreement between the more effective treatment and the cost-effective treatment, for various thresholds that may define good value. We found that under the benchmark assumption, disagreement between the two types of analyses occurs in 19 percent of cases. Disagreement is more likely to occur if a treatment intervention is musculoskeletal and less likely to occur if it is surgical or involves secondary prevention, or if the study was funded by a pharmaceutical company., (Project HOPE—The People-to-People Health Foundation, Inc.)

Purpose: Results of a survey regarding shortages of injectable oncology drugs in U.S. hospitals and health systems are presented., Methods: An online survey was sent to all members of the American Society of Health-System Pharmacists self-identified as directors of pharmacy. Survey participants provided information on the extent to which their facilities were affected by oncology drug shortages, strategies for responding to shortages, and the effects of shortages on costs, patient safety, and outcomes., Results: Ninety-eight percent of the 358 survey respondents reported at least one drug shortage during the previous 12 months, with 70% reporting instances of an inadequate supply to treat patients and 63% reporting that their facility had completely run out of at least one injectable oncology drug. Sixty-two percent of respondents reported using alternative drug regimens due to shortages; 46% reported drug dosage changes, 43% reported treatment delays, and 21% reported patient referrals to or from other facilities as a result of shortages. Survey respondents indicated the use of various strategies to manage oncology drug shortages (e.g., increasing inventories of certain drugs, identifying alternatives and substitution protocols, altered purchasing practices), all of which have led to cost increases. Twenty-five percent of respondents reported safety events resulting from oncology drug shortages. Only 40% of respondents agreed that currently available information is useful in mitigating the effects of shortages., Conclusion: Shortages of injectable oncology drugs appear to be widespread and to be having a significant impact on patient care. Currently available information about shortages does not meet administrative or clinical needs.

It is universally recognized that the prevention of sudden cardiac death (SCD) in youth is an important public health initiative. The best approach remains uncertain. Many European and Asian countries support the use of electrocardiograms (ECGs). In the United States, this is highly controversial. Many debate its cost-effectiveness. We designed a comprehensive economic model of two of the most prevalent causes of SCD identifiable by ECG, hypertrophic cardiomyopathy (HCM) and long QT syndrome (LQTS), to determine the drivers of uncertainty in the estimate of cost-effectiveness. We compared the cost-effectiveness of screening with history and physical examination (H&P) plus ECG to the current United States standard, H&P alone, for the detection and treatment of HCM and LQTS. We used a Markov model on a theoretical cohort of healthy 12-year-olds over a 70-year time horizon from a societal perspective, employing extensive univariable and probabilistic sensitivity analyses, to determine drivers of costs and effectiveness. The incremental cost-effectiveness of adding ECGs to H&Ps was $41,400/life-year saved. The model was highly sensitive to the effect of identification and treatment of previously undiagnosed individuals with HCM; however, it was insensitive to many variables commonly assumed to be significant, including the costs of ECGs, echocardiograms, and genetic testing, as well as the sensitivity and specificity of ECGs. No LQTS-related parameters were significant. This study suggests that the key to determining the cost-effectiveness of ECG screening in the United States lies in developing a better understanding of disease progression in the previously undiagnosed HCM population.

Objectives: This study sought to characterize the prevalence of metabolic syndrome (MetS), its 5 components, and their pharmacological treatment in U.S. adults by sex and race/ethnicity over time., Background: MetS is a constellation of clinical risk factors for cardiovascular disease, stroke, kidney disease, and type 2 diabetes mellitus., Methods: Prevalence estimates were estimated in adults (≥ 20 years of age) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 (in 2-year survey waves). The biological thresholds, defined by the 2009 Joint Scientific Statement, were: 1) waist circumference ≥ 102 cm (males adults) and ≥ 88 cm (female adults); 2) fasting plasma glucose ≥ 100 mg/dl; 3) blood pressure of ≥ 130/85 mm Hg; 4) triglycerides ≥ 150 mg/dl; and 5) high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl (male adults) and <50 mg/dl (female adults). Prescription drug use was estimated for lipid-modifying agents, anti-hypertensives, and anti-hyperglycemic medications., Results: From 1999 and 2000 to 2009 and 2010, the age-adjusted prevalence of MetS (based on biologic thresholds) decreased from 25.5% (95% confidence interval [CI]: 22.5% to 28.6%) to 22.9% (95% CI: 20.3% to 25.5%). During this period, hypertriglyceridemia prevalence decreased (33.5% to 24.3%), as did elevated blood pressure (32.3% to 24.0%). The prevalence of hyperglycemia increased (12.9% to 19.9%), as did elevated waist circumference (45.4% to 56.1%). These trends varied considerably by sex and race/ethnicity. Decreases in elevated blood pressure, suboptimal triglycerides, and high-density lipoprotein-cholesterol prevalence have corresponded with increases in anti-hypertensive and lipid-modifying drugs, respectively., Conclusions: The increasing prevalence of abdominal obesity, particularly among female adults, highlights the urgency of addressing abdominal obesity as a healthcare priority. The use of therapies for MetS components aligns with favorable trends in their prevalence., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with epidermal growth factor receptor (EGFR) mutation-positive stage IV adenocarcinoma have improved survival with tyrosine kinase inhibitor (TKI) treatments, but the cost effectiveness of personalized first-line therapy using EGFR mutation testing is unknown., Methods: We created a decision analytic model comparing the costs and effects of platinum combination chemotherapy with personalized therapy in which patients with EGFR mutation-positive tumors were treated with erlotinib. We used two testing strategies: testing only those with tissue available and performing a repeat biopsy if tissue was not available versus three nontargeted chemotherapy regimens (ie, carboplatin and paclitaxel; carboplatin and pemetrexed; and carboplatin, pemetrexed, and bevacizumab)., Results: Compared with a carboplatin plus paclitaxel regimen, targeted therapy based on testing available tissue yielded an incremental cost-effectiveness ratio (ICER) of $110,644 per quality-adjusted life year (QALY), and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Probabilistic sensitivity analysis revealed substantial uncertainty around these point estimates. With a willingness to pay of $100,000 per QALY, the testing strategy was cost effective 58% of the time, and the rebiopsy strategy was cost effective 54% of the time. Personalized therapy with an EGFR TKI was more favorable when the nontargeted chemotherapy regimen was more expensive. Compared with carboplatin, pemetrexed, and bevacizumab, ICERs were $25,547 per QALY for the testing strategy and $44,036 per QALY for the rebiopsy strategy., Conclusion: Although specific clinical circumstances should guide therapy, our cost-effectiveness analysis supports the strategy of testing for EGFR mutations in patients with stage IV or recurrent adenocarcinoma of the lung, rebiopsying patients if insufficient tissue is available for testing, and treating patients with EGFR mutations with erlotinib as first-line therapy.

Background: Improving inhaled corticosteroid (ICS) adherence should improve asthma outcomes., Objective: In a randomized controlled trial we tested whether an individualized problem-solving (PS) intervention improves ICS adherence and asthma outcomes., Methods: Adults with moderate or severe asthma from clinics serving urban neighborhoods were randomized to PS (ie, defining specific barriers to adherence, proposing/weighing solutions, trying the best, assessing, and revising) or standard asthma education (AE) for 3 months and then observed for 3 months. Adherence was monitored electronically. Outcomes included the following: asthma control, FEV(1), asthma-related quality of life, emergency department (ED) visits, and hospitalizations. In an intention-to-treat-analysis longitudinal models using random effects and regression were used., Results: Three hundred thirty-three adults were randomized: 49 ± 14 years of age, 72% female, 68% African American, 7% Latino, mean FEV(1) of 66% ± 19%, and 103 (31%) with hospitalizations and 172 (52%) with ED visits for asthma in the prior year. There was no difference between groups in overall change in any outcome (P > .20). Mean adherence (61% ± 27%) decreased significantly (P = .0004) over time by 14% and 10% in the AE and PS groups, respectively. Asthma control improved overall by 15% (P = .002). In both groups FEV(1) and quality of life improved by 6% (P = .01) and 18% (P < .0001), respectively. However, the improvement in FEV(1) only occurred during monitoring but not subsequently after randomization. Rates of ED visits and hospitalizations did not significantly decrease over the study period., Conclusion: PS was not better than AE in improving adherence or asthma outcomes. However, monitoring ICS use with provision of medications and attention, which was imposed on both groups, was associated with improvement in FEV(1) and asthma control., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Canine parvovirus (CPV) and canine coronavirus (CCoV) are considered the main pathogens responsible for acute gastroenteritis in dogs. From a collection of 250 samples, seven CPV strains and three CCoV strains were identified in symptomatic Irish dogs. Samples were screened for the viruses using polymerase chain reaction (PCR) and typed via DNA sequence analysis. Three CPV strains were characterized as CPV-2a, while four others were characterized as CPV-2b. To date, CPV-2c remains unreported in Ireland. Two CCoV strains were characterized as CCoV-II and one as CCoV-I. In the case of one sample, PH4/09/Ire, a mixed infection with CPV and CCoV was detected.

Low-income countries experience significant morbidity and mortality from avoidable infectious diseases, but all too often life-saving innovative vaccines are only available in high-income markets. The Generic Open (GO) license proposal posits that an increase in generic entry will lower prices through greater competition and increase vaccine availability in low-income markets. However, the GO proposal, as currently structured, is unlikely to function as envisioned in the vaccine market. Innovator vaccine firms will be unlikely to participate in the program because the payments in the GO license do not adequately compensate firms for all lost profits. Additionally, the price reductions from competitive entry are unlikely because the vaccine market is already characterized by low, and in some cases unsustainable, prices. I propose a potential adaptation where developing world vaccine manufacturers serve as contract suppliers to innovator firms for a given period of time. Donors could also share in the initial costs of capacity with the developing world manufacturers. Sales of developing world manufactured vaccines would be sold solely to UN procurement agencies under a confidential pricing or rebate system. This would increase overall product availability, maintain market separation, and decrease costs to UN agencies.

Recent studies have shown that ultrasound (US)-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to improve low-frequency (20 kHz) US methods for enhancing the transport of insulin in vitro across human skin. The feasibility of using US produced by small, lightweight novel transducers was explored for enhancing the transport of insulin across skin. Previous investigators have used US devices such as large, heavy sonicators or commercially obtained transducers for this type of research. The experiments carried out in this study used two low-profile novel US transducer arrays, the stack and standard array, for improved transport of insulin. The stack array generated a spatial peak temporal peak intensity (I(SPTP)) of 15.4 +/- 0.6 mW/cm(2) and the standard array had an I(SPTP) of 173.7 +/- 1.2 mW/cm(2). Spectrophotometeric absorption techniques were used for determining insulin transport in vitro across human skin. Compared with passive transmission (4.1 +/- 0.5 U) over an exposure period of 1 h, the standard array facilitated over a sevenfold increase in the noninvasive transdermal transport of Humulin R insulin (45.9 +/- 12.9 U). Using Humalog insulin with the standard array, there was a fourfold increase in the US-facilitated transmission over that in the control. These promising results indicate that low-frequency US can be used in a practical device for enhanced transport across the stratum corneum.