Telangiectasia Macularis Eruptiva Perstans: Report of Three Cases.

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.

Electrocardiographic screening for hypertrophic cardiomyopathy and long QT syndrome: the drivers of cost-effectiveness for the prevention of sudden cardiac death.

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.

Effect of the Medicare Part D coverage gap on medication use among patients with hypertension and hyperlipidemia.

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.

Problem solving to improve adherence and asthma outcomes in urban adults with moderate or severe asthma: a randomized controlled trial.

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.

Treatment of Gorham-Stout disease with zoledronic acid and interferon-α: a case report and literature review.

Gorham-Stout disease is a rare disease characterized by osteolysis, angiomatosis, and soft-tissue swelling. It is a diagnosis of exclusion and has an unknown etiology. Chylothorax is a common complication of the disease that is associated with a high mortality rate. There is no standard of treatment. We report a case of a 16-year-old female with Gorham-Stout disease and recurrent pleural effusions who was successfully treated with concurrent zoledronic acid and peg-interferon α-2b.

Guselkumab improves work productivity in patients with moderate-to-severe psoriasis with or without depression and anxiety: results from the VOYAGE 2 comparator study versus adalimumab.

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.

Addressing supply side barriers to introduction of new vaccines to the developing world.

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.

Importance of assessing and adjusting for cross-study heterogeneity in network meta-analysis: a case study of psoriasis.

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.

Young patients with risk factors prevalent in the elderly - differences in comorbidity depending on severity of psoriasis: a nationwide cross-sectional study in Swedish health registers.

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.

Comparative effectiveness and cost-effectiveness analyses frequently agree on value.

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.

Impact of shortages of injectable oncology drugs on patient care.

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.

Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010.

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.

Cutaneous leishmaniasis and rickettsial African tick-bite fever: a combination of exotic traveler's diseases in the same patient.

BACKGROUND: Cutaneous leishmaniasis and rickettsial African tick-bite fever are two zoonoses increasingly diagnosed in industrialized nations due to more international travel to endemic areas. METHODS: A 52-year-old American nurse was evaluated for a 0.5 cm well-demarcated, tender, shallow ulcer on her wrist, nonproductive cough, fever, chills, and night sweats, all of which began three weeks after travel to Botswana and a visit to a game reserve, where she reported being scratched on the ankle by a cheetah. RESULTS: This cutaneous finding was strongly suggestive of leishmaniasis, but the systemic symptoms were perplexing. Although excisional biopsy showed only nonspecific changes, a specimen sent to the United States Centers for Disease Control revealed leishmania promastigotes of L. tropica. Initial Rickettsia typhi titers and many other serologic tests were negative. However, four weeks after admission, R. typhi IgG titer was 1 : 64 and R. rickettsii IgG was 1 : 1024. CONCLUSION: Thus, our patient had two tropical diseases simultaneously.

Cost effectiveness of personalized therapy for first-line treatment of stage IV and recurrent incurable adenocarcinoma of the lung.

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.

Albuterol and levalbuterol use and spending in Medicare beneficiaries with chronic obstructive pulmonary disease.

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 ß-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, levalbuterol-only 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.