Topical treatments for early-stage mycosis fungoides using Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria: A systematic review.

BACKGROUND: Mycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists. OBJECTIVE: The purpose of this study was to systematically review and assess the evidence on topical treatments for early-stage (IA, IB, IIA) MF. METHODS: We performed a literature search via MEDLINE, Embase, Web of Science, and Cochrane databases. Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria were used to assess the certainty of the data. RESULTS: Two searches yielded 1252 references; 26 met the inclusion criteria and included literature on nitrogen mustard, retinoids, corticosteroids, carmustine, fluorouracil, methotrexate-laurocapram, hexadecylphosphocholine, peldesine, ingenol mebutate, topical methotrexate with oxygen flow-assisted LP3 carrier, and resiquimod. Most studies were single intervention, observational series. Nitrogen mustard, with the most published reports, was effective with 12%-82% early-stage MF patients (total n > 1000) achieving complete remission (CR) (low certainty evidence). Clinical CR was achieved among 10%-60% treated with topical retinoids (low certainty evidence). Two moderate-sized retrospective case series on topical steroids had 18%-63% CR (low certainty evidence). Only single studies were available for the other therapies. CONCLUSIONS: For most outcomes of interest, the GRADE certainty for topical therapies for early-stage MF was low. Further randomized controlled trials and inclusion of quality of life indicators are needed.

Incidence, Clinical Features, Management, and Prevention of Herpes Zoster in Patients Receiving Antitumor Necrosis Factor Therapy: A Clinical Review.

Tumor necrosis factor (TNF) inhibitors have been used as an excellent therapeutic option in a variety of chronic inflammatory conditions. However, a recognized significant adverse effect of TNF inhibitor therapy is the increased risk of infections. The influence of TNF inhibitors on the course of coexisting or newly developed viral infections has not been extensively investigated. Therefore, we reviewed the recent publications to highlight the incidence, clinical features, management, and prevention of herpes zoster in patients who are receiving TNF inhibitors.

Human induced pluripotent stem cell line with genetically encoded fluorescent voltage indicator generated via CRISPR for action potential assessment post-cardiogenesis.

Genetically encoded fluorescent voltage indicators, such as ArcLight, have been used to report action potentials (APs) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). However, the ArcLight expression, in all cases, relied on a high number of lentiviral vector-mediated random genome integrations (8-12 copy/cell), raising concerns such as gene disruption and alteration of global and local gene expression, as well as loss or silencing of reporter genes after differentiation. Here, we report the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease technique to develop a hiPSC line stably expressing ArcLight from the AAVS1 safe harbor locus. The hiPSC line retained proliferative ability with a growth rate similar to its parental strain. Optical recording with conventional epifluorescence microscopy allowed the detection of APs as early as 21 days postdifferentiation, and could be repeatedly monitored for at least 5 months. Moreover, quantification and analysis of the APs of ArcLight-CMs identified two distinctive subtypes: a group with high frequency of spontaneous APs of small amplitudes that were pacemaker-like CMs and a group with low frequency of automaticity and large amplitudes that resembled the working CMs. Compared with FluoVolt voltage-sensitive dye, although dimmer, the ArcLight reporter exhibited better optical performance in terms of phototoxicity and photostability with comparable sensitivities and signal-to-noise ratios. The hiPSC line with targeted ArcLight engineering design represents a useful tool for studying cardiac development or hiPSC-derived cardiac disease models and drug testing.

Access to Dermatological Care with an Innovative Online Model for Psoriasis Management: Results from a Randomized Controlled Trial.

Background:Many patients with chronic skin diseases lack regular access to dermatologists in the United States and suffer poor clinical outcomes.Introduction:We performed a 12-month randomized controlled trial to evaluate the impact of an online, collaborative connected health (CCH) model for psoriasis management on access to specialty care.Materials and Methods:The 300 enrolled patients were randomized to online or in-person care. We compared distance traveled as well as transportation and in-office waiting time between the two groups and obtained patient and provider perspectives on CCH.Results:At baseline, no differences existed between the groups in difficulties obtaining specialty care. Over 12 months, the mean (standard deviation [SD]) distance traveled to and from appointments was 174.8 (±577.4) km/person for the in-person group and 2.2 (±14.2) km/person for the online group (p = 0.0003). The mean (SD) time spent on transportation and in-office waiting for in-person appointments was 4.0 (±4.5) h/person for the in-person group and 0.1 (±0.4) h/person for the online group (p = 0.0001). Patients found CCH to be safe, accessible, equitable, efficient, effective, and patient-centered. Providers found CCH to be useful for providing psoriasis care.Discussion:The CCH model resulted in significantly less distance traveled as well as transportation and in-office waiting time compared to in-person care. Both patients and providers were highly satisfied with CCH.Conclusions:The CCH model resulted in increased access to specialty care and enabled patient-centered, safe, and effective management of psoriasis patients.

Trends in National Institutes of Health Funding of Principal Investigators in Dermatology Research by Academic Degree and Sex.

IMPORTANCE: National Institutes of Health (NIH) grants are becoming increasingly competitive in the academic research arena. Identifying NIH funding disparities is an important step in improving academic diversity. OBJECTIVE: To examine recent NIH funding trends in dermatology. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study with linear regression analysis and repeated-measures analysis of variance of all NIH grants awarded to departments of dermatology from fiscal year 2009 to 2014. Funding data were exported from the NIH Research Portfolio Online Reporting Tools Expenditures and Results. Publication data were drawn from Scopus. All NIH-funded principal investigators in dermatology were categorized by their academic degree and sex. MAIN OUTCOMES AND MEASURES: The NIH funding trends were compared by investigator degree (MD, PhD, or MD/PhD) and sex. RESULTS: A total of 1292 NIH-funded grants were awarded to dermatology research from fiscal year 2009 through 2014. Adjusted NIH funding for dermatologic research diminished by 4.6% from $67.3 million in 2009 to $64.2 million in 2014, with a nadir of $58.6 million in 2013. Funding for the NIH's Research Project Grant Program (R01) decreased by 21.0% from $43.9 million to $34.7 million during this period. The dollar amount of NIH funding significantly trended down for investigators with an MD degree by $1.35 million per year from $23.6 million in 2009 to $18.4 million in 2014 (P = .02) while there was no significant change in NIH funding for MD/PhD (from $17.6 million in 2009 to $19.8 million in 2014; P = .44) and PhD investigators (from $26.1 million in 2009 to $25.9 million in 2014; P = .74). Similarly, the total dollar amount of R01 grants awarded to principal investigators with only an MD degree trended down by $1.4 million per year from $13.2 million in 2009 to $6.0 million in 2014 (P < .001). The number of female investigators with NIH grants in dermatology trended down significantly compared with the trend of their male counterparts (from 49 women in 2009 to 43 women in 2014 vs from 84 men in 2009 to 97 men in 2014; P = .04). CONCLUSIONS AND RELEVANCE: There is a downward trend in NIH funding for female and MD-only dermatology investigators. Departmental support and junior faculty mentorship for women and MD investigators is crucial for maintaining their presence in NIH-funded dermatology research.

The history of open access medical publishing: a comprehensive review.

Dermatology Online Journal became the first medical open access journal in the early 1990's. Today, thousands of open access medical journals are available on the Internet. Despite criticisms surrounding open access, these journals have allowed research to be rapidly available to the public. In addition, open access journal policies allow public health research to reach developing countries where this research has the potential to make a substantial impact. In the future, open access medical journals will likely continue to evolve with technology, changing how medical research is accessed and presented.

Patient-centered, direct-access online care for management of atopic dermatitis: a randomized clinical trial.

IMPORTANCE: New models of health care delivery for dermatological care have the potential to increase access and improve patient-centered outcomes. OBJECTIVE: To compare effectiveness of a direct-access, online model for follow-up dermatologic care in pediatric and adult patients with atopic dermatitis with that of in-person office visits. DESIGN, SETTING, AND PARTICIPANTS: This was a 1-year, randomized controlled equivalency clinical trial in medically underserved areas, outpatient clinics, and the general community. Participants included children and adults with atopic dermatitis with access to the Internet, computers, and digital cameras. INTERVENTIONS: After an initial in-person visit, patients were randomized 1:1 to direct-access online or usual in-person care for follow-up management of atopic dermatitis. In the direct-access online group, patients captured and transmitted clinical images and history asynchronously to dermatologists online; dermatologists evaluated the clinical information, provided recommendations and education, and prescribed medications online asynchronously. In the in-person group, patients visited dermatologists in their offices for follow-up care. MAIN OUTCOMES AND MEASURES: Atopic dermatitis disease severity as assessed by patient-oriented eczema measure (POEM) and investigator global assessment (IGA). RESULTS: A total of 156 children and adults were randomized. Between baseline and 12 months, the mean (SD) within-group difference in POEM score in patients in the direct-access online group was -5.1 (5.48) (95% CI, -6.32 to -3.88); in the in-person group, the within-group difference was -4.86 (4.87) (95% CI, -6.27 to -3.46). The difference in the change in POEM scores between the 2 groups was 0.24 (6.59) (90% CI, -1.70 to 1.23), which was contained within the predetermined 2.5 equivalence margin. The percentage of patients achieving clearance or near-clearance of their disease (IGA score of 0 or 1) was 38.4% (95% CI, 27.7% to 49.3%) in the direct-access online group and 43.6% (95% CI, 32.6%-54.6%) in the in-person group. The difference in the percent of patients achieving clearance or near-clearance between the 2 groups was 5.1% (90% CI, 1.7%-8.6%), which was contained within the predetermined 10% equivalence margin. CONCLUSIONS AND RELEVANCE: The direct-access online model results in equivalent improvements in atopic dermatitis clinical outcomes as in-person care. Direct-access online care may represent an innovative model of delivering dermatological services to patients with chronic skin diseases. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00985894.