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People's interest in looking good shows no signs of waning as the `90s set in. Looking good used to mean having a dark tan; now it means fewer wrinkles and [...]

IMPORTANCE: Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children. OBJECTIVE: To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016. MAIN OUTCOMES AND MEASURES: PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe). RESULTS: Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, −3.13; 95% CI, −4.33 to −1.94; P < .001; and PGA effect, −0.31; 95% CI, −0.56 to −0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18). CONCLUSIONS AND RELEVANCE: Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.

Biologic agents such as adalimumab, etanercept, golimumab, certolizumab, ustekinumab, brodalumab, secukinumab, ixekizumab, dupilumab, alefacept, rituximab, omalizumab, tildrakizumab, and guselkumab are now indicated in the treatment of dermatologic disorders. This review reports on current prevention, risk, and management of infection in patients receiving biologic therapy for dermatologic disorders. Although risk of infection in patients receiving biologic agents for management of a dermatologic disorder is well-known, it appears to continue to be a low risk. However, optimal prevention and management of some infection risks remain an unmet need. Although the overall risk for infection during biologic therapy for dermatologic disorders appears to remain low, there remains concern about the level of risk for reactivation of tuberculosis, as well as hepatitis B and C, and the risk for other, often uncommon, serious infection remains unknown. Continued pharmacovigilance serves to mitigate risk as well as promote optimal management of dermatologic disorders with biologic agents.

IMPORTANCE: There remains little experimental evidence and no randomized clinical trial to date to confirm the benefit of platelet-rich plasma (PRP) for facial rejuvenation. OBJECTIVE: To investigate whether PRP injection improves the visual appearance, including texture and color, of photodamaged facial skin. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, participants and raters were masked to groupings. The setting was an academic-based, urban outpatient dermatology practice in Chicago, Illinois. Participants were adults aged 18 to 70 years with bilateral cheek rhytids of Glogau class II or greater. The duration of the study was August 21, 2012, to February 16, 2016. INTERVENTIONS: Each participant received 3 mL intradermal injections of PRP to one cheek and sterile normal saline to the contralateral cheek. MAIN OUTCOMES AND MEASURES: Primary outcomes were photoaging scores (with subscores for fine lines, mottled pigmentation, roughness, and sallowness) as rated by 2 masked dermatologists. Secondary outcomes included participant self-assessment scores of improvement on a 5-point scale (worsening, no change, mild improvement, moderate improvement, or significant improvement), participant overall satisfaction scores on a 4-point scale (not satisfied, slightly satisfied, moderately satisfied, or very satisfied), and participant-reported or investigator-observed adverse events. RESULTS: Of 27 enrolled participants, 19 (mean [SD] age, 46.37 [10.88] years; 17 female) were analyzed. Reported adverse events, which were not associated with the study agent, included redness (n = 18), swelling (n = 16), bruising (n = 14), pruritus (n = 1), skin scaling (n = 1), and dryness of skin (n = 1). No participants reported any adverse events at 12 months. Mean (SD) photoaging scores rated by 2 dermatologists showed no significant difference between PRP and normal saline for fine lines (baseline, 1.00 [0.75] vs 1.05 [0.78]; 2 weeks, 0.95 [0.71] vs 0.95 [0.71]; 3 months, 0.95 [0.71] vs 0.95 [0.71]; 6 months, 0.95 [0.71] vs 0.95 [0.71]), mottled pigmentation (baseline, 1.21 [0.53] vs 1.21 [0.54]; 2 weeks, 1.16 [0.60] vs 1.16 [0.60]; 3 months, 1.00 [0.47] vs 1.11 [0.46]; 6 months, 1.16 [0.69] vs 1.16 [0.69]), skin roughness (baseline, 0.47 [0.61] vs 0.47 [0.61]; 2 weeks, 0.47 [0.61] vs 0.47 [0.61]; 3 months, 0.47 [0.61] vs 0.47 [0.61]; 6 months, 0.37 [0.60] vs 0.37 [0.68]), and skin sallowness (baseline, 1.11 [0.88] vs 1.11 [0.88]; 2 weeks, 0.95 [0.85] vs 0.95 [0.85]; 3 months, 0.58 [0.61] vs 0.58 [0.61]; 6 months, 0.37 [0.68] vs 0.37 [0.68]). At 6 months after a single treatment, participants rated the PRP-treated side as significantly more improved compared with normal saline for texture (mean [SD] self-assessment score, 2.00 [1.20] vs 1.21 [0.54]; P = .02) and wrinkles (mean [SD] self-assessment score, 1.74 [0.99] vs 1.21 [0.54]; P = .03). CONCLUSIONS AND RELEVANCE: Masked participants noted that both fine and coarse texture improved significantly more with a single treatment of PRP than with normal saline. Both participants and raters found PRP to be nominally but not significantly superior to normal saline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01372566

IMPORTANCE: Although hyaluronidase is known to remove hyaluronic acid fillers, use of low doses has not been well studied. OBJECTIVE: To assess the effectiveness and dose-related effect of small quantities of hyaluronidase to treat hyaluronic acid filler nodules. DESIGN, SETTING, AND PARTICIPANTS: Split-arm, parallel-group, randomized clinical trial at an urban academic center. Participants were 9 healthy women. Recruitment and follow-up occurred from February 2013 to March 2014; data analysis occurred from February to July 2016. INTERVENTIONS: Each participant received aliquots (buttons) of either of 2 types of hyaluronic acid fillers into bilateral upper inner arms, respectively. At 1, 2, and 3 weeks each button was treated with a constant volume (0.1 mL) of variable-dose hyaluronidase (1.5, 3.0, or 9.0 U per 0.1 mL) or saline control. MAIN OUTCOMES AND MEASURES: Both a blinded dermatologist and the participant independently assessed detectability. RESULTS: Seventy-two treatment sites on 9 women (mean [SD] age, 45.8 [15.7] years) received all interventions and were analyzed. There was a significant difference in physician rater assessment between saline and hyaluronidase at 4 weeks (visual detection: mean difference = 1.15; 95% CI, 0.46-1.80; P < .001; palpability: mean difference = 1.22; 95% CI, 0.61-1.83; P < .001) and 4 months (visual detection: mean difference = 0.77; 95% CI, 0.33-1.26; P = .001; palpability: mean difference = 0.82; 95% CI, 0.38-1.25; P < .001) that was mirrored by participant self-assessment at 4 weeks (visual detection: mean difference = 0.87; 95% CI, 0.26-1.48; P = .006; palpability: mean difference = 1.59; 95% CI, 1.41-1.77; P < .001) and 4 months (visual detection: mean difference = 1.31; 95% CI, 1.09-1.53; P < .001; palpability: mean difference = 1.52; 95% CI, 1.03-2.01; P < .001), and hyaluronidase was associated with greater resolution of buttons compared with normal saline. The 9.0-unit hyaluronidase injection sites were significantly less palpable than the 1.5-unit sites at both 4 weeks (mean difference = 0.50; 95% CI, 0.01-.99; P = .045) and 4 months (mean difference = 0.47; 95% CI, 0.14-0.81; P = .007). Dose dependence was more notable for Restylane-L. CONCLUSIONS AND RELEVANCE: Although very small doses of hyaluronidase can remove hyaluronic acid fillers from patient skin, slightly higher doses often result in more rapid resolution. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01722916

‘TAMO 411’ (Reg. No. CV‐384, PI 675450) winter oat (Avena sativaL.) was developed and released by Texas A&M AgriLife Research in 2012 based on the merits of its excellent grain yield, volume weight, forage potential, winter survival, and straw strength as compared to all recent Texas A&M AgriLife Research oat releases. It was also highly resistant to crown rust and moderately resistant to stem rust races prevalent in Texas during the time of its release. Authorized seed classes of TAMO 411 in the United States are breeder, foundation, registered, and certified. TAMO 411 was submitted for US Plant Variety Protection (PVP) under Public Law 91‐577 with the Certification Only option and a PVP certificate has been issued (Certificate No. 201500356).

ABSTRACTIntroduction: Skin cancers, including both malignant melanoma (MM) and nonmelanoma skin cancer (NMSC), are the most commonly diagnosed cancers in the US. The incidence of both MM and NMSC continues to rise.Areas covered: Current evidence for an association between four of the most commonly prescribed classes of drugs in the U.S. and risk for MM and NMSC is reported. Medline was searched (January 2000 to May 2017) for each drug in the classes and for ‘basal cell carcinoma’, ‘squamous cell carcinoma’, ‘non-melanoma skin cancer’, ‘skin cancer’ and ‘melanoma’. Skin cancer risk information was reported for: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins).Expert opinion: Since skin cancer risk is associated with all four classes of these commonly prescribed drugs that represent nearly 20% of the Top 100 drugs in the U.S., these important findings warrant enhanced education, especially for prescribers and those patients at high risk for skin cancer.

IMPORTANCE: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. OBJECTIVE: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used systemic medications or phototherapy for at least 3 months from December 1, 1990, to September 16, 2014. MAIN OUTCOMES AND MEASURES: The minimal core data set included age, sex, severity of psoriasis, systemic interventions, monitoring, adverse events (AEs), and reason for discontinuation. RESULTS: For 390 children (203 girls and 187 boys; mean [SD] age at diagnosis, 8.4 [3.7] years) with psoriasis who used 1 or more systemic medications, the mean interval between diagnosis and starting systemic therapy was 3.0 years. Methotrexate was used by 270 patients (69.2%), biologic agents (primarily etanercept) by 106 (27.2%), acitretin by 57 (14.6%), cyclosporine by 30 (7.7%), fumaric acid esters by 19 (4.9%), and more than 1 medication was used by 73 (18.7%). Of 270 children taking methotrexate, 130 (48.1%) reported 1 or more AEs associated with methotrexate, primarily gastrointestinal (67 [24.8%]). Folic acid 6 days per week (odds ratio, 0.16; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 0.08-0.58; P = .003) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Methotrexate-associated hepatic transaminase elevations were associated with obesity (35 of 270 patients [13.0%]), but a folic acid regimen was not. Injection site reactions occurred in 20 of 106 patients (18.9%) treated with tumor necrosis factor inhibitors, but did not lead to discontinuation of treatment. Having 1 or more AEs related to medication, gastrointestinal AE, laboratory abnormality, or AE leading to discontinuation of the drug was more likely with methotrexate than tumor necrosis factor inhibitors, but having 1 or more infections related to medication (predominantly upper airway) was less likely. Six patients developed a serious treatment-related AE (methotrexate, 3; fumaric acid esters, 2; and adalimumab, 1), but methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. No patient developed tuberculosis or a malignant neoplasm. CONCLUSIONS AND RELEVANCE: Medication-related AEs occur less often with tumor necrosis factor inhibitors than with methotrexate. Folic acid administration 6 or 7 times per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis.

To assess the validity of using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) code 710.3 to identify adult patients with dermatomyositis in outpatient and inpatient settings. Electronic medical records of adult patients with ICD‐9 code 710.3 between January 2001 and November 2014 (n = 511) were examined. Physician diagnosis, clinical findings, and diagnostic testing results were recorded. A dermatomyositis rating scale was assigned based on classic cutaneous findings and at least 2 additional clinical and diagnostic findings from the Bohan criteria. Sensitivity and positive predictive values (PPVs) were determined. Sensitivity analyses were performed to evaluate the accuracy of multiple ICD‐9 codes in the outpatient setting, as well as primary and secondary inpatient codes. The sensitivity and PPV for multiple 710.3 ICD‐9 codes in the outpatient setting were 0.89 and 0.35, respectively. The PPV for primary and secondary 710.3 inpatient codes was 0.95 and as high as 0.8. However, the sensitivity of ICD‐9 code 710.3 was poor in the inpatient setting (primary 0.23 and secondary 0.26). The most common reason for failure to meet appropriate dermatomyositis criteria was miscoding as diabetes mellitus (32%), followed by diagnosis at an outside institution (19%), dermatomyositis as a rule‐out diagnosis (10%), cutaneous dermatomyositis (8%), and juvenile dermatomyositis (6%). One or more occurrences of ICD‐9 code 710.3 is insufficient to support the diagnosis of dermatomyositis in the outpatient setting. However, ICD‐9 710.3 codes appear to be valid in the inpatient setting.

Parts of this course are reprinted with permission from: 'Drug-induced skin diseases,' in Pharmacotherapy: A Pathophysiologic Approach. New York, Elsevier Sciences Publishing Co., 1988. AN ONGOING CE PROGRAM OF THE [...]

Skin reactions resulting from medication use are a common problem. Skin rash is a frequent reason for patient visits to physicians and may occur in approximately 2% to 3% of [...]

Switchgrass (Panicum virgatumL.) is an important emerging biofuel crop. In breeding nurseries, plants are typically widely spaced; however, production is in densely planted swards. This disconnect may hinder cultivar improvement. This study measured the efficiency of low-density, spaced-plant selection on improving biomass and ethanol yield in a high-density, simulated sward. Fifty-six full-sib families were clonally replicated in two adjacent nurseries in Knoxville, TN. The spaced-plant nursery consisted of single plants on 1-m centers. The simulated-sward nursery was created by planting four by seven plants on 0.33-m centers with 1-m alleys. In 2013 and 2014, biomass yield, ethanol yield, and morphological traits were evaluated. Trait means, correlations, and efficiency of indirect selection (E) were calculated. Significant interaction (p< 0.05) between year and nursery was observed for all traits except ethanol yield. The identified high-yielding ideotype differed between biomass and ethanol yield and between spaced-plant and simulated-sward nurseries. Selection under spaced-plant conditions for simulated-sward performance was efficient for ethanol yield (E= 0.96) but highly inefficient for biomass yield (E= -0.31). Several morphological traits evaluated under spaced-plant conditions were identified as efficient indirect selectors for simulated-sward biomass or ethanol yield. Results suggest selections for sward biomass yield may be more appropriate under sward-like conditions, but that spaced-plant nurseries are efficient for selection of ethanol yield performance under sward-like conditions and for indirect selection of sward yield traits using morphological traits.

Switchgrass (Panicum virgatumL.) takes 3 yr to reach maximum biomass yields, delaying selection and cultivar improvement. This study evaluated the efficiency of early selection in improving third‐year biomass and ethanol yields in lowland switchgrass. Fifty‐six full‐sib families were planted in Knoxville and Crossville, TN, with 1‐m spacing in a randomized complete block design. In 2012 to 2014, plants were evaluated for biomass yield, ethanol yield, and morphological traits at 8 wk after emergence and in years one through three. Trait means, efficiency of indirect selection, and genetic gain were calculated. Biomass yield differed significantly by year (92 g in yr 1, 1069 g in yr 2, and 1425 g in yr 3) while ethanol yield did not (x¯=63mgg‐1). Juvenile selection was ineffective. Biomass selection was most efficient using first‐year fall height with genetic gains per year 2.4 times those of direct selection on third‐year biomass. First‐year biomass and second‐year biomass, fall height, spring height, and tiller diameter also exhibited high efficiency (1.3 to 1.9). For ethanol yield, negative efficiency indicated selection for low first‐year height and low second‐year spring height, and tiller diameter would result in 1 to 1.3 times the genetic gain expected from direct selection on third‐year ethanol yield. Results indicate that early selection and indirect selection using morphological traits may speed yield improvement due to greater selection efficiency and higher genetic gains.

Hematopoietic stem cell transplant, a life-saving therapeutic option for some patients with malignant and non-malignant disease, may be complicated by a variety of cutaneous and systemic sequelae. Dermatologists are an integral part of the multidisciplinary effort involved in the care of stem cell transplant patients, as skin tissue may be the initial, and/or only, site of graft-versus-host disease (GVHD). Consequently, prompt diagnosis and treatment of cutaneous eruptions in the early post-transplant period may contribute to a reduction in morbidity and mortality. An important confounding issue is the clinical and histopathologic overlap of features among common cutaneous eruptions in stem cell transplant patients, with particular difficulties associated with differentiating GVHD from both cutaneous reactions to drugs (CRDs) as well as viral exanthema, including viral reactivation. We review challenges in the initial diagnosis of cutaneous eruptions following hematopoietic stem cell transplantation and provide an update on approaches to the differential diagnosis for GVHD, CRDs, and viral exanthema.

IMPORTANCE: Two meta-analyses conclude that finasteride treatment of androgenic alopecia (AGA) is safe but do not assess quality of safety reporting. OBJECTIVE: To assess safety reporting for clinical trial reports of finasteride for AGA. DATA SOURCES: MEDLINE, ClinicalTrials.gov, and a clinical data repository for an academic medical center. STUDY SELECTION: Published clinical trial reports for finasteride treatment of AGA. DATA EXTRACTION AND SYNTHESIS: For each trial, we assessed quality of adverse event reporting, extracted the number and type of adverse events in treatment and placebo groups, and assessed duration of safety evaluation and adequacy of blinding. Two observers independently extracted the data; differences were resolved by consensus. We assessed generalizability in a large cohort of men prescribed finasteride, 1.25 mg/d or less, by assessing for eligibility in the finasteride-AGA pivotal trials. MAIN OUTCOMES AND MEASURES: Quality was assessed as adequate, partially adequate, inadequate, or no events reported. We used funnel plots of the hazard ratio to assess bias. RESULTS: Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection. No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was 1 year or less for 26 of 34 trials (76%). Of 5704 men in the clinical data repository who were treated for AGA with finasteride, 1.25 mg/d or less, for AGA, only 31% met inclusion criteria for the pivotal trials referenced in the manufacturer’s full prescribing information and 33% took finasteride for more than 1 year. CONCLUSIONS AND RELEVANCE: Available toxicity information from clinical trials of finasteride in men with AGA is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of AGA, most would have been excluded from the pivotal studies that supported US Food and Drug Administration approval for AGA. Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.

IMPORTANCE: Keratosis pilaris (KP) is a common skin disorder of follicular prominence and erythema that typically affects the proximal extremities, can be disfiguring, and is often resistant to treatment. Shorter-wavelength vascular lasers have been used to reduce the associated erythema but not the textural irregularity. OBJECTIVE: To determine whether the longer-wavelength 810-nm diode laser may be effective for treatment of KP, particularly the associated skin roughness/bumpiness and textural irregularity. DESIGN, SETTING, AND PARTICIPANTS: We performed a split-body, rater-blinded, parallel-group, balanced (1:1), placebo-controlled randomized clinical trial at a dermatology outpatient practice of an urban academic medical center from March 1 to October 1, 2011. We included all patients diagnosed as having KP on both arms and Fitzpatrick skin types I through III. Of the 26 patients who underwent screening, 23 met our enrollment criteria. Of these, 18 patients completed the study, 3 were lost to or unavailable for follow-up, and 2 withdrew owing to inflammatory hyperpigmentation after the laser treatment. INTERVENTIONS: Patients were randomized to receive laser treatment on the right or left arm. Each patient received treatment with the 810-nm pulsed diode laser to the arm randomized to be the treatment site. Treatments were repeated twice, for a total of 3 treatment visits spaced 4 to 5 weeks apart. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the difference in disease severity score, including redness and roughness/bumpiness, with each graded on a scale of 0 (least severe) to 3 (most severe), between the treated and control sites. Two blinded dermatologists rated the sites at 12 weeks after the initial visit. RESULTS: At follow-up, the median redness score reported by the 2 blinded raters for the treatment and control sides was 2.0 (interquartile range [IQR], 1-2; P = .11). The median roughness/bumpiness score was 1.0 (IQR, 1-2) for the treatment sides and 2.0 (IQR, 1-2) for the control sides, a difference of 1 (P = .004). The median overall score combining erythema and roughness/bumpiness was 3.0 (IQR, 2-4) for the treatment sides and 4.0 (IQR, 3-5) for the control sides, a difference of 1 (P = .005). CONCLUSIONS AND RELEVANCE: Three treatments with the 810-nm diode laser may induce significant improvements in skin texture and roughness/bumpiness in KP patients with Fitzpatrick skin types I through III, but baseline erythema is not improved. Complete treatment of erythema and texture in KP may require diode laser treatment combined with other laser or medical modalities that address redness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01281644

IMPORTANCE: Neocollagenesis can be achieved using a dermal rolling needle device, thereby reducing the appearance of acne scars. OBJECTIVE: To determine the efficacy of a needling device for treatment of acne scars. DESIGN, SETTING, AND PARTICIPANTS: We performed a single-center, rater-blinded, balanced (1:1), split-face, placebo-controlled, parallel-group randomized clinical trial at an urban academic institution. The study took place from November 30, 2009, through July 27, 2010. Twenty healthy adults (age range, 20-65 years) with acne scars on both sides of the face were enrolled. Fifteen individuals completed the study, and no enrolled participants were withdrawn for adverse effects. INTERVENTIONS: For each participant, one side of the face was randomized for needling. Three needling treatments were performed at 2-week intervals. MAIN OUTCOMES AND MEASURES: Two blinded dermatologists separately rated participants’ acne scars based on standard digital photographs obtained at baseline and at the 3-month and 6-month follow-up visits on the quantitative global scarring grading system. RESULTS: Mean scar scores were significantly lower in the treatment group compared with baseline at 6 months (mean difference, 3.4; 95% CI, 0.2-6.5; P = .03) and nominally but not significantly lower compared with baseline at 3 months (mean difference, 2.4; 95% CI, −0.01 to 4.8; P = .052). In the control group, mean scar scores did not vary significantly from baseline at 3 months (mean difference, 1.0; 95% CI, −1.4 to 3.4; P = .96) and at 6 months (mean difference, 0.4; 95% CI, −2.3 to 3.5; P > .99). The needling procedure was not particularly painful, with a mean pain rating of 1.08 of 10. Participants perceived a 41% mean improvement in overall scar appearance on the treated side. No adverse events were reported. CONCLUSIONS AND RELEVANCE: After 3 needling treatments, there was improvement in the appearance of acne scars over time compared with the control group, with minimal pain reported. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00974870

Interest in soybean [Glycine max(L.) Merr.] isoflavones has increased in recent years owing to numerous reported health benefits. Consequently, quantitative trait loci (QTL) detection for marker‐assisted breeding for isoflavones is being examined for genetic gains. This study sought to detect QTL for soybean isoflavones in a population of 274 recombinant inbred lines derived from a cross between ‘Essex’ and ‘Williams 82’ that were subdivided and tested by maturity (early, mid, and late). The field tests were conducted in three environments in 2009 (Knoxville, TN; Harrisburg, IL; and Stuttgart, AR). The population was genotyped with 480 polymorphic single nucleotide polymorphism markers. Isoflavones for each replicate were analyzed by near infrared reflectance spectroscopy, whose prediction equation was based on high performance liquid chromatography. Each maturity test, containing 91 or 92 recombinant inbred lines, was analyzed separately for QTL. In total, 21 QTL were detected: 7 for genistein (chromosomes 5, 6, 9, 13, 17, and 19), 5 for daidzein (chromosomes 5, 6, 9, 13, and 19), 3 for glycitein (chromosomes 6, 9, and 20), and 6 for total isoflavone content (chromosomes 5, 6, 9, 13, and 19). Of these 21 QTL, 12 were confirmed or positional confirmations from other studies. Utilization of these QTL could potentially lead to marker‐assisted selection approaches for genetic gains in improving soybean isoflavones.

The incidences of life-threatening toxicities such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are inconsistently reported. The potential association of anticancer agents with SJS or TEN has not been systematically investigated. We searched the literature (Ovid: 1950 to June 2013 and PubMed: 1948 to June 2013) using terms for SJSTEN and anticancer therapies. Primary case reports, case series, and clinical trials were included. In addition, MedWatch, the Food and Drug Administration Adverse Event Reporting System (FAERS), was searched (1968 to August 2012) for SJSTEN reports associated with anticancer therapies. Proportional reporting ratios (PRR>2, N>3), empirical Bayes geometric mean (EBGM>2, N>3), and lower 95 confidence interval (EBGM0.05>2) were used as thresholds to constitute a signal of association between SJSTEN and anticancer drugs. There were 46 SJS and 37 TEN cases associated with 18 and 22 anticancer drugs in the literature, respectively. Among cases in the FAERS, significant signals were associated with SJS for bendamustine and with TEN for bendamustine, busulfan, chlorambucil, fludarabine, lomustine, and procarbazine. Several drugs reported in the published literature to be associated with SJSTEN were not found to have significant signals in FAERS. Proactive pharmacovigilance to detect and define safety signals serves to aid oncology practitioners in the recognition of possible, yet uncommon, serious, andor life-threatening skin reactions.

Objectives:To summarize reports of anaphylaxis associated with gadolinium-based contrast agents (GBCAs) reported to the Food and Drug Administrations Adverse Event Reporting System (FAERS), examine the safety signals of anaphylaxis from GBCAs, and perform a literature review of relevant case reports.Methods:FAERS (1/1988-8/2012) was searched using groups of preferred event terms for anaphylaxis combined with all drug names for GBCAs Signal detection involved determination of proportional reporting ratios (PRRs) and empirical Bayes geometric means (EBGM). Published case reports were identified through a Medline search (1/1988-7/2013).Results:There were 614 GBCA FAERS reports of anaphylaxis, resulting in a safety signal (PRR 6.2, 95% confidence interval (CI) 5.7 – 6.7; EBGM 5.1 CI 5.6 – 6.6). Among GBCAs, 43% were associated with gadopentetate dimeglumine (PRR 4.9, CI 4.3 – 5.5; EBGM 4.8, CI 4.3 – 5.4), 29% with gadobenate dimeglumine (PRR 17.5, CI 15.2 – 20.2; EBGM 17.1, CI 14.6 – 19.8) , and 17% with gadoteridol (PRR 5.7, CI 4.7 – 6.8; EBGM 5.6, CI 4.6 – 56.7). There were 14 anaphylaxis case reports in the literature.Conclusions:GBCAs used as medical imaging agents, can cause life-threatening or fatal anaphylaxis. There were differences in disproportionality of reporting between between agents. Although differences in numbers of reports of anaphylaxis reflect relative utilization rates of the various agents, disproportionality analyses (PRR, EBGM) disclose significant safety signals of anaphylaxis associated with most GBCAs.

IMPORTANCE Detailed information regarding perioperative risk and adverse events associated with Mohs micrographic surgery (MMS) can guide clinical management. Much of the data regarding complications of MMS are anecdotal or report findings from single centers or single events. OBJECTIVES To quantify adverse events associated with MMS and detect differences relevant to safety. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective inception cohort study of 21 private and 2 institutional US ambulatory referral centers for MMS. Participants were a consecutive sample of patients presenting with MMS for 35 weeks at each center, with staggered start times. EXPOSURE Mohs micrographic surgery. MAIN OUTCOMES AND MEASURES Intraoperative and postoperative minor and serious adverse events. RESULTS Among 20 821 MMS procedures, 149 adverse events (0.72%), including 4 serious events (0.02%), and no deaths were reported. Common adverse events reported were infections (61.1%), dehiscence and partial or full necrosis (20.1%), and bleeding and hematoma (15.4%). Most bleeding and wound-healing complications occurred in patients receiving anticoagulation therapy. Use of some antiseptics and antibiotics and sterile gloves during MMS were associated with modest reduction of risk for adverse events. CONCLUSIONS AND RELEVANCE Mohs micrographic surgery is safe, with a very low rate of adverse events, an exceedingly low rate of serious adverse events, and an undetectable mortality rate. Common complications include infections, followed by impaired wound healing and bleeding. Bleeding and wound-healing issues are often associated with preexisting anticoagulation therapy, which is nonetheless managed safely during MMS. We are not certain whether the small effects seen with the use of sterile gloves and antiseptics and antibiotics are clinically significant and whether wide-scale practice changes would be cost-effective given the small risk reductions.

Purpose: To determine the relationship between boxed warnings issuance by the US Food and Drug Administration (FDA) and the proportional reporting rates of the associated adverse drug reactions (ADRs) to the FDA's Adverse Event Reporting System (FAERS) for multiple myeloma (MM) drugs.Methods: We compiled a list of all FDA approved MM drugs and identified their associated ADR boxed warnings, through FDA's website and physician desk reference. Drugs that were issued boxed warnings after their market launch were included in the analysis, i.e., melphalan, thalidomide, vincristine, carmustine and doxorubicin. For each drug/ADR boxed warning combination, we retrieved all reported cases from the FAERS and calculated their Empiric Bayes Geometric Means (EBGMs), in pre- and post-boxed warning periods. Chi-square tests were performed to compare serious adverse drug events before and after boxed warnings for all drug/ADR combinations.Results: A total of 10 drug/ADR boxed warning combinations were identified, of which EBGM signals increased for six combinations after a boxed warning was issued. Reports of serious adverse drug events also increased significantly (p < 0.05).Conclusion: Boxed warnings were associated with increased FAERS reporting, indicating increased awareness of ADRs for MM drugs. Proactive pharmacovigilance programs, such as the FDA's Mini-Sentinel Project, may improve timeliness of detection of rare ADRs.

OBJECTIVE To assess the safety of a novel microneedle device on facial skin of healthy individuals of all Fitzpatrick skin types. DESIGN Subject- and live rater–blinded, sham-controlled, randomized trial. SETTING University-based ambulatory dermatology service providing both primary and referral care. PARTICIPANTS Healthy adults recruited from postings. INTERVENTION Device or sham applied with finger pressure to the right or left sides, respectively, of the participants' lateral forehead, temple, and nasolabial fold. At the 24-hour visit, a larger area (3 × 3 matrix) at the central forehead was treated with the device, and the participants applied the device to their chins. MAIN OUTCOME MEASURE Live blinded rater determination of local skin reaction scores (SRSs). RESULTS At the 5-minute skin assessment, the median SRS was 1 for all skin type and age groups. There was no median pain score higher than 1 for any age or skin type group. For the sham device, median SRSs were 0 at all time points for all age and skin type groups. Mean SRSs for the device and sham were significantly different only for the lateral forehead at 5 and 30 minutes (P = .04). CONCLUSIONS The microneedle device appears to be safe and well tolerated in both sexes and various skin types and ages. Facial skin application of the device elicits mild, self-limited, and rapidly resolving erythema marginally greater than that associated with the sham control. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01257763

Background Pruritus is a debilitating aspect of atopic dermatitis (AD). Acupuncture has been reported to diminish pruritus, but self-administered acupressure has not been previously evaluated.Objectives To evaluate the effectiveness of acupressure on the severity of eczema in a pilot trial.Methods Adult patients with AD were randomised to an intervention group (acupressure with standard of care) or a control group (standard of care alone). Subjects in the intervention group performed acupressure using a 1.2 mm acupellet at the LI11 point, applying pressure for 3 min three times per week for 4 weeks. The severity of itching and AD at baseline and at 4 weeks were measured on a visual analogue scale (VAS), the Investigator's Global Assessment (IGA) and the Eczema Area and Severity Index (EASI).Results Fifteen subjects were enrolled, 12 of whom completed the study between November 2009 and May 2011. There was no significant change between baseline and follow-up survey scores within the control group. In the investigation group there was a decrease in the VAS score (p=0.05) and EASI lichenification (p=0.03), although without significant change in the overall EASI score. Comparison of the scores between groups showed a greater decrease in VAS in the experimental group than in the control group (p=0.04), and a decrease in the IGA (p=0.03) and EASI lichenification score (p=0.03). The overall EASI scores were unchanged.Conclusion Subjects using acupressure at LI11 for 4 weeks had improvement in pruritus and lichenification. Acupressure may prove to be an easily administered alternative treatment, but larger-scale studies are needed to confirm these preliminary findings.

OBJECTIVE To report the financial impact of diagnosing and treating the dermatologic toxicities (dTs) that develop in patients receiving targeted anticancer therapies. DESIGN Single-center retrospective and prospective medical record data extraction. SETTING Department of Dermatology, Northwestern University, Chicago, Illinois. PATIENTS One hundred thirty-two adults who presented between November 1, 2005, and June 30, 2008, and who were diagnosed as having 1 primary cancer type and were treated with 1 molecularly targeted agent. MAIN OUTCOME MEASURE Standard billable costs to the patient for dT-related medications, clinic visits, laboratory and diagnostic testing, and therapeutic procedures. RESULTS The 132 patients had a median of 3 clinic visits for dT management with a median cost of $1920 per patient. Sorafenib was associated with the most costly overall median cost per patient ($2509 per patient), and imatinib was associated with the least costly overall median cost per patient ($1263 per patient). Among the 7 targeted drugs and all 10 dTs, the most costly dT (measured by cost of treatment with medications) was hand/foot skin reaction, associated with sorafenib therapy (median cost, $968 per patient) (P   &lt;  .001). The second most costly dT was panitumumab-associated acneiform eruption (median cost, $933 per patient) (P   &lt;  .001). CONCLUSION The cost of diagnosis and treatment of dTs associated with targeted agents contributes to the overall economic burden of cancer care. Efforts toward the prevention of dTs may be important for decreasing the financial burden in oncology.

OBJECTIVE: To review published data on thalidomide, with emphasis on current knowledge about mechanism of action, new and/or potential dermatologic and nondermatologic therapeutic applications, well-known and emerging adverse effects, and current indications for its safe use.DATA SOURCES: Review articles, in vitro research studies, references from retrieved articles, case reports, and clinical trials were identified from a computerized literature search using MEDLINE and OVID (1966—January 2003) and on the Cochrane Clinical Trials Register (January 2003). Information available from meetings' abstract books, Internet, or pharmaceutical companies was also considered.STUDY SELECTION AND DATA EXTRACTION: All articles identified as relevant, including those from non-English literature, were considered in an attempt to provide to the reader both the theoretical basis and practical guidelines for thalidomide pharmacotherapy.DATA SYNTHESIS: Thalidomide has hypnosedative, antiangiogenic, antiinflammatory, and immunomodulatory properties. Moreover, it has been shown to selectively inhibit the production of tumor necrosis factor-α and reduce the expression of various integrin receptors on the membrane of leukocytes and other cell types in a dose-dependent fashion. Controlled trials demonstrated the efficacy of thalidomide in a number of diseases, including erythema nodosum leprosum, lupus erythematosus, aphthosis, graft-versus-host disease, prurigo nodularis, and actinic prurigo. Single case reports or studies in small series have also suggested a possible role for thalidomide in numerous other dermatologic and nondermatologic disorders. Possibly severe and sometimes irreversible risks related to the clinical use of thalidomide include teratogenicity and neurotoxicity.CONCLUSIONS: Although teratogenicity and neurotoxicity are significant adverse effects requiring cautious use, thalidomide is an effective therapeutic modality in a variety of difficult-to-treat disorders and, providing careful selection of patients, should offer an acceptable risk-to-benefit ratio.

Erythema multiforme major (EMM; Stevens‐Johnson syndrome) is a cutaneous disorder associated with a wide variety of factors including ingestion of drugs such as phenytoin and exposure to intracranial radiation therapy. Based on observations of a 47‐year‐old black man with brain metastases who developed EMM after combined phenytoin and radiation therapy, we conducted a MEDLINE literature search for articles on similar cases from 1966 to the present. Twenty cases were identified that support the hypothesis that EMM is associated with combined phenytoin and radiation therapy. The reaction, or its severity, has no relationship to the phenytoin or radiation therapy dosage, or to the histologic type of brain tumor. Also, EMM has no apparent age or gender predisposition in association with phenytoin‐radiation therapy. Thus this is a clinical phenomenon that occurs with unusual frequency in patients with brain tumor who undergo radiation therapy while taking phenytoin. Phenytoin and other anticonvulsants such as phenobarbital and carbamazepine induce cytochrome P450 3A and produce oxidative reactive intermediates that may be implicated in hypersensitivity reactions such as EMM. Both carbamazepine and barbiturates have shown cross‐sensitivity with phenytoin; furthermore, a case of EMM in a patient receiving carbamazepine and whole brain radiation therapy has been reported. As carbamazepine, valproate, and barbiturates have been associated with EMM, gabapentin may be considered as alternative anticonvulsant therapy when appropriate.

Topical capsaicin has been introduced in the U.S. and Canada as a cream indicated for temporary relief of neuralgia following episodes of herpes zoster infections and in the treatment of diabetic neuropathy. Although capsaicin is clinically used as an external analgesic for temporary relief of neuralgia, it has also been widely used as a research tool to study peripheral pain. Capsaicin apparently works to release substance P from sensory nerve fibers and after repeated applications, depletes neurons of substance P. Clinical investigations of topical capsaicin include trials in chronic pain syndromes such as postherpetic neuralgia, postmastectomy neuroma, reflex sympathetic dystrophy syndrome, diabetic neuropathy, rheumatoid arthritis, psoriasis, hemodialysis-associated itching, and vulvar vestibulitis. In addition, therapeutic benefits of capsaicin cream on apocrine chromhidrosis have been described. Further clinical studies are warranted in several of these conditions to establish the efficacy of topical capsaicin. Serious or unexpected adverse reactions from clinical use have not been reported to date. Considering the paucity of safe and effective treatments for the conditions mentioned above, capsaicin cream appears to warrant further clinical investigations to establish its efficacy in a variety of chronic pain syndromes.

OBJECTIVE: To describe the role of the clinical pharmacist in a Hansen's disease (HD, leprosy) clinic and to describe the development, validation, and operation of a dapsone compliance monitoring program.RATIONALE: HD remains a major, worldwide healthcare problem. Dapsone is the drug of choice for treatment of HD; however, high rates of noncompliance with this agent have been reported by many treatment centers. The assessment of compliance in HD patients is important to help distinguish between treatment failure secondary to noncompliance or to the development of resistance.SETTING: In the US, the Chicago Regional Hansen's Disease Center at the University of Illinois at Chicago is one of ten centers that provide comprehensive care to patients diagnosed with this condition. This article reviews the clinical pharmacy services and dapsone compliance program in the clinic encompassing the years 1983–93.RESULTS: The clinical pharmacist provides a variety of clinical services in the clinic as well as coordinating the clinical research program. A pharmacist-generated dapsone compliance program led to improvement in compliance rates and clinical outcome. This improvement in compliance has been sustained over an extended period of time.CONCLUSIONS: The clinical pharmacy services performed in the HD clinic provide a model for pharmacy involvement in other chronic disease states. The dapsone compliance program has been successful in improving patient care and obtaining reimbursement for clinical pharmacy services.

Mupirocin is an investigational topical antibiotic used for treatment and prophylaxis of bacterial skin infections. Mupirocin differs from other antibiotics in its synthesis, structure, and mechanism of action. In vitro, mupirocin possesses antimicrobial activity against staphylococci, streptococci, Hemophilus influenzae, and Neisseria gonorrhoeae. Few studies comparing mupirocin to other topical antibiotics are available. Initial studies comparing mupirocin to inactive vehicle in the treatment of impetigo indicate an overall 92 percent pathogen eradication rate with active drug and 58 percent eradication rate with vehicle. Overall response to treatment of secondary skin infections was favorable in 91 percent of patients treated with mupirocin and 77 percent of those treated with vehicle. Although incidence is not greater than placebo, adverse effects have included pruritus, burning, dry skin, and erythema. Additional trials and clinical use should further help determine the role of mupirocin in the treatment of minor, primary, and secondary skin infections.

immune-mediated cutaneous reactions to drugs are usually categorized into four distinct types: Type 1, immediate; Type 11, cytotoxic; Type III, immune-complex: and Type IV, cell-mediated. Nonimmunologic skin reactions are also recognized. Beyond immune vnonimmune classifications, cutaneous drug reactions are generally described according to morphologic patterns of reaction. Common types of reactivity usually include maculopapular and urticarial eruptions. In addition, less common reactions include fixed drug eruption, hyperpigmentation, vasculitis, erythema multiforme, toxic epidermal necrolysis, photosensitivity, and alopecia. The drugs most frequently associated with these reactions can be identified and the pharmacist, by accomplishing a thorough systematic drug history, may play a significant role in determining likelihood of drug cause.

Salt tolerance of mature Williams Bon Cretien pear trees was assessed in a field trial on a duplex, slowly permeable clay loam. The trees were irrigated with a range of salinities; electrical conductivity of irrigation water (ECw) of 0.2 to 1.4 dS/m by flood for seven years or 0.2 to 2.1 dS/m by microjet sprinklers for nine years. Water-table levels were maintained below 3 m by a groundwater pump. Yield and leaf ion content were assessed during the treatment period. Aspects of growth and physiology were monitored in the 0.2 and 2.1 dS/m microjet treatments during the seventh irrigation season.

We observed two patients on theophylline therapy with concomitant severe psoriasis and a two- to threefold greater theophylline clearance than that reported in healthy, nonsmoking adults. There were no factors known to induce theophylline clearance. In both cases, the induction of theophylline metabolism was relatively selective for the 1-methyluric acid pathway. The altered metabolism in these patients appeared to correlate with the clinical severity of the disease. The data suggest the possibility that an observed lack of efficacy for theophylline in psoriasis may be related to pharmacokinetic effects. The concept that altered drug metabolism may occur in the presence of skin disease has important implications for pharmacotherapeutics in dermatology.

Isotretinoin, an isomer of retinoic acid, recently has been approved by the Food and Drug Administration for treatment of severe, recalcitrant acne. The most impressive effects include inhibition of sebum production and a reversible decrease in sebaceous gland size. Isotretinoin has proved to be an effective drug; response to therapy has been seen in virtually 100 percent of patients treated. Almost all patients experience reversible cutaneous and mucous-membrane symptoms while on isotretinoin treatment. Other common side effects include conjunctivitis (38 percent) and eye irritation (50 percent). The recommended dosage is 1–2 mg/kg/d for no longer than 16 weeks. Isotretinoin is currently the treatment of choice for severe, recalcitrant acne; however, because of potential side effects associated with retinoids, isotretinoin should be reserved for those patients who are unresponsive to conventional therapy, including topical and systemic antibiotics.

Topical metronidazole gel (0.75%) was compared to placebo gel in a randomized, double-blind, placebo-controlled, split-face clinical trial for the treatment of 59 patients with acne rosacea. Statistically significant differences in inflammatory lesions, erythema, and global assessments were seen at three, six, and nine weeks post-baseline in favor of the active treatment side. It did not, however, alter the telangiectatic component of the disease. No known drug-related side effects were detected, and the low topical dose along with low serum levels of metronidazole indicate a high safety profile for this therapeutic agent. This work suggests that metronidazole gel, as specifically formulated, is safe and effective in reducing the symptomatology of acne rosacea.

• Sensory neuropathies developed in three of four patients with prurigo nodularis who had been treated with thalidomide. The serum samples of the patients who had neuropathy produced morphologic changes in cultured dorsal root ganglion cells. These observed changes support the postulate that thalidomide induces primary neuronal degeneration.(Arch Dermatol 1984;120:1466-1470)

• A 1% minoxidil topical solution was used to treat 48 patients with alopecia areata, ie, 24 patients with patchy disease and 24 patients with alopecia totalis or alopecia universalis. Twenty-five patients had terminal hair regrowth; in 11 of the 25 patients, it was cosmetically acceptable. No clinical features of the disease seemed to indicate the likelihood of hair regrowth. Hair regrowth began approximately two months after the initiation of treatment and was not uniformly well maintained after the treatment was terminated. One patient had an allergic contact dermatitis reaction to the minoxidil solution; no systemic side effects were seen. No notable systemic absorption was found in 18 adult patients. Effects on cutaneous blood flow or the immune system or some direct effect on hair follicles are possible mechanisms by which minoxidil therapy might stimulate hair growth.(Arch Dermatol 1984;120:457-463)