Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Efficacy of the iron-chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have examined the efficacy of using the iron-chelating agent Deferiprone (DFP) for patients with PD. We conducted this meta-analysis to summarize and synthesize evidence from published randomized controlled trials about the efficacy of DFP for PD patients. METHODS: A comprehensive literature search of four electronic databases was performed, spanning until February 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan software. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS: Three RCTs with 431 patients were included in this analysis. DFP did not significantly improve UPDRS-III score compared to placebo (Standardized mean difference -0.06, 95% CI [-0.69, 0.58], low certainty evidence). However, it significantly reduced iron accumulation in the substantia nigra, putamen, and caudate as measured by T2*-weighted MRI (with high certainty evidence). CONCLUSION: Current evidence does not support the use of DFP in PD patients. Future disease-modification trials with better population selection, adjustment for concomitant medications, and long-term follow up are recommended.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND:  Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE:  To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS:  A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS:  The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION:  The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12):54-60.   doi:10.36849/JDD.7691.

Managing hyperglycemia and rash associated with alpelisib: expert consensus recommendations using the Delphi technique.

Hyperglycemia and rash are expected but challenging adverse events of phosphatidylinositol-3-kinase inhibition (such as with alpelisib). Two modified Delphi panels were conducted to provide consensus recommendations for managing hyperglycemia and rash in patients taking alpelisib. Experts rated the appropriateness of interventions on a 1-to-9 scale; median scores and dispersion were used to classify the levels of agreement. Per the hyperglycemia panel, it is appropriate to start alpelisib in patients with HbA1c 6.5% (diabetes) to <8%, or at highest risk for developing hyperglycemia, if they have a pre-treatment endocrinology consult. Recommend prophylactic metformin in patients with baseline HbA1c 5.7% to 6.4%. Metformin is the preferred first-line anti-hyperglycemic agent. Per the rash panel, initiate prophylactic nonsedating H1 antihistamines in patients starting alpelisib. Nonsedating H1 antihistamines and topical steroids are the preferred initial management for rash. In addition to clinical trial evidence, these recommendations will help address gaps encountered in clinical practice.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE: To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS: A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION: The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12): doi:10.36849/JDD.7691e.

Treatment Satisfaction and Acceptability of 20% Aminolevulinic Acid Photodynamic Therapy for the Treatment of Actinic Keratoses of the Face, Scalp, and Upper Extremities.

Background: Actinic keratoses (AKs) are precancerous, dysplastic, epidermal lesions caused by chronic sun exposure that may progress to squamous cell carcinoma. Aminolevulinic acid 20% solution with blue light photodynamic therapy (ALA-PDT) has previously been shown to be superior to vehicle plus PDT (VEH-PDT) for treatment of AKs of the face, scalp, and upper extremities. Objective: We report detailed patient satisfaction data for ALA-PDT. Methods: Patient satisfaction for ALA-PDT versus VEH-PDT and patient-reported acceptability of ALA-PDT versus previous treatments for AKs were assessed in three randomized, vehicle-controlled studies (two Phase II and one Phase III) in adults. Patients in the Phase II studies were treated on the scalp and/or face, and those in the Phase III study were treated on the upper extremities. Results: A total of 234, 166, and 269 patients were enrolled in the two Phase II studies and one Phase III study, respectively; overall, 79.8 percent of patients were male. Overall treatment satisfaction ranged from 79 to 88 percent for ALA-PDT, compared to 35 to 56 percent for VEH-PDT. Patients generally considered ALA-PDT to be equivalent to or more acceptable than prior treatments, including cryotherapy, 5-fluorouracil, imiquimod, previous PDT, and surgery. Similar proportions of patients receiving ALA-PDT or VEH-PDT on the upper extremities considered in-office time, side effects/adverse events (AEs), and duration of side effects/AEs to be acceptable. Limitations: The majority of patients were male, and no statistical comparisons were conducted. Conclusion: Patients were generally satisfied with ALA-PDT for the treatment of AKs of the face, scalp, and upper extremities and considered ALA-PDT to be equal to or more acceptable than previous treatments. Trial Registry Information: ClinicalTrials.gov: NCT01475955; NCT02239679; NCT02137785.

Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action.

Actinic keratosis (AK) is a common pre-neoplastic skin lesion constituted by uncontrolled proliferation of atypical keratinocytes that may evolve to squamous cell carcinoma. With global prevalence increasing, AK is expected to be the most common carcinoma of the skin. Tirbanibulin is a reversible tubulin polymerization inhibitor with potent anti-proliferative and anti-tumoral effects. In-vivo and in-vitro studies have shown that tirbanibulin significantly inhibits cell proliferation, tumor growth and downregulates Src signaling with no overt toxicity. Early phase and Phase III trials have shown high lesion clearance, compliance, and few side effects of once daily tirbanibulin treatment. This review discusses tirbanibulin anti-cancer activity, focusing on tubulin polymerization and Src signaling inhibitory effects, highlighting relevant literature and novel preclinical results from the ATNXUS-KX01-001 study. Furthermore, we address the relevant findings obtained in recent clinical trials to evaluate the safety, efficacy, pharmacokinetics, clearance efficacy, and side effects of the 1% tirbanibulin ointment applied once daily. In summary, we highlight preclinical and clinical evidence on the use of tirbanibulin as an effective and safe treatment option for AK.

Profile of Tirbanibulin for the Treatment of Actinic Keratosis.

Actinic keratosis (AK) is a chronic disease resulting from deleterious effects of long-term, cumulative, epidermal exposure to ultraviolet (UV) light. UV-induced mutations in p53, ras, and p16 genes lead to the emergence of abnormal epidermal actinic keratosis (AKs) cells, which proliferate while avoiding apoptosis and may lead to invasive squamous cell carcinoma. There are both lesion-targeted and field-directed topical treatments. This review is of new and emerging information on tirbanibulin and tirbanibulin 1% ointment, which is approved for topical field treatment of actinic keratosis on the face and scalp. Potent antiproliferative and proapoptotic activities result from tirbanibulin's inhibition tubulin polymerization and disruption of microtubule formation and Src kinase signaling. Tirbanibulin 1% ointment is an effective treatment of facial and scalp AK after five consecutive once-daily applications, as measured by complete and partial clearance and percent reduction in the number of lesions. Localized skin reactions are usually mild to moderate, resolving within a month. The short and well-tolerated course of therapy results in very high patient adherence to the treatment regimen.

Safety and Efficacy of TGF-ß1/COX-2 Silencing Therapeutic in Adults With Cutaneous Squamous Cell Carcinoma In Situ.

This single-center, open label, dose escalation cohort study evaluated the safety and efficacy of various doses of intralesional injections of TGF-β1/COX-2 combined with histidine-lysine polypeptide (siRNA/HKP) nanoparticle silencing therapeutic in patients with cutaneous in situ squamous cell carcinoma. Twenty-five patients (mean age: 67, SD: 10 years; 52% men) with cutaneous in situ squamous cell carcinoma participated. TGF-β1/COX-2 siRNA/HKP nanoparticle therapeutic was injected weekly for up to 6 weeks based on the following dosing cohorts: 10 μg/treatment, 20 μg/treatment, 30 μg/treatment, 60 μg/treatment, and 120 μg/treatment. The primary endpoint was the proportion of subjects with complete histological clearance. Also evaluated were the incidence/severity of treatment emergent adverse events and serious adverse events and incidence/severity of Local Skin Response. Twenty-five subjects received the TGF-β1/COX-2 siRNA/HKP nanoparticle therapeutic; 19 (76%) achieved histological clearance. In the 30 μg/treatment group and 60 μg/treatment group, percent cleared was 80% and 100%, respectively. Five subjects had 7 adverse events. There were no severe or serious adverse events; none led to treatment discontinuation, study interruption, or were related to the investigational product. Local skin response was none to minimal in most subjects, with improvement observed in the 10 μg/treatment, 20 μg/treatment, 30 μg/treatment, and 60 μg/treatment cohorts. Intralesional TGF-β1/COX-2 siRNA/HKP nanoparticle therapeutic injections appear to be noninvasive, safe, and efficacious in treating cutaneous in situ squamous cell carcinoma. The recommended doses for future study of the investigational product are 30 μg/treatment and 60 μg/treatment. J Drugs Dermatol. 2022;21(5):472-477. doi:10.36849/JDD.6384.

Expert Recommendations on the Evaluation of Sunscreen Efficacy and the Beneficial Role of Non-filtering Ingredients.

A variety of non-filtering agents have been introduced to enhance sunscreen photoprotection. Most of those agents have only weak erythema protective properties but may be valuable and beneficial in supporting protection against other effects of UV radiation, such as photoimmunosuppression, skin aging, and carcinogenesis, as well as photodermatoses. The question arises how to measure and evaluate this efficacy since standard SPF testing is not appropriate. In this perspective, we aim to provide a position statement regarding the actual value of SPF and UVA-PF to measure photoprotection. We argue whether new or additional parameters and scales can be used to better indicate the protection conferred by these products against the detrimental effects of natural/artificial, UV/visible light beyond sunburn, including DNA damage, photoimmunosuppression and pigmentation, and the potential benefits of the addition of other ingredients beyond traditional inorganic and organic filters to existing sunscreens. Also, we debate the overall usefulness of adding novel parameters that measure photoprotection to reach two tiers of users, that is, the general public and the medical community; and how this can be communicated to convey the presence of additional beneficial effects deriving from non-filtering agents, e.g., biological extracts. Finally, we provide a perspective on new challenges stemming from environmental factors, focusing on the role of the skin microbiome and the role of air pollutants and resulting needs for photoprotection.

2020 IDEOM Annual Meeting: Actinic Keratosis Stakeholders Survey Identifies Gaps in Research and Care.

This is a report of the survey results from the International Dermatology Outcome Measures (IDEOM) actinic keratosis (AK) workgroup. The purpose of the survey was to compile a list of gaps within AK care and management that require refinement. The results were discussed at the IDEOM annual meeting held virtually on October 23–24, 2020. This built a framework with which the AK workgroup, which consisted of physicians, patients, and pharmaceutical scientists, discussed at length in their breakout session at the meeting. The electronic survey was distributed to patients, pharmaceutical scientists, and leading physician experts in the field via email on September 22, 2020, with a deadline of October 2, 2020. The survey consisted of three open-ended prompts concerning key gaps and/or unmet needs in (1) the care of AKs, (2) outcome measurement of AKs in clinical trials and, (3) the measurement of AKs in clinical practice. The results were qualitative, with a response rate of 47%. Responses included reform of outcome measures for clinical trials, a methodology for evaluating the efficacy of preventative measures, and a comparison of treatments to establish a treatment protocol, among other efforts. This paper will also provide a brief overview of the current state of the AK outcome measures, emphasizing the heterogeneity of the measures and detailing the AK workgroup's future efforts to create a reliable and applicable core outcome measure set. J Drugs Dermatol. 2022;21(2):128-134. doi:10.36849/JDD.6360.

Advances and Considerations in the Management of Actinic Keratosis: An Expert Consensus Panel Report.

BACKGROUND: Actinic Keratosis (AK) is a potentially pre-malignant tumor with a poorly defined risk of progression to invasive squamous cell carcinoma (SCC). Because of the typical need for recurrent cycles of AK treatment, outcomes can be limited by both therapeutic efficacy and patient adherence. OBJECTIVE: To synthesize the available and most current literature into overarching principles to provide guidance on the management of AKs, improving patient experiences and treatment outcomes. METHODS: A systematic review querying epidemiology, natural history, prognosis, management of AKs as well as the mechanism of action of and adherence to current AK therapy was conducted. After reviewing the literature, an expert consensus panel consisting of 10 expert dermatologists and dermatopathologists used a modified Delphi process to develop statements regarding the pathogenesis and management of AKs. Final statements were only adopted with a supermajority vote (≥7/10). RESULTS: The panel developed 7 consensus statements regarding AKs pathogenesis and management. CONCLUSION: The poorly defined risk for AK progression into invasive SCC without universally accepted clinical-histopathological factors highlights the importance of long-term efficacious treatment. To effectively counsel and treat patients with actinic keratoses, dermatologists must understand how newer therapeutic approaches with mechanisms of action that have more rapid onset of action, shorter treatment courses, and less intense local skin reaction (LSRs) may promote adherence and improve long-term outcomes. J Drugs Dermatol. 2021;20(8):888-893. doi:10.36849/JDD.6078 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia.

PURPOSE: Chemotherapy-induced alopecia (CIA) negatively affects psychosocial health and quality of life (QoL). Currently, there are no approved pharmacologic agents to prevent CIA. Here, we evaluated the safety, tolerability, and potential signal of efficacy of topical calcitriol (BPM31543) on CIA prevention. MATERIALS AND METHODS: This Phase 1 trial included 23 female patients with breast cancer, gynecologic cancer, or sarcomas receiving a taxane-based chemotherapy. Patients received a 3 + 3 dose-escalation regimen at 5, 10, 20, 40, 60, and 80 µg/mL, with 3-6 patients per group. Patients applied topical BPM31543 to the scalp twice a day for 2 weeks prior to chemotherapy and continued until chemotherapy treatment was completed. The maximum tolerated dose (MTD) during first 28 day application was determined. Adverse event (AE) monitoring, pharmacokinetics, blinded photographic assessments, and patient self-assessment were evaluated. RESULTS: Out of 23 patients treated with BPM31543, 8 patients experienced at least 1 treatment-related adverse event (AE). The majority of AEs were mild to moderate in severity. Only 1 patient experienced SAEs (vomiting, nausea, fever, and flank pain) considered treatment related. Alopecia < 50% from baseline was observed in 8 patients at Week 7, and, of which 2 patients had < 50% alopecia maintained at Week 15. There were no detectable effects of topical BPM31543 on serum levels of calcitriol. CONCLUSIONS: BPM31543 applied topically twice daily to the scalp is safe and well tolerated in patients receiving taxane-based chemotherapy. No DLT was observed at up to 80 µg/mL, and MTD was not reached. Based on the data from this trial, BPM31543 represents a promising therapy and warrants further investigation in Phase 2/3 trials.

Assessing keloid recurrence following surgical excision and radiation.

Keloids are a fibroproliferative disorder that can result from a cutaneous injury to the reticular dermis. Recurrence rates as high as 100% have been reported following surgical excision alone. Consequently, a variety of post-surgical techniques have been employed to prevent keloid recurrence, including the use of radiation. Although numerous studies have shown post-excisional X-rays, electron beam, lasers and brachytherapy can reduce the rate of keloid recurrence, numerous inconsistencies, including a wide range of definitions for keloid recurrence, make it difficult to compare study outcomes. The review aims to examine the various means for defining keloid recurrence in clinical trials involving the use of radiation therapy. Searches of the Cochrane Library and PubMed were performed to identify the available information for post-surgical keloid recurrence following radiation therapy. Each identified study was reviewed for patient follow-up and criteria used to define keloid recurrence. The search results included clinical studies with external beam radiation, brachytherapy and superficial radiation therapy. Many studies did not include a definition of keloid recurrence, or defined recurrence only as the return of scar tissue. Other studies defined keloid recurrence based on patient self-assessment questionnaires, symptoms and scar elevation and changes in Kyoto Scar Scale, Japan Scar Workshop Scale and Vancouver Scar Scale scores. The results of this review indicate keloidectomy followed by radiation therapy provide satisfactory recurrence rates; however, clinical studies evaluating these treatments do not describe treatment outcomes or use different definitions of keloid recurrence. Consequently, recurrence rates vary widely, making comparisons across studies difficult. Keloid recurrence should be clearly defined using both objective and subjective measures.

Efficacy and safety of ingenol disoxate gel in field treatment of actinic keratosis on full face, scalp or large area (250 cm2) on the chest: results of four phase 3 randomized controlled trials.

INTRODUCTION: Actinic keratosis (AK) is a skin condition arising from chronic exposure to ultraviolet light and may lead to the development of malignancies. This trial aimed to evaluate efficacy and safety of ingenol disoxate gel (IngDsx, 0.018% for face/chest [FC]; 0.037% for scalp [S]), versus vehicle. METHODS: Four identical phase 3 trials in patients with AK on the full face/up to 250cm2 of chest or full balding scalp, with an initial 8-week period and 12-month follow-up, were conducted. FC and S trials were pooled for analysis. The primary endpoint was complete clearance at Week 8. RESULTS: Across trials, 616 patients were randomized to FC and 626 to S, with 410 and 420 assigned to receive IngDsx, respectively. In the FC and S trials, 25.9% and 24.5% of patients in the IngDsx group, respectively, achieved the primary endpoint. IngDsx was relatively well tolerated. During extended follow-up, there were more identified non-melanoma skin malignancies in the IngDsx group than vehicle group; HR: 2.38 (95% CI: 1.28, 4.41). CONCLUSION: Treatment with IngDsx was superior to vehicle on all clinical endpoints, patient-reported and cosmetic outcomes. During the 12-month follow-up, slightly increased skin malignancies in the treatment area were identified, potentially due to unintentional detection bias.

Efficacy of aminolevulinic acid 20 % solution photodynamic therapy in the treatment of actinic keratoses on the upper extremities: A post hoc analysis of a phase 3, randomized, vehicle-controlled trial.

BACKGROUND: Photodynamic therapy with 5-aminolevulinic acid is indicated for targeted treatment of actinic keratoses on the face, scalp, and upper extremities. This was a post hoc analysis of a phase 3 randomized trial assessing the efficacy of aminolevulinic acid/photodynamic therapy for treatment of actinic keratoses on the upper extremities. METHODS: Adults with 4-15 grade 1-2 actinic keratosis lesions on ≥1 upper extremity were randomized (1:1) to receive aminolevulinic acid/photodynamic therapy or vehicle/photodynamic therapy applied to individual lesions followed by occlusion and blue light treatment. Assessments included the clearance rate of treated lesions vs baseline, cumulative disease area clearance, and complete clearance by lesion size. RESULTS: There were 135 and 134 patients randomized to aminolevulinic acid/photodynamic therapy and vehicle/photodynamic therapy groups, respectively. At 12 weeks, clearance of treated lesions (80.6 % vs 45.5 %; P <0.0001) and the mean decrease in cumulative disease area (82.4 % vs 42.6 %; P <0.0001) was significantly higher for aminolevulinic acid/photodynamic therapy vs vehicle/photodynamic therapy, respectively. Rates of complete clearance and clearance by cutpoint (≥90 %, ≥85 %, ≥80 %, or ≥75 % clearance) were numerically higher for aminolevulinic acid/photodynamic therapy. Clearance of lesions was higher for aminolevulinic acid/photodynamic therapy vs vehicle/photodynamic therapy regardless of baseline lesion size. Aminolevulinic acid/photodynamic therapy was well tolerated with adverse events consistent with those expected with photodynamic therapy. CONCLUSIONS: Aminolevulinic acid photodynamic therapy is effective and well tolerated for the treatment of actinic keratosis lesions of the extremities.

Cerebral Venous Sinus Thrombosis Related to Iron-Deficiency Anemia.

Cerebral venous sinus thrombosis (CVST) is an uncommon diagnosis associated with life-threatening and long-term neurological consequences in children. It is characterized by non-specific symptoms, including fever, altered mental status and focal neurological deficits. Etiologic factors include infection, trauma, prothrombotic disorders and importantly, iron-deficiency anemia. Iron-deficiency anemia is a preventable risk factor of CVST as it is commonly caused by excessive cow milk consumption in infants and toddlers. Diagnosis is mainly made with MRI and magnetic resonance venography (MRV). Prompt anticoagulation is a key therapeutic intervention, and in the case of associated iron deficiency, iron repletion and elimination or limitation of milk from diet are also required. Thus, it is essential for physicians to have a high level of suspicion to diagnose CVST, given its non-specific presentation. This is a case report of a two-year-old boy who presented to the pediatric emergency department with vomiting and altered mental status and was ultimately diagnosed with CVST.

Spike-associated networks and intracranial electrographic findings.

Functional connectivity is providing new insights into the network nature of epilepsy with growing clinical applications. Our objective was to validate a novel magnetoencephalography-based method to non-invasively measure the epileptic network. We retrospectively identified pediatric and adult patients with refractory focal epilepsy who underwent pre-surgical magnetoencephalography with subsequent intracranial electrographic monitoring. Magnetoencephalography tracings were visually reviewed, and interictal epileptiform discharges ("spikes") were individually marked. We then evaluated differences in whole-brain connectivity during brief epochs preceding the spikes and during the spikes using the Network-Based Statistic to test differences at the network level. In six patients with statistically-significant network differences, we observed substantial overlap between the spike-associated networks and electrographically active areas identified during intracranial monitoring (the spike-associated network was 78% and 83% sensitive for intracranial electroencephalography-defined regions in the irritative and seizure onset zones, respectively). These findings support the neurobiological validity of the spike-associated network method. Assessment of spike-associated networks has the potential to improve surgical planning in epilepsy surgery patients by identifying components of the epileptic network prior to implantation.

Rethinking the Journal Impact Factor and Publishing in the Digital Age.

Clinical and experimental literature search has changed significantly over the past few decades, and with it, the way in which we value information. Today, our need for immediate access to relevant and specific literature, regardless of specialty, has led to a growing demand for open access to publications. The Journal Impact Factor (JIF) has been a long-time standard for representing the quality or "prestige" of a journal, but it appears to be losing its relevance. Here, we define the JIF and deconstruct its validity as a modern measure of a journal's quality, discuss the current models of academic publication, including their advantages and shortcomings, and discuss the benefits and shortcomings of a variety of open-access models, including costs to the author. We have quantified a nonsubscribed physician's access to full articles associated with dermatologic disease and aesthetics cited on PubMed. For some of the most common dermatology conditions, 23.1 percent of citations (ranging from 17.2% for melasma to 31.9% for malignant melanoma) were available as free full articles, and for aesthetic procedures, 18.9 percent of citations (ranging from 11.9% for laser hair removal to 27.9% for botulinum toxin) were available as free full articles. Finally, we discuss existing alternative metrics for measuring journal impact and propose the adoption of a superior publishing model, one that satisfies modern day standards of scholarly knowledge pursuit and dissemination of scholarly publications for dermatology and all of medical science.