ABSTRACT
BACKGROUND: UV-A radiation contributes to photoaging/photocarcinogenesis by generating inflammation and oxidative damage. Current photoprotective strategies are limited by the availability/utilization of UV-A filters, highlighting an unmet need. Cannabidiol (CBD), having anti-inflammatory/antioxidant properties via regulation of nuclear erythroid 2-related factor, heme oxygenase 1, and peroxisome proliferator-activated receptor gamma, could potentially mitigate damage from UV-A exposure. OBJECTIVE/METHODS: This is a prospective, single-center, pilot clinical trial (NCT05279495). Nineteen participants applied nano-CBD (nCBD) or vehicle (VC) cream to randomized, blinded buttock sites twice daily for 14 days; then, the treated sites were irradiated with ≤3× UV-A minimal erythema dose. After 24 hours, punch biopsies were obtained for histology, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: At 24 hours, 21% of participants had less observed erythema on CBD-treated skin than on VC skin. Histologically, nCBD-treated skin had reduced UV-A-induced epidermal hyperplasia than VC (P = .01). Immunohistochemistry detected reduced cytoplasmic/nuclear 8-oxoguanine glycosylase 1 staining in nCBD-treated skin compared with VC (P < .01). Quantitative mtDNA polymerase chain reaction demonstrated that UV-A-induced deletion of ND4 (proxy:4977 bp deletion; P = .003) and ND1 (proxy:3895 bp deletion; P = .002) was significantly reduced by in vivo nCBD treatment compared with VC. LIMITATIONS: Small sample size is this study's limitation. CONCLUSION: Topically applied nCBD cream reduced UV-A-induced formation of a frequent mutagenic nuclear DNA base lesion and protected against mtDNA mutations associated with UV-A-induced skin aging. To our knowledge, this trial is the first to identify UV-protective capacity of CBD-containing topicals in humans.
ABSTRACT
OBJECTIVE: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. METHODS: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53). RESULTS: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05). CONCLUSIONS: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation.
Subject(s)
Connectome , Memory Disorders , Humans , Amnesia/diagnostic imaging , Brain/diagnostic imaging , Brain/pathology , Prefrontal Cortex/pathology , Datasets as TopicABSTRACT
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.
Subject(s)
Keratosis, Actinic , Patient Reported Outcome Measures , Patient Satisfaction , Quality of Life , Humans , Keratosis, Actinic/drug therapy , Keratosis, Actinic/diagnosis , Male , Female , United States , Aged , Middle Aged , Treatment Outcome , Aged, 80 and over , Administration, Cutaneous , Ointments , Follow-Up Studies , Adult , Surveys and Questionnaires/statistics & numerical dataABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell , Skin Neoplasms , Humans , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/therapy , Prognosis , Transcriptome , ConsensusABSTRACT
BACKGROUND: Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD). OBJECTIVE: The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment. METHODS: We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI). RESULTS: Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (ß-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory. CONCLUSIONS: iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Subject(s)
Basal Nucleus of Meynert , Cognitive Dysfunction , REM Sleep Behavior Disorder , Aged , Female , Humans , Male , Basal Nucleus of Meynert/diagnostic imaging , Basal Nucleus of Meynert/pathology , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Hippocampus/diagnostic imaging , Hippocampus/pathology , Magnetic Resonance Imaging , Olfactory Bulb/diagnostic imaging , Olfactory Bulb/pathology , REM Sleep Behavior Disorder/complications , REM Sleep Behavior Disorder/diagnostic imaging , REM Sleep Behavior Disorder/pathology , Neural PathwaysABSTRACT
To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants' motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee's scale), clinical grading of spasm intensity (Chen's scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc's scale). In Round 2, clinicians rated the same cohort with simplified scale wording after consensus training. For each round, we evaluated the IRR using the intraclass correlation coefficient [ICC (2,1) single-rater, absolute-agreement, 2-way random model]. The scales exhibited IRR that ranged from "poor" to "moderate"; the mean ICCs were 0.41, 0.43, 0.47, 0.43, and 0.65 for the JRS, HSGS, Lee's, Chen's, and Tunc's scales, respectively, for Round 1. In Round 2, the corresponding IRRs increased to 0.63, 0.60, 0.59, 0.53, and 0.71. In both rounds, Tunc's scale exhibited the highest IRR. For clinical assessments of HFS motor severity based on video observations, we recommend using Tunc's scale because of its comparative reliability and because clinicians interpret the scale easily without modifications or the need for consensus training.
Subject(s)
Dystonia , Hemifacial Spasm , Humans , Hemifacial Spasm/diagnosis , Reproducibility of ResultsABSTRACT
OBJECTIVE: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease. METHODS: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence. RESULTS: In LBD patients, there were no significant differences in EEG features derived from 90, 60, and thirty 2-second epochs (all P >0.05). There were no significant differences in EEG features derived from 3 different groups of thirty 2-second epochs (all P >0.05). When analyzing EEG features derived from ninety 2-second epochs, we found that LBD had significantly reduced dominant frequency, reduced dominant frequency variability, and reduced dominant frequency prevalence alpha compared with the non-LBD group (all P <0.05). These same differences were observed between the LBD and non-LBD groups when analyzing thirty 2-second epochs. CONCLUSIONS: There were no differences in EEG features derived from 1 minute versus 3 minutes of EEG data, and both durations of EEG data equally differentiated LBD from non-LBD.
Subject(s)
Alzheimer Disease , Dementia , Lewy Body Disease , Parkinson Disease , Humans , ElectroencephalographyABSTRACT
BACKGROUND: Molluscum contagiosum (MC) is an acute infection caused by the molluscum contagiosum virus (MCV) with a worldwide incidence of approximately 8,000 cases per 100,000 individuals annually. Greater than 90% of MC cases occur in the pediatric population, and affected adults are more likely to be younger or immunocompromised. MC has minimal inflammation initially; however, a strong inflammatory response can occur during resolution of the infection, termed the beginning of the end (BOTE). MC infections may last months to years, and it is hypothesized that persistent infections may be due to suppression of immunity by MCV proteins, thus affecting MC’s clinical progression. OBJECTIVE: We reviewed the current proposed mechanisms of MCV immune evasion and discuss potential therapeutic options for MC treatment. METHODS: A literature search was conducted using electronic databases (Pubmed, Google Scholar, Medline). RESULTS: We compiled 18 original research articles and identified 11 proteins produced by MCV that are postulated to participate in evasion of host immunity through various molecular pathways. These proteins and/or their downstream pathways may be influenced by MC treatments in phase 3 development, including berdazimer gel 10.3% and VP-102 cantharidin, 0.7%. CONCLUSION: MCV is distinctive in evading immune surveillance by inhibiting or dampening several immune pathways via the production of viral proteins. The result is decreasing local inflammatory response which contributes to the prolonged survival of MCV in the epidermis. Persistent MC can be a nuisance for some patients and treatment may be desired. Currently, no treatment has been approved by the US Food and Drug Administration (FDA). Two approaches in the pipeline may affect the immune avoidance mechanisms; nevertheless, their exact mechanisms between the potential therapeutics and viral proteins remain enigmatic. J Drugs Dermatol. 2023;22(2):182-189. doi:10.36849/JDD.7230.
Subject(s)
Molluscum Contagiosum , Molluscum contagiosum virus , Humans , Child , Molluscum contagiosum virus/metabolism , Molluscum Contagiosum/epidemiology , Molluscum Contagiosum/drug therapy , Cantharidin , Viral ProteinsABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell , Skin Neoplasms , Humans , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , Consensus , Prognosis , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/therapy , TranscriptomeABSTRACT
Planetary health provides a perspective of ecological interdependence that connects the health and vitality of individuals, communities, and Earth's natural systems. It includes the social, political, and economic ecosystems that influence both individuals and whole societies. In an era of interconnected grand challenges threatening health of all systems at all scales, planetary health provides a framework for cross-sectoral collaboration and unified systems approaches to solutions. The field of allergy is at the forefront of these efforts. Allergic conditions are a sentinel measure of environmental impact on human health in early life-illuminating how ecological changes affect immune development and predispose to a wider range of inflammatory noncommunicable diseases (NCDs). This shows how adverse macroscale ecology in the Anthropocene penetrates to the molecular level of personal and microscale ecology, including the microbial systems at the foundations of all ecosystems. It provides the basis for more integrated efforts to address widespread environmental degradation and adverse effects of maladaptive urbanization, food systems, lifestyle behaviors, and socioeconomic disadvantage. Nature-based solutions and efforts to improve nature-relatedness are crucial for restoring symbiosis, balance, and mutualism in every sense, recognizing that both personal lifestyle choices and collective structural actions are needed in tandem. Ultimately, meaningful ecological approaches will depend on placing greater emphasis on psychological and cultural dimensions such as mindfulness, values, and moral wisdom to ensure a sustainable and resilient future.
Subject(s)
Ecosystem , Environment , HumansABSTRACT
BACKGROUND: Non-specific low back pain is a common, potentially disabling condition usually treated with self-care and non-prescription medication. For chronic low back pain, current guidelines recommend exercise therapy. Yoga is a mind-body exercise sometimes used for non-specific low back pain. OBJECTIVES: To evaluate the benefits and harms of yoga for treating chronic non-specific low back pain in adults compared to sham yoga, no specific treatment, a minimal intervention (e.g. education), or another active treatment, focusing on pain, function, quality of life, and adverse events. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 August 2021 without language or publication status restrictions. SELECTION CRITERIA: We included randomized controlled trials of yoga compared to sham yoga, no intervention, any other intervention and yoga added to other therapies. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Our major outcomes were 1. back-specific function, 2. pain, 3. clinical improvement, 4. mental and physical quality of life, 5. depression, and 6. ADVERSE EVENTS: Our minor outcome was 1. work disability. We used GRADE to assess certainty of evidence for the major outcomes. MAIN RESULTS: We included 21 trials (2223 participants) from the USA, India, the UK, Croatia, Germany, Sweden, and Turkey. Participants were recruited from both clinical and community settings. Most were women in their 40s or 50s. Most trials used iyengar, hatha, or viniyoga yoga. Trials compared yoga to a non-exercise control including waiting list, usual care, or education (10 trials); back-focused exercise such as physical therapy (five trials); both exercise and non-exercise controls (four trials); both non-exercise and another mind-body exercise (qigong) (one trial); and yoga plus exercise to exercise alone (one trial). One trial comparing yoga to exercise was an intensive residential one-week program, and we analyzed this trial separately. All trials were at high risk of performance and detection bias because participants and providers were not blinded to treatment, and outcomes were self-assessed. We found no trials comparing yoga to sham yoga. Low-certainty evidence from 11 trials showed that there may be a small clinically unimportant improvement in back-specific function with yoga (mean difference [MD] -1.69, 95% confidence interval [CI] -2.73 to -0.65 on the 0- to 24-point Roland-Morris Disability Questionnaire [RMDQ], lower = better, minimal clinically important difference [MCID] 5 points; 1155 participants) and moderate-certainty evidence from nine trials showed a clinically unimportant improvement in pain (MD -4.53, 95% CI -6.61 to -2.46 on a 0 to 100 scale, 0 no pain, MCID 15 points; 946 participants) compared to no exercise at three months. Low-certainty evidence from four trials showed that there may be a clinical improvement with yoga (risk ratio [RR] 2.33, 95% CI 1.46 to 3.71; assessed as participant rating that back pain was improved or resolved; 353 participants). Moderate-certainty evidence from six trials showed that there is probably a small improvement in physical and mental quality of life (physical: MD 1.80, 95% CI 0.27 to 3.33 on the 36-item Short Form [SF-36] physical health scale, higher = better; mental: MD 2.38, 95% CI 0.60 to 4.17 on the SF-36 mental health scale, higher = better; both 686 participants). Low-certainty evidence from three trials showed little to no improvement in depression (MD -1.25, 95% CI -2.90 to 0.46 on the Beck Depression Inventory, lower = better; 241 participants). There was low-certainty evidence from eight trials that yoga increased the risk of adverse events, primarily increased back pain, at six to 12 months (RR 4.76, 95% CI 2.08 to 10.89; 43/1000 with yoga and 9/1000 with no exercise; 1037 participants). For yoga compared to back-focused exercise controls (8 trials, 912 participants) at three months, we found moderate-certainty evidence from four trials for little or no difference in back-specific function (MD -0.38, 95% CI -1.33 to 0.62 on the RMDQ, lower = better; 575 participants) and very low-certainty evidence from two trials for little or no difference in pain (MD 2.68, 95% CI -2.01 to 7.36 on a 0 to 100 scale, lower = better; 326 participants). We found very low-certainty evidence from three trials for no difference in clinical improvement assessed as participant rating that back pain was improved or resolved (RR 0.97, 95% CI 0.72 to 1.31; 433 participants) and very low-certainty evidence from one trial for little or no difference in physical and mental quality of life (physical: MD 1.30, 95% CI -0.95 to 3.55 on the SF-36 physical health scale, higher = better; mental: MD 1.90, 95% CI -1.17 to 4.97 on the SF-36 mental health scale, higher = better; both 237 participants). No studies reported depression. Low-certainty evidence from five trials showed that there was little or no difference between yoga and exercise in the risk of adverse events at six to 12 months (RR 0.93, 95% CI 0.56 to 1.53; 84/1000 with yoga and 91/1000 with non-yoga exercise; 640 participants). AUTHORS' CONCLUSIONS: There is low- to moderate-certainty evidence that yoga compared to no exercise results in small and clinically unimportant improvements in back-related function and pain. There is probably little or no difference between yoga and other back-related exercise for back-related function at three months, although it remains uncertain whether there is any difference between yoga and other exercise for pain and quality of life. Yoga is associated with more adverse events than no exercise, but may have the same risk of adverse events as other exercise. In light of these results, decisions to use yoga instead of no exercise or another exercise may depend on availability, cost, and participant or provider preference. Since all studies were unblinded and at high risk of performance and detection bias, it is unlikely that blinded comparisons would find a clinically important benefit.
Subject(s)
Low Back Pain , Yoga , Adult , Humans , Female , Male , Low Back Pain/therapy , Quality of Life , Treatment Outcome , Physical Therapy ModalitiesABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell , Skin Neoplasms , Adult , Aged , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Cohort Studies , Cyclooxygenase 2 , Female , Humans , Male , RNA, Small Interfering/adverse effects , RNA, Small Interfering/genetics , Skin Neoplasms/drug therapy , Skin Neoplasms/genetics , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/therapeutic useABSTRACT
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.
Subject(s)
Keratosis, Actinic , Humans , Keratosis, Actinic/drug therapy , Outcome Assessment, Health Care , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Alopecia/chemically induced , Alopecia/prevention & control , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Calcitriol , Female , Humans , Quality of LifeABSTRACT
OBJECTIVE: To evaluate the relationship between health-related quality of life (HR-QoL) and both physical and psychiatric factors in a large, international, multicentre cohort of patients with isolated dystonia, the Dystonia Coalition. METHODS: Natural history data from 603 patients with isolated dystonia (median age 57 years (IQR: 48 to 64 years), 67.0% women) were prospectively acquired and analysed. HR-QoL (RAND 36-Item Health Survey), severity of depressive symptoms, generalised anxiety (Hospital Anxiety and Depression Scale) and social anxiety (Liebowitz Social Anxiety Scale) were assessed. Dystonia severity (Burke-Fahn-Marsden Dystonia Rating Scale) and dystonic tremor were examined. Statistical predictors of HR-QoL were calculated using saturated path analysis. RESULTS: Reduced HR-QoL was strongly associated with the degree of depressive symptoms and generalised and social anxiety (8/8 RAND 36 subscales, p≤0.001). Increased dystonia severity was associated with worse physical functioning, physical and emotional role functioning and social functioning (all p≤0.001). The presence of tremor correlated with worse physical functioning and pain (all p≤0.006). Younger age was associated with reduced emotional well-being and vitality (all p≤0.006). There were no HR-QoL differences between sexes. CONCLUSION: HR-QoL in isolated dystonia is strongly associated with psychiatric and physical features. While current standard of care focus on motor aspects of dystonia, comprehensive care should address both physical and mental aspects of health.
ABSTRACT
BACKGROUND: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility. OBJECTIVE: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach. METHODS: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal. RESULTS: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10-8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10-6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10-8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823). CONCLUSION: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.
Subject(s)
Genome-Wide Association Study , Torticollis , Death Domain Receptor Signaling Adaptor Proteins/genetics , Gene Frequency , Genetic Predisposition to Disease/genetics , Guanine Nucleotide Exchange Factors/genetics , Humans , Polymorphism, Single Nucleotide/genetics , Reproducibility of Results , Torticollis/geneticsABSTRACT
BACKGROUND AND PURPOSE: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread. METHODS: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping. RESULTS: Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread. CONCLUSIONS: This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.
Subject(s)
Dystonia , Dystonic Disorders , Adult , Databases, Factual , Dystonia/epidemiology , Dystonic Disorders/complications , Dystonic Disorders/epidemiology , Humans , Tremor/epidemiology , Tremor/etiologyABSTRACT
Keloid and hypertrophic scars are fibroproliferative disorders resulting from abnormal wound healing in genetically susceptible individuals. Current therapies are often ineffective. Kynurenine shows promise as a topical treatment for keloids and hypertrophic scars. In this study, healthy adult male and female subjects seeking treatment for mature keloid scars were enrolled. Subjects were randomized in double-blind fashion to receive kynurenic acid 0.5% (FS2) cream (Group 1), an active onion extract comparator treatment (Group 2), or the inactive vehicle (Group 3). Each treatment was applied twice-daily. Qualitative assessments were made using the Vancouver Scar Scale (VSS), as well as the Patient and Observer Scar Assessment Scales (POSAS). Among subjects in Group 1, there was a substantial decrease in mean PGSS scores after 30 days of treatment that continued to trend downward, becoming significant versus Group 2 at days 90 and 180 (P<0.05) and versus Group 3 at day 180 (P<0.01). Based on mean VSS scores, subjects in Group 1 achieved beneficial effects that became significant versus Group 2 at day 90 (P<0.01), day 120 (P<0.05), and day 180 (P<0.001) and versus Group 3 at day 180 (P<0.05). There were no significant improvements in Groups 2 or 3. There were no adverse events or local skin reactions. The twice-daily application of FS2 Cream represents a potentially new and effective treatment for mature keloid scars. J Drugs Dermatol. 2021;20(9):964-968. doi:10.36849/JDD.6197.
Subject(s)
Cicatrix, Hypertrophic , Keloid , Administration, Topical , Adult , Cicatrix, Hypertrophic/drug therapy , Double-Blind Method , Female , Humans , Keloid/drug therapy , Keloid/pathology , Male , Skin/pathology , Treatment OutcomeABSTRACT
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.
Subject(s)
Keratosis, Actinic , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Consensus , Humans , Keratosis, Actinic/diagnosis , Keratosis, Actinic/therapy , Treatment OutcomeABSTRACT
Vegetable intake is far below recommendations among African-American adolescents living in economically-underserved urban areas. While the National School Lunch Program (NSLP) helps overcome access barriers, vegetable intake remains challenging and novel interventions are required. A two-year, multi-phase, school-based intervention was conducted at an urban, economically-underserved, and predominantly African-American high school in Baltimore, Maryland to determine whether stakeholder-informed addition of spices and herbs to NSLP vegetables would increase intake. The stakeholder engagement phase included assessment of NSLP vegetable attitudes/preferences among 43 school stakeholders and subsequent student sensory testing. The second phase was conducted in the school cafeteria and consisted of eight weeks comparing student intake of typical vegetable recipes versus otherwise-identical recipes with spices and herbs. 4,570 student lunch plates were included in the vegetable intake comparison. Vegetable intake was measured by lunch tray plate waste. Willingness to try vegetables was assessed by the difference between plate waste and estimated mean vegetable served weight. Intake of typical vegetable recipes and vegetable recipes with spices and herbs was compared with student's t-test. Chi-square test was used to compare willingness to try vegetables. Total vegetable intake was 18.2% higher (8.22 grams per meal, p<0.0001) with spices and herbs than with typical recipes. There were no differences in trying vegetables with spices and herbs, although student-led advocacy was associated with increased trying vegetables with spices and herbs (78.8% with advocacy, 67.5% without advocacy, p<0.0001). The addition of spices and herbs to vegetables in the NSLP was feasible and associated with small increases in vegetable intake at an urban, economically-underserved, and predominantly African-American high school.