Would You Rather: Quantifying Traumatic Brain Injury Survivor Perceptions of Functional Status Through Their Surrogates.

OBJECTIVE: To quantify health utilities of the Glasgow Outcome Scale-Extended (GOSE) states after actual traumatic brain injury (TBI). BACKGROUND: Recovery after TBI is measured using the GOSE, a validated clinical trial endpoint. A recent public survey quantified the health utilities of some GOSE states after hypothetical TBI as worse than death. However, no health utilities exist for disability after actual TBI. METHODS: This national computer-adaptive survey followed Enhancing the Quality and Transparency of Health Research-Checklist for Reporting Results of Internet E-Surveys guidelines and recruited adult TBI survivors (injury >1 year prior) through their available surrogates. Using a standard gamble approach in randomized order, participants gave preferences for post-TBI categorical health states ranging from GOSE 2 to GOSE 8. We calculated median (interquartile range) health utilities for each GOSE state, from -1 (worse than death) to 1 (full health), with 0 as reference (death, GOSE 1). RESULTS: Of 515 eligible, 298 surrogates (58%) consented and completed the scenarios on TBI survivors' behalf. TBI survivors had a current median GOSE 5 (3-7). GOSE 2, GOSE 3, and GOSE 4 were rated worse than death by 89%, 64%, and 38%, respectively. The relationship was nonlinear, and intervals were unequal between states, with a bimodal distribution for GOSE 4. CONCLUSIONS: In this index study of actual post-TBI disability, poor neurological outcomes represented by GOSE 2 to GOSE 4 were perceived as worse than death by at least one in 3 survivors. Similar to previously reported public perceptions after a hypothetical TBI, these long-term perceptions may inform earlier post-TBI shared decision-making, as well as help shape value-based research and quality of care. LEVEL OF EVIDENCE: Level II-economic and value-based evaluations.

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis.

OBJECTIVE: The objective of this article is to review abrocitinib, an oral Janus kinase (JAK) 1 inhibitor, for the treatment of patients with moderate-to-severe atopic dermatitis (AD). DATA SOURCES: A literature search of MEDLINE (PubMed) was performed for articles from inception through end-March 2022 using the following search terms: atopic dermatitis, abrocitinib, PF-04965842, methotrexate, cyclosporine, dupilumab, ruxolitinib, and JAK-STAT pathway. STUDY SELECTION AND DATA EXTRACTION: English articles relating to pharmacology, pharmacokinetics, efficacy, and safety of abrocitinib, and other conventional systemic medications for AD, were included. DATA SYNTHESIS: Across phase IIb and phase III clinical trials, abrocitinib was efficacious with an average of 47.5% patients on 200 mg abrocitinib and 32.0% on 100 mg abrocitinib achieving an Investigator's Global Assessment (IGA) of 0 or 1 at 12 weeks. In comparison with dupilumab 300 mg subcutaneously every other week, patients on abrocitinib 200 mg once daily had improved disease severity and itch response. The majority of adverse events were not severe and self-limited. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Prior to Food and Drug Administration (FDA) approval of abrocitinib, prednisone was the only FDA-approved oral medication for AD. Although biologics such as dupilumab have revolutionized care, some patients prefer oral medications. Compared with clinical trials of conventional AD treatments, abrocitinib appears more effective. CONCLUSIONS: Abrocitinib is an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who have not responded to systemic medications or when contraindicated otherwise.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). BACKGROUND: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. METHODS: This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. RESULTS: Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. CONCLUSION: Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Cidofovir in the Management of Non-Genital Warts: A Review.

INTRODUCTION: Cutaneous warts are one of the most frequent reasons for visits to the dermatologist. While there are many treatment options available and commonly used to treat warts, recurrence of lesions is common and complete clearance is rarely achieved. Cidofovir is an antiviral agent that has activity against various DNA viruses, including HPV, the virus that results in verrucae. OBJECTIVE: We examined the literature on the use of cidofovir in the treatment of non-genital warts to further assess its safety and efficacy.  Methods: A review of the literature using PubMed and Google Scholar databases was conducted to find relevant case reports and studies on the use of cidofovir in the treatment of non-genital warts.  Results: Thirteen case reports, five case series, six retrospective chart reviews, and one clinical study were reviewed and included. There were a total of 603 patients, 46.2% males and 53.7% females. Of 603 patients included in this review, 212 (35.2%) were treated with topical cidofovir for their warts. Clearance was achieved in 55.2%. There was no recurrence of lesions after clearance at two months to three years post-treatment (mean of 15.8 months). Of the 212 patients treated with topical cidofovir, 37 (17.4%) reported local side effects such as erythema, pruritus, and burning.  Discussion/Conclusion: Treatment options for recalcitrant non-genital warts are limited and have varying efficacy. Topical cidofovir may serve as an effective, safe, and affordable alternative for the clearance of recalcitrant non-genital warts, but controlled clinical trials are needed.J Drugs Dermatol. 2023;22(10):1009-1016  doi:10.36849/JDD.7258.

Topical Ivermectin Is Associated With Improved Erythematotelangiectatic, Papulopustular, and Phymatous Rosacea in a Secondary Analysis.

Rosacea has variable clinical presentation consisting of four overlapping phenotypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1 Rosacea's pathogenesis involves increased cutaneous density of Demodex folliculorum mites, which drive inflammation through activation of Toll-like receptor-2.1,2 Thus, topical ivermectin (IVM) 1.0% cream's anti-inflammatory and acaricidal activity provides an effective and targeted treatment for moderate-to-severe rosacea. However, literature assessing IVM is limited to efficacy in treating the papulopustular presentation, limiting generalizability.1,3,4 Although our primary endpoint was to assess patient adherence, the objective of this secondary analysis was to assess IVM efficacy in rosacea, regardless of clinical presentation.

The Patient-Physician Relationship and Adherence: Observations From a Clinical Study.

Improved patient-physician relationships (PPR) are associated with better patient satisfaction and disease outcomes, however, there is limited literature assessing how PPR affects adherence in dermatology. We recruited 30 subjects with a clinical diagnosis of rosacea. Subjects were instructed to use ivermectin 1% cream once daily for 3 months and adherence was measured using the Medication Event Monitoring System cap. The Patient-Doctor Relationship Questionnaire (PDRQ-9), a validated questionnaire assessing patients’ perceived strength of the relationship with their doctor, was completed. Mean adherence for all subjects over three months of the study was 62%. PDRQ-9 scores positively correlated with adherence rates for 3 months of treatment (r(26)=0.52; P=0.006). The perceived strength of the PPR may have a role in patients’ adherence to their medications. Improving the PPR, through empathy and effective communication, may facilitate better medication adherence and treatment outcomes. Perche PO, Singh R, Cook MK, et al. The patient-physician relationship and adherence: observations from a clinical study. J Drugs Dermatol. 2023;22(8):838-839. doi:10.36849/JDD.7103.

Topical Moisturizer Meaningfully Reduces Disease Severity in Atopic Patients With Xerosis.

BACKGROUND: Repairing the epidermal barrier is critically important in atopic dermatitis (AD), but the effect of moisturizer on quality of life (QOL) is not well characterized.  Objective: To assess whether the use of a moisturizer improves QOL in atopic patients with xerosis.  Methods: Thirty-five (35) adults with xerosis and AD received a moisturizer designed for AD to apply daily for three months. Adherence was assessed with electronic monitors. Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI) at baseline and follow-up.  Results: Mean adherence to the moisturizer was 46%. Dryness improved from 1.9 at baseline to 1.4 at follow-up (P=0.02). DLQI improved from 3.3 at baseline to 1.5 at 3 months (P=0.005). The "feeling self-conscious or embarrassed due to their skin condition" DLQI item improved from 0.79 at baseline to 0.14 at 3 months (P=0.0009).  Conclusion: Moisturizers are the foundation of AD treatment. Even non-medicated topical emollients can improve QOL in patients with AD.  J Drugs Dermatol. 2023;22(12):e51-e52.     doi:10.36849/JDD.7036e.

Dermatology through the lens of social media: A qualitative study among adolescents.

Social media (SM) use has accelerated at an unprecedented pace and dermatology literature evaluating SM use is primarily centered on the quality and quantity of dermatologic content, with minimal research on how adolescent patients experience such content. We recruited 15 patients between the ages of 13-18 years from the Atrium Health Wake Forest Baptist Department of Dermatology to interview regarding their experience with dermatologic content on SM. Despite most participants' insightful comments on SM use and the relative lack of dermatologic content validation on SM, many participants adopted skin care advice from SM. Adolescents are particularly vulnerable to social influence and it is important dermatologists understand how pervasive skin-related content is on these platforms.

Prevalence and Risk Factors for Intensive Care Unit Delirium After Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Delirium remains understudied after traumatic brain injury (TBI). We sought to identify independent predictors of delirium among intensive care unit (ICU) patients with TBI. METHODS: This single-center retrospective cohort study evaluated adult patients with TBI requiring ICU admission. Outcomes included delirium days within the first 14 days, as assessed by the Confusion Assessment Method-ICU (CAM-ICU). Models were adjusted for age, sex, insurance, Marshall head computed tomography classification, presence of subarachnoid hemorrhage (SAH), Injury Severity Score (ISS), need for cardiopulmonary resuscitation, maximum admission Glasgow Coma motor score, glucose level, hemoglobin level, and pupil reactivity. RESULTS: Delirium prevalence was 60%, with a median duration of 4 days (interquartile range: 2-8) among ICU patients with TBI (n = 2,664). Older age, higher ISS, maximum motor score < 6, Marshall class II-IV, and SAH were associated with risk of increased delirium duration (all p < 0.001). CONCLUSIONS: In this large cohort, ICU delirium after TBI affected three of five patients for a median duration of 4 days. Age, general injury severity, motor score, and features of intracranial hemorrhage were predictive of more TBI-associated delirium days. Given the high prevalence of ICU delirium after TBI and its impact on hospitalization, further work is needed to understand the impact of delirium and TBI on outcomes and to determine whether delirium risk can be minimized.

Oral Vitamin A for Acne Management: A Possible Substitute for Isotretinoin.

BACKGROUND: Recent changes to the iPLEDGE platform left providers without the ability to prescribe isotretinoin to their patients. A potential substitute for isotretinoin could be beneficial when the drug is unavailable. Prior to the FDA approval of isotretinoin, a vitamin A derivative, vitamin A was studied for its use in acne management. OBJECTIVE: To review the potential of vitamin A to serve as a substitute for isotretinoin when the latter drug is inaccessible. METHODS: We conducted a review of published literature from 1931 to 2021, regarding the use of vitamin A in acne treatment, using PubMed and Google Scholar databases. Nine studies were selected after reviewing articles for relevancy to our topic. RESULTS: Eight out of the 9 studies noted improvement in patients’ acne with vitamin A use. Ranges of doses used were 36,000 I/U daily to 500,000 I/U daily, with 100,000 I/U daily being the most common. Side effects were mainly mucocutaneous in nature. LIMITATIONS: Many of the trials included in our review were published over 50 years prior and lack standardized components of clinical trials today. CONCLUSION: Oral vitamin A could potentially serve as a substitute for isotretinoin in acne management for select patients. However, due to its teratogenicity, potential for toxicity, and long half-life, strict monitoring under the care of a medical provider is prudent. Since vitamin A is available without a prescription, strict monitoring cannot be assured, and especially careful patient selection and education would be essential. J Drugs Dermatol. 2022;21(6):683-686. doi:10.36849/JDD.6781.

The use of oral vitamin A in acne management: a review.

BACKGROUND: Changes to the iPLEDGE platform on December 13, 2021 made isotretinoin virtually inaccessible for many patients. Prior to the FDA approval of isotretinoin, a derivative of vitamin A, in 1982, vitamin A was used for severe acne. OBJECTIVE: To review the efficacy, safety, affordability, and practicality of vitamin A as a substitute for isotretinoin when the latter is inaccessible. METHODS: A literature review of PubMed was conducted using the key words: oral vitamin A, retinol, isotretinoin, Accutane, acne, iPLEDGE, hypervitaminosis A, and side effects. RESULTS: We identified 9 studies (8 clinical trials and one case report); acne improved in 8 studies. Dosages ranged from 36,000IU daily to 500,000IU with 100,000IU as the most common. Mean duration until clinical improvement was 7 weeks to four months after initiation of therapy. Mucocutaneous side effects were most common, along with headaches, which resolved with either continued treatment or cessation. CONCLUSION: Oral vitamin A is efficacious for the treatment of acne vulgaris, although the available studies have limited controls and outcomes. Side effects are qualitatively similar to those of isotretinoin and avoiding pregnancy for at least three months after stopping treatment is critical; like isotretinoin, vitamin A is a teratogen.

Management and Challenges of Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients, and can be classified into mild, moderate, and severe by the Glasgow coma scale (GCS). Prehospital, initial emergency department, and subsequent intensive care unit (ICU) management of severe TBI should focus on avoiding secondary brain injury from hypotension and hypoxia, with appropriate reversal of anticoagulation and surgical evacuation of mass lesions as indicated. Utilizing principles based on the Monro-Kellie doctrine and cerebral perfusion pressure (CPP), a surrogate for cerebral blood flow (CBF) should be maintained by optimizing mean arterial pressure (MAP), through fluids and vasopressors, and/or decreasing intracranial pressure (ICP), through bedside maneuvers, sedation, hyperosmolar therapy, cerebrospinal fluid (CSF) drainage, and, in refractory cases, barbiturate coma or decompressive craniectomy (DC). While controversial, direct ICP monitoring, in conjunction with clinical examination and imaging as indicated, should help guide severe TBI therapy, although new modalities, such as brain tissue oxygen (PbtO2) monitoring, show great promise in providing strategies to optimize CBF. Optimization of the acute care of severe TBI should include recognition and treatment of paroxysmal sympathetic hyperactivity (PSH), early seizure prophylaxis, venous thromboembolism (VTE) prophylaxis, and nutrition optimization. Despite this, severe TBI remains a devastating injury and palliative care principles should be applied early. To better affect the challenging long-term outcomes of severe TBI, more and continued high quality research is required.

Exploring the potential utility of a wearable accelerometer for estimating impact forces in ballet dancers.

Excessive forces and/or loading rates during landing may place ballet dancers at risk for overuse injury. The ability to estimate and monitor the landing forces of ballet dancers could help to improve injury prevention and rehabilitation; however, force platforms are not conducive to testing outside of a laboratory. Fortunately, it may be possible to indirectly assess landing forces via a wearable accelerometer. The purposes of this study were to examine the relationship between impact accelerations, recorded via a pelvis-worn accelerometer, and the peak forces and loading rates during performance of a common ballet manoeuvre, and to examine if a wearable accelerometer is sensitive to fatigue-related changes in landing forces. Fifteen ballet dancers continuously performed a ballet manoeuvre until self-determined exhaustion while impact accelerations and landing forces were simultaneously recorded using an accelerometer and force platforms. We observed very strong, positive relationships between the impact accelerations and the peak forces and loading rates during the landings. In addition, the changes in impact accelerations with fatigue paralleled the changes in the peak forces and loading rates. As a result, it appears that a wearable accelerometer could be used to estimate and monitor landing forces in ballet dancers.

Surrogate Perception of Disability after Hospitalization for Traumatic Brain Injury.

BACKGROUND: The Glasgow Outcome Scale Extended (GOSE) is a measure of recovery after traumatic brain injury (TBI). Public surveys rate some GOSE states as worse than death. Direct family experience caring for patients with TBI may impact views of post-TBI disability. STUDY DESIGN: We conducted a national cross-sectional computer-adaptive survey of surrogates of TBI dependents incurring injury more than 1 year earlier. Using a standard gamble approach in randomized order, surrogates evaluated preferences for post-TBI GOSE states from GOSE 2 (bedridden, unaware) to GOSE 8 (good recovery). We calculated median (interquartile range [IQR]) health utilities for each post-TBI state, ranging from -1 to 1, with 0 as reference (death = GOSE 1), and assessed sociodemographic associations using proportional odds logistic regression modeling. RESULTS: Of 515 eligible surrogates, 298 (58%) completed scenarios. Surrogates were median aged 46 (IQR 35 to 60), 54% married, with Santa Clara strength of faith 14 (10 to 18). TBI dependents had a median GOSE5 (3 to 7). Median (IQR) health utility ratings for GOSE 2, GOSE 3, and GOSE 4 were -0.06 (-0.50 to -0.01), -0.01 (-0.30 to 0.45), and 0.30 (-0.01 to 0.80), rated worse than death by 91%, 65%, and 40%, respectively. Surrogates rated GOSE 4 (daily partial help) worse than the general population. Married surrogates rated GOSE 4 higher (p < 0.01). Higher strength of faith was associated with higher utility scores across GOSE states (p = 0.034). CONCLUSIONS: In this index study of surrogate perceptions about disability after TBI, poor neurologic outcomes-vegetative, needing all-day or partial daily assistance-were perceived as worse than death by at least 1 in 3 surrogates. Surrogate perceptions differed from the unexposed public. Long-term perceptions about post-TBI disability may inform earlier, tailored shared decision-making after neurotrauma.