Association between dermatology follow-up and melanoma survival: A population-based cohort study.

BACKGROUND: Guidelines recommend that patients with melanoma undergo dermatologic examination at least annually. Adherence to follow-up and its impact on survival are unclear. OBJECTIVE: To determine the level of adherence to annual dermatologic follow-up in patients with primary cutaneous melanoma, identify predictors for better adherence, and evaluate whether adherence was associated with melanoma-related mortality. METHODS: Retrospective inception cohort analysis of adults with primary invasive melanoma in Ontario, Canada from 2010 to 2013 with follow-up until December 31, 2018. RESULTS: Adherence to dermatologic follow-up was variable with only 28.0% of patients seeing a dermatologist at least annually (median follow-up 5.0 years). Younger age, female sex, higher income, greater access to dermatology care, stage 2/3 melanoma, prior keratinocyte carcinoma, fewer comorbidities, and any outpatient visit in the 12 months prior to melanoma diagnosis were predictors for adherence. Greater adherence to annual dermatology visits was associated with reduced melanoma-specific mortality compared with lower levels of adherence (adjusted hazard ratio 0.64, 95% CI 0.52-0.78). LIMITATIONS: Observational study design and inability to identify skin examinations performed by non-dermatologists. CONCLUSION: Adherence to annual dermatology visits after melanoma diagnosis was low. Greater adherence may promote better patient survival but warrants confirmation in further research including randomized trials.

Estimates of congenital cytomegalovirus-attributable infant mortality in high-income countries: A review.

As many as 5%-10% of infants with symptomatic congenital cytomegalovirus (cCMV) disease, or 0.4%-0.8% of all liveborn infants with cCMV infection, die in early infancy in high-income countries. However, estimates are uncertain due to several potential biases that can result from data limitations and study designs. First, infants with cCMV infections who die prior to diagnosis, which usually occurs at 1-4 weeks after birth, may be excluded from both the count of deaths and the denominator of cCMV births, resulting in left truncation and immortal time biases. These 'biases' are features of the data and do not reflect bias on the part of researchers, but understanding the potential existence of threats to validity can help with interpretation of findings. Left truncation of infant deaths occurring prior to diagnosis of cCMV can result in understatement of the burden of infant deaths due to cCMV. Conversely, overestimation of infant deaths associated with symptomatic cCMV may occur in clinical case series owing to greater representation of relatively severely affected infants owing to ascertainment and referral biases. In this review, we summarise the characteristics of 26 studies that reported estimates of cCMV-associated infant deaths, including potential biases or limitations to which those estimates may have been subject. We discuss study designs whose implementation might generate improved estimates of infant deaths attributable to cCMV. More complete estimates of the overall public health impact of cCMV could inform current and future screening, prevention, and vaccine research.

The Acne Education Project: An educational initiative to improve acne health literacy and promote help-seeking behavior in young adolescents.

BACKGROUND: Acne vulgaris is an inflammatory skin condition that is associated with poor acne health literacy. Diminished acne health literacy leads to delays in the access of health care, resulting in mismanagement, disfigurement, and psychosocial morbidity. This study evaluates the potential role of early acne education in young adolescent populations to improve acne health literacy and facilitate help-seeking behavior. METHODS: The Acne Education Project is a Canadian medical student-led initiative founded to create evidence-based resources to increase acne health literacy. A 45-min interactive Zoom presentation on acne was created and delivered to 2292 students ages 9-13 in British Columbia, Canada. A quality improvement survey was administered pre-intervention, immediate post-intervention, and 1-month post-intervention to evaluate baseline acne knowledge and knowledge retention to guide presentation and resource development. RESULTS: Responses from 676 unique individuals were collected. Analysis using linear mixed-effects models demonstrated that respondents were significantly more confident in their general knowledge of acne, strategies to prevent acne, identification of psychosocial sequelae of acne, and more willing to seek help immediately post-intervention (p < .001). Differences in scores were not fully preserved in magnitude at the 1-month post-intervention assessment. However, students still scored significantly higher in all categories compared to the pre-intervention baseline (p < .001). CONCLUSION: Our findings suggest that early acne education can improve acne health literacy and promote help-seeking behavior. Given the potential long-term implications, further research is needed to explore the long-term impact of early acne education and the benefit of integrating acne education into the public education curriculum in Canada.

The Attitudes of Patients Toward Orthopaedic Post-surgical Scars.

Background Post-surgical scars (PSS) are an expected consequence of surgery. Several factors have previously been associated with PSS satisfaction including patient age and time elapsed post-operative. Little data are available regarding patient attitudes toward orthopaedic PSS. Knowledge of patient attitudes and the various associated factors may allow physicians to administer peri-operative care to mitigate the potential negative effects of PSS. Our study aims to investigate the attitudes of patients toward their PSS using quantitative scar assessment scales and to identify factors associated with PSS satisfaction. Methods We conducted a retrospective study with a follow-up. We included all patients with orthopaedic PSS on their upper or lower limbs between two and 18 weeks postoperative attending Cork University Hospital, Ireland, between February and August 2022. Patients completed an initial baseline questionnaire and then a follow-up questionnaire six months post-operative. The Patient and Observer Scar Assessment Scale (POSAS) evaluated PSS satisfaction. The European Quality of Life 5 Domain (EQ-5D), alongside several Likert scales, evaluated the patient's quality of life (QoL). Results In total, 91 patients were included. The mean POSAS score was 28.41 (95% CI, 25.85-30.97). Younger patient age (p=0.045) and decreased time passed post-operatively (p=0.002) were associated with poorer PSS satisfaction. Patients reporting their PSS appearing worse than expected were more likely to agree that their QoL had been adversely affected by it (p=0.001). Conclusion Most patients were satisfied with their orthopaedic PSS. This study identified several factors associated with poor PSS satisfaction. Our finding, which associated patient scar expectations and QoL, is novel and has not been previously examined. Accordingly, peri-operative interventions, including scar expectation management, may be implemented to mitigate scar-related QoL impact.

Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization.

Cetylpyridinium chloride (CPC) is an antimicrobial used in numerous personal care and janitorial products and food for human consumption at millimolar concentrations. Minimal information exists on the eukaryotic toxicology of CPC. We have investigated the effects of CPC on signal transduction of the immune cell type mast cells. Here, we show that CPC inhibits the mast cell function degranulation with antigen dose-dependence and at non-cytotoxic doses ∼1000-fold lower than concentrations in consumer products. Previously we showed that CPC disrupts phosphatidylinositol 4,5-bisphosphate, a signaling lipid critical for store-operated Ca2+ entry (SOCE), which mediates degranulation. Our results indicate that CPC inhibits antigen-stimulated SOCE: CPC restricts Ca2+ efflux from endoplasmic reticulum, reduces Ca2+ uptake into mitochondria, and dampens Ca2+ flow through plasma membrane channels. While inhibition of Ca2+ channel function can be caused by alteration of plasma membrane potential (PMP) and cytosolic pH, CPC does not affect PMP or pH. Inhibition of SOCE is known to depress microtubule polymerization, and here we show that CPC indeed dose-dependently shuts down formation of microtubule tracks. In vitro data reveal that CPC inhibition of microtubules is not due to direct CPC interference with tubulin. In summary, CPC is a signaling toxicant that targets Ca2+ mobilization.

Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization.

Cetylpyridinium chloride (CPC) is an antimicrobial used in numerous personal care and janitorial products and food for human consumption at millimolar concentrations. Minimal information exists on the eukaryotic toxicology of CPC. We have investigated the effects of CPC on signal transduction of the immune cell type mast cells. Here, we show that CPC inhibits the mast cell function degranulation with antigen dose-dependence and at non-cytotoxic doses ∼1000-fold lower than concentrations in consumer products. Previously we showed that CPC disrupts phosphatidylinositol 4,5-bisphosphate, a signaling lipid critical for store-operated Ca 2+ entry (SOCE), which mediates degranulation. Our results indicate that CPC inhibits antigen-stimulated SOCE: CPC restricts Ca 2+ efflux from endoplasmic reticulum, reduces Ca 2+ uptake into mitochondria, and dampens Ca 2+ flow through plasma membrane channels. While inhibition of Ca 2+ channel function can be caused by alteration of plasma membrane potential (PMP) and cytosolic pH, CPC does not affect PMP or pH. Inhibition of SOCE is known to depress microtubule polymerization, and here we show that CPC indeed dose-dependently shuts down formation of microtubule tracks. In vitro data reveal that CPC inhibition of microtubules is not due to direct CPC interference with tubulin. In summary, CPC is a signaling toxicant that targets Ca 2+ mobilization.

Sleep Disturbances in Children With Atopic Dermatitis: A Scoping Review.

Atopic dermatitis (AD) is associated with various quality of life concerns including poor sleep. Sleep impairments in children with AD are associated with increased risk of short stature, metabolic syndrome, mental illness and neurocognitive dysfunction. Although the association between AD and sleep disturbance is well established, the specific types of sleep disturbance in pediatric AD patients and their underlying mechanisms are not fully understood. A scoping literature review was performed to characterize and summarize the types of sleep disturbance in children (less than 18 years of age) with AD. 31 papers met inclusion criteria and extracted data were analyzed in an iterative manner. Two types of sleep disturbances were found to be more prevalent in pediatric AD patients in comparison to controls. One category was related to loss of sleep (increased frequency or duration of awakenings, increased sleep fragmentation, delayed sleep onset, decreased total sleep duration, and decreased sleep efficiency). Another category was associated with unusual behaviors during sleep (restlessness/limb movement/scratching, sleep-disordered breathing including obstructive sleep apnea and snoring, nightmares, nocturnal enuresis and nocturnal hyperhidrosis). Some mechanisms underlying these sleep disturbances include pruritus and induced scratching and increased proinflammatory markers induced by sleep loss. Sleep disturbance appears to be associated with AD. We recommend clinicians to consider interventions that may reduce sleep disturbances in children with AD. Further investigation of these sleep disturbances is needed to elucidate pathophysiology, develop additional treatments, and reduce negative impacts on the health outcomes and quality of life in pediatric AD patients.

Generation of unfolded outer membrane protein ensembles defined by hydrodynamic properties.

Outer membrane proteins (OMPs) must exist as an unfolded ensemble while interacting with a chaperone network in the periplasm of Gram-negative bacteria. Here, we developed a method to model unfolded OMP (uOMP) conformational ensembles using the experimental properties of two well-studied OMPs. The overall sizes and shapes of the unfolded ensembles in the absence of a denaturant were experimentally defined by measuring the sedimentation coefficient as a function of urea concentration. We used these data to model a full range of unfolded conformations by parameterizing a targeted coarse-grained simulation protocol. The ensemble members were further refined by short molecular dynamics simulations to reflect proper torsion angles. The final conformational ensembles have polymer properties different from unfolded soluble and intrinsically disordered proteins and reveal inherent differences in the unfolded states that necessitate further investigation. Building these uOMP ensembles advances the understanding of OMP biogenesis and provides essential information for interpreting structures of uOMP-chaperone complexes.

Revisiting macromolecular hydration with HullRadSAS.

Hydration of biological macromolecules is important for their stability and function. Historically, attempts have been made to describe the degree of macromolecular hydration using a single parameter over a narrow range of values. Here, we describe a method to calculate two types of hydration: surface shell water and entrained water. A consideration of these two types of hydration helps to explain the "hydration problem" in hydrodynamics. The combination of these two types of hydration allows accurate calculation of hydrodynamic volume and related macromolecular properties such as sedimentation and diffusion coefficients, intrinsic viscosities, and the concentration-dependent non-ideality identified with sedimentation velocity experiments.

Perspectives and knowledge of acne vulgaris among young adolescents.

Acne occurs in up to 90% of young adolescents, but prior research has found that this population exhibits a limited understanding of acne and is vulnerable to myths and misinformation accumulated from family members, friends, and social media. We created a virtual presentation on skin hygiene, acne prevention, and acne-associated stigma for adolescent youth (aged 9-13) to improve acne health literacy, which was reviewed by three board-certified dermatologists. A descriptive cross-sectional study using data collected for quality improvement (n = 209, total) revealed that approximately half (n = 102/202, 50.5%) of all students believed that acne could not be treated with medications, only 34.0% (n = 67/197) believed acne could impact their mental health, and most students incorrectly believed that dirt buildup (n = 124/209, 59.3%) and poor hygiene (n = 125/209, 59.8%) were pathogenic for acne. Our results stress the necessity of early evidence-based educational interventions as a cornerstone to breaking self-perpetuating myths and misinformation that may lead to acne mismanagement, delayed access to healthcare, and permanent scarring later in life.

Transition of Topical Therapy Formulation in Psoriasis: Insights from a Canadian Practice Reflective.

Patient preferences for psoriasis treatment may affect treatment adherence and disease control; changing topical formulation may improve adherence and patient acceptance of treatment. This study explored dermatologists' reasons for transitioning psoriasis patients from an ointment or gel (Dovobet®) formulation to an aerosol foam (Enstilar®) formulation of calcipotriol and betamethasone dipropionate (Cal/BD), and to assess the success of this transition. Medical records of 81 Canadian patients from 9 dermatologists were retrospectively reviewed for symptoms affecting quality of life, reasons for transitioning treatment, and whether transition was successful. Reasons for transition included efficacy, quality of life, and patient adherence. At follow-up, median psoriasis severity and body surface area affected had decreased from baseline, and patients experienced improved quality of life. Itch and itch-related sleep loss, which were identified as burdensome in 63% of patients at baseline, had resolved in 33% and improved in 54% of patients at follow-up. Dermatologists deemed the transition successful in 85% of patients, with the most common reasons being patient-reported success, clearance of signs/symptoms, and continued prescription refills. Transition from Cal/BD ointment or gel to aerosol foam was generally deemed successful by patients and dermatologists, and was associated with improved quality of life and improved itch control.

Treatments for Primary Delusional Infestation: Systematic Review.

BACKGROUND: Delusional infestation, also known as Ekbom syndrome, is a rare delusional disorder characterized by the fixed belief that one is infested with parasites, worms, insects, or other organisms. Although delusional infestation is a psychiatric condition, patients often consult dermatologists with skin findings, and it is currently unclear what treatments are recommended for this disorder. OBJECTIVE: We aimed to systematically review and describe the treatment and management of patients presenting with primary delusional infestation. METHODS: A systematic search was conducted using Ovid on MEDLINE, Embase, PsycINFO, and the Cochrane Register of Clinical Trials. Relevant data, including treatment, dosage, response, adherence, and side effects, were extracted and analyzed. RESULTS: A total of 15 case series were included, comprising 280 patients (mean age 53.3 years, 65.4% female) with delusional infestation. Overall, aripiprazole had the highest complete remission rate at 79% (11/14), although this was limited to 14 patients. Among drug classes, selective serotonin reuptake inhibitors were the most effective with a 79% (11/14) complete remission rate and 43% (9/21) partial remission rate in patients with comorbid depression, anxiety, or trichotillomania. First-generation antipsychotics and second-generation antipsychotics had similar complete remission rates (56/103, 54.4% vs 56/117, 47.9%, respectively) and partial remission rates (36/103, 35% vs 41/117, 35%, respectively). CONCLUSIONS: Due to the rarity of delusional infestation, we only found 15 case series. However, we found that first-generation antipsychotics appear to be similar in effectiveness to second-generation antipsychotics for the treatment of primary delusional infestation. Larger studies and randomized controlled trials are needed to evaluate the efficacy of pharmacological therapy for delusional infestation. TRIAL REGISTRATION: PROSPERO CRD42020198161; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198161.

The Impact of Acne Treatment on Skin Bacterial Microbiota: A Systematic Review.

BACKGROUND: Microbial strains such as Cutibacterium acnes have been examined as contributors to the pathogenesis of acne. Given the prevalence of the disease among adolescents and adults, the overutilization of antimicrobial agents may breed resistance and alter commensal microflora. OBJECTIVES: To characterize the impact of acne treatment on the diversity and relative abundance of the cutaneous microbial community, particularly of the bacterial flora. METHODS: An electronic search was conducted of Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on June 5, 2020. Interventional and observational studies examining patients receiving acne treatment with culture-independent, community-level analysis of the cutaneous microbiome were included. RESULTS: Nine studies with 170 treated acne patients were included. Five studies reported a significant change in alpha diversity following treatment, 3 of which examining systemic antibiotics reported significant increases in diversity. Two of 3 studies examining effects of benzoyl peroxide reported a decrease in diversity. However, trends in diversity were heterogeneous among studies. CONCLUSIONS: While individual variability in microbiome composition, and study-level heterogeneity in study sampling techniques may limit quantitative synthesis, our results support findings that acne treatment, including those not considered to have antimicrobial properties, alters the composition of the cutaneous microbiome.PROSPERO registration: CRD42020190629.

Risk of Vulvar Squamous Cell Carcinoma in Lichen Sclerosus and Lichen Planus: A Systematic Review.

OBJECTIVES: The objectives of this study were to determine: 1) the prevalence of lichen sclerosus (LS) and lichen planus (LP) present in association with vulvar squamous cell carcinoma (VSCC), and 2) the incidence and absolute risk of developing VSCC in LS and LP. METHODS: A search was performed of MEDLINE, EMBASE and CINAHL databases. Three independent reviewers screened articles published before September 1, 2020, first on title/abstract and then on the full text. Women with a history of VSCC, human papillomavirus, smoking, or autoimmune disease were excluded. Newcastle-Ottawa observational study scales were used to assess the risk of bias and methodological quality of the included studies. Of the 3132 studies assessed, 31 were selected for analysis. Due to study heterogeneity, a qualitative synthesis was conducted. RESULTS: The prevalence of LS and LP in association with VSCC ranged from 0% (95% CI 0-5) to 83% (95% CI 36-100) and 1% (95% CI 0-7) to 33% (95% CI 4-78), respectively. The incidence of VSCC ranged from 1.16 (95% CI 0.03-6.44) to 13.67 (95% CI 5.50-28.17) per 1000 person-years for LS. The absolute risk of developing VSCC in patients ranged from 0.0% (95% CI 0.0-5.52) to 21.88% (95% CI 9.28-39.97) with LS and was 1.16% (95% CI 0.1-4.1) with LP. Incidence was not calculable for LP owing to study characteristics. CONCLUSIONS: This review provides evidence that there is an increased risk of developing VSCC in women with LS, while associations with LP are less clear. Early identification, treatment, and long-term follow-up are essential to prevent potential malignant progression of these vulvar dermatoses.

Therapeutic Options for the Treatment of Darier's Disease: A Comprehensive Review of the Literature.

Darier's disease (also known as keratosis follicularis or dyskeratosis follicularis) is an autosomal dominant inherited disorder which manifests as hyperkeratotic greasy papules in the first or second decade of life. Aside from symptom management and behavioral modifications to avoid triggers, there are currently no validated treatments for Darier's disease (DD). However, a variety of treatments have been proposed in the literature including retinoids, steroids, vitamin D analogs, photodynamic therapy, and surgical excision. The purpose of this review article is to identify therapeutic options for treating DD and to outline the evidence underlying these interventions. A search was conducted in Medline for English language articles from inception to July 4, 2020. Our search identified a total of 474 nonduplicate studies, which were screened by title and abstract. Of these, 155 full text articles were screened against inclusion/exclusion criteria, and 113 studies were included in our review. We identified Grade B evidence for the following treatments of DD: oral acitretin, oral isotretinoin, systemic Vitamin A, topical tretinoin, topical isotretinoin, topical adapalene gel, topical 5-flououracil, topical calciptriol and tacalcitol (with sunscreen), grenz ray radiation, and x-ray radiation. All other evidence for treatments of DD consisted of case reports or case series, which is considered grade C evidence. Considering the quality and quantity of evidence, clinicians may consider initiating a trial of select topical or oral retinoids first in patients with localized or generalized DD, respectively.

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer.

Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. A confirmatory phase III trial evaluating sacituzumab govitecan vs. chemotherapy of the provider's choice was published in April 2021. Based on this trial, the FDA granted sacituzumab govitecan full regulatory approval. This antibody-drug conjugate is composed of a monoclonal antibody targeted at Trop-2 and contains the active metabolite of irinotecan, SN-38, as a cytotoxic side moiety. In a phase III clinical trial, sacituzumab govitecan demonstrated a median progression-free survival of 5.7 months vs. 1.7 months with chemotherapy. It is now an additional option for patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

Hair Removal Practices: A Literature Review.

Hair removal practices have evolved from adhering to social, cultural, and religious traditions to meeting aesthetic standards. Hair removal methods can be divided into two categories: 1) depilation, which involves removing the hair shaft and includes shaving and chemical depilatories, and 2) epilation, which involves removing the hair shaft, follicle, and bulb, and includes plucking, threading, waxing, sugaring, lasers, intense pulsed light system, electrolysis, and photodynamic therapy. Furthermore, an eflornithine hydrochloride 13.9% cream (Vaniqa®, neither an epilatory or depilatory technique), has been US FDA- and Health Canada-approved to slow the rate of facial hair growth and to be used in combination with other hair removal methods. All methods are temporary except for electrolysis, and each technique has advantages and disadvantages in terms of efficacy and adverse events. Importantly, most studies examining the efficacy of hair removal techniques are limited to darker hair and fairer skin, and further research is required especially for those with light-colored hair.

Essential Principles of Preoperative Assessment in Internal Medicine: A Case-Based Teaching Session.

Introduction: Preoperative assessment is a core competency for internal medicine residents, but one with limited educational resources available presently. Ideally, residencies would provide an introduction to this topic prior to their residents performing preoperative assessments in clinic or during internal medicine consultation rotations. Methods: We developed a 120-minute case-based teaching session on preoperative assessment for PGY 2 residents where they reviewed a series of cases, applied preoperative risk calculators, and made recommendations on medication management using the same online tools they employ while working clinically. Interspersed lecture sections reviewed guiding principles, detailed key trials, and explored nuances of the topic. We performed pre- and posttests of knowledge and also obtained learner feedback. Results: Thirty-three out of 40 participants completed the pre- and posttests. The session was rated highly (M = 4.0 out of 5) and was viewed as preferable to a lecture-based approach (M = 4.4 out of 5); mean participant knowledge improved from 11.7 to 17.5 (p < .001) out of 22 points possible. The most consistently offered feedback was to give more time for the session than the 120 minutes allotted. Discussion: A teaching session mixing lecture with review of composite cases and application of preoperative assessment tools with immediate feedback improved knowledge and was viewed as enjoyable and preferable to lecture alone by participants. We recommend providing more time for the teaching by increasing the session length from 120 minutes to 140 minutes.

Moisturizers and Cleansers in the Management of Skin Conditions Caused by Personal Protective Equipment and Frequent Handwashing.

During the COVID-19 pandemic, prolonged usage of personal protective equipment (PPE) and frequent handwashing has exacerbated or caused skin diseases, particularly amongst frontline workers. Skin conditions, such as atopic dermatitis, irritant contact dermatitis, and hand eczema, affect patients' quality of life and their ability to work. These conditions can be managed by frequent moisturization and washing with gentle cleansers. In this review, we discuss the properties of effective moisturizers and cleansers for patients with skin diseases related to enhanced infection control procedures.