Rhabdoid tumor predisposition syndrome: A historical review of treatments and outcomes for associated pediatric malignancies.

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS. In this manuscript, we review the genetic and clinical features of RTPS and, using known registry data and clinical reports, review associated tumor types ATRT, RTK, and EERT, closing with potential new approaches to treatment. We propose collaborative international efforts to study the use of SMARC (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin)-targeting agents, high-dose consolidative therapy, and age-based irradiation of disease sites in RTPS.

Performing Platform Governance: Facebook and the Stage Management of Data Relations.

Controversies surrounding social media platforms have provided opportunities for institutional reflexivity amongst users and regulators on how to understand and govern platforms. Amidst contestation, platform companies have continued to enact projects that draw upon existing modes of privatized governance. We investigate how social media companies have attempted to achieve closure by continuing to set the terms around platform governance. We investigate two projects implemented by Facebook (Meta)-authenticity regulation and privacy controls-in response to the Russian Interference and Cambridge Analytica controversies surrounding the 2016 U.S. Presidential Election. Drawing on Goffman's metaphor of stage management, we analyze the techniques deployed by Facebook to reinforce a division between what is visible and invisible to the user experience. These platform governance projects propose to act upon front-stage data relations: information that users can see from other users-whether that is content that users can see from "bad actors", or information that other users can see about oneself. At the same time, these projects relegate back-stage data relations-information flows between users constituted by recommendation and targeted advertising systems-to invisibility and inaction. As such, Facebook renders the user experience actionable for governance, while foreclosing governance of back-stage data relations central to the economic value of the platform. As social media companies continue to perform platform governance projects following controversies, our paper invites reflection on the politics of these projects. By destabilizing the boundaries drawn by platform companies, we open space for continuous reflexivity on how platforms should be understood and governed.

Meta-analysis assessing the sensitivity and specificity of 18F-FDG PET/CT for the diagnosis of prosthetic valve endocarditis (PVE) using individual patient data (IPD).

IMPORTANCE: The use of 18F-FDG PET/CT in diagnostic algorithms for PVE has increased since publication of studies and guidelines advocating its use. The assessment of test accuracy has been limited by small study sizes. We undertook a systematic review using individual patient data (IPD) meta-analysis techniques. OBJECTIVE: To estimate the summary sensitivity and specificity of 18F-FDG PET/CT in diagnosing PVE. We also assessed the effect of patient factors on test accuracy as defined by changes in the odds ratios associated with each factor. The effect of the PET/CT study on the final diagnosis was also assessed when compared to the preliminary Duke classification to determine in which patient group 18F-FDG PET/CT had the greatest utility. STUDY SELECTION: Studies were included if PET/CT was performed for suspicion of PVE and IPD of both the PET/CT result and final diagnosis defined by a gold-standard assessment was available. There were 3 possible final diagnoses ("definite PVE," "possible PVE," and "rejected PVE"). RESULTS: Seventeen studies were included with IPD available for 537 patients (from 538 scans). The summary sensitivity and specificity were 85% (95% CI 74.2%-91.8%) and 86.5% (95% CI 75.8%-92.9%) respectively when patients with final diagnosis of "possible PVE" were classified as positive for PVE. When this group was classified as negative for PVE, sensitivity was 87.4% (95% CI 80.4%-92.1%) and specificity was 84.9% (95% CI 71.5%-92.6%). Patients with a known pathogen (especially coagulase negative staphylococcal species), elevated CRP, a biological or aortic valve infection appeared more likely to have an accurate PET/CT diagnosis. Those with a mechanical valve, prior antibiotic treatment or a transcatheter aortic valve replacement valve were less likely to have an accurate test. Time since valve implantation and the presence of surgical adhesive did not appear to affect test accuracy. Of the patients with a preliminary Duke classification of "possible PVE," 84% received a more conclusive final diagnosis of "definite" or "rejected" PVE after the PET/CT study. CONCLUSIONS AND RELEVANCE: 18F-FDG PET/CT has high sensitivity and specificity in diagnosing PVE and the diagnostic utility is greatest in patients with a preliminary Duke classification of "possible PVE." Some patient factors appear to affect test accuracy, though these results should be interpreted with caution given low patient numbers for subgroup analyses.

Association of neutrophil-lymphocyte ratio with survival in peripheral early-stage non-small cell lung cancer after stereotactic body radiation therapy.

BACKGROUND: The role of neutrophil-lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. We performed an observational cohort study to determine the role of pretreatment NLR in predicting survival of early-stage NSCLC patients after single fraction SBRT. METHODS: A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Optimal threshold of neutrophil-lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate outcomes. RESULTS: A total of 286 patients were included for analysis with median follow up of 19.7 months. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02-1.10, p = 0.005) and PFS (aHR 1.05, 95% CI 1.01-1.09, p = 0.013). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05-1.18, p < 0.001). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching. CONCLUSIONS: Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after single fraction SBRT.

Veil-of-ignorance reasoning favors the greater good.

The "veil of ignorance" is a moral reasoning device designed to promote impartial decision making by denying decision makers access to potentially biasing information about who will benefit most or least from the available options. Veil-of-ignorance reasoning was originally applied by philosophers and economists to foundational questions concerning the overall organization of society. Here, we apply veil-of-ignorance reasoning in a more focused way to specific moral dilemmas, all of which involve a tension between the greater good and competing moral concerns. Across 7 experiments (n = 6,261), 4 preregistered, we find that veil-of-ignorance reasoning favors the greater good. Participants first engaged in veil-of-ignorance reasoning about a specific dilemma, asking themselves what they would want if they did not know who among those affected they would be. Participants then responded to a more conventional version of the same dilemma with a moral judgment, a policy preference, or an economic choice. Participants who first engaged in veil-of-ignorance reasoning subsequently made more utilitarian choices in response to a classic philosophical dilemma, a medical dilemma, a real donation decision between a more vs. less effective charity, and a policy decision concerning the social dilemma of autonomous vehicles. These effects depend on the impartial thinking induced by veil-of-ignorance reasoning and cannot be explained by anchoring, probabilistic reasoning, or generic perspective taking. These studies indicate that veil-of-ignorance reasoning may be a useful tool for decision makers who wish to make more impartial and/or socially beneficial choices.

Generating Options and Choosing Between Them Depend on Distinct Forms of Value Representation.

Humans have a remarkable capacity for flexible decision-making, deliberating among actions by modeling their likely outcomes. This capacity allows us to adapt to the specific features of diverse circumstances. In real-world decision-making, however, people face an important challenge: There are often an enormous number of possibilities to choose among, far too many for exhaustive consideration. There is a crucial, understudied prechoice step in which, among myriad possibilities, a few good candidates come quickly to mind. How do people accomplish this? We show across nine experiments (N = 3,972 U.S. residents) that people use computationally frugal cached value estimates to propose a few candidate actions on the basis of their success in past contexts (even when irrelevant for the current context). Deliberative planning is then deployed just within this set, allowing people to compute more accurate values on the basis of context-specific criteria. This hybrid architecture illuminates how typically valuable thoughts come quickly to mind during decision-making.

HPLC-MS/MS analysis of anthocyanins in human plasma and urine using protein precipitation and dilute-and-shoot sample preparation methods, respectively.

A high-performance liquid chromatography tandem-mass spectrometry (HPLC-MS/MS) method has been developed to analyze anthocyanins in urine and plasma to further understand their absorption, distribution, metabolism and excretion. The method employed a Synergi RP-Max column (250 × 4.6 mm, 4 µm) and an API 4000 mass spectrometer. A gradient elution system consisted of mobile phase A (water-1% formic acid) and mobile phase B (acetonitrile) with a flow rate of 0.60 mL/min. The gradient was initiated at 5% B, increased to 21% B at 20 min, and then increased to 40% B at 35 min. The analysis of anthocyanins presents a challenge because of the poor stability of anthocyanins during sample preparation, especially during solvent evaporation. In this method, the degradation of anthocyanins was minimized using protein precipitation and dilute-and-shoot and sample preparation methods for plasma and urine, respectively. No interferences were observed from endogenous compounds. The method has been used to analyze anthocyanin concentrations in urine and plasma samples from volunteers administered saskatoon berries. Cyanidin-3-galactoside, cyanidin-3-glucoside, cyanidin-3-arabinoside, cyanidin-3-xyloside and quercetin-3-galactoside, the five major flavonoid components in saskatoon berries, were identified in plasma and urine samples.

Treatment of Atopic Dermatitis in the United States: Analysis of Data from the National Ambulatory Medical Care Survey.

Introduction: Atopic dermatitis (AD) affects both adult and pediatric patients, and multiple practitioners encounter and manage AD. However, differences with regard to the treatment of AD between specialties are not well characterized. OBJECTIVE: The primary objective of this study was to determine if there is a difference between dermatologists and non-dermatology specialties with regard to treatment strategies for AD and to describe those differences. METHODS: Data from the 1993-2010 National Ambulatory Medical Care (NAMCS) and National Hospital Ambulatory Care (NHAMCS) Surveys were used to characterize outpatient visits made for AD. Differences in demographic, geographic and seasonal characteristics were obtained and compared. Additionally, the frequency of medications prescribed at dermatologist visits were compared to other specialties. PRIMARY OUTCOME MEASURES: Frequency of modalities used in the treatment of atopic dermatitis between dermatologists and non-dermatology specialties. RESULTS: An estimated 3.7 million visits for AD were made to outpatient offices and hospital departments from 1993 to 2010. The rates per capita of visits for atopic dermatitis were similar when evaluated by gender and season. However, Caucasians were almost 50% less likely than African Americans or individuals of other minority races to have visits for AD. Topical corticosteroids (TCS) were mentioned at 52% of visits, and dermatologists were more likely than non-dermatologists to prescribe TCS, emollients, and topical calcineurin inhibitors. CONCLUSIONS: Dermatologists were more likely to recommend TCS, emollients, and topical calciuneurin inhibitors for the treatment of AD. Dermatologists were also more likely to prescribe higher potency TCS in comparison to non-dermatology specialties, and these differences may ultimately affect patient care. As a result, there remains a disparity between dermatologists and non-dermatology specialties with regard to evidence-based approaches to the treatment of AD.

J Drugs Dermatol. 2017;16(3):250-255.

A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia.

INTRODUCTION: Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia primarily affecting women of African descent on the crown of the scalp. Limited data exists regarding evidence-based treatment for CCCA.

OBJECTIVE: To examine photos of subjects with CCCA before and after treatment in order to evaluate results of treatment and compare results of different treatment regimens.

METHODS: Photographs of 15 subjects with CCCA before and after treatment were evaluated by two blinded investigators who assigned disease severity scores to photographs based on a published scale: Central Scalp Alopecia Photographic Scale in African American Women.

RESUTLS: Median change in severity score (post-treatment severity score - pre-treatment severity score) was 0.5 (P = 0.58) for all 15 subjects receiving a series of 7 to 8 intralesional steroid injections along with topical steroids (Class I/II) +/- minoxidil and +/- anti-dandruff shampoo, indicating worsening of disease after treatment. Subjects receiving minoxidil versus those who did not (0.25 vs 0.5; P = 0.38) and subjects receiving anti-dandruff shampoo versus those who did not (0.0 vs 0.5; P = 0.42) demonstrated no statistically significant difference in pre- and post-treatment severity scores. Of 15 subjects, 5/15 (33.3%) had decreased severity scores, 8/15 (53.3%) had increased severity scores, and 2/15 (13.3%) had no change in severity scores.

CONCLUSIONS: Although no statistically significant difference was found in pre- versus post-treatment disease severity, this may indicate intralesional steroid injections and topical steroids +/- minoxidil and +/- anti-dandruff shampoo halt disease progression.

J Drugs Dermatol. 2017;16(4):317-320.

Characterization of Patients' Quality of Life and Experience in the Course of Acne Treatment.

Few studies provide qualitative data on the acne treatment experience. This study describes patients' personal experiences of acne treatment. Video interviews were made of 27 teenagers and young adults with acne treated for 12 weeks with adapalene/benzoyl peroxide gel. Transcripts were then coded and qualitatively analyzed. Four thematic domains affecting quality of life and experience were identified: clinical manifestations, self-perception, social placement, and perception of control. Successful treatment increased self-esteem and performance at work and school. Successful acne treatment improves patients' quality of life by improving appearance and self-perception, satisfaction with social placement, and perception of control.

Treatment of Molluscum Contagiosum with Imiquimod in the United States: A Retrospective Cross-Sectional Study.

Since there are concerns that imiquimod is being overprescribed for children with molluscum despite its limited efficacy, we used data from two nationally representative surveys to determine the rate at which imiquimod was being prescribed for molluscum contagiosum in the United States. From 1999-2010, there were an estimated 6.4 million visits for molluscum (95% CI: 5.5, 7.3 million), and imiquimod was prescribed at 7.0% of these visits (95% CI: 3.4, 11). Given the low frequency of patients being treated with imiquimod for molluscum, the concerns of its overuse may be unfounded.

Dermatology Residents are Prescribing Tanning Bed Treatment.

Although 90% of dermatologists discourage the use of tanning beds, about half of psoriasis patients report using tanning beds and most of these note improvement. The purpose of this investigation was to determine if dermatology residents are advocating the tanning bed use to their patients.

A significant proportion of thalassemia major patients have adrenal insufficiency detectable on provocative testing.

Advances in chelation therapy and noninvasive monitoring of iron overload have resulted in substantial improvements in the survival of transfusion-dependent patients with thalassemia major. Myocardial decompensation and sepsis remain the major causes of death. Although endocrine abnormalities are a well-recognized problem in these iron-overloaded patients, adrenal insufficiency and its consequences are underappreciated by the hematology community. The aims of this study were to determine the prevalence of adrenal insufficiency in thalassemia major subjects, to identify risk factors for adrenal insufficiency, and to localize the origin of the adrenal insufficiency within the hypothalamic-pituitary-adrenal axis. Eighteen subjects with thalassemia major (18.9±9.3 y old, 7 female) were tested for adrenal insufficiency using a glucagon stimulation test. Those found to have adrenal insufficiency (stimulated cortisol <18 µg/dL) subsequently underwent an ovine corticotropin-releasing hormone (oCRH) stimulation test to define the physiological basis for the adrenal insufficiency. The prevalence of adrenal insufficiency was 61%, with an increased prevalence in males over females (92% vs. 29%, P=0.049). Ten of 11 subjects who failed the glucagon stimulation test subsequently demonstrated normal ACTH and cortisol responses to oCRH, indicating a possible hypothalamic origin to their adrenal insufficiency.

Training for prescribing in-office and home phototherapy.

BACKGROUND/PURPOSE: One reason phototherapy use is lacking in the United States may be inadequate phototherapy education during dermatology training. The purpose of this study was to estimate the level of dermatology resident training with prescribing phototherapy and to see whether inadequate education may be contributing to the underuse of phototherapy in the United States. METHODS: A questionnaire was developed to assess resident education and comfort with prescribing phototherapy from the resident perspective. Botulinum toxin and radiation therapy training were used as positive and negative controls, respectively. Responses were tabulated and comparisons made using Fisher's exact test and Cochran-Armitage trend test. RESULTS: A total of 88 residents responded. 42% and 81% of respondents reported not receiving didactic education on prescribing in-office and home phototherapy, respectively, compared to 13% for botulinum toxin and 91% for radiation therapy. 29% and 76% reported not being comfortable prescribing in-office and home phototherapy, respectively, compared to 36% for botulinum toxin and 91% for radiation therapy. Phototherapy education satisfaction was positively correlated with comfort of prescribing, and comfort prescribing was positively correlated with actual prescribing of phototherapy. CONCLUSIONS: Training for prescribing phototherapy is lacking. Augmenting phototherapy training may help make home phototherapy more accessible for patients.

Treatment of Alopecia Areata in the United States: A Retrospective Cross-Sectional Study.

BACKGROUND: Alopecia Areata (AA) is a non-scarring alopecia that affects millions of Americans, however the way it is treated and which patients seek treatment is not well characterized. OBJECTIVE: To better understand how AA was being treated in the United States, what type of patients are seen for AA, and what physicians treated them. METHODS: We analyzed data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2001 to 2010. We tabulated patient characteristics, the physicians who treated AA and what treatments were prescribed for AA. RESULTS: There were an estimated 2.6 million outpatient visits for AA. Patients with AA were most commonly treated by a dermatologists (84.8%). Patients were most commonly treated with topical and injected corticosteroids (61.0%) followed by minoxidil (5.9%) and topical tacrolimus (5.7%). Males made fewer visits per 1,000 capita compared to females (P=0.01). LIMITATIONS: The NAMCS and NHAMCS do not record severity of disease data. CONCLUSIONS: Topical and injected corticosteroids are the mainstay of treatment for AA, however the use of steroid sparing agents such as minoxidil is low. Despite no studies demonstrating efficacy, topical tacrolimus was used almost as frequently as minoxidil.

Five-Year Trend in the Number of Dermatologic Clinical Drug Trials Registered on ClinicalTrials.gov.

BACKGROUND: There is a reported global decrease in the number of clinical trials conducted in recent years. We aimed to determine if this declining trend can be extrapolated to dermatologic clinical trials. METHODS: We conducted a query of ClinicalTrials.gov for dermatologic clinical trials from 2009 to 2013 for 6 common skin conditions: acne, psoriasis, rosacea, eczema and atopic dermatitis, actinic keratosis, and skin cancer. Results were sorted by condition and number of study subjects. This study did not involve any participants apart from the researchers. RESULTS: Although there is an increasing trend in the number of trials performed annually, the results were not significant (P =.08). The average number of patients per study has not significantly changed (P =.12), but there was a significant increase in the number of large studies (201+ subjects) conducted over time (P =.002). Although there was significant variation based on dermatologic condition studied (global statistic P=.01), only skin cancer demonstrated a significant change in the number of studies registered annually (ß=10.6 studies/year, P =.04). CONCLUSIONS AND RELEVANCE: The sky does not appear to be falling, at least not yet, with regard to continued development of treatments for patients with skin disease.

The rosacea patient journey: a novel approach to conceptualizing patient experiences.

The motivation for rosacea patients to seek and adhere to treatment is not well characterized. A patient journey is a map of the steps a patient takes as he/she progresses through different segments of the disease from diagnosis to management, including all the influences that can push him/her toward or away from certain decisions. We sought to examine each step of the rosacea patient journey to better understand key patient care boundaries faced by rosacea patients. A PubMed search of articles indexed for MEDLINE as well as a search of the National Rosacea Society Web site (http://www.rosacea.org) were conducted to identify articles and materials that quantitatively or qualitatively described rosacea patient experiences. Current literature pertaining to the rosacea patient journey was summarized. The rosacea patient journey is discussed. It is a useful tool to gain insight on patient experiences. Better understanding of the patient perspective by dermatologists can lead to better patient adherence to treatment and thus improved quality of life and satisfaction.

The US 2009 A(H1N1) influenza epidemic: quantifying the impact of school openings on the reproductive number.

BACKGROUND: There is limited information on differences in the dynamics of influenza transmission during time periods when schools are open compared with periods when they are closed. METHODS: Data on school openings, influenza surveillance, and absolute humidity were incorporated into a regression model to estimate the increase in the reproductive number for the 2009 A(H1N1) influenza pandemic associated with the opening of school in 10 US states. RESULTS: The estimate for the average increase in the reproductive number for the 2009 A(H1N1) influenza pandemic associated with the beginning of the school year was 19.5% (95% credible interval = 10%-29%). CONCLUSIONS: Whether schools are open or closed can have a major impact on community transmission dynamics of influenza.

Risk factors for leptomeningeal carcinomatosis in patients with brain metastases who have previously undergone stereotactic radiosurgery.

Our objective was to explore the hypothesis that the risk of leptomeningeal dissemination (LMD) in patients who underwent stereotactic radiosurgery (SRS) for brain metastases is influenced by the site of the primary cancer, the addition of whole brain radiation therapy (WBRT), surgical resection, and control over their systemic disease. We conducted a retrospective cohort analysis of 805 patients who were treated with SRS for brain metastases between 1999 and 2012 at the Wake Forest Baptist Medical Center, and excluded all patients with evidence of LMD before SRS. The primary outcome was LMD. Forty-nine of 795 patients developed LMD with a cumulative incidence of 6.2% (95% Confidence Interval (CI), 4.7-8.0). Median time from SRS to LMD was 7.4 months (Interquartile Range (IQR), 3.3-15.4). A colorectal primary site (Hazard Ratio (HR), 4.5; 95% CI 2.5-8.0; p < 0.0001), distant brain failure (HR, 2.0; 95% CI 1.2-3.2; p = 0.007), breast primary site (HR, 1.6; 95% CI 1.0-2.7; p = 0.05), the number of intracranial metastases at time of initial SRS (HR, 1.1; 95% CI 1.0-1.2; p = 0.02), and age (by 5-year interval) (HR, 0.9; 95% CI 0.8, 0.9; p = 0.0006) were independent factors associated with LMD. There was no evidence that surgical resection before SRS altered the risk of LMD (HR, 1.1; 95 % CI 0.6-2.0, p = 0.78). In patients who underwent SRS for brain metastases, a colorectal or breast primary site, distant brain failure, younger age, and an increased number of intracranial metastases were independently associated with LMD. Given its relative rarity as an outcome, multi-institutional prospective studies will likely be necessary to validate and quantify these relationships.

The duration of acne treatment.

BACKGROUND: Acne has a ~90% lifetime prevalence, however the duration of the condition and its treatment is not well characterized. The purpose of this study was to estimate for how long acne patients are treated. METHODS: Electronic patient records from an academic practice were queried to identify dermatology visits with an acne diagnosis (ICD-9: 706.1) between January 1, 2009 and June 1, 2012. The duration of care for acne treatment was calculated as the time between the earliest and latest visits. Kaplan Meier analyses were used to describe treatment duration RESULTS: 1,130 patients had at least one visit acne-related visit to a dermatologist, with 631 (56%) having only one visit and 499 (44%) having multiple visits over the study period. For patients with multiple visits, the mean duration from first to last visit was 0.57 year (95% CI: 0.52, 0.62); 25% ceased visiting in 0.25 year, 50% in 0.40 year, and 75% in 0.64 year. CONCLUSION: Our study provides a lower limit on the duration of acne treatment. The duration of acne treatment is longer than the duration of typical acne clinical trials. Understanding the duration of the disease can help set patients' treatment expectations, which may help improve adherence.