Keratoacanthoma and Cutaneous Squamous Cell Carcinoma With PD-1 and PD-L1 Inhibitor Use.

This cross-sectional study assesses risk of dermatological immune-related adverse events associated with immunotherapy for cancer.

Safety Signal between Azacitidine and Pericarditis.

BACKGROUND: Drug-induced pericarditis is an important cause of pericarditis and if unnoticed and unmanaged can lead to constrictive pericarditis, pericardial effusion, and cardiac tamponade. OBJECTIVE: The objective of this analysis was to determine if a significant signal exists between azacitidine use and pericarditis. METHODS: A pharmacovigilance analysis was performed using the FDA Adverse Event Database. RESULTS: 48 reports of azacitidine-induced pericarditis with azacitidine as the suspect drug were identified. The most common indications for azacitidine use in the adverse event reports were myelodysplastic syndrome (48%) and acute myelogenous leukemia (27%). Physicians reported 44% of the azacitidine-induced pericarditis reports, while other health professional reported 52% of the reports. The disproportionality analysis showed a proportional reporting ratio of 5.0, χ2 of 149.8, reporting odds ratio of 5.0, and IC025 of 1.8. Literature review found 3 case reports of azacitidine-induced pericarditis. CONCLUSION: The signal between azacitidine and pericarditis was found to be statistically significant. Clinicians should be aware of the possible risk of pericarditis when prescribing azacitidine. If there is suspicion for azacitidine-induced pericarditis, clinicians should consider discontinuation of azacitidine to improve patient's symptoms and reduce the likelihood of the development of constrictive pericarditis, pericardial effusion, and cardiac tamponade.

Immune-Response Modifiers: Characteristics of High-Volume Prescribers.

BACKGROUND: Oral small molecules (OSM) and biologic immune response modifier drugs share some indications for use but have a different side effect profiles. As such, certain providers may be more likely to prescribe one over the other. OBJECTIVE: To investigate the profile of providers who are high-volume prescribers of OSMs and biologic immune response modifier drugs. METHODS: The study was comprised of a retrospective analysis of data from physicians in the Medicare Provider Utilization and Payment Data: Part D Prescriber. RESULTS: Out of 14,982 dermatology providers, 424 prescribed both more than 1000 patient-days' supply of OSMs and more than 1000 patient-days' supply of biologic immune modifiers annually. For both OSMs and biologic immune modifiers, being male or being a provider with more than 4 years of experience were each found to be statistically significant characteristics of high-volume prescribers (P<.01). Solo or group practice was not a significant characteristic for high-volume prescribers of OSMs or biologic immune response modifiers; but when comparing the average provider prescribing OSMs with the average provider prescribing biologic immune response modifiers, those prescribing OSMs were more likely to be working in a group practice. CONCLUSION: The 4 years' post-residency may be instrumental in helping providers become more comfortable in prescribing high volumes of biologic immune modifiers and OSMs. In addition, the higher volume prescriptions of both immune response modifiers by males may be due to males being more risk tolerant. J Drugs Dermatol. 2022;21(12):1283-1288. doi:10.36849/JDD.6891R1.

Artificial intelligence image recognition of melanoma and basal cell carcinoma in racially diverse populations.

BACKGROUND: Artificial intelligence (AI) image recognition models have been relatively successful in diagnosing cutaneous manifestations in individuals with light skin tone. However, when these models are tested on the same cutaneous manifestations in individuals with darker or brown skin tone, the performance of the model drops due to a paucity of such images available for model training. OBJECTIVE: The objective of this study was to improve the performance of AI models in recognizing cutaneous diseases in individuals with darker skin tone. METHODS: Unsupervised computer darkening of skin color with preservation of the dermatological disease/lesion characteristics in images of light-skinned individuals with basal cell carcinoma (BCC), and melanoma was performed. RESULTS: Training an AI model on these artificially "darkened" images as compared to training on the original "light-skinned" images resulted in a higher sensitivity, specificity, positive predictive value, negative predictive value, F1 score and area under the receiver-operating characteristic curve of the AI model in differentiating between BCC and melanoma in individuals with brown skin tone. CONCLUSION: Use of unsupervised image to image translation in medical AI image recognition models has the potential to significantly improve their accuracy in diagnosing diseases in individuals with racially diverse skin tone.

Risk Factors That Are Associated With Outliers in Mohs Micrographic Surgery in the National Medicare Population, 2018.

BACKGROUND: Physician variation exists in the mean number of stages performed per Mohs micrographic surgery (MMS) case. Physicians who are outliers in medical practice may be leading to a higher health care cost burden. OBJECTIVE: To identify factors that influence being a high outlier in the mean stages per MMS case. MATERIALS AND METHODS: The study comprised a retrospective analysis of 2018 data from physicians who billed Medicare Part B for Current Procedural Terminology (CPT) 17311 and 17312 (MMS of the head, neck, hands, feet, or genitalia) and/or CPT 17313 and 17314 (MMS of the trunk, arms, or legs). RESULTS: For CPT 17311 and 17312, the odds ratio for being an outlier for a physician in a solo practice relative to a multiphysician facility is 2.4 (1.6-3.8), for a physician who is not an American College of Mohs Surgery (ACMS) member relative to a ACMS member is 2.0 (1.2-3.2), and for a practice located in the West, Northeast, and South is 7.7 (2.8-21.6), 6.2 (2.1-18.6), and 1.8 (0.6-5.4), respectively, relative to in the Midwest. CONCLUSION: Physicians who are practicing solo, practicing in the West or Northeast, and are not ACMS members are more likely to be a high outlier in the mean stages per MMS case.

United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019.

BACKGROUND: Skin cancer is the most common cancer worldwide. OBJECTIVE: To evaluate the burden of skin cancer in the US from 1990 to 2019. METHODS: Age-standardized incidence, prevalence, disability-adjusted life years (DALY), and mortality rates from skin cancer in the US were evaluated from the Global Burden of Disease 2019. RESULTS: Incidence, prevalence, DALY, and mortality rates for melanoma per 100,000 persons in 2019 were 17.0, 138, 64.8, and 2.2, respectively; for squamous cell carcinoma, rates were 262, 314, 26.6, and 0.8, respectively; and for basal cell carcinoma, rates were 525, 51.2, 0.2, and zero, respectively. Incidence and prevalence rates of melanoma and non-melanoma skin cancer (NMSC) have increased since 1990, while mortality rates have remained fairly stable. Males have had higher incidence, prevalence, DALY, and mortality rates from melanoma and NMSC every year since 1990. Incidence and prevalence of melanoma was relatively higher in the northern half of the US than in the southern half. LIMITATIONS: Global Burden of Disease is derived from estimation and mathematical modeling. CONCLUSIONS: Health care professionals can utilize differences and trends noted in this study to guide allocation of resources to reduce incidence and morbidity from skin cancer.

Sanitation, Obesity, and Low Body Mass Index as Risk Factors for Bacterial Skin Infections.

BACKGROUND: Bacterial skin infections can cause significant disability and can lead to mortality with inadequate treatment. OBJECTIVE: To determine whether sanitation and body mass index (BMI) are statistically significant risk factors for the incidence and prognosis of bacterial skin infections. METHODS: Country-level data regarding the age-standardized rates of incidence, prevalence, and years lived with disability (YLD) from bacterial skin infection per 100 000 persons from the Global Burden of disease dataset, and country-level data on age-standardized prevalence of obesity (BMI ≥30) and low BMI (BMI <18.5) from World Health Organization Global Health Observatory data repository were analyzed. Regression models were created to examine the effects of sanitation, obesity, and low BMI on the burden of bacterial skin infections. RESULTS: The percentage of population using basic sanitation services was positively associated with incidence, prevalence, and YLD from bacterial skin infections (P < .05). After controlling for sanitation, in countries with more than 50% of the population using basic sanitation services, obesity was positively associated with incidence, prevalence, and YLD from bacterial skin infections (P < .05). In countries with less than or equal to 50% of the population using basic sanitation services, low BMI was positively associated with incidence, prevalence, and YLD from bacterial skin infections (P < .05). CONCLUSIONS: Improving sanitation access in all countries, reducing the percentage of obese population in countries with good sanitation/hygiene techniques, and addressing malnutrition in countries with poor sanitation/hygiene techniques may help to reduce the burden of bacterial skin infections.

Performance of Artificial Intelligence Imaging Models in Detecting Dermatological Manifestations in Higher Fitzpatrick Skin Color Classifications.

BACKGROUND: The performance of deep-learning image recognition models is below par when applied to images with Fitzpatrick classification skin types 4 and 5. OBJECTIVE: The objective of this research was to assess whether image recognition models perform differently when differentiating between dermatological diseases in individuals with darker skin color (Fitzpatrick skin types 4 and 5) than when differentiating between the same dermatological diseases in Caucasians (Fitzpatrick skin types 1, 2, and 3) when both models are trained on the same number of images. METHODS: Two image recognition models were trained, validated, and tested. The goal of each model was to differentiate between melanoma and basal cell carcinoma. Open-source images of melanoma and basal cell carcinoma were acquired from the Hellenic Dermatological Atlas, the Dermatology Atlas, the Interactive Dermatology Atlas, and DermNet NZ. RESULTS: The image recognition models trained and validated on images with light skin color had higher sensitivity, specificity, positive predictive value, negative predictive value, and F1 score than the image recognition models trained and validated on images of skin of color for differentiation between melanoma and basal cell carcinoma. CONCLUSIONS: A higher number of images of dermatological diseases in individuals with darker skin color than images of dermatological diseases in individuals with light skin color would need to be gathered for artificial intelligence models to perform equally well.

Pyoderma gangrenosum adverse event with Rituximab use: A postmarketing pharmacovigilance analysis.

Rituximab is a monoclonal antibody that is used for the treatment of certain malignancies and autoimmune conditions. Pyoderma gangrenosum is a rare painful ulcer that can be fatal in some cases and can also reoccur after treatment. The objective of this paper was to analyze whether a statistically significant signal exists between Rituximab and pyoderma gangrenosum in the Food and Drug Administration Adverse Event Reporting System (FAERS). A disproportionality analysis was carried out on cases from January 1, 2004 to March 31, 2019 in the FAERS. Frequentist methods of relative reporting ratio, reporting odds ratio (ROR), and proportional reporting ratio (PRR) and the Bayesian-based IC025 metric were used in order to assess the adverse event signal. Thirty-two cases were found in FAERS in which the drug Rituximab was administered and pyoderma gangrenosum was reported as an adverse event. The lower 95% CI of the information component was 0.97, the lower 95% CI of ROR was 2.18, the PRR was 3.09 and Chi-squared was 42.16, which indicates a statistically significant signal. The signal is supported by six case reports in the literature that describe a total of 14 patients who developed pyoderma gangrenosum after Rituximab administration. When administering Rituximab, clinicians should monitor for the occurrence of symptoms representing pyoderma gangrenosum.

Risk of bronchospasm and coronary arteriospasm with sugammadex use: a post marketing analysis.

INTRODUCTION: Sugammadex is used for the reversal of neuromuscular blockade caused by rocuronium bromide and vecuronium bromide. As part of the post licensing phase of drug development, adverse events related to the use of sugammadex are still being uncovered and being reported. The potential association between sugammadex and adverse events bronchospasm and coronary arteriospasm using a retrospective pharmacovigilance signal analysis was carried out. METHODS: Food and Drug Administration's Adverse Event Reporting System database was used to run disproportionality analyses to investigate the potential association of sugammadex with bronchospasm or coronary arteriospasm. In this analysis we report the adverse event signal using frequentist methods of Relative reporting ratio (RRR), proportional reporting ratio (PRR), reporting odds ratio (ROR) and the Bayesian based Information Component metric. RESULTS: A statistically significant disproportionality signal is found between sugammadex and bronchospasm (n = 44; chi-squared = 2993.87; PRR = 71.95 [95% CI: 54.00-95.85]) and sugammadex and coronary arteriospasm (n = 6; chi-squared = 209.39; PRR = 43.82 [95% CI: 19.73-97.33]) as per Evans criteria. Both statistically significant disproportionality signals persisted when stratified by gender. Based upon dynamic cumulative PRR graph, the PRR value has steadily increased and the 95% CI narrowed since December 2012. CONCLUSION: The results of the pharmacovigilance analysis highlight a statistically significant disproportionality signal between sugammadex usage and bronchospasm and coronary arteriospasm adverse events. Physicians need to be aware of these adverse events when using sugammadex. The results of the pharmacovigilance signal analysis highlight a statistically significant disproportionality signal between sugammadex usage and bronchospasm and coronary arteriospasm adverse events. Physicians need to be aware of these adverse events when using sugammadex.

Disproportionality analysis of bullous pemphigoid adverse events with PD-1 inhibitors in the FDA adverse event reporting system.

Objectives: Bullous pemphigoid, an autoimmune dermatological disease, may be associated with the use of a relatively new anti-cancer drug class, PD-1 inhibitors, which includes pembrolizumab and nivolumab. This paper analyzes the signals between PD-1 inhibitors and bullous pemphigoid based upon the reported real-world data. Methods: A pharmacovigilance analysis was performed on the publicly available Adverse Event Reporting System database of Food and Drug Administration. Disproportionality ratios were used to examine a signal between PD-1 inhibitors and bullous pemphigoid. A heat map was generated to depict the signal between PD -1 inhibitor use and skin toxicity adverse events. Results: The analysis indicated that there is a significant signal (PRR = 13.82 [95% CI: 9.99-19.11], Chi-squared with Yates' correction = 420.48) between pembrolizumab use and bullous pemphigoid and that there is a significant signal (PRR = 13.19 [95% CI: 10.57-16.46], Chi-squared with Yates' correction = 869.71) between nivolumab use and bullous pemphigoid. The signals remained statistically significant after stratifying for sex and age for both pembrolizumab and nivolumab. The signal is supported by 35 case reports in which there was evidence of PD-1 inhibitor use and a pemphigoid adverse event. Conclusion: When prescribing PD-1 inhibitors, physicians should monitor closely for symptoms of bullous pemphigoid.

Resting-state functional connectivity of subcortical locomotor centers explains variance in walking capacity.

Walking capacity influences the quality of life and disability in normal aging and neurological disease, but the neural correlates remain unclear and subcortical locomotor regions identified in animals have been more challenging to assess in humans. Here we test whether resting-state functional MRI connectivity (rsFC) of midbrain and cerebellar locomotor regions (MLR and CLR) is associated with walking capacity among healthy adults. Using phenotypic and MRI data from the Nathan Kline Institute Rockland Sample (n =119, age 18-85), the association between walking capacity (6-min walk test distance) and rsFC was calculated from subcortical locomotor regions to 81 other gait-related regions of interest across the brain. Additional analyses assessed the independence and specificity of the results. Walking capacity was associated with higher rsFC between the MLR and superior frontal gyrus adjacent to the anterior cingulate cortex, higher rsFC between the MLR and paravermal cerebellum, and lower rsFC between the CLR and primary motor cortex foot area. These rsFC correlates were more strongly associated with walking capacity than phenotypic variables such as age, and together explained 25% of the variance in walking capacity. Results were specific to locomotor regions compared with the other brain regions. The rsFC of locomotor centers correlates with walking capacity among healthy adults. These locomotion-related biomarkers may prove useful in future work aimed at helping patients with reduced walking capacity.

Passive immunity to pandemic H1N1 2009 by swine flu parties.

The general population is concerned about the probable devastating effects of pandemic H1N1 2009. Based upon the 1918 Spanish flu pandemic, scientific publications and theories, the idea of swine flu parties to achieve passive immunity against pandemic H1N1 2009 has been proposed. Public health officials have asked the general public not to resort to this method. However, no concrete evidence of the reasoning behind the recommendation has been given. In this paper, we have dynamically modeled the effect of swine flu parties on the immunity achieved and associated mortality for a period of two years. The simulations show that the public should not organize or participate in swine flu parties as they will likely increase swine flu-associated mortality.