Association of sociodemographic characteristics with utilization of sentinel lymph node biopsy for American Joint Committee on Cancer 8th edition T1b cutaneous melanoma.

Sentinel lymph node biopsy (SLNB) is an important staging and prognostic tool for cutaneous melanoma (CM). However, there exists a knowledge gap regarding whether sociodemographic characteristics are associated with receipt of SLNB for T1b CMs, for which there are no definitive recommendations for SLNB per current National Comprehensive Cancer Network guidelines. We performed a retrospective analysis of the 2012-2018 National Cancer Database, identifying patients with American Joint Committee on Cancer staging manual 8th edition stage T1b CM, and used multivariable logistic regression to analyze associations between sociodemographic characteristics and receipt of SLNB. Among 40,458 patients with T1b CM, 23,813 (58.9%) received SLNB. Median age was 62 years, and most patients were male (57%) and non-Hispanic White (95%). In multivariable analyses, patients of Hispanic (aOR 0.67, 95%CI 0.48-0.94) and other (aOR 0.78, 95%CI 0.63-0.97) race/ethnicity, and patients aged > 75 (aOR 0.33, 95%CI 0.29-0.38), were less likely to receive SLNB. Conversely, patients in the highest of seven socioeconomic status levels (aOR 1.37, 95%CI 1.13-1.65) and those treated at higher-volume facilities (aOR 1.29, 95%CI 1.14-1.46) were more likely to receive SLNB. Understanding the underlying drivers of these associations may yield important insights for the management of patients with melanoma.

Inflation-Adjusted Trends in Medicare Reimbursement for Common Dermatologic Procedures, 2007-2021.

IMPORTANCE: Medicare enrollment, dermatologist utilization of Medicare, and dermatologic procedural volume have all increased over time. Despite this, there are limited studies evaluating changes in Medicare reimbursement within dermatology. OBJECTIVE: To identify trends in Medicare reimbursement for 46 common dermatologic procedures from 2007 to 2021. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, reimbursement data were obtained from the Centers for Medicare & Medicaid Services Physician Fee Schedule for commonly used dermatologic Current Procedural Terminology (CPT) codes from 2007 to 2021. The CPT codes in several major dermatologic categories were analyzed, including skin biopsy, shave removal, benign/premalignant/malignant destruction, benign/malignant excision, Mohs micrographic surgery, simple/intermediate/complex repair, flap, graft, and laser/phototherapy. All procedure prices were adjusted for inflation to January 2021 dollar value. MAIN OUTCOMES AND MEASURES: The primary outcomes were percentage changes and cumulative annual growth rates of pricing for each dermatologic procedure. RESULTS: From 2007 to 2021, there was a mean decrease in dermatologic procedure reimbursement of -4.8% after adjusting for inflation. Mean inflation-adjusted changes in reimbursements during this time period significantly varied by procedure type, including skin biopsy (+30.3%), shave removal (+24.5%), benign/premalignant/malignant destruction (-7.5%), Mohs micrographic surgery (-14.4%), benign/malignant excision (-3.9%), simple/intermediate/complex repair (-9.9%), flap repair (-14.1%), graft repair (-12.0%), and laser/phototherapy (-6.6%; P < .001). Changes in reimbursement did not vary by anatomical risk categories. CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional analysis suggest that changes in Medicare reimbursement can have several downstream effects, including concomitant private insurance changes and decreased patient access. Future adjustments in reimbursement should balance high-value care with sustainable pricing to optimize patient access.

Powered muscle stimulators: an investigation into newly FDA 510(k) approved devices marketed for muscle toning and esthetic benefit.

Introduction: Powered muscle stimulators have been popularized in recent years due to their muscle toning effects. This study aims to describe marketing trends and reporting of adverse effects of powered muscle stimulators.Methods: We performed a cross-sectional retrospective analysis of records from the United States FDA database for 510(k) premarket approval of powered muscle stimulators between January 1, 2000 and December 31, 2018. The FDA MAUDE database was reviewed for adverse events reported with device usage.Results: One hundred and seventeen devices received 510(k) premarket approval between 2000 and 2018, with the first approval occurring in 2001. Initially, devices were marketed to assist with muscle toning and strengthening, but more recent indications include the treatment of pain, increased local muscle blood circulation, and prevention of post-surgical venous thrombosis. Thirty-six adverse event reports have been submitted and published in the MAUDE database over the past 10 years by 11% of manufacturers.Discussion: Powered muscle stimulators are growing increasingly popular amongst consumers and healthcare providers due to their ease of use and perceived esthetic, muscle strength, and pain relief benefits. Additional investigation to determine optimal treatment parameters and potential adverse effects is necessary due to the growing popularity of these devices.

Monitoring Onion Thrips (Thysanoptera: Thripidae) Susceptibility to Spinetoram in New York Onion Fields.

Onion thrips (Thrips tabaci Lindeman) is a severe pest of onion (Allium cepa L.). Their management relies on frequent applications of foliar insecticides, including spinetoram (Radiant® SC), which has a novel mode of action and is effective at controlling large populations. However, despite being widely used for the past 10 yr, susceptibility to spinetoram has not been evaluated formally in New York state, where nearly 3,000 hectares of onion are planted annually. Over 2 yr (2017-2018), the susceptibility of onion thrips to spinetoram was assessed from populations collected in commercial onion fields in New York. LC50s for adults were generated from feeding assays and ranged from 2.07 to 5.08 ppm, but grower reports indicate that onion thrips populations continue to be susceptible to spinetoram. Moreover, both regional and temporal variations in susceptibility were similar among these populations based on survival at individual concentrations tested, despite significant differences in LC50s. These results suggest some genetic heterogeneity among onion thrips populations and serve as a valuable reference for the continued monitoring of onion thrips susceptibility to spinetoram, contributing to ongoing efforts to manage insecticide resistance in this system.

Over-the-counter light therapy for acne: a cross-sectional retrospective analysis.

Acne vulgaris affects a large portion of the population and drives many patients to seek over-the-counter (OTC) treatments. Light-emitting diode (LED) therapy has recently emerged as a potential therapeutic option for inflammatory acne. We used the U.S. Food and Drug Administration (FDA) 510(k) premarket submission database to assess the growth in OTC LED therapy devices for treatment of acne. We also used Google Trends data in searches for "acne light therapy mask" to characterize growth in consumer interest in these devices. Overall, 35 LED devices received pre-market approval from 2000 to 2018, with a peak in approvals in 2016. Similarly, there was a dramatic increase in public interest in these devices in 2016. Only two devices were associated with company-approved trials. The current regulatory process requires little evidence to substantiate specified uses and a better understanding of practice guidelines and the efficacy of this treatment modality is required.

A review of the FDA's 510(k) approvals process for electromagnetic devices used in body contouring.

Introduction: Greater demand for noninvasive techniques to reduce cellulite and contour the body has led to the growth of electromagnetic and radiofrequency devices. In this study, we aimed to characterize the evolution and safety of electromagnetic devices marketed in the U.S. over the last two decades. Methods: We examined records from a U.S. FDA database documenting premarket approval of electromagnetic devices between January 1, 2000 and October 31, 2018. Additionally, we searched the Manufacturer and User Facility Device Experience (MAUDE) database for reports of adverse events. Results: Thirty-one devices were approved from 2012-2018. Initially marketed to temporarily reduce muscle pain and cellulite, indications for these devices have expanded. The MAUDE database revealed 61 reports of adverse events including acute skin damage, dyspigmentation, infection, hair growth, scarring, and others. Discussion: Although electromagnetic devices are gaining increasing public attention and marketed to be safe, the frequency and types of adverse events are not well-documented. Importantly, the MAUDE database has limitations including submission of incomplete, inaccurate, untimely, or unverified data make determining the true number of adverse events difficult. Further investigation is greatly needed to define appropriate parameters and outcomes for the use of electromagnetic devices in body contouring and skin enhancement.

Shedding light on the FDA's 510(k) approvals process: low-level laser therapy devices used in the treatment of androgenetic alopecia.

Introduction: Low-level laser therapy has demonstrated superior efficacy relative to other nonsurgical treatment options for the treatment of androgenetic alopecia. Methods: Records from a public U.S. FDA database for premarket approval of low-level laser therapy devices approved between January 1 2000 and July 15 2018 were reviewed. Results: 47 devices received 510(k) premarket approval, with an increasing number of devices available since 2007. More options are now available and product indications have expanded for use in a wider audience, including both men and women. Discussion: Growing recognition of lasers has led to an increasing number of devices available as well as innovative options in terms of design and convenience. In the past few years, these devices have adopted broader indications for use in both men and women. However, marketed indications have not been adequately explored and current devices on the market have the potential to mislead consumers.

Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.

The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate acute inflammation in vivo has not been established in humans. In a double-blinded, placebo-controlled interventional trial, 20 healthy adults were randomized to receive either placebo or a high dose of vitamin D3 (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of UVR. Compared with placebo, participants receiving vitamin D3 (200,000 international units) demonstrated reduced expression of proinflammatory mediators tumor necrosis factor-α (P = 0.04) and inducible nitric oxide synthase (P = 0.02) in skin biopsy specimens 48 hours after experimental sunburn. A blinded, unsupervised hierarchical clustering of participants based on global gene expression profiles revealed that participants with significantly higher serum vitamin D3 levels after treatment (P = 0.007) demonstrated increased skin expression of the anti-inflammatory mediator arginase-1 (P = 0.005), and a sustained reduction in skin redness (P = 0.02), correlating with significant expression of genes related to skin barrier repair. In contrast, participants with lower serum vitamin D3 levels had significant expression of proinflammatory genes. Together the data may have broad implications for the immunotherapeutic properties of vitamin D in skin homeostasis, and implicate arginase-1 upregulation as a previously unreported mechanism by which vitamin D exerts anti-inflammatory effects in humans.

Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients.

BACKGROUND: Glucarpidase rapidly reduces methotrexate plasma concentrations in patients experiencing methotrexate-induced renal dysfunction. Debate exists regarding the role of glucarpidase in therapy given its high cost. The use of reduced-dose glucarpidase has been reported, and may allow more institutions to supply this drug to their patients. This report explores the relationship between glucarpidase dosage and patient outcomes in pediatric oncology patients. METHODS: The authors evaluated data from 26 patients who received glucarpidase after high-dose methotrexate. Decrease in plasma methotrexate concentrations and time to renal recovery were evaluated for an association with glucarpidase dosage, which ranged from 13 to 90 units/kg. RESULTS: No significant relationship was found between glucarpidase dosage (units/kg) and percent decrease in methotrexate plasma concentrations measured by TDx (P > 0.1) or HPLC (P > 0.5). Patients who received glucarpidase dosages <50 units/kg had a median percent reduction in methotrexate plasma concentration of 99.4% (range, 98-100) measured by HPLC compared to a median percent reduction of 99.4% (range, 77.2-100) in patients who received ≥50 units/kg. Time to SCr recovery was not related to glucarpidase dosage (P > 0.8). CONCLUSIONS: The efficacy of glucarpidase in the treatment of HDMTX-induced kidney injury was not dosage-dependent in this retrospective analysis of pediatric oncology patients.

Carbon monoxide protects against hemorrhagic shock and resuscitation-induced microcirculatory injury and tissue injury.

UNLABELLED: Traumatic injury is a significant cause of morbidity and mortality worldwide. Microcirculatory activation and injury from hemorrhage contribute to organ injury. Many adaptive responses occur within the microcirculatory beds to limit injury including upregulation of heme oxygenase (HO) enzymes, the rate-limiting enzymes in the breakdown of heme to carbon monoxide (CO), iron, and biliverdin. Here we tested the hypothesis that CO abrogates trauma-induced injury and inflammation protecting the microcirculatory beds. METHODS: C57Bl/6 mice underwent sham operation or hemorrhagic shock to a mean arterial pressure of 25 mmHg for 120 minutes. Mice were resuscitated with lactated Ringer's at 2× the volume of maximal shed blood. Mice were randomized to receive CO-releasing molecule or inactive CO-releasing molecule at resuscitation. A cohort of mice was pretreated with tin protoporphyrin-IX to inhibit endogenous CO generation by HOs. Primary mouse liver sinusoidal endothelial cells were cultured for in vitro experiments. RESULTS: Carbon monoxide-releasing molecule protected against hemorrhagic shock/resuscitation organ injury and systemic inflammation and reduced hepatic sinusoidal endothelial injury. Inhibition of HO activity with tin protoporphyrin-IX exacerbated liver hepatic sinusoidal injury. Hemorrhagic shock/resuscitation in vivo or cytokine stimulation in vitro resulted in increased endothelial expression of adhesion molecules that was associated with decreased leukocyte adhesion in vivo and in vitro. CONCLUSIONS: Hemorrhagic shock/resuscitation is associated with endothelial injury. Heme oxygenase enzymes and CO are involved in part in diminishing this injury and may prove useful as a therapeutic adjunct that can be harnessed to protect against endothelial activation and damage.

Angiogenesis inhibitor therapies for advanced renal cell carcinoma: toxicity and treatment patterns in clinical practice from a global medical chart review.

The aim of this study was to assess the treatment patterns and safety of sunitinib, sorafenib and bevacizumab in real-world clinical settings in US, Europe and Asia. Medical records were abstracted at 18 community oncology clinics in the US and at 21 tertiary oncology centers in US, Europe and Asia for 883 patients ≥ 18 years who had histologically/cytologically confirmed diagnosis of advanced RCC and received sunitinib (n=631), sorafenib (n=207) or bevacizumab (n=45) as first-line treatment. No prior treatment was permitted. Data were collected on all adverse events (AEs) and treatment modifications, including discontinuation, interruption and dose reduction. Treatment duration was estimated using Kaplan-Meier analysis. Demographics were similar across treatment groups and regions. Median treatment duration ranged from 6.1 to 10.7 months, 5.1 to 8.5 months and 7.5 to 9.8 months for sunitinib, sorafenib and bevacizumab patients, respectively. Grade 3/4 AEs were experienced by 26.0, 28.0 and 15.6% of sunitinib, sorafenib and bevacizumab patients, respectively. Treatment discontinuations occurred in 62.4 (Asia) to 63.1% (US) sunitinib, 68.8 (Asia) to 90.0% (Europe) sorafenib, and 66.7 (Asia) to 81.8% (US) bevacizumab patients. Globally, treatment modifications due to AEs occurred in 55.1, 54.2 and 50.0% sunitinib, sorafenib and bevacizumab patients, respectively. This study in a large, global cohort of advanced RCC patients found that angiogenesis inhibitors are associated with high rates of AEs and treatment modifications. Findings suggest an unmet need for more tolerable agents for RCC treatment.

Safety and treatment patterns of angiogenesis inhibitors in patients with metastatic renal cell carcinoma: evidence from US community oncology clinics.

Safety and treatment patterns of sunitinib and sorafenib in metastatic renal cell carcinoma (mRCC) had been previously reported using retrospective chart review of patients treated in US tertiary centers. Because practice patterns may vary between hospital- and office-based settings, this study examined safety and treatment patterns of these agents in US community oncology clinics. Medical records were retrospectively reviewed for 250 patients with mRCC treated at 18 community oncology clinics. Eligible patients were ≥18 years old and received ≥1 prescription for sunitinib (n = 131) or sorafenib (n = 119) as first-line anti-angiogenic treatment. Rates of adverse events (AEs) and treatment modifications were analyzed; reasons for treatment modifications were examined. Median duration of first-line sunitinib and sorafenib treatment was 5.9 and 5.5 months, respectively. Among patients treated with sunitinib and sorafenib, 86% (30%) and 87% (28%), respectively, experienced ≥1 all-grade (grade 3/4) AE. The most common AEs were fatigue/weakness in sunitinib (all-grade: 42%; grade 3/4: 5%) and skin rash in sorafenib (all-grade: 35%; grade 3/4: 6%). Sixty-two and 64% of patients treated with sunitinib and sorafenib, respectively, had ≥1 treatment modification due to AEs. Recorded AE rates in patients with mRCC treated with angiogenesis inhibitors in community practice tended to be lower than in tertiary centers, possibly due to shorter treatment duration. Rates of treatment modifications due to AEs tended to be higher in community practice. This study provides evidence from an office-based setting of unmet need for agents that may provide improved tolerability in mRCC.

Treatment of transfusional iron overload in patients with myelodysplastic syndrome or severe anemia: data from multicenter clinical practices.

BACKGROUND: Patients with myelodysplastic syndrome (MDS) or severe anemia requiring repeated red blood cell (RBC) transfusions risk developing transfusional iron overload, which can reduce survival. Iron chelation therapy (ICT) has been shown to improve survival and quality of life in patients; however, ICT utilization in clinical practices is not well understood. STUDY DESIGN AND METHODS: Medical records of patients diagnosed with MDS or severe anemia at least 6 months before data extraction, aged at least 21 years at diagnosis, and who received at least one RBC transfusion were reviewed. ICT eligibility was defined as at least 20 units of RBCs transfused or at least two serum ferritin levels exceeding 1000 microg/L. Study endpoint was ICT treatment rate among ICT-eligible patients with lower-risk MDS (International Prognostic Scoring System [low or intermediate-1]; World Health Organization [refractory anemia {RA}, refractory anemia with ringed sideroblasts {RARS}, refractory cytopenia with multilineage dysplasia {RCMD}, refractory cytopenia with multilineage dysplasia and ringed sideroblasts, or 5q]; French-American-British [RA/RARS]). RESULTS: Among 78 ICT-eligible patients with lower-risk MDS, 32 (41%) received ICT. At ICT initiation, treated patients received on average 13.3 transfusions (27.6 units) and mean first post-ICT initiation serum ferritin was twice the MDS Foundation recommendation at 1949 microg/L. Median overall survival for all ICT-eligible patients was significantly longer for those ICT-treated patients than untreated patients (8.7 years vs. 4.7 years, log-rank p = 0.02; multivariate hazard ratio 0.372, p = 0.03). CONCLUSION: This study finds only 41% of ICT-eligible patients with lower-risk MDS received ICT in clinical practice, and treatment was initiated later than recommended. Receipt of ICT was associated with significantly longer survival.

Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains.

Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Both AdAce1 and AdAce2 were highly similar (95 and 93% amino acid identity, respectively) with the Ace genes of Tribolium castaneum. Both AdAce1 and AdAce2 have the conserved residues characteristic of AChE (catalytic triad, intra-disulfide bonds, and so on). Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. Several single nucleotide polymorphisms (SNPs) were detected, but only one non-synonymous mutation was found (A271S in AdAce2). No SNPs were exclusively found in the resistant strains, the A271S mutation does not correspond to any mutations previously reported to alter sensitivity of AChE to organophosphates or carbamates, and the A271S was found only as a heterozygote in one individual from one of the resistant A. diaperinus strains. This suggests that tetrachlorvinphos resistance in the Kennebec and Waycross strains of A. diaperinus is not due to mutations in either AChE gene. The sequences of AdAce1 and AdAce2 provide new information about the evolution of these important genes in insects.