Compliance with sentinel lymph node biopsy guidelines for invasive melanomas treated with Mohs micrographic surgery.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has not been studied for invasive melanomas treated with Mohs micrographic surgery using frozen-section MART-1 immunohistochemical stains (MMS-IHC). The primary objective of this study was to assess the accuracy and compliance with National Comprehensive Cancer Network (NCCN) guidelines for SLNB in a cohort of patients who had invasive melanoma treated with MMS-IHC. METHODS: This retrospective cohort study included all patients who had primary, invasive, cutaneous melanomas treated with MMS-IHC at a single academic center between March 2006 and April 2018. The primary outcomes were the rates of documenting discussion and performing SLNB in patients who were eligible based on NCCN guidelines. Secondary outcomes were the rate of identifying the sentinel lymph node and the percentage of positive lymph nodes. RESULTS: In total, 667 primary, invasive, cutaneous melanomas (American Joint Committee on Cancer T1a-T4b) were treated with MMS-IHC. The median patient age was 69 years (range, 25-101 years). Ninety-two percent of tumors were located on specialty sites (head and/or neck, hands and/or feet, pretibial leg). Discussion of SLNB was documented for 162 of 176 (92%) SLNB-eligible patients, including 127 of 127 (100%) who had melanomas with a Breslow depth >1 mm. SLNB was performed in 109 of 176 (62%) SLNB-eligible patients, including 102 of 158 melanomas (65%) that met NCCN criteria to discuss and offer SLNB and 7 of 18 melanomas (39%) that met criteria to discuss and consider SLNB. The sentinel lymph node was successfully identified in 98 of 109 patients (90%) and was positive in 6 of those 98 patients (6%). CONCLUSIONS: Combining SLNB and MMS-IHC allows full pathologic staging and confirmation of clear microscopic margins before reconstruction of specialty site invasive melanomas. SLNB can be performed accurately and in compliance with consensus guidelines in patients with melanoma using MMS-IHC.

Evolution of Excisional Surgery Practices for Melanoma in the United States.

IMPORTANCE: National Comprehensive Cancer Network guidelines for melanoma have consistently recommended wide local excision as the standard of care since their inception. Although surgery with more comprehensive margin assessment (eg, Mohs surgery) has been advocated for certain subsets of melanoma, how often these techniques are used in clinical practice is uncertain. OBJECTIVE: To examine trends in the use of comprehensive margin assessment surgery for melanoma by tracking claims data for Mohs surgery. DESIGN, SETTING, AND PARTICIPANTS: This national cross-sectional analysis examined claims data from the Optum Clinformatics Data Mart, a nationally representative database. The study cohort consisted of 79 108 patients undergoing surgical excision for melanoma from January 1, 2001, through December 31, 2016. Data were analyzed from January 1, 2001, through December 31, 2016. MAIN OUTCOMES AND MEASURES: The primary outcome was the likelihood of a melanoma being treated with Mohs surgery over time, evaluated by multivariable logistic regression and expressed as the odds of treatment per additional calendar year. RESULTS: Among 79 108 patients with melanoma (median age, 63 years [interquartile range {IQR}, 51-73]; 47 407 men [59.9%]), 75 047 were treated with conventional excision (median age, 62 years [IQR, 50-73 years]; 44 786 men [59.7%]) and 4061 with Mohs surgery (median age, 67 years [IQR, 56-76 years]; 2621 men [64.5%]). Mohs surgery was used in 5.1% of all surgical cases, with the rate of Mohs surgery increasing 304% from 2.6% in 2001 to 7.9% in 2016. Odds of receiving Mohs surgery for melanoma increased significantly in more recent calendar years (odds ratio [OR], 1.02 per calendar year; 95% CI, 1.01-1.03; P < .001). Immunohistochemistry (IHC) use was only coded with Mohs surgery in 1087 cases (26.8%), and the odds of receiving Mohs surgery with IHC increased in more recent calendar years (OR, 1.13 per calendar year; 95% CI, 1.10-1.15; P < .001). Use of Mohs surgery and Mohs surgery with IHC for melanoma differed widely across geographic census divisions with greater than 3-fold variation between the regions with highest and lowest use in every period (eg, for 2013 through 2016, the East South Central region used Mohs surgery in 8.8% of melanoma excisions compared with 2.6 in the New England region). CONCLUSIONS AND RELEVANCE: Despite stable guidelines for melanoma surgery, the results of this study suggest that surgical practices for melanoma are evolving. Wide variations in surgical practice patterns for melanoma are present in the United States. This study's findings suggest that the effect of variations in surgical techniques on outcomes requires scrutiny and further study.

Merkel Cell Carcinoma: Updates on Staging and Management.

Merkel cell carcinoma is an aggressive neuroendocrine carcinoma with increasing incidence over the past few decades. The TNM Staging System used for Merkel cell carcinoma was updated by the American Joint Committee on Cancer in 2017. Clinical practice guidelines were updated by the National Comprehensive Cancer Network on August 31, 2018. This article reviews the most recent evidence-based updates on staging and management.

Two-Year Outcomes of Vagal Nerve Blocking (vBloc) for the Treatment of Obesity in the ReCharge Trial.

BACKGROUND: The ReCharge Trial demonstrated that a vagal blocking device (vBloc) is a safe and effective treatment for moderate to severe obesity. This report summarizes 24-month outcomes. METHODS: Participants with body mass index (BMI) 40 to 45 kg/m2, or 35 to 40 kg/m2 with at least one comorbid condition were randomized to either vBloc therapy or sham intervention for 12 months. After 12 months, participants randomized to vBloc continued open-label vBloc therapy and are the focus of this report. Weight loss, adverse events, comorbid risk factors, and quality of life (QOL) will be assessed for 5 years. RESULTS: At 24 months, 123 (76 %) vBloc participants remained in the trial. Participants who presented at 24 months (n = 103) had a mean excess weight loss (EWL) of 21 % (8 % total weight loss [TWL]); 58 % of participants had ≥5 % TWL and 34 % had ≥10 % TWL. Among the subset of participants with abnormal preoperative values, significant improvements were observed in mean LDL (-16 mg/dL) and HDL cholesterol (+4 mg/dL), triglycerides (-46 mg/dL), HbA1c (-0.3 %), and systolic (-11 mmHg) and diastolic blood pressures (-10 mmHg). QOL measures were significantly improved. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. The primary related serious adverse event rate was 4.3 %. CONCLUSIONS: vBloc therapy continues to result in medically meaningful weight loss with a favorable safety profile through 2 years. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01327976.

A population-based study of the comparative effectiveness of second-generation antipsychotics vs older antimanic agents in bipolar disorder.

OBJECTIVES: Numerous antimanic treatments have been introduced over the past two decades, particularly second-generation antipsychotics (SGAs). However, it is not clear whether such newer agents provide any advantage over older treatments. METHODS: A historical cohort design investigated the nationwide population of outpatients with bipolar disorder treated in the Department of Veterans Affairs who were newly initiated on an antimanic agent between 2003 and 2010 (N=27 727). The primary outcome was likelihood of all-cause hospitalization during the year after initiation, controlling for numerous demographic, clinical, and treatment characteristics. Potential correlates of effect were explored by investigating time to initiation of a second antimanic agent or antidepressant. RESULTS: After control for covariates, those initiated on lithium or valproate monotherapy, compared to those beginning SGA monotherapy, were significantly less likely to be hospitalized, had a longer time to hospitalization, and had fewer hospitalizations in the subsequent year. Those on combination treatment had a significantly higher likelihood of hospitalization, although they also had a longer time to addition of an additional antimanic agent or antidepressant. CONCLUSIONS: The present analysis of a large and unselected nationwide population provides important complementary data to that from controlled trials. Although various mechanisms may be responsible for the results, the data support the utilization of lithium or valproate, rather than SGAs, as the initial antimanic treatment in bipolar disorder. A large-scale, prospective, randomized, pragmatic clinical trial comparing the initiation of SGA monotherapy to that of lithium or valproate monotherapy is a logical next step.

New directions for HIV vaccine development from animal models.

PURPOSE OF REVIEW: The development of a preventive HIV vaccine remains an unresolved challenge. Animal models that can predict the results of HIV vaccine efficacy trials and identify the immune mechanisms responsible for vaccine protection would be most useful for HIV vaccine development. The purpose of the current review is to critique recent developments in the use of animal models of HIV infection in preclinical studies of AIDS vaccines and to describe how the use of improved animal models can inform the development of an HIV vaccine. RECENT FINDINGS: The results of preclinical experiments with candidate HIV vaccines can vary with the SIV challenge virus used. It is now known that there is considerable variability in the neutralization sensitivity and that the level of viral sequence diversity within the challenge stocks varies. This has allowed more realistic preclinical vaccine studies with heterologous vaccine antigens and challenge viruses. Further, the dose of challenge virus and the route of virus challenge can modify the efficacy of candidate vaccines in preclinical studies. SUMMARY: Recent experiments demonstrate that nonhuman primate models of AIDS can reproduce the complex biology of HIV transmission, recapitulate the results of HIV vaccine efficacy trials in humans and be used to identify correlates of protection.

Percutaneous tibial nerve stimulation for the long-term treatment of overactive bladder: 3-year results of the STEP study.

PURPOSE: We report the long-term efficacy and safety of percutaneous tibial nerve stimulation with the Urgent® PC Neuromodulation System for overactive bladder after 3 years of therapy. MATERIALS AND METHODS: Fifty participants in the randomized, double-blind SUmiT (Sham Effectiveness in Treatment of Overactive Bladder Symptoms) Trial who met the primary effectiveness end point after 12 weekly percutaneous tibial nerve stimulation treatments were enrolled in this prospective study to assess long-term outcomes with percutaneous tibial nerve stimulation. STEP (Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation) Study patients were prescribed a fixed schedule 14-week tapering protocol followed by a personal treatment plan aimed at sustaining overactive bladder symptom improvement. Overactive bladder and quality of life questionnaires were completed every 3 months and 3-day voiding diaries were completed every 6 months. RESULTS: A total of 29 patients completed the 36-month protocol and received a median of 1.1 treatments per month after a 14-week treatment tapering protocol. A Bayesian model estimated that 77% (95% CI 64-90) of patients maintained moderate or marked improvement in overactive bladder symptoms at 3 years. Compared to baseline, median voids per day decreased from 12.0 (IQR 10.3-13.7) to 8.7 (IQR 7.3-11.3), nighttime voids per night decreased from 2.7 (IQR 1.7-3.3) to 1.7 (IQR 1.0-2.7) and urge incontinence episodes per day decreased from 3.3 (IQR 0.7-6.0) to 0.3 (IQR 0.0-1.0) (all p <0.0001). All quality of life parameters remained markedly improved from baseline through 3 years (all p <0.0001). One patient experienced 2 mild treatment related adverse events of bleeding at the needle site during followup. CONCLUSIONS: Most STEP participants with an initial positive response to 12 weekly percutaneous tibial nerve stimulation treatments safely sustained overactive bladder symptom improvement to 3 years with an average of 1 treatment per month.

Topical anesthetics for dermatologic procedures: a review.

BACKGROUND: Practitioners are increasingly using topical anesthetics to decrease the pain associated with superficial dermatologic, aesthetic, and laser procedures. Numerous lidocaine-containing products are available, but comprehensive reviews are lacking regarding their relative safety profiles and appropriate dermatologic uses. MATERIALS AND METHODS: A literature review of currently available topical anesthetics, their safety profiles, and dermatologic uses was conducted. RESULTS: Factors that should be considered to reduce the risk of side effects associated with the use of topical anesthetics include the amount of product used, body location, size of the surface area, and duration of product application. Many case reports document adverse outcomes associated with the use of compounded products that the Food and Drug Administration has not approved that have inappropriately high anesthetic concentrations and from the use of topical anesthetics on excessively large skin surface areas during laser treatments. CONCLUSIONS: Lidocaine-containing products play an integral role in cutaneous anesthesia by providing patient comfort with minimal side effects. Careful attention must be paid to the particular anatomic location, the total surface area covered, and the duration of anesthetic skin contact.

A randomized, double-blind comparison of the total dose of 1.0% lidocaine with 1:100,000 epinephrine versus 0.5% lidocaine with 1:200,000 epinephrine required for effective local anesthesia during Mohs micrographic surgery for skin cancers.

OBJECTIVE: We sought to compare total lidocaine dose and patient comfort when using 1.0% lidocaine with 1:100,000 epinephrine versus 0.5% lidocaine with 1:200,000 epinephrine during Mohs micrographic surgery. METHODS: In all, 149 patients were randomized to receive 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine during Mohs micrographic surgery. The total dose of lidocaine and measures of patient comfort were recorded. RESULTS: Compared with the 1.0% lidocaine group, there was a 52% reduction in lidocaine dose in the 0.5% group (mean difference, 147.85 mg; 95% confidence interval, 108.15-187.55; P < .001). Patient comfort was equivalent in both groups, as evidenced by the similar mean visual analog scale scores (P = .48) and mean volumes of rescue lidocaine administered (P = .18). LIMITATIONS: No lidocaine blood levels were measured, and one Mohs surgeon performed all surgeries. CONCLUSION: The dose of 0.5% lidocaine with 1:200,000 epinephrine provides pain control equivalent to 1.0% lidocaine with 1:100,000 epinephrine at approximately half the total lidocaine dose.

Whither or wither microbicides?

After disappointing results from all efficacy trials conducted to date, the field of microbicides research now faces substantial challenges. Poor coordination among interested parties and the choice of nonvalidated scientific targets for phase III studies have hampered progress and created mistrust about the use of microbicides as a method to prevent HIV-1 sexual transmission. Although new promising strategies are available, there will need to be serious reappraisals of how decisions are made to advance the next generations of candidates into clinical trials, and the use of appropriate animal models in this process will be critical.

Satisfaction with mental health services in older primary care patients.

OBJECTIVE: This study examines whether older adult primary care patients are satisfied with two intervention models designed to ameliorate their behavioral health problems. METHODS: A total of 1,052 primary care patients aged 65 and older with depression, anxiety, or at-risk drinking were randomly assigned to and participated in either integrated care (IC) or enhanced specialty referral (ESR) model and completed the Client Satisfaction Questionnaire (CSQ) administered at three-month follow-up assessment. RESULTS: Older adult patients' satisfaction with IC (mean: 3.4, standard deviation [SD]: 0.60) was significantly higher than that with ESR (mean: 3.2, SD: 0.78), but the absolute difference was modest. Regression results showed that patients who used the IC model, attended the treatment service twice or more, or showed clinical improvement were more likely to express greater satisfaction. Stigma toward mental illness was negatively associated with satisfaction with mental health services. CONCLUSIONS: Older adults are more likely to have greater satisfaction with mental health services integrated in primary care settings than through enhanced referrals to specialty mental health and substance abuse clinics.