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Treating actinic keratosis (AK) and photodamaged skin is critical to reduce the risk of progression to skin cancer. Laser resurfacing for AK treatment is available as either lesion-directed or field therapy. Laser resurfacing removes the superficial epidermis and dermis containing actinic damage, promoting re-epithelialization of healthy skin. Although laser resurfacing has been explored as a modality for AK treatment in the literature, studies summarizing its efficacy in the treatment of AK are lacking. This review summarizes existing research on laser resurfacing as a monotherapy for AK treatment, highlighting the various laser resurfacing modalities available for AK treatment as well as their complications and efficacy in comparison to other therapies. Despite longer healing time, fully ablative laser resurfacing, including carbon dioxide and erbium-doped yttrium aluminum garnet were found to be more effective for AK treatment than fractional ablative techniques. Although some studies suggest laser resurfacing monotherapy as less efficacious than photodynamic therapy, and equally effective to 5-fluorouracil and 30% trichloroacetic acid, clinical trials of larger sample size are required to establish stronger evidence-based conclusions. Moreover, laser resurfacing used as lesion-directed therapy, as opposed to the usual field-therapy, requires further investigation.

What is known and Objective A pandemic can strain all aspects of the healthcare system, including the ability to monitor the safety of medication use. Reviewing the adequacy of medication safety practices during the COVID‐19 pandemic is critical to informing responses to future pandemics. The purpose of this study was to evaluate medication safety practices at a height of both COVID‐19 cases and hydroxychloroquine use. Methods This was a multicentre observational point prevalence study. Adult inpatients receiving hydroxychloroquine for COVID‐19 between March 22 and 28, 2020 were included. The primary outcome was the percentage of patients receiving appropriate QTc monitoring. Secondary outcomes included QTc prolongation, early discontinuation of hydroxychloroquine and ventricular arrhythmias. Results and discussion A total of 59% (167/284) of patients treated with hydroxychloroquine received appropriate QTc monitoring. QTc prolongation occurred in 25%. Hydroxychloroquine was prematurely discontinued in 1.4% of patients, all due to QTc prolongation. Ventricular arrhythmia occurred in 1.1%. What is new and Conclusion Medication safety practices were suboptimal with regard to hydroxychloroquine monitoring at the height of the COVID‐19 pandemic. Preparation for future pandemics should devote considerable attention to medication safety., This point prevalence study found that at the height of the COVID‐19 pandemic use of hydroxychloroquine was widespread despite being unproven. At the same time, medication safety practices in the form of QTc monitoring were suboptimal. Preparation for future pandemics should devote considerable attention to medication safety.

The Fourth Annual Symposium on Hidradenitis Suppurativa (SHSA) took place on November 1-3, 2019, at the Westin Book Cadillac Hotel in Detroit, Michigan. This symposium was a joint meeting of the US Hidradenitis Suppurativa Foundation and the Canadian Hidradenitis Suppurativa Foundation. This cross-disciplinary meeting with experts from around the world was an opportunity to discuss the most recent advances in the study of hidradenitis suppurativa (HS) pathogenesis, clinical trials, classification, scoring systems, complementary/alternative medical treatments, diet, pain management, surgical and laser treatment, and ultrasonographic assessment. A special preconference workshop was held on the use of neodymium-doped yttrium-aluminum-garnet laser hair reduction, sinus tract deroofing, and carbon dioxide laser excision with ultrasonographic mapping and tumescent anesthesia for the treatment of HS. The focused workshops on establishing an HS clinic, setting up an HS support group, the Hidradenitis Suppurativa Prospective Observational Registry and Biospecimen Repository, and wound care were held during the meeting. A special program called HS Ambassadors was established for patients who may have questions about the conference presentations, and in addition, a meet and greet for patients and HS Ambassadors was arranged. To facilitate networking between those early in their careers and clinical and research experts, a mentoring reception was held.

Hidradenitis suppurativa (HS) is a chronic, inflammatory disease affecting approximately 1% of the global population. While age- and sex-specific prevalence of HS is well documented in literature, few studies have explored trends in racial predilections for HS. The objective of this study is to investigate the race-specific prevalence of HS. MEDLINE and EMBASE searches were conducted in the OVID database. Keywords included variations of “race,” “ethnicity,” “country,” “prevalence,” and “Hidradenitis suppurativa.” Studies were included if they were written in English or French, conducted on human participants, and had data on HS and race-specific prevalence. Meta-analyses, systematic and literature reviews, and irrelevant articles were excluded. Thirty-nine out of 184 articles met the inclusion criteria after abstract and full-text screening. Population distribution was scaled according to country-specific demographics reports. These demographic reports were extracted from each country’s national statistics report. The average HS prevalence rates were highest in African American populations (1.3%), lowest in Hispanics/Latinos (0.07%), and intermediate amongst Caucasian populations (0.75%). Total prevalence in all other ethnic groups (0.17%) was minor in comparison to African American and Caucasian populations. Since the highest rates of HS were found among African American population, literature has highlighted the possibility of a genetic etiology in HS development. However, further literature examining race-specific prevalence of HS internationally is required to accurately assess the frequency and underlying etiology of HS among varying racial populations.

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder that involves painful nodules, abscesses, and tunnels of intertriginous sites. Although the etiology has not been fully elucidated, recent studies have highlighted its association with chromosomal abnormalities.We present a rare case of HS in a patient with Trisomy 1q;13 and systematically summarize the association between HS and chromosomal abnormalities. A search was conducted using MEDLINE and EMBASE in OVID database. Original studies reporting HS among human subjects with chromosomal abnormalities were included. Patient demographics, disease symptomology, clinical features, and treatment histories were extracted and summarized.Thirteen studies describing 428 cases met the inclusion criteria. Of the 13 articles, nine studies reported patients with HS and Down syndrome (DS), one article investigated HS and Smith-Magenis syndrome (SMS), and three articles analyzed HS and Patau syndrome (PS). While increased prevalence of HS was found in populations with DS, with suggested mechanisms involving amyloid precursor protein cleavage product, keratinocyte proliferation, and follicular plugging, the associations between HS and both SMS and PS remain inconclusive because of limited studies with small sample size.Although evidence suggests that the genetic regulation of chromosome 21 may be implicated in the association between HS and DS, this association may be confounded by additional factors that increase the risk of HS. Further research with larger sample sizes must be conducted to strengthen our understanding of the association between HS and chromosomal abnormalities.

Mindfulness and acceptance-based psychotherapies have gained popularity in the last few decades as a “third wave” of cognitive behavioral therapy (CBT). Acceptance is an important factor in all of these psychotherapies and stems from Asian philosophies, therefore similarities are necessarily seen between the psychotherapies themselves. This paper aims to demonstrate the ways in which acceptance-based psychotherapies converge by virtue of sharing the same philosophical root, as well as how they diverge in their applications of this concept. Specifically, this paper will examine similarities and differences in the concept of acceptance amongst the therapeutic models of rational emotive behavior therapy (REBT), dialectical behavior therapy, acceptance and commitment therapy, and mindfulness-based cognitive therapy, as compared to the Asian philosophical traditions of Buddhism and Hinduism. Acceptance in these psychotherapies will first be collectively compared with that of the Asian philosophical traditions, then key similarities and differences will be highlighted among the psychotherapies themselves. A secondary aim of this paper is to illustrate REBT as an acceptance-based psychotherapy, though it is not often included in discussions of third wave acceptance-based CBTs.

Socioeconomic status (SES) has led to treatment and survival disparities; however, limited data exist for non‐small cell lung cancer (NSCLC). This study investigates the impact of SES on NSCLC diagnostic imaging, treatment, and overall survival (OS), and describes temporal disparity trends. The Ontario Cancer Registry was used to identify NSCLC patients diagnosed between 2007 and 2016. Through linkage to administrative datasets, patients’ demographics, imaging, treatment, and survival were obtained. Based on median household neighborhood income, the Ontario population was divided into five income quintiles (Q1‐Q5; Q1 = lowest income). Multivariable regressions assessed SES association with OS, imaging, treatment receipt, and treatment delay, and their interaction with year of diagnosis to understand temporal trends. Endpoints were adjusted for demographics, stage and comorbidities, along with treatments and imaging for OS. A total of 50 542 patients were identified. Higher SES patients (Q5 vs. Q1) showed improved 5‐year OS (hazard ratio, 0.89; 95% confidence interval [CI], 0.87‐0.92; P .05) despite widening income inequality., Longstanding socioeconomic disparities in non‐small cell lung cancer imaging, treatments, and survival persist without improvement despite a universal health care system. Although these socioeconomic disparities remain largely unchanged over time, further exploratory research is necessary to better understand their causal pathways in efforts to reduce these inequalities.

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.

Background:. Patients born with a cleft lip and palate undergo multiple surgical procedures, increasing the infants’ exposure to anesthesia and potential risk of neurocognitive delays. In addition, these numerous procedures lead to greater use of hospital resources. This study analyzes the differences in anesthetic exposure and perioperative characteristics between performing combined versus separate primary palatoplasty (PP) and placement of bilateral myringotomy tubes (BMT). Methods:. We reviewed patients younger than 2 years who underwent PP and BMT at our institution from June 2014 to January 2019. Patients who underwent PP and BMT during the same admission (combined group = 74) and during separate admissions (separate group = 26) were studied. Due to the small sample size in the separate group, additional data for this group were gathered by propensity score matching by gender, race, and American Society of Anesthesiology class. Statistical analyses were carried out to identify significant differences between the 2 groups. Linear regression was performed to compare perioperative variables. Results:. One hundred patients met the inclusion criteria. There were no significant differences in demographic characteristics or American Society of Anesthesiology class, surgery and anesthesia duration, dosage of intraoperative dexmedetomidine, hospital length of stay, and perioperative complications (P > 0.05). Per contra, combined group had significantly lower intraoperative dosages of fentanyl (P = 0.01) and shorter postoperative care unit stay (P = 0.047). Conclusions:. This study documents decreased postoperative care unit time and anesthesia drug exposure without increased length of stay or perioperative complications in patients undergoing combined PP and BMT. These results support combining PP and BMT to reduce exposure to potentially neurotoxic medications and to increase efficient utilization of hospital resources.

Background Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, overall similarities in the clinical presentation of these dermatological manifestations have not yet been summarized. Objective This review aims to provide an overview of various cutaneous manifestations in patients with COVID-19 through three case reports and a literature review. Methods A literature search was conducted using PubMed, OVID, and Google search engines for original and review articles. Studies written in the English language that mentioned cutaneous symptoms and COVID-19 were included. Results Eighteen articles and three additional cases reported in this paper were included in this review. Of these studies, 6 are case series and 12 are case report studies. The most common cutaneous manifestation of COVID-19 was found to be maculopapular exanthem (morbilliform), presenting in 36.1% (26/72) patients. The other cutaneous manifestations included: a papulovesicular rash (34.7%, 25/72), urticaria (9.7%, 7/72), painful acral red purple papules (15.3%, 11/72) of patients, livedo reticularis lesions (2.8%, 2/72) and petechiae (1.4%, 1/72). Majority of lesions were localized on the trunk (66.7%, 50/72), however, 19.4% (14/72) of patients experienced cutaneous manifestations in the hands and feet. Skin lesion development occurred before the onset of respiratory symptoms or COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days. Majority of the studies reported no correlation between COVID-19 severity and skin lesions. Conclusion Infection with COVID-19 may result in dermatological manifestations with various clinical presentations, which may aid in the timely diagnosis of this infection.

Streptococci bacteremia is an unusual source of sepsis from spontaneous cerebrospinal fluid (CSF) rhinorrhea due to sphenoid meningoencephalocele. A spontaneous cause of CSF rhinorrhea should be on the differential along with trauma and congenital and neoplastic lesions. Moxifloxacin 400 mg daily for 2 weeks has a satisfactory CSF penetration to treat Streptococcus viridans bacteremia due to CSF rhinorrhea.

Adherence is a multifaceted behavioral process involving individuals, families, medical providers, communities, and health-care systems. Each of these factors represents a target for behavioral interventions to improve patient adherence. This chapter will describe adherence interventions centred on psychological principles of patients, health care providers, and health systems. Patient-based psychological approaches involve developing self-management techniques, or learning how particular behaviors associate with a health outcome, such as cognitive behavioral therapy. Physician-based strategies involve using motivational interviewing to help patients better understand their behavior and its consequences, or developing a sense of accountability in the patient-provider relationship. System-based approaches include scheduling longer appointment times, continuity of care, and communication with patients. Psychology offers useful theories, models, and strategies to promote practical strategies to promote adherence in patients suffering from chronic dermatological conditions.

PurposeTo summarize the current literature on the use and clinical efficacy of extended-infusion (EI) beta-lactam antibiotics, including piperacillin–tazobactam, meropenem, and cefepime.SummaryGram-negative infections are a serious concern among hospitalized patients and require innovative pharmacokinetic dosing strategies to achieve clinical success, especially as the emergence of resistant gram-negative pathogens has outpaced the development of new antibiotics. Beta-lactam antibiotics exhibit time-dependent activity, which means that optimal efficacy is achieved when free drug concentrations stay above the minimum inhibitory concentration for an extended duration of the recommended dosage interval. EI piperacillin–tazobactam therapy has demonstrated improved clinical outcomes and decrease mortality in critically ill patients with gram-negative infections, particularly Pseudomonas aeruginosa infections. EI meropenem has shown higher therapeutic success rates for patients with febrile neutropenia and shorter intensive care unit (ICU) length of stay (LOS) with a reduction in ventilator days in patients with multidrug-resistant ventilator-associated pneumonia. However, a larger study showed no difference in clinical outcomes between standard-infusion and EI meropenem. EI cefepime has been associated with decreased mortality and shorter ICU LOS in patients with Pseudomonas aeruginosa infections. Common challenges associated with EI beta-lactam antibiotics include Y-site incompatibilities, lack of intravenous access, and tubing residuals. It is important to note that factors such as diverse patient populations and study methodology, along with various antibiotic dose regimens, may have contributed to conflicting data on EI beta-lactam therapy.ConclusionBased on most published literature, there appears to be a favorable trend toward use of EI beta-lactam therapy in clinical practice, particularly in critically ill patients with gram-negative infections.

Pyoderma gangrenosum (PG) is a rare destructive, ulcerative, and inflammatory cutaneous disease. PG can be associated with inflammatory bowel disease (IBD), arthritis, autoinflammatory syndromes, and hematological malignancies. Multiple reports in the literature have found an association between PG and solid organ tumors. This article provides a summary and review of PG in patients with solid organ malignancies. We performed a PubMed search using the terms pyoderma gangrenosum, paraneoplastic pyoderma gangrenosum, cancer, malignancy, tumor, and solid organ malignancy. Out of 529 papers screened, 19 relevant cases were included that reported patients above the age of 12 years old with antecedent, coincident, or subsequent occurrence of PG in association with a solid organ malignancy. The most common malignancies associated with PG were found in the breast (n = 6, 31.6%). In a majority of the cases, the site of PG was found to be the lower extremities (n = 12, 63.2%). Almost all cases were presented with ulcerative PG subtype (n = 18, 94.7%). Moreover, 78.9% of cases (n = 15) were reported to have PG prior to tumor diagnosis. PG lesions resolved in 100% of patients after either tumor or PG-specific treatment. We identified a strong temporal relationship between ulcerative PG and its associated solid organ malignancy. Other associations with breast cancer and lower extremity location exist but are not as strong.

Tympanostomy tube placement, adenotonsillectomy, and cochlear implant placement are common otolaryngologic procedures performed on children everyday around the world. Young children are more likely to develop chronic otitis media due to their immaturely developed eustachian tubes. Myringotomy and tympanostomy tube placement helps to decrease their risk of further developing otitis media and hearing loss. This procedure is very brief but requires children to lie very still; therefore, general anesthesia is usually necessary. Adenotonsillectomies are usually necessitated for the treatment of recurrent tonsillitis or obstructive symptoms. Obstructive sleep apnea predisposes these children to increased perioperative risks with general anesthesia, and many of these patients should be monitored overnight postoperatively.

Background An antibiotic time out is when a clinician is prompted to reevaluate antibiotic therapy for appropriateness after 48–72 hrs. The purpose of this study is to evaluate the impact of a prescriber-led electronic antibiotic timeout alert. Methods This was a retrospective cohort study conducted at seven hospitals of a health system. The alert prompts prescribers to reevaluate antibiotic therapy after > 72 hours upon opening the electronic chart. Prescribers can then choose to “Continue”, “Renew”, “Discontinue” or “Defer” for each antibiotic. The alert fires for every time the chart is opened, for every prescriber, every time any antibiotic has been active for > 72 hours and no action response (i.e., “Continue”, “Renew”, “Discontinue”) has been selected. This was a 6 month study from November 1, 2018 – April 30, 2019. The primary outcome measure was the percentage of patients having > 1 antibiotic discontinued via the electronic antibiotic timeout alert. Secondary outcomes included frequency of timeout alerts per patient, and percentage of discontinuations per response, by drug, by indication and by patient age. Results A total of 213950 alerts fired for 13263 patients during the study period. 94.2% and 0.4% of responses were “Defer” and “Discontinue”, respectively. The average number of alerts per patient was 16.1. The percentage of patients who had at least one discontinuation was 5.3%. 38.2% of patients had no response other than “Defer”. There were a total of 10306 action responses, 4.8% of which were “Discontinue”. Among action responses, discontinue rates for the indications of “COPD exacerbation”, “Prophylaxis, Surgical/Procedural”, “Prophylaxis, Immunosuppression”, “Osteomyelitis” were 9.6%, 12%, 1.3% and 1%, respectively. Azithromycin and trimethoprim/sulfamethoxazole had discontinuation rates of 9.3% and 0.9%, respectively. Patient age had a significant impact on discontinuation rates with rates of 4.7%, 3.5%, and 10.9% for patients > 18, 2–17 and < 2 years of age (p< 0.001). Conclusion An electronic antibiotic timeout alert implemented at seven hospitals was largely ignored. This alert may be refined by limiting it to antibiotic orders with specific features associated with higher rates of discontinuation. Disclosures All Authors: No reported disclosures

Highlights • COVID-19 pandemic-induced psychosocial stressors and stay-at-home orders may exacerbate eating disorder-related triggers. • Appropriate management of eating disorders is crucial to help mitigate long-term impacts such as increased risk of suicide.

e15062 Background: Conventional anticancer drugs have been developed to improve overall survival (OS) and/or progression-free survival (PFS) in the palliative intent setting. However, long-term survival is often limited by acquired biologic resistance. In contrast to conventional anticancer drugs, ICIs putatively preserve long-term survival in a small subset of patients. However, in the absence of a gold-standard definition, long-term survival improvement has not been adequately quantified. Long-term survival rate difference has been proposed as a method of quantifying long-term survival. However, there a paucity of literature demonstrating statistical improvements in survival rate. Therefore, the objective of the study was to quantify the improvement in long-term survival rate in OS and PFS improvement in ICIs compared with non-ICIs. Methods: The FDA Hematology/Oncology Approvals & Safety Notification web page was searched for RCTs cited in oncology drug approvals between 01-2011 and 06-2019. The most recent OS and PFS updates were used when available. OS and PFS curves were digitized to reconstruct pseudo individual patient data as per established methods. Survival rate improvement at 1, 2 and 3 years were calculated as differences between the experimental arm and control arm. Survival rate improvements across RCTs at 1, 2 and 3 years were pooled using a random-effects model and the results were compared between ICI and non-ICIs. Subgroup analyses were conducted for melanoma and non-small cell lung cancer. Results: We identified 130 RCTs (22 ICIs, 108 non-ICIs) for analysis. The absolute OS rate improvement was 9.5% in ICIs and 4.9% in non-ICIs at 1-year (difference = 4.6%, p < 0.001), 10.3% in ICIs and 4.9% in non-ICIs at 2-years (difference = 5.3%, p < 0.001), and 10.2% in ICIs and 5.1% in non-ICIs at 3-years (difference = 4.6% p 0.006). The absolute PFS rate improvement was 10.3% in ICIs and 17.7% in non-ICIs at 1-year (difference = -7.3% p < 0.001), and 8.9% in ICIs and 15.5% in non-ICIs at 2-years (difference = -6.6% p < 0.001). Conclusions: Long-term OS survival rate improvements, while statistically significant were only modestly higher in ICIs compared to non-ICIs. PFS survival rate differences were statistically lower in ICIs compared to non-ICIs. While ICIs represent an important shift towards long-term survival, greater emphasis should be placed on rigorously evaluating long-term survival rate improvement and reporting of future novel therapies.

Objective For those with type 2 diabetes mellitus (T2DM), impact of short-term high-dose glucocorticoid exposure on beta-cell function is unknown. This study aims to compare the impact on beta-cell function and insulin resistance of prednisone 40 mg between adults with newly diagnosed T2DM and healthy adults. Methods Five adults with T2DM and five healthy adults, all between 18–50 years, were enrolled. T2DM diagnosis was less than one year prior, HbA1c

Study Objectives Although sleep disturbance is common in acutely ill patients during and after a hospitalization, how hospitalization affects sleep in general medicine patients has not been well characterized. We describe how sleep and activity patterns vary during and after hospitalization in a small population of older, predominately African American general medicine patients. Methods Patients wore a wrist accelerometer during hospitalization and post-discharge to provide objective measurements of sleep duration, efficiency, and physical activity. Random effects linear regression models clustered by subject were used to test associations between sleep and activity parameters across study days from hospitalization through post-discharge. Results We recorded 404 nights and 384 days from 54 patients. Neither nighttime sleep duration nor sleep efficiency increased from hospitalization through post-discharge (320.2 vs. 320.2 min, p = 0.99; 74.0% vs. 71.7%, p = 0.24). Daytime sleep duration also showed no significant change (26.3 vs. 25.8 min/day, p = 0.5). Daytime physical activity was significantly less in-hospital compared to post-discharge (128.6 vs. 173.2 counts/min, p < 0.01) and increased 23.3 counts/min (95% CI = 16.5 to 30.6, p < 0.01) per hospital day. A study day and post-discharge period interaction was observed demonstrating slowed recovery of activity post-discharge (β 3 = −20.8, 95% CI = −28.8 to −12.8, p < 0.01). Conclusions Nighttime sleep duration and efficiency and daytime sleep duration were similar in-hospital and post-discharge. Daytime physical activity, however, was greater post-discharge and increased more rapidly during hospitalization than post-discharge. Interventions, both in hospital and at home, to restore patient sleep and sustain activity improvements may improve patient recovery from illness.

Ethical principles affect daily decision-making in pediatric anesthesiology. These medical decisions are interlaced with the ethical components of informed consent and obligations to the child and family. Informed consent in pediatrics includes the concepts of best interest, in which the parents or other surrogate decision-makers choose acceptable treatment for the child, and assent, which enables children to participate in decision-making to the best of their ability. Of equal significance to informed consent, the process of informed refusal requires anesthesiologists to more fully inform children and their guardians about risks and benefits while respecting refusal of assent and avoiding coercion. Pediatric considerations regarding end-of-life therapy are slightly different than adult considerations. To help resolve these ethical dilemmas, ethics committees are available for consultations to assist the medical team, family members, and patients in order to make the best decision for the child.

Because cord blood (CB) lacks memory T and B cells and recent decreases in herd immunity to vaccine-preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine-eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five patients (63%; engrafting units median HLA-allele match 5/8; range, 2 to 7/8) received protein conjugated vaccines, and 63 patients (median age, 34 years; range, .9 to 64) were evaluated for responses. Median vaccination time was 17 months (range, 7 to 45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19F, 23F) were seen in children and adults (60% versus 49%, P = .555). Responses to tetanus, diphtheria, pertussis, Haemophilus influenzae, and polio were observed in children (86% to 100%) and adults (53% to 89%) even if patients had prior GVHD or rituximab. CD4+CD45RA+ and CD19+ cell recovery significantly influenced tetanus and polio responses. In a smaller cohort responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side effects were identified, and all vaccinated patients survived (median follow-up, 57 months). Although GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients.

BackgroundMinocycline (MINO), a tetracycline antibiotic, has been available since the 1960s. The intravenous (IV) formulation was withdrawn from the market in 2005 but was reintroduced in the US market in 2009. The drug has potent activity against methicillin-resistant Staphylococcus aureus (MRSA) a

Key Points Question How frequently do immune checkpoint inhibitor (ICI) agents vs non-ICI agents qualify for American Society of Clinical Oncology Value Framework version 2 (ASCO-VF v2) tail-of-the-curve bonuses or European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) immunotherapy-triggered long-term plateau adjustments? Findings In this cohort study of 100 randomized clinical trials comparing ICI with non-ICI agents, ASCO-VF v2 tail-of-the-curve bonuses and ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments were not awarded to ICI agents more often than non-ICI agents. Meaning The ASCO-VF v2 and ESMO-MCBS v1.1 may be flawed in accurately capturing long-term survival., This study of 100 randomized clinical trials determines how frequently immune checkpoint inhibitor (ICI) and non-ICI anticancer agents displayed trends of long-term durable survival as defined by the American Society of Clinical Oncology (ASCO) Value Framework and the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale., Importance Recently, anticancer agents have generated excitement owing to their capacity to preserve long-term durable survival in some patients who are represented by a tail of the survival curve. However, because traditional measures of clinical benefit may not accurately capture durable survival, amendments to various valuation frameworks have been proposed to capture this benefit. Objectives To determine how frequently immune checkpoint inhibitor (ICI) anticancer agents vs non-ICI anticancer agents displayed trends of long-term durable survival, as defined by the American Society of Clinical Oncology Value Framework version 2 (ASCO-VF v2) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1), as well as to further analyze the degree of agreement between ASCO and ESMO frameworks. Design, Setting, and Participants In this cohort study, anticancer agents from phase 2 or 3 randomized clinical trials (RCTs) cited for clinical efficacy evidence in drug approval by the US Food and Drug Administration between January 2011 and March 2018 were identified. Data required for the ASCO-VF v2 tail-of-the-curve bonus and the ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments were extracted from relevant RCTs. Frequency and difference in proportions were calculated to determine how often survival benefits were awarded to anticancer agents overall and to ICI and non-ICI anticancer agents individually. Main Outcomes and Measures American Society of Clinical Oncology Value Framework v2 tail-of-the-curve bonuses and ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments. Results In total, 247 RCTs were identified, and 100 RCTs involving 57 164 patients were included, with 14 examining ICI agents (1 ipilimumab, 5 pembrolizumab, 5 nivolumab, 2 atezolizumab, and 1 durvalumab) and 86 examining non-ICI agents (74 targeted therapy, 8 chemotherapy, 3 hormone therapy, and 1 radiopharmaceutical). Randomized clinical trials were awarded ASCO-VF v2 tail-of-the-curve bonuses more often than ESMO-MCBS v1.1 immunotherapy-triggered long-term plateau adjustments (ASCO-VF v2, 45.0% [8 of 14 ICI RCTs and 37 of 86 non-ICI RCTs] vs ESMO-MCBS v1.1, 2.6% [1 of 12 ICI RCTs and 1 of 66 non-ICI RCTs). Randomized clinical trials for ICIs were not more likely to receive an ASCO-VF v2 bonus or ESMO-MCBS v1.1 adjustment than non-ICI RCTs (ASCO-VF: risk difference, 0.14; 95% CI, −0.14 to 0.42; P = .32; ESMO-MCBS: risk difference, 0.07; 95% CI, −0.09 to 0.23; P = .40). Poor agreement was found between the framework algorithms in identifying long-term survival benefits from RCTs (κ = 0.01; 95% CI, −0.23 to 0.22; P = .50). Conclusions and Relevance The ASCO-VF v2 and ESMO-MCBS v1.1 may require additional refinement to accurately capture the benefit of durable long-term survival, or ICI agents may not preserve long-term survival as conventionally thought.

2585 Background: Recently, anti-cancer agents have generated excitement due to their capacity to preserve long-term survival in some patients, represented by a “tail of the survival curve”. However, as traditional measures of clinical benefit may not accurately capture long-term survival, amendments to various valuation frameworks have been proposed to capture this benefit. The purpose of this study was to determine how frequently immune checkpoint inhibitor vs. non-immune checkpoint inhibitor anti-cancer agents, displayed trends of long-term survival, as defined by the American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), as well as to analyze the degree of agreement between ASCO and ESMO frameworks. Methods: Anti-cancer agents from phase II or III randomized controlled trials (RCTs) cited for clinical efficacy evidence in drug approval by the Food and Drug Administration (FDA) between January 2011 and March 2018 were identified. Data required for ASCO-VF and ESMO-MCBS were extracted. Difference in how often long-term survival bonuses were awarded were calculated in all RCTs, as well as immune checkpoint inhibitor and non-immune checkpoint inhibitor RCTs individually. Cohen’s Kappa statistic was calculated to evaluate agreement between ASCO-VF and ESMO-MCBS. Results: 100 RCTs were analyzed. RCTs were awarded ASCO-VF version 2 (v2) “tail of the curve” bonuses more often than ESMO-MCBS version 1.1 (v1.1) “immunotherapy-triggered” long-term plateau adjustments (45% vs. 2.6%). Comparing to non-immune checkpoint inhibitor RCTs, immune checkpoint inhibitor RCTs were not more likely to receive ASCO-VF v2 bonuses/ESMO-MCBS v1.1 adjustments (p = 0.32/ p = 0.40). Long-term survival agreement between the two frameworks was poor (kappa: 0.01; p = 0.50). Conclusions: The ASCO-VF v2 and ESMO-MCBS v1.1 may require additional refinement in order to accurately capture the benefit of long-term survival or immune checkpoint inhibitor and non-immune checkpoint inhibitor agents may not preserve substantially different long-term survival populations.