Faculty Bibliography

This post-hoc analysis of the ALLEGRO phase 2b/3 study (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral Janus kinase 3/TEC family kinase inhibitor, in patients with alopecia totalis (AT) and alopecia universalis (AU). Patients aged ≥ 12 years with alopecia areata (AA) and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg loading dose) or placebo for 24 weeks. In a subsequent 24-week extension period, the ritlecitinib groups continued their doses and patients initially assigned to placebo switched to ritlecitinib (200/50 or 50 mg daily). In this analysis, clinician- and patient-reported hair regrowth outcomes were assessed at weeks 24 and 48 in four AA subgroups: AT/AU, AT, AU, and non-AT/AU. Safety was monitored throughout. Of the 718 randomized patients, 151 (21%) and 147 (20%) were defined as having AT or AU, respectively. At week 24, Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp hair loss) response rates were higher in the ritlecitinib-treated AT/AU, AT, and AU groups (7%-14%, 7%-21%, and 4%-10%, respectively) vs the placebo group (0% in the AT/AU, AT, and AU groups). The proportions of patients with a SALT score of ≤20 increased through week 48 (AT/AU, 13%-31%; AT, 11%-27%; AU, 6%-41%). Additionally, at week 24, 25%-43%, 32%-42%, and 12%-50% of patients with AT/AU, AT, and AU, respectively, who received ritlecitinib achieved a moderately or greatly improved response based on the Patient Global Impression of Change scale. Response rates generally increased through week 48 and were similar across AA subgroups. In patients with AT/AU, ritlecitinib was well tolerated with a safety profile consistent with that of the overall AA population. Ritlecitinib demonstrated clinical efficacy, patient-reported improvement, and an acceptable safety profile in patients with AT and AU through week 48. A plain language summary of this study is available at https://doi.org/10.25454/pfizer.figshare.26879161. Clinicaltrials.gov: NCT03732807.

PURPOSE OF REVIEW/OBJECTIVE:Current biological findings provide new insights into the genetics driving growth of low-grade gliomas in pediatric patients. This has provided new targets for novel therapies. The purpose of this paper is to review novel therapies for pediatric low-grade gliomas that have been published in the past 24 months. RECENT FINDINGS/RESULTS:Low-grade gliomas are often driven by mitogen activated protein kinase (MAPK) alterations either with BRAF V600E point mutations or BRAF fusions. Current advances have also highlighted novel fusions of fibroblast growth factor receptor (FGFR), myeloblastosis family of transcription factors (MYB), meningioma 1 tumor suppressor (MN1), neurotrophic receptor kinase family of receptors (NTRK), Kristen RAS (Rat Sarcoma Virus) oncogene homolog in mammals (KRAS), Receptor tyrosine kinase ROS proto oncogene 1 (ROS1), protein kinase C alpha (PRKCA), and platelet derive growth factor receptor (PDGFR) amplification. Novel therapies have been employed and are showing encouraging results in pediatric low-grade gliomas. Current trials are underway with newer generation pan RAF inhibitors and mitogen activated protein kinase - kinase (MEK) inhibitors. Other early phase clinical trials have provided safety data in pediatric patients targeting FGFR fusion, NTRK fusion, PDGFR amplification and ROS1 mutations. SUMMARY/CONCLUSIONS:Historical treatment options in pediatric low-grade gliomas have utilized surgery, radiation therapy and conventional chemotherapy. Recently greater insight into their biology has found that alterations in MAPK driven pathways are often the hallmark of tumorigenesis. Targeting these novel pathways has led to tumor control and shrinkage without the use of conventional chemotherapy. Caution should be taken however, since these treatment options are still novel, and we do not fully appreciate the long-term effects. Nonetheless a new era of targeted medicine is here.

Ecological momentary assessment (EMA) is a method of data collection that entails prompting individuals to report their experiences (e.g., thoughts, feelings, and behaviors) in real time over the course of their day-to-day lives. By providing rich information about how these experiences unfold over time within an individual, EMA has the potential to substantially advance our understanding of grief. However, there is uncertainty about how bereaved adults will respond to EMA, especially among those with high prolonged grief symptom severity. Accordingly, we evaluated the feasibility and acceptability of an EMA protocol in bereaved adults with low and high prolonged grief severity. Participants completed six 12-item EMA surveys per day on their smartphones for 17 days. Adherence was high (mean survey completion = 90%, median = 96%), and only 6% of participants withdrew. Adherence remained high in those with high prolonged grief symptom severity (mean = 86%; median = 96%). On average, participants reported agreement that survey frequency and length were acceptable. There was no evidence for systematic worsening of symptoms during EMA data collection. Together, these findings suggest that EMA is feasible, acceptable, and safe for bereaved adults, including those with high prolonged grief symptom severity.

BACKGROUND/UNASSIGNED:Chronic pain is highly prevalent in US military Veterans, and pain interdisciplinary teams (IDTs) are the gold standard in pain care. There is no standard or guidance for how best to develop and implement pain interdisciplinary teams within complex health care systems. OBJECTIVES/UNASSIGNED:The purpose of this quality improvement project was to evaluate the effectiveness of the standard 9-step Lean 6 Sigma (LSS) methodology in redesigning a pre-existing VA outpatient pain clinic solely offering interventional pain services into an efficient, sustainable pain IDT program. METHODS/UNASSIGNED:The initial evaluation process at a VA Medical Center that primarily serves rural Veterans was redesigned with the a priori goal of developing an efficient, sustainable IDT program that decreased driving days (ie, in-person appointments) required for a comprehensive initial pain evaluation, decreased number of consults required for initial pain evaluations, increased the number of consults to Whole Health services, and increased compliance with policies and standards. Feedback from administrators, clinicians, and Veterans was used to identify inefficiencies then iteratively design, test, and finalize a redesigned service called the PREVAIL Interdisciplinary Team Track (PREVAIL IDT Track). Baseline data was collected for 1 year followed by sustainment data for 14 months. Results were analyzed using descriptive statistics. RESULTS/UNASSIGNED:PREVAIL IDT Track decreased the number of in-person appointments from 5 to 2, decreased consults required for evaluations from 5 to 1, increased the number of unique consults to Whole Health education classes, and made the VA fully compliant with policies and standards. To date, 486 Veterans have participated in the redesigned program, including 167 graduates and 212 current enrollees in this sustained clinical program. CONCLUSION/UNASSIGNED:The success of PREVAIL IDT Track suggests that LSS may be a promising method for redesigning sustainable pain IDTs in VA that improve efficiency.

The current study examined onset and maintenance insomnia as mediators of the bidirectional relation between anxiety and depressive symptoms over a three-year period. The sample included 3,415 US community-dwelling Medicare beneficiaries aged 66-103. Participants completed measures of types of insomnia, anxiety symptoms, and depressive symptoms at four time points. Analyses included two double mediation models adjusted for baseline depressive or anxiety symptoms, chronic health problem burden, use of sleep medications, age, and sex. Both covariate-adjusted models showed significant direct relations between anxiety and depressive symptoms, and these relations were modestly partially mediated by onset and maintenance insomnia. In older adults, onset and maintenance insomnia are distinct outcomes of both anxiety and depressive symptoms and also predictors of each symptom cluster. Further research testing these models is warranted and, if supported, may support prevention and treatment studies focused on primary and secondary prevention of these problems in older adults.

BACKGROUND:by Philips Healthcare). A multi-specialty group of physician POCUS experts (n = 35) acquired three standard ultrasound views (abdominal right upper quadrant, cardiac apical 4-chamber, and superficial neck and lung views) in random order on the same standardized patients and rated the image quality. Afterward, a final survey of the overall ease of use, image quality, and satisfaction of each handheld was completed. RESULTS:. The 5 most desirable characteristics of handhelds were image quality, ease of use, portability, probe size, and battery life. Ultimately, all 6 handhelds had notable advantages and disadvantages, with no single device having all desired qualities or features. CONCLUSIONS:was rated highest for overall ease of use and was the most preferred handheld for purchase by POCUS experts.

BACKGROUND:Open Hartmann's procedure has traditionally been the procedure of choice to treat complicated diverticulitis. We analyzed the ACS-NSQIP database to compare outcomes in patients who underwent emergent laparoscopic Hartmann's procedure (LHP) to those who had an open Hartmann's procedure (OHP). STUDY DESIGN/METHODS:Data analyzed from 2015 to 2019 using ICD-10 codes. Patients were matched on several important covariates using a propensity score matching method (PSM). Patients were matched in a 4:1 ratio of controls to cases based on the propensity score. RESULTS:We identified 5026, of which 456 had LHP and 4570 had OHP. PSM analysis yielded 369 LHP and 1476 OHP patients. LHP had lower rates of superficial surgical site infection (SSSI) compared to OHP (2.44% vs. 5.89%, p = 0.007). LHP had similar post-operative outcomes compared to OHP, including 30-day mortality (5.15% vs. 2.98%, p = 0.060), organ space surgical site infection (OSSSI) (14.36% vs. 12.60%, p = 0.161), wound disruption (1.36% vs. 2.44%, p = 0.349), median LOS (8 vs. 9 days, p = 0.252), readmission within 30 days (11.92% vs. 8.67%, p = 0.176), rate of reoperation (6.0 vs. 6.5%, p = 0.897), and discharge to home (76% vs. 77%, p = 0.992). LHP had longer operative times compared to OHP (median 129 vs. 118 min, p < 0.0001). CONCLUSION/CONCLUSIONS:The LHP is associated with lower rates of SSSI. However, it is not associated with lower rates of mortality, OSSSI, readmissions and reoperations within 30 days. Surgical times are longer in LHP. More studies are needed to determine whether LHP offers advantages in the long-term, particularly in rates of incisional hernia and colostomy closure.

BACKGROUND/UNASSIGNED:Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized. METHODS/UNASSIGNED:This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest. RESULTS/UNASSIGNED:Our findings showed that the SCAD with cardiac arrest population had significantly higher comorbidities, including cardiac arrhythmias, congestive heart failure, pulmonary circulation disorders, liver diseases, solid tumors, coagulopathy, fluid disorders, chronic kidney disease (CKD), anemia secondary to deficiency, psychosis, neurological disorders, carotid artery disease, atrial fibrillation, ventricular arrhythmias (ventricular tachycardia (VT), ventricular fibrillation (VF)), and acute myocardial infarction (AMI), compared to the SCAD without cardiac arrest population. Likewise, for SCAD patients who did not have an ICD in place, we found increasing age, fluid and electrolyte disorders, uncomplicated diabetes, neurological disorders, peripheral vascular disease, pulmonary circulatory disorders, cardiac arrhythmias, and congestive heart failure to be associated with greater mortality. CONCLUSIONS/UNASSIGNED:SCAD patients with certain comorbidities (e.g., pulmonary diseases, liver diseases, cancers, coagulopathy, and CKD) who presented with AMI or congestive heart failure should be monitored closely for ventricular arrhythmias as they have a higher chance of progressing to cardiac arrest. ICD therapy can be considered for these patients, but data on the success of this treatment option are limited, and more research needs to be performed to determine whether the benefits of this outweigh the risks.

BACKGROUND/UNASSIGNED:Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of probiotics to a specialized formula has also been proposed as a potential approach to possibly increase the benefit. We systematically reviewed specialized formulas for infants with CMA to inform the updated World Allergy Organization (WAO) DRACMA guidelines. OBJECTIVE/UNASSIGNED:To systematically review and synthesize the available evidence about the use of specialized formulas for the management of individuals with CMA. METHODS/UNASSIGNED:We searched from inception PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations, for randomized and non-randomized trials of any language investigating specialized formulas with or without probiotics. We included all studies irrespective of the language of the original publication. The last search was conducted in January 2024. We synthesized the identified evidence quantitatively or narratively as appropriate and summarized it in the evidence profiles. We conducted this review following the PRISMA, Cochrane methods, and the GRADE approach. RESULTS/UNASSIGNED:GG) showed no significant effect, as supported by low to very low CoE. CONCLUSIONS/UNASSIGNED:Currently available studies comparing eHF-CM, AAF, HRF, and SF provide very low certainty evidence about their effects in infants with IgE-mediated and non-IgE-mediated CMA. Our review revealed several limitations in the current body of evidence, primarily arising from concerns related to the quality of studies, the limited size of the participant populations and most importantly the lack of diversity and standardization in the compared interventions. It is therefore imperative for future studies to be methodologically rigorous and investigate a broader spectrum of available interventions. We encourage clinicians and researchers to review current World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines for suggestions on how to use milk replacement formulas in clinical practice and what additional research would be the most beneficial.