Richard M. Fairbanks Foundation

In the United States, adult human papillomavirus (HPV) vaccination coverage remains low at 20-50%, depending on age, and cervical cancer (CC) screening rates range from 68 to 76%. Few studies have evaluated characteristics of women who are both HPV vaccinated and up to date (UTD) with screening as an integrated outcome. The purpose of the present study was to classify women into four prevention categories and examine factors associated with being double protected compared to unprotected. Data were gathered via an online survey from a sample of low-income women (household income < USD 50,000) provided by a research survey company (n = 719). Women were classified into four categories: vaccinated only, screened only, both vaccinated and screened (double protected), or neither (unprotected). Sociodemographic characteristics, healthcare access, and Health Belief Model constructs were assessed. Multivariable logistic regression compared women who were double protected with those unprotected (n = 274). Most women were UTD with screening only (57.8%), while 15.5% were double protected and 22.6% were unprotected. Younger age (Odds Ratio [OR = 0.93; 95% Confidence Interval [CI]: 0.89, 0.98), having ≥1 medical visit in the past year (OR = 4.16; 95% CI: 1.74, 9.95), higher perceived CC risk (OR = 3.65; 95% CI: 1.41, 9.43), greater perceived benefits of CC screening (OR = 1.96; 95% CI: 1.45, 2.66), and higher HPV knowledge (OR = 1.09; 95% CI: 1.01, 1.17) were associated with higher odds of being double protected. A substantial proportion of low-income women lack comprehensive CC prevention. Integrated, bundled prevention strategies that simultaneously promote HPV vaccination and screening may be important to reduce CC disparities.

Obesity is an established risk factor for cardiovascular disease (CVD); however, the overall and sex-specific relationships across the full spectrum of body mass index (BMI), particularly severe obesity defined as class 2 (BMI 35 to <40.0 kg/m2) and class 3 (BMI ≥40 kg/m2), and long-term CVD outcomes remain incompletely described. We included 289 875 participants (mean age, 60.3 years; 79.2% women) from 21 cohorts of the Cross-Cohort Collaboration enrolled between 1948 and 2015 with harmonized BMI data, a BMI ≥18.5 kg/m2, and at least one of nine adjudicated outcomes: time to first fatal and non-fatal myocardial infarction (MI), fatal and nonfatal stroke, heart failure (HF), atrial fibrillation (AF), total coronary heart disease (CHD), total CVD, CHD mortality, CVD mortality, and all-cause mortality. Multivariable Cox proportional hazard models with restricted cubic splines were used to estimate the hazard ratio (HR) of BMI for each outcome, adjusting for demographic and clinical risk factors. Over 19.2 median years (25th, 11.6; 75th, 23.5 percentile) of follow-up, there were a total of 15 542 incident MI events, 15 467 incident stroke events, 14 172 incident HF events, 9066 diagnosed AF, and 113 918 total deaths, of which 14 647 were CHD-related and 28 879 were CVD-related. Overall, compared with individuals with normal weight, those with class 2 and class 3 obesity had the highest risk of HF (HR, 2.1, 95% CI, 2.0-2.3, and HR, 3.0, 95% CI, 2.7-3.2, respectively) and AF (HR, 1.8, 95% CI 1.7-2.0, and HR, 2.8, 95% CI, 2.5-3.1, respectively). Compared with men, women experienced higher relative increases in the risk associated with severe obesity for outcomes stroke, CVD, and all-cause mortality (P for interaction: <0.001, 0.003, and <0.001, respectively). Furthermore, in men, no increase in stroke risk was observed with higher BMI categories (P trend=0.49), whereas in women, the risk of stroke plateaued across obesity subclasses (compared with normal weight) yet remained significantly increased. Higher BMI was robustly associated with increased risk for most outcomes, particularly HF and AF, even after adjusting for traditional risk factors. Observed sex differences in the relative hazard of higher BMI categories and stroke, total CVD, and all-cause mortality suggest potential differences in underlying biological mechanisms.

BackgroundRecognizing patient symptoms is fundamental to medicine, research, and public health. However, symptoms are often underreported in coded formats even though they are routinely documented in physician notes. Large language models (LLMs), noted for their generalizability, could help bridge this gap by mimicking the role of human expert chart reviewers for symptom identification.ObjectiveThe primary objective of this multisite study was to measure the accurate identification of infectious respiratory disease symptoms using LLMs instructed to follow chart review guidelines. The secondary objective was to evaluate LLM generalizability in multisite settings without the need for site-specific training, fine-tuning, or customization.MethodsFour LLMs were evaluated: GPT-4, GPT-3.5, Llama2 70B, and Mixtral 8×7B. LLM prompts were instructed to take on the role of chart reviewers and follow symptom annotation guidelines when assessing physician notes. Ground truth labels for each note were annotated by subject matter experts. Optimal LLM prompting strategies were selected using a development corpus of 103 notes from the emergency department at Boston Children’s Hospital. The performance of each LLM was measured using a test corpus with 202 notes from Boston Children’s Hospital. The performance of an International Classification of Diseases, Tenth Revision (ICD-10)–based method was also measured as a baseline. Generalizability of the most performant LLM was then measured in a validation corpus of 308 notes from 21 emergency departments in the Indiana Health Information Exchange.ResultsSymptom identification accuracy was superior for every LLM tested for each infectious disease symptom compared to an ICD-10–based method (F1-score=45.1%). GPT-4 was the highest scoring (F1-score=91.4%; P<.001) and was significantly better than the ICD-10–based method, followed by GPT-3.5 (F1-score=90.0%; P<.001), Llama2 (F1-score=81.7%; P<.001), and Mixtral (F1-score=83.5%; P<.001). For the validation corpus, performance of the ICD-10–based method decreased (F1-score=26.9%), while GPT-4 increased (F1-score=94.0%), demonstrating better generalizability using GPT-4 (P<.001).ConclusionsLLMs significantly outperformed an ICD-10–based method for respiratory symptom identification in emergency department electronic health records. GPT-4 demonstrated the highest accuracy and generalizability, suggesting that LLMs may augment or replace traditional approaches. LLMs can be instructed to mimic human chart reviewers with high accuracy. Future work should assess broader symptom types and health care settings.

Chronic kidney disease (CKD) is a growing public health concern globally, with primary care physicians (PCPs) playing a pivotal role in its early detection and management. This review explores the epidemiology, risk factors, screening strategies, and clinical manifestations of CKD within primary care settings. PCPs are integral in recognizing at‐risk populations, initiating timely screening through eGFR and albuminuria tests, and managing modifiable risk factors like hypertension and diabetes. The article discusses current guideline‐recommended pharmacologic therapies—including RAAS inhibitors, SGLT2 inhibitors, GLP‐1 receptor agonists, and non‐steroidal MRAs—that slow disease progression. Lifestyle modifications and dietary interventions are emphasized as essential components of care. Additionally, the review outlines key indications for nephrology referral and the management of common CKD complications, such as anemia and mineral‐bone disorder. By embracing a proactive and multidisciplinary approach, PCPs can significantly influence CKD outcomes, reduce progression to end‐stage renal disease, and improve overall patient prognosis.

BackgroundMaternal and neonatal morbidity and mortality remain high in low-income and middle- income countries (LMICs), and staffing schedules may contribute to adverse pregnancy outcomes. Particularly, during the nighttime and on weekends, provider staffing is often limited, which may make it difficult for pregnant persons to receive quality care. We leveraged existing data collected in a pharmacovigilance pregnancy project, named Measuring Adverse Pregnancy and Newborn Congenital Outcomes (MANGO) study, to determine any associations between nighttime/weekend deliveries and adverse (1) maternal, (2) birth, or (3) neonatal outcomes.MethodsWe conducted a secondary analysis of prospective data from the MANGO study, which documents delivery outcomes for pregnant persons at the Moi Teaching and Referral Hospital in western Kenya, from September 2020-November 2023. We utilized multivariable Poisson regression models, with log link, robust standard errors, and adjusted for several covariates, to assess the association between nighttime/weekend deliveries and adverse composite maternal, birth, or neonatal outcomes.ResultsA total of 25,911 neonates born to 25,247 pregnant persons were included. More than half of deliveries occurred during nighttime (6pm to 7am)/weekends (62.6%). In multivariate modeling, nighttime/weekend delivery was associated with a reduced risk of adverse composite maternal outcomes (adjusted risk ratio [aRR] 0.92, 95% confidence interval [CI]: 0.88, 0.96) and composite birth outcomes (aRR 0.92, 95% CI: 0.88, 0.96). No association was found between nighttime/weekend delivery and neonatal death. In post-hoc analyses, weekend deliveries were associated with reduced risk of emergency Caesarean deliveries, preterm birth, and low birth weight. Having advanced maternal age, obstetric complications, and transferring to the hospital for delivery were associated with adverse maternal and birth outcomes. Poor APGAR score was strongly associated with neonatal death.ConclusionsNighttime/weekend deliveries were associated with better maternal and birth outcomes, perhaps due to decreased emergency Caesarean deliveries for high-risk pregnancies or other factors. Greater attention to individual-level factors, such as obstetric complications, may be considered to improve outcomes for pregnant persons and their neonates. Future research may focus on under-resourced, non-tertiary hospitals to offer a more generalizable view of this exposure-outcome relationship in LMICs.

Abstract Introduction Point of care for burn survivors has traditionally been the inpatient burn unit. Advances in burn care have resulted in significantly reduced length of stay or allowed survivors to avoid admission. However, an outpatient shift within burn care only emphasizes a growing need for rehabilitation resources. This study surveyed burn centers within the United States (US) to determine current outpatient burn clinic structure and evaluate utilization of burn therapy. Methods A 20-question survey was electronically distributed to burn clinicians at burn centers within the US. Questions included the location of their burn clinic, operational hours, dedicated staff, and utilization of burn therapy services. Chi-square test was used to analyze frequency differences between American Burn Association (ABA) verified and non-verified centers with significance set at &amp;lt; 0.05. Results The survey was completed by representatives of 54 burn centers treating Adults (n=17), Pediatric (n=7), or both (n=30). Burn centers were ABA verified (61%, n=33) and non-verified (39%, n=21) centers. Outpatient clinics included permanently dedicated burn therapists at 65% (n=35) of responding burn centers (OT= 32, PT =28) (Table 1). Respondents reported that therapy services in the outpatient clinics saw “Almost all patients,” 15% (n=8) of the time, while the majority stated therapist saw “Most” (30%, n=16) or “Some” patients (24%, n=13). Only 7 centers report standing therapy orders, while the majority report pre-screening by APPs/physicians (n=43). Only 39% (n=21) reported that reconstructive patients were “Often” referred for therapy. The greatest barriers to outpatient follow up were “distance from burn center”(n=43) and “transportation”(n=30), with 50% of respondents offering transportation support for patients. Verified burn centers were statistically more likely to have either PT or OT dedicated to the burn clinic (79%, p=0.007) than non-verified centers. However, there was no difference in verification status for therapy treating “Most” or “All” patients (50%, p=0.112), and having a dedicated burn therapy treatment space (59%, p=0.067) Conclusions Outpatient Burn Rehabilitation is currently being underutilized, with many centers setting standards below those established for inpatient burn care. Transitioning care to the outpatient setting does not eliminate, or reduce patients’ need for specialized burn therapy. Hospital, physician, and outpatient leaders must consider the rehabilitative needs of burn patients as care is shifted to outpatient and ensure adequate therapy involvement in care. Applicability of Research to Practice Burn centers must prepare to treat an increasing number of burn survivors throughout the entire burn continuum of care. Therapy resources must be optimized within the outpatient setting to match the shift in care toward the ambulatory environment to adequately support burn survivors. Funding for the Study N/A

Abstract Introduction Palliative care is a commonly used consultation service in the trauma world, however, interestingly, only 2% of burn patients, a subset of trauma patients, have the luxury of a palliative care consult during hospitalization. The early introduction of palliative care during a burn survivor’s hospitalization may reduce miscommunication, the feeling of hopelessness, and incongruent care coordination. The purpose of this study is to evaluate the incidence of palliative care consultations on a verified adult burn center by comparing pre- and post- intervention data following the implementation of a palliative care assessment tool, the Palliative Care Problem Severity Score (PCPSS). Methods A retrospective chart review was conducted to analyze the pre- and post-intervention groups. Specifically, 57 patient charts were reviewed for the presence of palliative care in the three months leading up to project implementation. After the project was initiated and the PCPSS was implemented, post-intervention chart reviews were completed on a total of 33 patients. A Fisher’s Exact Test was used for data analysis. Demographic data was also collected for the pre- and post-intervention groups for further comparison. Results A Fisher’s Exact Test was conducted to appropriately measure pre- and post-intervention data. The test was able to sufficiently evaluate the effectiveness of the PCPSS, rendering statistically significant results (p = 0.029). Objectively, only one out of 57 patients (1.75%) received a palliative care consultation in the pre-intervention group while five out of 33 patients (15.15%) received a palliative care consultation in the post-intervention group, resulting in a 13.4% increase in palliative care consultations after the implementation. The PCPSS was able to reduce the time from patient admission to initial palliative care consultation from 44 to 2.8 days. Conclusions Advanced Practice Providers can be at the forefront of the palliative care movement within the burn specialty by streamlining the use of the PCPSS within their practice. The results of the chosen palliative care assessment tool surpassed the expectations of the initially proposed project, and its effects will linger in the lives of the burn patients whose outcomes were optimized by the introduction of palliative care early in the acute phase of their burn injury. Applicability of Research to Practice Ultimately, the implementation of the PCPSS is the first step towards formalizing a palliative care consultation process within adult verified burn centers. The project’s results can formalize a palliative care consultation standard within a verified adult burn center while bridging the identified literature gap between two specialty services that, if united, will provide limitless resources to burn survivors from the time of injury to rehabilitation. Funding for the Study N/A

There is a global mental health crisis: mental illness is underrecognized, underdiagnosed, and undertreated with adverse effects on mental, physical, and social health. In the United States, there is an insufficient number of traditional psychiatric and psychological resources to provide the mental health care needed to solve this crisis. Community-based interventions could be an important adjunct to traditional mental health care. An evaluation of peer-reviewed articles was performed describing community-based interventions and identified 3 approaches with some evidence of effectiveness: (1) interventions that enhance community mental health literacy to improve recognition of early signs of mental illness for early engagement and provide community, family, and peer support; (2) community clinics providing social, medical, and mental health care and support to transition-age youth (15-25 years); and (3) social networking activities to enhance interactions among elders suffering from social isolation and loneliness. Multisector, multidisciplinary, and multicomponent interventions involving health care providers and community-based organizations had the best evidence of effectiveness and should target transition-age youth and elders.

Abstract The existence of asymptomatic precursor lesions that are known to predate invasive pancreatic ductal adenocarcinoma (PDAC) by years provides a compelling rationale for cancer interception efforts. One such precursor is intraductal papillary mucinous neoplasm (IPMN). Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) imaging of metabolites in tissue sections from resected patient IPMN cases (N=23) and from a KrasG12D/GnasR201C mouse model of IPMN, we have made a discovery of long chain hydroxylated sulfatide species as being selectively enriched in IPMN. Spatial transcriptomics analysis of serial sections from the same IPMN tissues confirmed cognate transcripts, including ceramide galactosyltransferase (CGT, also known as UGT8) and galactose-3-O-sulfotransferase (CST, also known as Gal3St1) enzymes that, respectively, catalyze the addition of galactose from UDP-galactose to ceramide and the O-sulfation of the galactose residue on galactosylceramide (GalCer), to also be highly enriched in IPMN. Functional studies using CRISPR/cas9 UGT8 knockout Kras;Gnas IPMN cells demonstrated that loss of UGT8, the key enzyme that produces the sulfatide precursor GalCer, results in attenuation of sulfatide biosynthesis and impaired mitochondrial function, as evidenced by reduced mitochondrial respiration and ATP production. These changes were met with concomitant decreases in proliferation and invasiveness, and increased susceptibility to intrinsic apoptosis. Targeting of sulfatide metabolism using a selective small molecule inhibitor of UGT8 suppressed sulfatide biosynthesis, induced ceramide-mediated compensatory mitophagy, and subsequent apoptosis in Kras;Gnas IPMN cells. In vivo, UGT8 inhibition suppressed tumor growth in an IPMN allograft model. In conclusion, our work identifies enhanced sulfatide metabolism as an early metabolic alteration in cystic pre-cancerous lesions of the pancreas that persists through invasive neoplasia and represents an actionable vulnerability for PDAC early interception. Citation Format: Riccardo Ballarò, Yihui Chen, Fredrik I Thege, Rongzhang Dou, Jimin Min, Michele Yip-Schneider, Jianjun Zhang, Ranran Wu, Ehsan Irajizad, Yuki Makino, Kimal I Rajapakshe, Mark W Hurd, Ricardo A León-Letelier, Edwin Ostrin, Jody Vykoukal, Jennifer B Dennison, Kim-Anh Do, Samir Hanash, Robert A Wolff, Paola A Guerrero, Michael P Kim, C Max Schmidt, Anirban Maitra, Johannes F Fahrmann. Disruption of sulfatide metabolism by targeting UGT8 is an actionable metabolic vulnerability for pancreatic cancer early interception [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-13.