Haskins Laboratories

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    30445 research outputs found

    Association Of Immune Checkpoint Inhibitor Approval On Suicide Rates Among Patients With Cancer: A Pre-Post Analysis With Seer

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    Objective: Patients with cancer are at elevated suicide risks compared to the general population, and patients diagnosed with advanced cancers have higher suicide risks compared to those diagnosed with early-staged cancers. Immune Checkpoint Inhibitors (ICIs) were initially approved to treat metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC), and an unpublished study observed a decreased suicide risk in patients with these cancers at all stages. This study evaluates suicide risks in patients with breast, colorectal, liver, pancreatic, and prostate cancer, of which ICIs have limited effects on, to assess if the lower suicide rates observed previously could be attributed to cancer-specific availability of ICIs. We hypothesize that potentially curative therapy will provide increased hope for patients with previously incurable disease and therefore be associated with decreased rates of death by suicide only in cancers which ICIs are effective, especially metastatic or advanced cancer. Methods: Data was obtained from the Surveillance, Epidemiology and End Results (SEER) database for patients diagnosed with breast, colorectal, liver, pancreatic, and prostate cancer between 2004 to 2010 (pre-period) and 2016 to 2019 (post-period). Difference-in-difference models were used to compare the difference in suicide rates during the pre- and post-periods. Multiple chi-square tests were performed to describe the baseline characteristics. In the aggregated level analysis, standardized mortality ratios of suicide were compared across periods (post vs. pre) and cancer stages (regional/advanced vs. localized). In the individual-level analysis, a Poisson regression was fitted to identify the association between suicide risk and period. Results: A total of 1,394,567 cases were identified from SEER, of which 0.2% died from suicide (N=2,097) and 99.8% died from other causes or were still alive (N=1,392,470). Among all patients, 61.7% were diagnosed with localized cancers (N=860,159), 26.0% were diagnosed with regional cancers (N=363,010), and 12.3% were diagnosed with advanced cancers (N=171,398). Pre-period cases accounted for 76.5% of all patients (N=1,066,346) and post-period cases accounted for 23.5% (N=360,621). Our aggregated-level model suggested that SMR of suicide for patients with regional/advanced cancers during the post-period of ICI approval was significantly higher. The individual-level model showed that suicide risk among patients with regional/advanced cancers was higher after the approval of ICIs at a borderline significance. Conclusions: Our findings suggest that suicide rates increased overall among cancer patients. We did not observe evidence that ICI adoption was associated with reduced suicide risk in patients with advanced-stage disease for which ICI treatments are not as effective. Future research may link SEER with claims data to examine suicide attempts instead of suicidal deaths and focus on sex-specific cancers to clarify whether the increased risk of suicide is associated with the sex difference

    Randomized Trial Of Exercise Vs. Usual Care On Inflammatory And Metabolic Biomarkers In Women With Breast Cancer Taking Aromatase Inhibitors

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    ABSTRACT Background: The Hormones and Physical Exercise (HOPE) study demonstrated efficacy of exercise in reducing AI-associated arthralgia in breast cancer survivors. Yet, the underlying mechanism for this relationship remains unclear. Prior research among breast cancer survivors highlights improvements in metabolic and inflammatory biomarkers related to exercise. This secondary analysis of HOPE examined the potential role of metabolic and inflammatory biomarkers in mediating the effect of exercise vs. usual care on AI-associated arthralgia. Methods: Our analysis included 80 participants (42 exercise arm, 38 usual care) enrolled in the HOPE study. The intervention was a year-long exercise program that included both supervised aerobic exercise and strength training. AI-associated arthralgia was measured using the Brief Pain Inventory (BPI) worst pain score. Eleven serum inflammatory and metabolic biomarkers were assessed at baseline, 6 and 12 months (M). We examined the effect of exercise on biomarker changes from baseline to 6M and baseline to 12M by study arm using paired T-tests. We also assessed if the biomarkers were potential mediators of the primary intervention effect on BPI worst pain score at baseline and 12M. We also studied associations between changes in biomarkers and in BPI worst pain score at 12M using unadjusted and adjusted linear regression models, controlling for age, baseline BMI, and randomization. Results: No significant differences were observed in the average biomarker changes by study arm at 6M or 12M, nor when stratified by weight loss status. Additionally, none of the biomarkers were significantly associated with BPI worst pain scores at baseline or 12M. Conclusion: In this secondary analysis of a year-long exercise trial among breast cancer survivors, the intervention did not result in changes in inflammatory or metabolic biomarkers. In addition, we did not find evidence that the improvement in AI-associated arthralgia was mediated through these biomarkers. Given this study was a treatment trial, future research focused on exercise and mechanisms preventing AI-associated arthralgia is needed

    Ai-Aki: Ai-Consulted Inpatient Care For Acute Kidney Injury

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    Acute kidney injury (AKI) increases the risk of death in hospitalized adults, and early medical chart review and involvement by a nephrologist may lead to improved patient outcomes. A Kidney Action Team—comprised of a pharmacist and a board-certified nephrologist or nephrology fellow—can serve as a remote consultation service to deliver recommendations for AKI patient diagnosis, initial work up, and care. We aimed to evaluate whether an AI-automated clinical decision support system for AKI could demonstrate predictive power comparable to that of human specialists, with regards to AKI evaluation and treatment. This study uses data from KAT-AKI (NCT04040296), a triple-masked, randomized controlled trial being conducted at two major US hospital systems. From November 2021 to December 2023, 3,000 participants were enrolled from six hospitals in Yale New Haven Health System. The median (IQR) age was 73.4 (62.2, 82.8) years, 1,411 (47.0%) were women, and 560 (18.7%) self-identified as Non-Hispanic Black. With two-thirds of this data, we trained a neural network with three hidden layers of 1,168 neurons each to jointly predict 70 recommendations of varying coarseness, collected from Kidney Action Teams. Following training and validation of the data, the final third was used as a test set, from which AUCs were calculated for all recommendations. The median (IQR) across all recommendations was 0.78 (0.72–0.89). This work demonstrates the ability of AI to generate recommendations that are fairly concordant with expert recommendations on AKI. This algorithm may be evaluated in a future trial to demonstrate benefit for patients in terms of clinical outcomes, potentially reducing resource burden and expanding the ability to provide expert-level consultation on AKI in resource-constrained settings

    Macronutrient Intake In Us Adults: Race, Gender, Age, Education

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    Background: The US has seen a consistent increase in obesity rates over the last sixty years across all racial and ethnic groups, with similar trends even among privileged groups. This study examines Macronutrient intake trends in US adults from 1999-2018 and their association with demographic factors: race ethnicity, age, gender, and education. Methods: We conducted a serial cross-sectional analysis of US adults using 24-hour dietary recall data from 10 NHANES survey cycles (1999-2018). Piecewise regression models identified significant dietary pattern changes over time, by demographic groups. Statistical analysis was done in R and SAS utilizing NHANES sampling weights. Results: Study sample included 50,666 respondents. Average BMI significantly increased from 28 to 30 (p\u3c0.001). From 1999 to 2018, estimated energy intake from saturated fat increased from 10.91% to 11.89% (increase in ~8.77 kcal, p \u3c 0.001), with higher increase in intake among those with higher education and older age. Protein intake increased from 15.46% to 15.80% (increase of ~9.67 kcal, p=0.029), with variations across age groups. Carbohydrate intake decreased from 50.36% to 46.27% (reduction of ~136.83 kcal, p\u3c0.001), particularly among those with higher education and older age. Conclusion: From 1999 to 2018 dietary intake of U.S. adults had increased saturated fat intake and decreased carbohydrate consumption. Trends varied by education level and age, and older adults and more educated participants had higher saturated fat intake and reduced carbohydrates. The study emphasizes the limitations of reductionist dietary approaches and advocates for holistic, food-based interventions in public health and nutrition

    Prevalence Of Perinatal Depression In Us Residents: Analysis Based On Nhanes 2017-2020 Pre-Pandemic

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    Objective:Perinatal depression, affecting over 10% of pregnant and postpartum women globally, is a significant but often underrecognized mental health issue. Untreated symptoms can persist for years, highlighting the need for early intervention. This study, using the most recent National Health and Nutrition Examination Survey (NHANES) data available, aims to assess trends in perinatal depression prevalence and mental health care utilization in US. Methods: NHANES data from 2017 to March 2020 were analyzed, focusing on pregnant and postpartum women who had given birth within the last 24 months as the target population. The Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms, and demographic characteristics along with access to mental health care were evaluated. T-tests and chi-square tests (p \u3c 0.05) were used for data analysis, with weights applied to provide nationally representative results. Results: The surveyed sample contains 295 pregnant and postpartum women, and 27 (9.2%, 95%CI: 5.9%, 12.4%) were identified as depressed (PHQ-9 score ≥10). When survey weights were applied, the estimated national depression prevalence was 8.2% (95%CI: 8.2%, 8.3%). Depressed perinatal women showed higher rates of mental health care seeking (50.1% vs. 6.4% for non-depressed). Conclusions: Awareness of mental healthcare utilization had increased but half of the depressed women were still not receiving any kind of treatment. Further research on perinatal depression and efforts to enhance screening and treatment are needed to better to support affected individuals and families

    Janus Kinase Inhibition In Granuloma Annulare: Two Single-Arm, Open-Label Clinical Trials

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    Granuloma annulare (GA) is an inflammatory cutaneous granulomatous diseasethat lacks satisfying and effective targeted therapies. Janus kinase (JAK) inhibitors are of interest as they inhibit upregulated cytokines in GA including IFN-γ, IL-4, IL-13, IL-15, IL-21, and oncostatin M. Further investigation is needed to establish the safety profile, optimal route or formulation, and efficacy of JAK inhibitors for GA. We conducted single-arm, open-label clinical trials of abrocitinib, a JAK1-specific inhibitor, and AC- 1101, a topically applied JAK inhibitor, in patients with GA and hypothesized that each medication would be safe, tolerable, and effective at treating GA. In the first study, adult patients with GA (n=10) were treated for 6 months with oral abrocitinib 200 mg and primarily assessed for change in body surface area (BSA) involvement along with other efficacy and safety outcomes. In the second study, adult patients with GA (n=13) were treated for 4 weeks with AC-1101, a topically applied tofacitinib citrate 2% gel, and primarily assessed for safety and tolerability, with secondary efficacy outcomes. After 1 month, patients treated with abrocitinib trended toward improvement in GA as measured by Granuloma Annulare Severity and Morphology Instrument (GASMI) and Granuloma Annulare-Investigator Global Assessment (GA-IGA) scores, with significant improvement in GA-IGA erythema scores (mean difference -0.5 points, p=0.03). Preliminary results indicate that the two patients who completed treatment with abrocitinib for 6 months experienced improvement in their GA with reduction in body surface area (BSA) involvement, GASMI, and GA-IGA scores. The other patients are actively enrolled in the trial and yet to complete 6 months of treatment. Treatment with AC-1101 was well-tolerated by patients with no significant change in Dermal Rating Scale scores before and after application, and GA-IGA induration scores significantly improved by a mean of 0.83 points (p=0.03) after 4 weeks of treatment. There were no serious adverse events in either trial. Oral abrocitinib demonstrates efficacy after 1 month of use, and two individual patients who completed 6 months of treatment experienced substantial clinical improvement. Further results from this trial will clarify the efficacy of abrocitinib over 6 months of use. AC-1101 was well-tolerated and demonstrated evidence of efficacy following 4 weeks of daily topical application. Both medicines demonstrated favorable safety profiles during these trials. JAK inhibition is a promising avenue for treatment of GA, and JAK1-specific inhibition with oral abrocitinib and topically applied AC-1101 are appealing options that warrant further investigation of their use in GA

    Trade and Domestic Distortions: The Case of Informality

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    We examine the effects of international trade in the presence of a set of domestic distortions giving rise to informality, a prevalent phenomenon in developing countries. In our quantitative model, the informal sector arises from burdensome taxes and regulations that are imperfectly enforced by the government. Consequently, smaller, less productive firms face fewer distortions than larger, more productive ones, potentially leading to substantial misallocation. We show that in settings with a large informal sector, the gains from trade are significantly amplified, as reductions in trade barriers imply a reallocation of resources from initially less distorted to more distorted firms. We confirm findings from earlier reduced-form studies that the informal sector mitigates the impact of negative labor demand shocks on unemployment. Nonetheless, the informal sector can exacerbate the adverse welfare effects of economic downturns, amplifying misallocation. Last, our research sheds light on the relationship between trade openness and cross-firm wage inequality

    Somatic Mutations In Aging, Paroxysmal Nocturnal Hemoglobinuria, And Myeloid Neoplasms

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    Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal blood disorder frequently associated with bone marrow failure that in rare instances can progress to leukemia. PNH clones of varying sizes occasionally present even in patients with hematologic malignancies and no known history of classical PNH, particularly in myelodysplastic neoplasms (MDS). Curiously, somatic driver mutations considered to be pathogenic and likely pathogenic in myeloid leukemias can be found in phenotypically normal, elderly individuals, as well as those with clonal disorders such as PNH, clonal hematopoiesis of indeterminate potential (CHIP), and age-related clonal hematopoiesis (ARCH). These mutations may be the critical link between PNH and the development of cancer. We suspect that PNH clones, derived from mutations in PIGA, may reflect a disordered bone marrow prone to additional genetic hits involved in tumorigenesis. It is uncertain, however, whether leukemic cells directly arise from PNH+ progenitors with additional genetic variants or if they are in fact distinct populations. Moreover, the specific driver mutations that underlie both PNH and myeloid neoplasms remains an area of active investigation. Our study aims to characterize the prevalence of myeloid neoplasm-associated somatic mutations in older adults and in patients who develop myeloid malignancies (MN+ patients), stratified by whether they also harbor PNH clones. We retrospectively examined the initial genetic evaluation by next-generation sequencing (NGS) of 197 individuals at Yale-New Haven Hospital and elicited the most common driver mutations and their association with age and PNH clonal presence. We demonstrated that pathogenic and likely pathogenic somatic mutations increased with age (average age of patients with one or more mutations was 69.8 years compared to 58.0 years in those with no mutations of interest, p\u3c 0.0001). Variants in SF3B1 (average age= 74.4 years, p= 0.0015), TP53 (average age= 72.8 years, p= 0.0057), SRSF2 (average age= 72.4 years, p= 0.0024), DNMT3A (average age= 71.9 years, p= 0.0059), TET2 (average age= 70.8 years, p= 0.0032), ASXL1 (average age= 70 years, p= 0.0052), and U2AF1 (average age= 69.7 years, p= 0.0082) were most commonly present in adults who were significantly older than those with no relevant mutations. Those with a diagnosis of a myeloid neoplasm were drastically more likely to harbor driver mutations (81.1% with at least one variant of interest vs. 23.5% among those without a myeloid neoplasm, p\u3c 0.0001), and had a greater number of mutations on average (1.95 vs. 0.38 mutations per patient, p\u3c 0.0001). Interestingly, MN+ patients who had a PNH clone ≥0.01% were significantly more likely to possess a neoplasm-associated mutation than those with no PNH clones (91.9% vs. 60.6%, p= 0.0005), indicating that the presence of PNH clones augments the odds of possessing cancer-related genetic lesions as early as the time of the initial evaluation. Specifically, patients who were both MN+ and PNH+ were more likely than their PNH- counterparts to have one or two pathogenic and likely pathogenic variants (58.1% vs. 27.3%), though they were equally likely to possess three or more mutations (33.9% vs. 33.3%). Furthermore, among all patients in the cohort ≥70 years, PNH presence significantly increased the overall likelihood of discovering relevant gene variants (78.9% vs. 48.7%, ?2 p= 0.0027). Among all patients, PNH clone presence was correlated with mutations in SF3B1 (85.7% of cases with SF3B1 variants had PNH clones compared 56.8% of cases with no mutations had PNH clones, Fisher’s exact test, p= 0.0402), and to a lesser degree, with RUNX1 (83.3% PNH+ cases, p= 0.0686) and DNMT3A (80.0% PNH+ cases, p= 0.0914). Finally, we qualitatively described that mutations in ASXL1, TET2, and SRSF2 tended to occur together; there were also concomitant mutations in TET2 with EZH2 and in SF3B1 with RUNX1. Therefore, we recommend early genetic screening of all elderly patients ≥70 years who present with PNH clones of any size in the peripheral blood as these patients have a higher likelihood of harboring pathogenic and likely pathogenic driver mutations. We demonstrated that certain neoplasm-associated mutations are common in elderly patients, while others correlated with PNH clone presence, and that some variants tend to co-occur. Future studies should address the molecular mechanisms of these lesions in leukemogenesis. The observation that PNH clone presence is significantly correlated with somatic mutations in MN+ disease suggests an important relationship between PNH clones and cancer, either as direct tumor precursor populations or as an incidental consequence of high genetic mutability in a vulnerable bone marrow

    A Hero\u27s Journey: Experiences Using A Therapeutic Comicbook In A Children’s Psychiatric Inpatient Unit

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    Children’s mental health care has been on the decline since the start of the century. The COVID-19 pandemic further unearthed this significant worsening of mental health in children with heightened levels of anxiety, depression, loneliness, anger, and fatigue leading to an increase in the number of emergency room visits and inpatient hospitalizations. Art and narrative-based interventions are known to improve patient outcomes and are a crucial component of pediatric inpatient psychiatric care. We discuss the process of adoption of a novel therapeutic comic book that was developed for children admitted to the hospital in a psychiatric inpatient unit at Yale-New Haven Hospital. A Hero’s Journey, a 38-page zine, is a short booklet that was created to demystify the experience of hospitalization, provide scaffolding for skill-building, and promote interaction and socialization. The zine was administered to patients and subsequently, 19 interviews were done with healthcare providers. Using qualitative research methods, a thematic analysis was performed. Three main domains were identified. The main domains of themes were: 1) Implementing or rolling-out of the zine: what worked and what did not work during the process of rollout; 2) Optimizing: the zine was appropriate in length and content for the patient population at hand; 3) Anticipating: the zine has potential areas for growth and development. The zine is a wonderful resource. Yet its implementation faced many challenges including staffing shortages and time constraints. Some ways to overcome these are having a champion for the zine, educating each user on the content, using individual pages of the zine instead of the whole booklet, and exploring avenues for personalization

    YPFS Lessons Learned Oral History Project: An Interview with Ádám Banai

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    The Yale Program on Financial Stability (YPFS) interviewed Ádám Banai regarding his time as an analyst and director of the National Bank of Hungary (Magyar Nemzeti Bank, or MNB) during the Global Financial Crisis (GFC) and in the subsequent era to date

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