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1.
Fam Med ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39383518

ABSTRACT

BACKGROUND AND OBJECTIVES: Cesarean section (c-section) rates among nulliparous, term, singleton, and vertex (NTSV) pregnancies are increasing, posing risk to the infant and birthing parent. To reach the Healthy People 2030 goal of an NTSV c-section rate below 23.6%, teams must remain aware of their NTSV c-section rate and implement mechanisms to reduce it. This project was conducted to assess the impact of quality improvement interventions implemented by family medicine residents to reduce a hospital's NTSV rate. METHODS: From 2021 to 2023, family medicine residents were educated on evidenced-based diagnosis of labor dystocia, failed induction of labor, arrest of dilation, and arrest of descent in first-time birthing parents. Learning was reinforced by implementing the Colorado Perinatal Care Quality Collaborative's labor dystocia checklist. Quarterly assessment of the hospital's NTSV rate and checklist utilization were monitored and widely reported. RESULTS: After the implementation of a standard checklist, the NTSV c-section rate at the tertiary care center declined from 35.6% in 2020 to a sustained rate below the 2030 Healthy People goal of 23.6%. Notably, patients with public insurance saw the greatest reduction in NTSV c-section rates. Hospital staff highlighted the benefits of using the checklist, including more effective electronic documentation of labor progression, improvement in team dynamics, and increased team communication. CONCLUSIONS: Using a labor dystocia checklist is a successful method for teams to reduce NTSV c-section rates and can be used as a training tool for family medicine and obstetrics and gynecology residency programs that care for laboring persons.

2.
J Am Geriatr Soc ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39315491

ABSTRACT

BACKGROUND: Unmet social and caregiving needs can make caregiving for a person with dementia more difficult. Although national policy encourages adoption of systematic screening for health-related social risks (HRSRs) in clinical settings, the accuracy of these risk-based screening tools for detecting unmet social needs is unknown. METHODS: We used baseline data from dementia caregivers (N = 343) enrolled in a randomized controlled trial evaluating CommunityRx-Dementia, a social care intervention conducted on Chicago's South Side. We assessed caregivers' (1) unmet social and caregiving needs by querying need for 14 resource types and (2) HRSRs using the Center for Medicare & Medicaid Services (CMS) Accountable Health Communities (AHC) screening tool. Using unmet social needs as the reference, we examined the sensitivity of the AHC tool to detect food, housing, and transportation needs. Analyses were stratified by gender. RESULTS: Most caregivers were women (78%), non-Hispanic (96%), Black (81%), partnered (58%) and had an annual household income ≥$50K (64%). Unmet social and caregiving needs were similarly prevalent among women and men caregivers (87% had ≥1 need, 43% had ≥5 needs). HRSRs were also prevalent. The most common HRSR was lack of social support (45%). Housing instability, difficulty with utilities and having any HRSRs were significantly more prevalent among women (all p < 0.05). The AHC screener had low sensitivity for detecting unmet food (39%, 95% confidence interval [CI]: 27%-53%), housing (42%, 95% CI: 31%-53%), and transportation (22%, 95% CI: 14%-31%) needs. Sensitivity did not differ by gender for food (41% for women and 30% for men, p = 0.72) or housing (44% for women and 29% for men, p = 0.37) needs. For transportation needs, sensitivity was 27% for women versus 0% for men (p = 0.01). CONCLUSIONS: Men and women caregivers have high rates of unmet social needs that are often missed by the CMS-recommended risk-based screening method. Findings indicate a role for need-based screening in implementing social care.

3.
JACC Adv ; 3(10): 101231, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39309662

ABSTRACT

Background: Data on real-world statin prescription in large, private health care networks and impacts on primary prevention of atherosclerotic cardiovascular disease (ASCVD) outcomes across race are scarce. Objectives: The purpose of this study was to investigate the impact of statin prescription on ASCVD outcomes within and across race in a large, nongovernmental health care system. Methods: Statin prescription in Black and White patients without ASCVD was evaluated (2013-2019). Guideline-directed statin intensity was defined as at least "moderate" for intermediate and high-risk patients. Statin prescription at index and ASCVD outcomes at follow-up (myocardial infarction/revascularization, stroke, mortality) were assessed via electronic health care records using International Classification of Diseases-9 and 10 codes. Cox regression models, adjusted for CVD risk factors, were used to calculate HRs for association between statin prescription and incident ASCVD events across race. Results: Among 270,079 patients, 7.6% (n = 20,477) and 92.4% (n = 249,602) identified as Black and White, respectively. Significantly fewer Black patients were prescribed statin therapy than White patients (13.6% vs 19.0%; P < 0.001). At a mean follow-up of 6 years, patients with "no statin" prescription vs guideline-directed statin intensity showed increased ASCVD in Black patients (HR: 1.40 [95% CI: 1.05-1.86]), and White patients (HR: 1.32 [95% CI: 1.21-1.45]; P < 0.05) and all-cause mortality. Intermediate and high-risk Black patients faced a 17% higher risk of mortality compared to White patients. However, the interaction between race and statin prescription was not a significant predictor of incident ASCVD events. Conclusions: Statins remain underprescribed. Although Black patients received proportionally less statin prescription than White patients, this was not associated with higher risk of mortality in Black patients.

4.
JACC Heart Fail ; 12(9): 1528-1539, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39152985

ABSTRACT

Atrial fibrillation (AF) and heart failure (HF)-specifically, heart failure with reduced ejection fraction (HFrEF)-often coexist, and each contributes to the propagation of the other. This relationship extends from the mechanistic and physiological to clinical syndromes, quality of life, and long-term cardiovascular outcomes. The risk factors for AF and HF overlap and create a critical opportunity to prevent adverse outcomes among patients at greatest risk for either condition. Increasing recognition of the linkages between AF and HF have led to widespread interest in designing diagnostic, predictive, and interventional strategies targeting all aspects of disease, from identifying genetic predisposition to addressing social determinants of health. Advances across this spectrum culminated in updated multisociety guidelines for management of AF, which includes specific consideration of comorbid AF and HF. This review expands on these guidelines by further highlighting relevant clinical trial findings and providing additional context for the evolving recommendations for management in this important and growing population.


Subject(s)
Atrial Fibrillation , Heart Failure , Stroke Volume , Humans , Heart Failure/physiopathology , Heart Failure/diagnosis , Atrial Fibrillation/physiopathology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Atrial Fibrillation/complications , Stroke Volume/physiology , Risk Factors , Quality of Life , Comorbidity , Practice Guidelines as Topic
6.
Int J Cancer ; 155(11): 1958-1968, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39155749

ABSTRACT

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.


Subject(s)
Antineoplastic Agents , Drug Approval , Neoplasms , United States Food and Drug Administration , Humans , Female , Neoplasms/drug therapy , Neoplasms/epidemiology , United States/epidemiology , Male , Antineoplastic Agents/therapeutic use , Middle Aged , Clinical Trials as Topic , Aged , Clinical Trials, Phase II as Topic , Patient Selection
7.
Am J Epidemiol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960630

ABSTRACT

The objective of this study was to determine whether exposure to structural racism-related state laws is associated with cardiovascular health among a racially and ethnically diverse sample of US adults. Data were from the Database of Structural Racism-Related State Laws and the Behavioral Risk Factor Surveillance System (BRFSS). The sample included 958,019 BRFSS 2011 and 2013 respondents aged 18+ from all 50 US states. The exposure was a summary index of 22 state laws related to the criminal legal system, economics and labor, education, healthcare, housing, immigration, and political participation. The outcome was the American Heart Association's Life's Simple 7 (LS7), a summary index of seven cardiovascular health indicators. Linear regression models included fixed effects for year and state to control for time trends and unmeasured time-invariant state-level contextual factors. In the full sample, a one standard deviation increase in the structural racism state legal index was associated with a 0.06-unit decrease in the LS7 (b=-0.06; 95% CI:-0.09, 0.02; p=0.001), controlling for individual- and state-level covariates. Contrary to expectations, stratified models revealed no statistically significant differences by race and ethnicity in the association between the structural racism state legal index and the LS7.

8.
bioRxiv ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39026694

ABSTRACT

Notch proteins are single pass transmembrane receptors that are activated by proteolytic cleavage, allowing their cytosolic domains to function as transcription factors in the nucleus. Upon binding, Delta/Serrate/LAG-2 (DSL) ligands activate Notch by exerting a "pulling" force across the intercellular ligand/receptor bridge. This pulling force is generated by Epsin-mediated endocytosis of ligand into the signal-sending cells, and results in cleavage of the force-sensing Negative Regulatory Region (NRR) of the receptor by an ADAM10 protease [Kuzbanian (Kuz) in Drosophila ]. Here, we have used chimeric Notch and DSL proteins to screen for other domains that can substitute for the NRR in the developing Drosophila wing. While many of the tested domains are either refractory to cleavage or constitutively cleaved, we identify several that mediate Notch activation in response to ligand. These NRR analogues derive from widely divergent source proteins and have strikingly different predicted structures. Yet, almost all depend on force exerted by Epsin-mediated ligand endocytosis and cleavage catalyzed by Kuz. We posit that the sequence space of protein domains that can serve as force-sensing proteolytic switches in Notch activation is unexpectedly large, a conclusion that has implications for the mechanism of target recognition by Kuz/ADAM10 proteases and is consistent with a more general role for force dependent ADAM10 proteolysis in other cell contact-dependent signaling mechanisms. Our results also validate the screen for increasing the repertoire of proteolytic switches available for synthetic Notch (synNotch) therapies and tissue engineering.

9.
Am Heart J ; 276: 60-69, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38996860

ABSTRACT

BACKGROUND: Black women with peripartum cardiomyopathy (PPCM) have a higher prevalence of hypertensive disorders of pregnancy (HDP) and worse clinical outcomes compared with non-Black women. We examined the impact of HDP on myocardial recovery in Black women with PPCM. METHODS: A total of 100 women were enrolled into the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months post-partum (PP). Women were followed for 12 months postpartum and outcomes including persistent cardiomyopathy (LVEF ≤35%), left ventricular assist device, (LVAD), cardiac transplantation, or death were examined in subsets based on race and the presence of HDP. RESULTS: Black women with HDP were more likely to present earlier compared to Black women without HDP (days PP HDP: 34 ± 21 vs 54 ± 27 days, P = .03). There was no difference in LVEF at study entry for Black women based on HDP, but better recovery with HDP at 6 (HDP: 52 ± 11% vs no HDP: 40 ± 14%, P = .03) and 12-months (HDP:53 ± 10% vs no HDP:40 ± 16%, P = .02). At 12-months, Black women overall had a lower LVEF than non-Black women (P < .001), driven by less recovery in Black women without HDP compared to non-Black women (P < .001). In contrast, Black women with HDP had a similar LVEF at 12 months compared to non-Black women (P = .56). CONCLUSIONS: In women with PPCM, poorer outcomes evident in Black women were driven by women without a history of HDP. In Black women, a history of HDP was associated with earlier presentation and recovery which was comparable to non-Black women.


Subject(s)
Black or African American , Cardiomyopathies , Hypertension, Pregnancy-Induced , Peripartum Period , Pregnancy Complications, Cardiovascular , Stroke Volume , Humans , Female , Pregnancy , Adult , Cardiomyopathies/physiopathology , Cardiomyopathies/ethnology , Cardiomyopathies/epidemiology , Pregnancy Complications, Cardiovascular/physiopathology , Pregnancy Complications, Cardiovascular/ethnology , Pregnancy Complications, Cardiovascular/epidemiology , Hypertension, Pregnancy-Induced/physiopathology , Hypertension, Pregnancy-Induced/ethnology , Hypertension, Pregnancy-Induced/epidemiology , Stroke Volume/physiology , Black or African American/statistics & numerical data , Echocardiography , Ventricular Function, Left/physiology , Heart Transplantation/statistics & numerical data , Heart-Assist Devices/statistics & numerical data
10.
Health Educ Res ; 39(5): 454-465, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-38965030

ABSTRACT

We sought to evaluate the acceptability and feasibility of a culturally tailored food box intervention for improving blood pressure (BP), food security and Body Mass Index (BMI) among Chickasaw Nation adults with uncontrolled hypertension. As part of the Chickasaw Healthy Eating Environments Research Study (CHEERS), we administered a group randomized pilot study in four tribal communities (two intervention, two control). Participants in the intervention communities received six heart-healthy food boxes, culturally tailored to traditional Chickasaw diet and current food context. Outcomes were measured over 6 months. We enrolled 262 participants, and 204 with complete data on key variables were included in the analysis. The food boxes were very popular, and we achieved high retention for follow-up data collection. Intervention community participants had 2.6 mmHg lower mean systolic BP and improved diet quality and BMI compared with control participants, although, as expected for a pilot study, the differences were not statistically significant. The culturally tailored diet intervention and randomized trial study design were acceptable and feasible for Chickasaw Nation adults with uncontrolled hypertension. Our findings support the value of tribal-food bank partnerships as a potential approach for reducing food insecurity and hypertension-related disparities in Native American communities.


Subject(s)
Blood Pressure , Body Mass Index , Hypertension , Indians, North American , Adult , Aged , Female , Humans , Male , Middle Aged , Diet, Healthy , Food Supply , Health Promotion/methods , Hypertension/ethnology , Hypertension/therapy , Indians, North American/psychology , Pilot Projects
11.
JAMA Cardiol ; 9(10): 935-943, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39018059

ABSTRACT

Importance: Racial disparities in cardiovascular health, including sudden cardiac death (SCD), exist among both the general and athlete populations. Among competitive athletes, disparities in health outcomes potentially influenced by social determinants of health (SDOH) and structural racism remain inadequately understood. This narrative review centers on race in sports cardiology, addressing racial disparities in SCD risk, false-positive cardiac screening rates among athletes, and the prevalence of left ventricular hypertrophy, and encourages a reexamination of race-based practices in sports cardiology, such as the interpretation of screening 12-lead electrocardiogram findings. Observations: Drawing from an array of sources, including epidemiological data and broader medical literature, this narrative review discusses racial disparities in sports cardiology and calls for a paradigm shift in approach that encompasses 3 key principles: race-conscious awareness, clinical inclusivity, and research-driven refinement of clinical practice. These proposed principles call for a shift away from race-based assumptions towards individualized, health-focused care in sports cardiology. This shift would include fostering awareness of sociopolitical constructs, diversifying the medical team workforce, and conducting diverse, evidence-based research to better understand disparities and address inequities in sports cardiology care. Conclusions and Relevance: In sports cardiology, inadequate consideration of the impact of structural racism and SDOH on racial disparities in health outcomes among athletes has resulted in potential biases in current normative standards and in the clinical approach to the cardiovascular care of athletes. An evidence-based approach to successfully address disparities requires pivoting from outdated race-based practices to a race-conscious framework to better understand and improve health care outcomes for diverse athletic populations.


Subject(s)
Death, Sudden, Cardiac , Healthcare Disparities , Sports Medicine , Humans , Sports Medicine/statistics & numerical data , Death, Sudden, Cardiac/ethnology , Death, Sudden, Cardiac/prevention & control , Death, Sudden, Cardiac/epidemiology , Healthcare Disparities/ethnology , Healthcare Disparities/statistics & numerical data , Cardiology , Social Determinants of Health , Athletes/statistics & numerical data , Health Status Disparities , Sports/statistics & numerical data
12.
Clin Cancer Res ; 30(14): 2986-2995, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38687597

ABSTRACT

PURPOSE: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications. EXPERIMENTAL DESIGN: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model. RESULTS: Of 3,328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs. 60 years nonmutated), had a higher prevalence of endometriosis (27.3% vs. 16.9%), and lower grades (grade 1/2, 43.2% vs. 8.1%, all P < 0.0001). The highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n = 9/9), mesonephric-like ovarian (83.3%, n = 5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival [hazard ratio (HR) = 1.3; P = 0.001]. Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN (28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS + MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy [8.4 years [(95% confidence interval (CI), 5.5-12.0) vs. 5.5 years (95% CI, 4.6-6.6); HR = 0.67; P = 0.031], this effect did not persist in multivariable analysis. CONCLUSIONS: RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.


Subject(s)
Genital Neoplasms, Female , Mutation , Humans , Female , Genital Neoplasms, Female/genetics , Genital Neoplasms, Female/pathology , Genital Neoplasms, Female/mortality , Middle Aged , Aged , Adult , Proto-Oncogene Proteins p21(ras)/genetics , Genomics/methods , Prognosis , Biomarkers, Tumor/genetics , ras Proteins/genetics , DNA-Binding Proteins , Transcription Factors
13.
Arch Public Health ; 82(1): 59, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671533

ABSTRACT

BACKGROUND: Dietary interventions are used for the treatment of hypertension. We evaluated the cost-efficacy of delivering boxes of healthy, culturally tailored foods and checks that can only be spent on produce in a Native American population. METHODS: We conducted a group randomized controlled trial from 2018 to 2020 with N = 2 treatment counties and N = 2 control counties and a total of N = 160 Native American adults with baseline stage 1 or stage 2 hypertension. Participants in the intervention group received monthly boxes of food that adheres to the Dietary Approaches to Stop Hypertension diet as well as checks that could only be spent on produce for 6 months. We measured blood pressure and quality of life at baseline and at a 6-month follow-up in both intervention and control groups. We used ordered logistic regression to estimate the effect of treatment on probability of blood pressure improvements. We then conducted a cost-efficacy analysis. RESULTS: We found that treatment was effective in reducing blood pressure in women with stage 1 hypertension at baseline. Based on this finding, we also estimate that this intervention satisfies normative cost-effectiveness thresholds, even when lifetime treatment is needed to preserve the impact, so long as treatment is only continued in those who respond to treatment. CONCLUSIONS: Direct delivery of healthy foods and checks that can only be spent on produce are a potentially cost-effective intervention for the management of hypertension among Native American women with stage 1 hypertension. Further research is needed to understand why we found an impact only for this group.

14.
Am Heart J Plus ; 392024 Mar.
Article in English | MEDLINE | ID: mdl-38469116

ABSTRACT

Background: Transcatheter aortic valve replacement (TAVR) are not offered equitably to vulnerable population groups. Adequate levels of insurance may narrow gaps among patients with higher social vulnerability index (SVI). Among a national population of individuals with commercial or Medicare insurance, we sought to determine whether SVI was associated with urgency of receipt of TAVR for aortic stenosis. Methods and results: Using Optum's de-identified Clinformatics Data Mart Database (CDM), we identified admissions for TAVR with aortic stenosis between January 2018 and March 2022. Admission urgency was identified by CDM claims codes. SVI was cross-referenced to patient zip codes and grouped into quintiles. Generalized linear mixed effects models were used to predict the probability of a TAVR admission being urgent based on SVI quintiles, adjusting for patient and hospital-level covariates. Results: Among 6680 admissions for TAVR [median age 80 years (interquartile range 75-85), 43.9 % female], 8.5 % (n = 567) were classified as urgent. After adjusting for patient and hospital-level variables, there were no significant differences in the odds of urgent admission for TAVR according to SVI quintiles [OR 5th (greatest social vulnerability) vs 1st quintile (least social vulnerability): 1.29 (95 % CI: 0.90-1.85)]. Conclusions: Among commercial or Medicare beneficiaries with aortic stenosis, SVI was not associated with admission urgency for TAVR. To clarify whether cardiovascular care delivery is improved across SVI with higher paying beneficiaries, future investigation should identify whether relationships between SVI and TAVR urgency vary for Medicaid beneficiaries compared to commercial beneficiaries.

15.
J Med Chem ; 67(6): 4376-4418, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38488755

ABSTRACT

In 2022, 23 new small molecule chemical entities were approved as drugs by the United States FDA, European Union EMA, Japan PMDA, and China NMPA. This review describes the synthetic approach demonstrated on largest scale for each new drug based on patent or primary literature. The synthetic routes highlight practical methods to construct molecules, sometimes on the manufacturing scale, to access the new drugs. Ten additional drugs approved in 2021 and one approved in 2020 are included that were not covered in the previous year's review.


Subject(s)
Drug Approval , United States , Japan , United States Food and Drug Administration , China
16.
Mol Cancer ; 23(1): 64, 2024 03 26.
Article in English | MEDLINE | ID: mdl-38532456

ABSTRACT

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable responses with PR and SD lasting > 6 months. The median progression-free survival on therapy with second RAF inhibitor in the rechallenge setting either as monotherapy or combination was shorter at 2.7 months (0.9-30.1 m) compared to 8.6 months (6.5-11.5 m) with RAF-1i. However, the median PFS with RAF-2i responders (PFS-2) improved at 12.8 months compared to 11.4 months with RAF-1i responders. The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF-aberrant cancers.


Subject(s)
Melanoma , Humans , Melanoma/pathology , Proto-Oncogene Proteins B-raf/genetics , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Prospective Studies , Mutation
17.
J Midwifery Womens Health ; 69(4): 586-592, 2024.
Article in English | MEDLINE | ID: mdl-38339840

ABSTRACT

Unintentional overdose is a leading driver of maternal death in Colorado. The high volume of maternal deaths from preventable causes lends questions to failures in our clinical and community-based care for pregnant and postpartum people. The Colorado Maternal Mortality Review Committee identified 3 main contributors including stigma in the community and health care system, fragmentation of the health care system, and the need for more clinician training. The Colorado Perinatal Care Quality Collaborative led a 3-pronged intervention to address these challenges and improve perinatal care. The first intervention, the Colorado Alliance for Innovation on Maternal Health Substance Use Disorder quality improvement initiative, partnered with birthing hospitals statewide to institute universal screening and timely referral for individuals at risk of substance use disorder (SUD) and perinatal mood and anxiety disorders. The second intervention, the Improve Perinatal Access, Coordination, and Treatment for Behavioral Health initiative, established a perinatal support network within communities. This program assists individuals with SUD, perinatal mood and anxiety disorders, or social needs to navigate the perinatal period. The third intervention, the Colorado Maternal Overdose Matters Plus program, has enhanced in-hospital access to pharmacotherapy for pregnant and postpartum individuals with SUD through training and technical support. These collaborative initiatives aim to minimize barriers to care by integrating inpatient screening, treatment referrals, pharmacotherapy access, and community care support to mitigate maternal mortality in Colorado.


Subject(s)
Perinatal Care , Pregnancy Complications , Quality Improvement , Substance-Related Disorders , Humans , Female , Colorado , Pregnancy , Substance-Related Disorders/therapy , Perinatal Care/standards , Perinatal Care/methods , Pregnancy Complications/prevention & control , Pregnancy Complications/therapy , Drug Overdose/prevention & control , Drug Overdose/therapy , Referral and Consultation , Health Services Accessibility , Maternal Mortality
18.
Res Sq ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38352591

ABSTRACT

Background Dietary interventions are used for the treatment of hypertension. We evaluated the cost-efficacy of delivering boxes of healthy, culturally tailored foods and checks that can only be spent on produce in a Native American population. Methods We conducted a group randomized controlled trial from 2018-2020 with N = 2 treatment counties and N = 2 control counties and a total of N = 160 Native American adults with baseline stage 1 or stage 2 hypertension. Participants in the intervention group received monthly boxes of food that adheres to the Dietary Approaches to Stop Hypertension diet as well as checks that could only be spent on produce for 6 months. We measured blood pressure and quality of life at baseline and at a 6-month follow-up in both intervention and control groups. We used ordered logistic regression to estimate the effect of treatment on probability of blood pressure improvements. We then conducted a cost-efficacy analysis. Results We found that treatment was effective in women with stage 1 hypertension at baseline. Based on this finding, we also estimate that this intervention satisfies normative cost-effectiveness thresholds, even when lifetime treatment is needed to preserve the impact, so long as treatment is only continued in those who respond to treatment. Conclusions Direct delivery of healthy foods and checks that can only be spent on produce are a potentially cost-effective intervention for the management of hypertension among Native American women with stage 1 hypertension. Further research is needed to understand why we found an impact only for this group.

19.
Circ Cardiovasc Qual Outcomes ; 17(1): e000124, 2024 01.
Article in English | MEDLINE | ID: mdl-38073532

ABSTRACT

The neighborhoods where individuals reside shape environmental exposures, access to resources, and opportunities. The inequitable distribution of resources and opportunities across neighborhoods perpetuates and exacerbates cardiovascular health inequities. Thus, interventions that address the neighborhood environment could reduce the inequitable burden of cardiovascular disease in disenfranchised populations. The objective of this scientific statement is to provide a roadmap illustrating how current knowledge regarding the effects of neighborhoods on cardiovascular disease can be used to develop and implement effective interventions to improve cardiovascular health at the population, health system, community, and individual levels. PubMed/Medline, CINAHL, Cochrane Library reviews, and ClinicalTrials.gov were used to identify observational studies and interventions examining or targeting neighborhood conditions in relation to cardiovascular health. The scientific statement summarizes how neighborhoods have been incorporated into the actions of health care systems, interventions in community settings, and policies and interventions that involve modifying the neighborhood environment. This scientific statement presents promising findings that can be expanded and implemented more broadly and identifies methodological challenges in designing studies to evaluate important neighborhood-related policies and interventions. Last, this scientific statement offers recommendations for areas that merit further research to promote a deeper understanding of the contributions of neighborhoods to cardiovascular health and health inequities and to stimulate the development of more effective interventions.


Subject(s)
Cardiovascular Diseases , Humans , American Heart Association , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Delivery of Health Care , United States/epidemiology , Residence Characteristics
20.
Plants (Basel) ; 12(23)2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38068639

ABSTRACT

Many plant species exhibit strong seed dormancy. This attribute benefits the species' long-term survival but can impede restoration when rapid establishment is required. Soaking seeds in gibberellic acid (GA3) can overcome dormancy and increase germination but this treatment may not be effective outside the laboratory. An easier and potentially more effective method to apply this hormone is to coat seeds with a GA3-impregnated polymer. Seed dormancy can also be mitigated by creating a favorable microsite with increased soil moisture. We compared the emergence and establishment of penstemon seeds coated with GA3 to those of uncoated seeds planted in shallow drill rows versus deep, U-shaped furrows. Overall, 6 times more Palmer's penstemon (Penstemon palmeri; p < 0.01) and 21 times more thickleaf penstemon (P. pachyphyllus; p < 0.001) established when coated with GA3, but GA3 coating did not affect the establishment of firecracker penstemon (P. eatonii; p = 1). Establishment was higher from deep furrows than shallow rows (p < 0.001). These results indicate that GA3 seed coating and deep, U-shaped furrows may improve the restoration success of some native forbs by breaking dormancy and providing a favorable microsite. Land managers could use these techniques to restore native forbs in dry, disturbed areas.

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