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Hypertension is an important modifiable risk factor for cardiovascular disease and affects nearly one-third of women in the U.S. Prior research has demonstrated declining rates of blood pressure (BP) control nationally among women, and there are significant racial and ethnic disparities in both hypertension prevalence and outcomes among U.S. women. However, national-level data on attitudes and awareness of women with hypertension are limited. To address this gap, data were analyzed from participants with self-reported hypertension enrolled in the American Heart Association's Research Goes Red Registry. Of 6170 women who responded as of February 2023, 1835 (30 %) reported a history of hypertension. The top health concerns reported among women with hypertension were weight, healthcare access and costs, and hypertension. Health concerns varied significantly by age, race, and ethnicity; younger women and Black and Hispanic women were more likely to report hypertension as their top concern. Among women with self-reported hypertension, 77 % reported knowing their BP, and 90 % reported being on an anti-hypertensive. Black and Hispanic women were less likely to know their BP compared to White women. Younger women were less likely to be treated for hypertension, and there were also disparities in treatment by employment status and among uninsured women. In this national registry of women in the U.S., gaps and disparities exist in awareness and treatment of hypertension, highlighting targets for quality improvement in hypertension care for women.
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BACKGROUND: Cholestatic pruritus and fatigue are debilitating conditions associated with primary biliary cholangitis (PBC) and can significantly impact patients' quality of life. Pruritus in PBC often worsens at night and patients frequently report sleep disturbance, which contributes to cognitive symptoms and fatigue. Linerixibat is an ileal bile acid transporter inhibitor in clinical development for the treatment of pruritus associated with PBC and was recently assessed versus placebo in the Phase 2b GLIMMER trial. This post-hoc analysis assesses the relationship between pruritus severity and sleep disturbance in participants of GLIMMER regardless of treatment group. METHODS: GLIMMER (NCT02966834), a multicenter, double-blind, randomized, placebo-controlled trial, recruited 147 patients with PBC and moderate-to-severe pruritus. Following 4 weeks single-blind placebo, patients (randomized 3:1) received linerixibat or placebo for 12 weeks (to Week 16). Participants graded their itch (twice daily) and its interference with sleep (once daily) in an electronic diary using a 0-10 numerical rating scale (NRS). Weekly and monthly itch scores were calculated as the mean of the worst daily itch score over the respective time period. At study visits, participants completed the 5-D itch scale and the PBC-40 quality of life questionnaire, both of which contain an item specific to itch-related sleep disturbance. The impact of pruritus on sleep was assessed post hoc through correlations between the changes in NRS, 5-D itch, and PBC-40. RESULTS: Strong correlations were found between change from baseline in weekly itch and sleep NRS scores (r = 0.88 [95% confidence interval (CI): 0.83; 0.91]) at the end of treatment (Week 16), as well as in monthly itch and sleep NRS scores (r = 0.84 [95% CI: 0.80; 0.87]). Patients with improved weekly pruritus score severity category demonstrated reduced perceived sleep interference on average. Itch responders (≥2-point improvement in weekly itch score from baseline) displayed larger improvements in weekly sleep NRS score, 5-D itch, and PBC-40 sleep items, than itch non-responders (<2-point improvement). CONCLUSIONS: A strong correlation exists between changes in pruritus severity and sleep interference in patients with PBC; pruritus reduction could generate concomitant improvement in sleep.
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Cirrose Hepática Biliar , Prurido , Qualidade de Vida , Transtornos do Sono-Vigília , Humanos , Prurido/tratamento farmacológico , Prurido/etiologia , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Cirrose Hepática Biliar/complicações , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etiologia , Idoso , Índice de Gravidade de Doença , Adulto , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Total serum bile acid (TSBA) levels are elevated in patients with primary biliary cholangitis (PBC) and may mediate cholestatic pruritus. Linerixibat, an ileal bile acid transporter inhibitor, improved pruritus in patients with PBC. We explored the relationship between linerixibat dose, TSBA concentration, and pruritus. METHODS: Data from Phase 1/2 trials were used to develop a population kinetic-pharmacodynamic model to characterize the linerixibat dose-TSBA relationship. Individual Bayesian parameter estimates for participants in the GLIMMER study were used to derive the area under the TSBA concentration curve over 24 h (AUC0-24). Time-matched post hoc estimates of AUC0-24 were correlated with pruritus reported on a 0-10 numerical rating scale. Baseline TSBA concentration was correlated with change from baseline (ΔBL) in monthly itch score (MIS). ΔBL in model-estimated TSBA AUC0-24 was correlated with time-matched ΔBL in weekly itch score (WIS) or MIS. RESULTS: Linerixibat dose dependently reduced TSBA AUC0-24, reaching steady state after 5 days. Baseline TSBA levels in GLIMMER did not correlate with ΔBL in MIS. ΔBL in TSBA AUC0-24 correlated with improved WIS over 12 weeks of treatment (r = 0.52, p < 0.0001). Of participants with a ≥30% decrease in TSBA AUC0-24, 60% were pruritus responders (≥2-point improvement in WIS from baseline). CONCLUSIONS: Linerixibat treatment leads to rapid, dose-dependent TSBA reductions. Baseline TSBA levels do not correlate with on-treatment pruritus change, suggesting they do not predict linerixibat response. Change in TSBA AUC0-24 correlates significantly with, and can be predictive of, pruritus improvement in patients with PBC.
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BACKGROUND: Remote monitoring (RM) of pacemakers and implantable cardioverter-defibrillators (ICDs) reduces morbidity and mortality. However, many patients are not adherent to RM. OBJECTIVE: To test the effect of informational postcards on RM adherence. DESIGN/PATIENTS: Stepped-wedge randomized controlled trial among Veterans with pacemakers and ICDs. INTERVENTION: In wave 1, Veterans who had sent at least 1 transmission within the past 2 years but had become non-adherent were randomly assigned to receive a postcard or no postcard. Those receiving postcards were randomized to 1 of 2 messages: (1) a"warning" postcard describing risks of non-adherence or (2) an "encouraging" postcard describing benefits of adherence. In wave 2, Veterans who had either not received a postcard in wave 1 or had since become non-adherent were mailed a postcard (again, randomized to 1 of 2 messages). Patients who did not send an RM transmission within 1 month were mailed a second, identical postcard. MAIN MEASURES: Transmission within 70 days. KEY RESULTS: Overall, 6351 Veterans were included. In waves 1 and 2, postcards were mailed to 5657 Veterans (2821 "warning" messages and 2836 "encouraging" messages). Wave 1 included 2178 Veterans as controls (i.e., not mailed a postcard), some of whom received a postcard in wave 2 if they remained non-adherent. In wave 2, 3473 postcards were sent. Of the 5657 patients mailed a postcard, 2756 (48.7%) sent an RM transmission within 70 days, compared to 530 (24.3%) of 2178 controls (absolute difference 24.4%, 95% confidence interval [CI] 22.2%, 26.6%). Of those who sent a transmission, 71.8% did so after the first postcard. Transmission rates at 70 days did not significantly differ between "warning" and "encouraging" messages (odds ratio 1.04, 95% CI 0.92, 1.18). CONCLUSIONS: Informational postcards led to a 24.4% absolute increase in adherence at 70 days among Veterans with pacemakers and ICDs who were non-adherent to RM.
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Desfibriladores Implantáveis , Marca-Passo Artificial , Veteranos , HumanosRESUMO
IL12 is a proinflammatory cytokine, that has shown promising antitumor activity in humans by promoting the recruitment and activation of immune cells in tumors. However, the systemic administration of IL12 has been accompanied by considerable toxicity, prompting interest in researching alternatives to drive preferential IL12 bioactivity in the tumor. Here, we have generated XTX301, a tumor-activated IL12 linked to the human Fc protein via a protease cleavable linker that is pharmacologically inactivated by an IL12 receptor subunit beta 2 masking domain. In vitro characterization demonstrates multiple matrix metalloproteases, as well as human primary tumors cultured as cell suspensions, can effectively activate XTX301. Intravenous administration of a mouse surrogate mXTX301 demonstrated significant tumor growth inhibition (TGI) in inflamed and non-inflamed mouse models without causing systemic toxicities. The superiority of mXTX301 in mediating TGI compared with non-activatable control molecules and the greater percentage of active mXTX301 in tumors versus other organs further confirms activation by the tumor microenvironment-associated proteases in vivo. Pharmacodynamic characterization shows tumor selective increases in inflammation and upregulation of immune-related genes involved in IFNγ cell signaling, antigen processing, presentation, and adaptive immune response. XTX301 was tolerated following four repeat doses up to 2.0 mg/kg in a nonhuman primate study; XTX301 exposures were substantially higher than those at the minimally efficacious dose in mice. Thus, XTX301 has the potential to achieve potent antitumor activity while widening the therapeutic index of IL12 treatment and is currently being evaluated in a phase I clinical trial.
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Interleucina-12 , Neoplasias , Humanos , Camundongos , Animais , Interleucina-12/metabolismo , Neoplasias/tratamento farmacológico , Citocinas , Transdução de Sinais , Índice Terapêutico , Microambiente TumoralRESUMO
We describe the methodology, design, and early results of a novel multidisciplinary co management clinic model with Addiction Medicine and Cardiology providers using contingency management to engage patients with stimulant-associated cardiomyopathy (SA-CMP). Stimulant use, including methamphetamine and cocaine, is increasing in prevalence nationally and is associated with cardiovascular complications. People with SA-CMP have higher rates of mortality and acute care use (eg, emergency department visits, hospital admissions) and lower rates of outpatient care engagement than individuals with non-SA-CMP. This population also has disproportionately elevated rates of mental health and other medical comorbidities, challenges with social determinants of health, including housing and food insecurity, and representation from communities of color. This multidisciplinary comanagement care delivery model, called Heart Plus, was developed and funded as a quality improvement project. It led to a 5-fold increase in outpatient care engagement with a concomitant 53% decrease in acute care use. All participants reported a decrease in stimulant use. With increased clinical stability, patients were able to better engage with outpatient resources for social determinants of health, such as case management, social work, and housing and food service programs. Patients were also empowered to take control over their health while knowing that health care providers cared about their well-being.
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TRIM24 is an oncogenic chromatin reader that is frequently overexpressed in human tumors and associated with poor prognosis. However, TRIM24 is rarely mutated, duplicated, or rearranged in cancer. This raises questions about how TRIM24 is regulated and what changes in its regulation are responsible for its overexpression. Here, we perform a genome-wide CRISPR-Cas9 screen by fluorescence-activated cell sorting (FACS) that nominated 220 negative regulators and elucidated a regulatory network that includes the KAP1 corepressor, CNOT deadenylase, and GID/CTLH E3 ligase. Knocking out required components of these three complexes caused TRIM24 overexpression, confirming their negative regulation of TRIM24. Our findings identify regulators of TRIM24 that nominate previously unexplored contexts for this oncoprotein in biology and disease. These findings were enabled by SLIDER, a new scoring system designed and vetted in our study as a broadly applicable tool for analysis of CRISPR screens performed by FACS.
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OBJECTIVES: We sought to characterize atherosclerotic cardiovascular disease (ASCVD) risk and metrics of cardiovascular health in persons with HIV (PWH) eligible for primary prevention of ASCVD. DESIGN: A cross-sectional study of PWH 40âyears and older without documented ASCVD who received care at three HIV clinics in San Francisco from 2019 to 2022. METHODS: We used ICD-10 codes and electronic health record data to assess ASCVD risk and cardiovascular health, as defined by the American Heart Association's Life's Essential 8 (LE8) metrics for nicotine exposure, BMI, lipids, glucose, and blood pressure (BP). RESULTS: Among 2567 PWH eligible for primary prevention of ASCVD, the median age was 55âyears, 14% were women, and 95% were on antiretroviral therapy. Seventy-seven percent had undergone complete assessment of ASCVD risk factors, and 50% of these patients had intermediate-high ASCVD risk (≥7.5%). Of those with hypertension, 39% were prescribed an antihypertensive. Among those eligible, 43% were prescribed a statin. The mean LE8 cardiovascular health score [0--100 (best health)] was 55.1 for nicotine exposure, 71.3 for BMI, 70.4 for lipids, 81.2 for blood glucose, 56.0 for BP, with an average score of 66.2 across the five metrics. Patients with Medicare insurance, black patients, and those with sleep apnea and chronic kidney disease had on average lower cardiovascular health scores; patients with undetectable viral loads had higher cardiovascular health scores. CONCLUSION: We highlight opportunities for improving primary prevention of ASCVD among PWH, especially in the areas of guideline-based therapy, nicotine exposure, and BP control.
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Aterosclerose , Doenças Cardiovasculares , Infecções por HIV , Inibidores de Hidroximetilglutaril-CoA Redutases , Idoso , Humanos , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Estudos Transversais , Nicotina , Medição de Risco , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Medicare , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Aterosclerose/complicações , Aterosclerose/epidemiologia , Fatores de Risco , LipídeosRESUMO
BACKGROUND: Enhanced Recovery After Surgery pathways provide evidence-based recommendations to optimize perioperative care. OBJECTIVE: This study aimed to holistically investigate the effect of implementing an Enhanced Recovery After Surgery pathway for all cesarean deliveries on postoperative pain experience. STUDY DESIGN: This was a prepost study comparing subjective and objective measures of postoperative pain before and after the implementation of an Enhanced Recovery After Surgery pathway for cesarean delivery. The Enhanced Recovery After Surgery pathway was developed by a multidisciplinary team and included preoperative, intraoperative, and postoperative components, with emphasis on preoperative preparation, hemodynamic optimization, early mobilization, and multimodal analgesia. All individuals undergoing cesarean delivery, whether scheduled, urgent, or emergent, were included. Demographic, delivery, and inpatient pain management data were obtained through medical record review. Of note, 2 weeks after discharge, patients were surveyed about their delivery experience, analgesic usage, and complications. The primary outcome was inpatient opioid use. RESULTS: The study included 128 individuals, 56 in the preimplementation cohort and 72 in the Enhanced Recovery After Surgery cohort. Baseline characteristics between the 2 groups were similar. The survey response rate was 73% (94/128). Opioid use in the first 48 hours postoperatively was significantly lower in the Enhanced Recovery After Surgery group than the preimplementation group (9.4 vs 21.4 morphine milligram equivalents 0-24 hours after delivery [P<.001]; 14.1 vs 25.4 morphine milligram equivalents 24-48 hours after delivery [P<.001]) with no increase in either average or maximum postoperative pain scores. Individuals in the Enhanced Recovery After Surgery group used fewer opioid pills after discharge (10 vs 20; P<.001). Patient satisfaction and complication rates did not change after the implementation of an Enhanced Recovery After Surgery pathway. CONCLUSION: The implementation of an Enhanced Recovery After Surgery pathway for all cesarean deliveries decreased both inpatient and outpatient postpartum opioid use without increasing pain scores or decreasing patient satisfaction.
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BACKGROUND AND AIMS: We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS: Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs. RESULTS: Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes. CONCLUSIONS: There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.
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Colangite Esclerosante , Cirrose Hepática Biliar , Humanos , Adulto Jovem , Adulto , Cirrose Hepática Biliar/complicações , Colangite Esclerosante/complicações , Colangite Esclerosante/tratamento farmacológico , Prurido/diagnóstico , Prurido/tratamento farmacológico , Prurido/etiologia , Ácidos Fíbricos/uso terapêutico , Qualidade de VidaRESUMO
AIM: To compare patient characteristics and outcomes between the overall and Japanese populations of GLIMMER. METHODS: GLIMMER was a multicenter, double-blind, randomized, placebo-controlled, Phase IIb study evaluating linerixibat for the treatment of pruritus in patients with primary biliary cholangitis. RESULTS: In total, 147 patients were randomized in the GLIMMER overall population with 38 patients comprising the Japanese population. Demographics and baseline clinical characteristics were similar across treatment groups and between both populations. A reduction in mean worst daily itch score from baseline to week 16 (primary endpoint) was seen in all groups, with the largest reduction observed with linerixibat 40 mg twice daily (BID; -2.92 [95% confidence interval: -5.07, -0.76] and -2.86 [95% confidence interval: -3.76, -1.95] for Japanese and overall populations, respectively). The highest proportion of responders was generally in the 40 mg BID group in both populations regardless of the responder definition applied. Improvements in health-related quality of life were generally consistent in both populations. In the Japanese and overall populations, on-treatment drug-related adverse events were reported in 25% and 19% of patients in the placebo group and 0%-86% and 31%-78% of patients in the linerixibat groups, respectively. Consistent with the mechanism of action, the most common events were gastrointestinal in nature. The effects of linerixibat on pharmacodynamic biomarkers favored BID dosing. CONCLUSIONS: Therapeutic responses and safety of linerixibat were consistent between the Japanese and overall populations of GLIMMER. Linerixibat may provide an effective treatment option for cholestatic pruritus in patients with primary biliary cholangitis. CLINICAL TRIAL REGISTRATION: NCT02966834.
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BACKGROUND AND AIMS: Patients with primary biliary cholangitis (PBC) often suffer with pruritus. We describe the impact of pruritus on quality of life and how it is managed in a real-world cohort. METHODS: TARGET-PBC is a longitudinal observational cohort of patients with PBC across the USA. Data include information from medical records for three years prior to the date of consent up to 5 years of follow-up. Enrolled patients were asked to complete patient-reported outcome surveys: PBC-40, 5-D itch, and the PROMIS fatigue survey. Kruskal-Wallis tests were used to compare differences in symptoms between groups. RESULTS: A total of 211 patients with completed PRO surveys were included in the current study. PRO respondents were compared with non-respondents in the TARGET-PBC population and were broadly similar. Pruritus was reported in 170 patients (81%), with those reporting clinically significant pruritus (30%) scoring worse across each domain of the PBC-40 and 5-D itch, more frequently having cirrhosis, and having significantly greater levels of fatigue. Patients reporting clinically significant pruritus were more likely to receive treatment, but 33% had never received treatment (no itch = 43.9%, mild itch = 38.3%). CONCLUSIONS: The prevalence of pruritus was high in this population, and those reporting clinically significant pruritus had a higher likelihood of having advanced disease and worse quality of life. However, this study found that pruritus in PBC is under-treated. This may be due in part to ineffectiveness of current treatments, poor tolerance, or the lack of FDA-approved medications for pruritus.
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Cirrose Hepática Biliar , Humanos , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/diagnóstico , Qualidade de Vida , Cirrose Hepática , Prurido/diagnóstico , Prurido/tratamento farmacológico , Prurido/epidemiologia , Fadiga/epidemiologia , Fadiga/etiologiaRESUMO
BACKGROUND & AIMS: GLIMMER assessed dose-response, efficacy, and safety of linerixibat, an ileal bile acid transporter inhibitor in development for cholestatic pruritus associated with primary biliary cholangitis (PBC). METHODS: GLIMMER was a Phase 2b, multicenter, randomized, parallel-group study in adults with PBC and moderate-to-severe pruritus (≥4 on 0-10 numerical rating scale [NRS]). After 4 weeks of single-blind placebo, patients with NRS ≥3 were randomized (3:1) to double-blind linerixibat/placebo for 12 weeks (to week 16), followed by single-blind placebo (to week 20). The primary objective was to investigate dose-related changes in mean worst daily itch (MWDI) score. RESULTS: One hundred forty-seven patients received placebo (n = 36) or linerixibat (once daily: 20 mg, n = 16; 90 mg, n = 23; 180 mg, n = 27; twice daily: 40 mg, n = 23; 90 mg, n = 22). Linerixibat groups exhibited ≥2-point mean reductions in MWDI from baseline at week 16; however, differences from placebo were not significant. Post hoc analysis of change from baseline in monthly itch score over the treatment period (Phase 3 endpoint) showed significant differences between placebo and linerixibat 180 mg once daily (P = .0424), 40 mg twice daily (P = .0105), and 90 mg twice daily (P = .0370). A significant relationship between total daily dose and response was observed post hoc in the per protocol population (P = .0542). Consistent with mechanism of action, diarrhea was the most frequent adverse event, and incidence increased with dose. CONCLUSIONS: Linerixibat effect on itch was not significantly different versus placebo in the primary intent-to-treat analysis but was associated with a significant dose-dependent reduction in itch in the per protocol population. A well-tolerated dose was identified for Phase 3 investigation for cholestatic pruritus in PBC. CLINICALTRIALS: gov ID: NCT02966834.
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Cirrose Hepática Biliar , Adulto , Humanos , Cirrose Hepática Biliar/complicações , Método Simples-Cego , Resultado do Tratamento , Prurido/tratamento farmacológico , Prurido/etiologia , Método Duplo-CegoRESUMO
INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb. METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region of XTX101 were included to enhance affinity for FcγRIII, which is expected to enhance potency through antibody-dependent cellular cytotoxicity. RESULTS: Biophysical, biochemical, and cell-based assays demonstrate that the function of XTX101 depends on proteolytic activation. In human CTLA-4 transgenic mice, XTX101 monotherapy demonstrated significant tumor growth inhibition (TGI) including complete responses, increased intratumoral CD8+T cells, and regulatory T cell depletion within the TME while maintaining minimal pharmacodynamic effects in the periphery. XTX101 in combination with anti-PD-1 mAb treatment resulted in significant TGI and was well tolerated in mice. XTX101 was activated in primary human tumors across a range of tumor types including melanoma, renal cell carcinoma, colon cancer and lung cancer in an ex vivo assay system. CONCLUSIONS: These data demonstrate that XTX101 retains the full potency of an Fc-enhanced CTLA-4 antagonist within the TME while minimizing the activity in non-tumor tissue, supporting the further evaluation of XTX101 in clinical studies.
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Antineoplásicos , Melanoma , Humanos , Camundongos , Animais , Antígeno CTLA-4 , Ipilimumab/uso terapêutico , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Melanoma/tratamento farmacológico , Modelos Animais de Doenças , Camundongos Transgênicos , Peptídeos/uso terapêutico , Microambiente TumoralRESUMO
Objective: Persons with HIV (PWH) have increased risk for atherosclerotic cardiovascular disease (CVD). Despite this increased risk, perceived cardiovascular risk among PWH is low, and interventions that are known to be beneficial in the general population, such as statins, have low uptake in this population. We sought to develop a bank of text messages about (1) the association between HIV and CVD and (2) advice on reducing cardiovascular risk. Methods: We developed an initial bank of 162 messages. We solicited feedback from 29 PWH recruited from outpatient clinics providing HIV care at a large urban tertiary medical center and a public hospital in San Francisco, California. Participants reviewed 7-10 messages each and rated message usefulness, readability, and potential impact on behavior on a scale from 1 (least) to 5 (most). We also collected open-ended feedback on the messages and data on preferences about message timing. Results: The average score for the messages was 4.4/5 for usefulness, 4.4/5 for readability, and 4.0/5 for potential impact on behavior. The text messages were iteratively revised based on participant feedback, and lowest-rated messages were removed from the message bank. The final message bank included 116 messages on diet (30.2%), physical activity (24.8%), tobacco (11.2%), the association between HIV and cardiovascular disease (9.5%), general heart health (6.9%), cholesterol (5.2%), blood pressure (4.3%), blood sugar (2.6%), sleep (2.6%), and weight (2.6%). Conclusion: We describe an approach for developing educational text messages on primary prevention of cardiovascular disease among PWH.
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State and local public health agencies are at the forefront of planning and responding to the health challenges of climate hazards but face substantial barriers to effective climate and health adaptation amidst concurrent environmental and public health crises. To ensure successful adaptation, it is necessary to understand and overcome these barriers. The U.S. Centers for Disease Control and Prevention Climate-Ready States and Cities Initiative (CRSCI) provides funding to state and local health departments to anticipate and respond to health impacts from climate change using the Building Resilience Against Climate Effects (BRACE) framework. This paper explores the barriers to and enablers of successful adaptation projects among BRACE West CRSCI grantees, including Arizona, California, Oregon, and the city and county of San Francisco. The barriers included competing demands such as the COVID-19 pandemic, dependence on partners with similar challenges, staff and leadership turnover, uncertain and complex impacts on at-risk populations, and inadequate resources. The enablers included effective partnerships, leadership support, dedicated and skilled internal staff, and policy windows enabling institutional change and reprioritization. These findings highlight effective strategies in the field that state and local health departments may use to anticipate potential barriers and establish their work in an environment conducive to successful adaptation.
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COVID-19 , Pandemias , COVID-19/epidemiologia , Centers for Disease Control and Prevention, U.S. , Mudança Climática , Humanos , Pandemias/prevenção & controle , Saúde Pública , Estados UnidosRESUMO
BACKGROUND: The dynamics of injection drug use and higher-risk sexual practices compound the risk of HIV and HCV acquisition. Published literature on people who inject drugs (PWID) has examined risk of infection assuming homogeneity of cohort behavior. Categorizing subgroups by injection and sexual risk can inform a more equitable approach to how syringe services programs (SSPs) adapt harm reduction resources and implementation of evidence-based interventions. We explored injection and sexual risk profiles among PWID to determine significant predictors of class membership. METHODS: Data were collected from 1,272 participants at an SSP in Miami-Dade County. Latent Class Analysis (LCA) examined how 10 injection/sexual behavior indicators cluster together to create profiles. Model fit statistics and multivariable multinomial latent class regression identified the optimal class structure and significant predictors of class membership. We assessed SSP visits, naloxone access, HIV/HCV testing and prevalence, and incidence of self-reported wounds. RESULTS: Three distinct profiles of injection/sexual risk were determined: Low Injection/High Sexual (LIHS) (9.4%); High Injection/Moderate Sexual (HIMS) (18.9%); and Low Injection/Low Sexual (LILS) (71.7%). Participants reporting gay/bisexual orientation and methamphetamine injection more likely belonged to the LIHS class. LIHS class members had higher prevalence of HIV, while those of HIMS reported increased hepatitis C prevalence. Compared to members of LILS, those of HIMS more likely experienced unstable housing, gay/bisexual orientation, heroin or speedball injection, and identifying as women. HIMS cohort members had more SSP visits, naloxone accessed, and higher wound incidence than those of LILS. CONCLUSIONS: Understanding PWID subgroups amplifies the importance of implementing evidencebased interventions such as PrEP for those engaging in highest risk behavior, with focused interventions of antiretroviral management and access to condoms for members of the LIHS class and HCV screening with wound care for those belonging to HIMS.
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Usuários de Drogas , Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Feminino , Florida/epidemiologia , Infecções por HIV/prevenção & controle , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Naloxona , Assunção de Riscos , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologiaRESUMO
CRISPR knockout fitness screens in cancer cell lines reveal many genes whose loss of function causes cell death or loss of fitness or, more rarely, the opposite phenotype of faster proliferation. Here we demonstrate a systematic approach to identify these proliferation suppressors, which are highly enriched for tumor suppressor genes, and define a network of 145 such genes in 22 modules. One module contains several elements of the glycerolipid biosynthesis pathway and operates exclusively in a subset of acute myeloid leukemia cell lines. The proliferation suppressor activity of genes involved in the synthesis of saturated fatty acids, coupled with a more severe loss of fitness phenotype for genes in the desaturation pathway, suggests that these cells operate at the limit of their carrying capacity for saturated fatty acids, which we confirm biochemically. Overexpression of this module is associated with a survival advantage in juvenile leukemias, suggesting a clinically relevant subtype.