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1.
J Gen Intern Med ; 39(12): 2150-2159, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38937366

RESUMEN

BACKGROUND: The effectiveness of hospital-based transitional opioid programs (TOPs), which aim to connect patients with substance use disorders (SUD) to ongoing treatment in the community following initiation of medication for opioid use disorder (MOUD) treatment in the hospital, hinges on successful patient transitions. These transitions are enabled by strong partnerships between hospitals and community-based organizations (CBOs). However, no prior study has specifically examined barriers and facilitators to establishing SUD care transition partnerships between hospitals and CBOs. OBJECTIVE: To identify barriers and facilitators to developing partnerships between hospitals and CBOs to facilitate care transitions for patients with SUDs. DESIGN: Qualitative study using semi structured interviews conducted between November 2022-August 2023. PARTICIPANTS: Staff and providers from hospitals affiliated with four safety-net health systems (n=21), and leaders and staff from the CBOs with which they had established partnerships (n=5). APPROACH: Interview questions focused on barriers and facilitators to implementing TOPs, developing partnerships with CBOs, and successfully transitioning SUD patients from hospital settings to CBOs. KEY RESULTS: We identified four key barriers to establishing transition partnerships: policy and philosophical differences between organizations, ineffective communication, limited trust, and a lack of connectivity between data systems. We also identified three facilitators to partnership development: strategies focused on building partnership quality, strategic staffing, and organizing partnership processes. CONCLUSIONS: Our findings demonstrate that while multiple barriers to developing hospital-CBO partnerships exist, stakeholders can adopt implementation strategies that mitigate these challenges such as using mediators, cross-hiring, and focusing on mutually beneficial services, even within resource-limited safety-net settings. Policymakers and health system leaders who wish to optimize TOPs in their facilities should focus on adopting implementation strategies to support transition partnerships such as inadequate data collection and sharing systems.


Asunto(s)
Proveedores de Redes de Seguridad , Humanos , Proveedores de Redes de Seguridad/organización & administración , Trastornos Relacionados con Sustancias/terapia , Investigación Cualitativa , Trastornos Relacionados con Opioides/terapia , Cuidado de Transición/organización & administración
2.
J Public Health Manag Pract ; 30(2): 255-266, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37938810

RESUMEN

OBJECTIVE: Telehealth is an essential tool to provide access to care while reducing infection exposure for high-risk populations during the COVID-19 pandemic. Our study aims to examine factors associated with telehealth availability and usage among Medicare and dual-eligible recipients 1 year after implementation of the Medicare's temporary telehealth waiver. DESIGN, SETTING, AND PARTICIPANT: A cross-sectional, phone survey with a national representative sample of Medicare recipients. We obtained a final study sample from the Winter 2021 COVID-19 Supplement of Medicare Current Beneficiary Survey dataset (N = 10 586). We examined associations for being offered and having had telehealth visits or any video telehealth visits during the pandemic since November 1, 2020. MAIN OUTCOME MEASURES: Our primary outcomes were being offered any telehealth, being offered any video telehealth, having had any telehealth visit, and having had any video telehealth. RESULTS: Although dual eligibility was not significantly associated with being offered or having had any telehealth services during the pandemic, those who were dual eligible were more likely to have had video telehealth visits (adjusted odds ratio = 1.39, 95% confidence interval 1.04-1.86, P = .03) compared with those with non-dual eligibility. Recipients with disability eligibility, technology access, and severe chronic conditions were more likely to have been offered or have had telehealth. At the same time, those who lived in the nonmetropolitan area were less likely to have been offered or have had telehealth, including video telehealth. CONCLUSIONS: Our findings suggest that the federal waivers to expand telehealth services were successful in continuing care for vulnerable Medicare recipients. The providers' specific outreach and intervention efforts to offer telehealth visits are crucial for dual-eligible recipients. To increase video telehealth uptake, technology access and services to rural areas should be prioritized.


Asunto(s)
COVID-19 , Telemedicina , Anciano , Estados Unidos/epidemiología , Humanos , COVID-19/epidemiología , Estudios Transversales , Medicare , Pandemias
3.
Curr Issues Mol Biol ; 45(3): 2474-2490, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36975532

RESUMEN

To overcome the limitation of conventional cancer treatments, photodynamic therapy (PDT) has been introduced as another treatment option. PDT provides a non-invasive, non-surgical way with reduced toxicity. To improve the antitumor efficacy of PDT, we synthesized a novel photosensitizer, a 3-substituted methyl pyropheophorbide-a derivative (Photomed). The purpose of the study was to evaluate the antitumor effect of PDT with Photomed comparing with the clinically approved photosensitizers Photofrin and Radachlorin. The cytotoxicity assay against SCC VII cells (murine squamous cell carcinoma) was performed to determine whether Photomed is safe without PDT and whether Photomed is effective against cancer cells with PDT. An in vivo anticancer efficacy study was also performed using SCC VII tumor-bearing mice. The mice were divided into small-tumor and large-tumor groups to identify whether Photomed-induced PDT is effective for not only small tumors but also large tumors. From in vitro and in vivo studies, Photomed was confirmed to be (1) a safe photosensitizer without laser irradiation, (2) the most effective photosensitizer with PDT against cancers compared to Photofrin and Radachlorin and (3) effective with PDT in treating not only small tumors but also large tumors. In conclusion, Photomed may contribute as a novel, potential photosensitizer for use in PDT cancer treatment.

4.
J Gen Intern Med ; 38(15): 3273-3282, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37227658

RESUMEN

BACKGROUND: Evidence suggests that harm reduction, a public health strategy aimed at reducing the negative consequences of a risky health behavior without requiring elimination of the behavior itself, may be a promising approach for minimizing drug-related harms while engaging individuals with substance use disorders (SUDs) in care. However, philosophical clashes between the medical and harm reduction models may pose barriers to adopting harm reduction approaches within medical settings. OBJECTIVE: To identify barriers and facilitators to implementing a harm reduction approach toward care within healthcare settings. We conducted semi-structured interviews with providers and staff at three integrated harm reduction and medical care sites in New York. DESIGN: Qualitative study using in-depth and semi-structured interviews. PARTICIPANTS: Twenty staff and providers across three integrated harm reduction and medical care sites across New York state. APPROACH: Interview questions focused on how harm reduction approaches were implemented and demonstrated in practice and barriers and facilitators to implementation, as well as questions based on the five domains of the Consolidated Framework for Implementation Research (CFIR). KEY RESULTS: We identified three key barriers to the adoption of the harm reduction approach that surrounded resource constraints, provider burnout, and interacting with external providers that do not have a harm reduction orientation. We also identified three facilitators to implementation, which included ongoing training both within and external to the clinic, team-based and interdisciplinary care, and affiliations with a larger healthcare system. CONCLUSIONS: This study demonstrated that while multiple barriers to implementing harm reduction informed medical care existed, health system leaders can adopt practices to mitigate barriers to adoption, such as value-based reimbursement models and holistic models of care that address the full spectrum of patient needs.


Asunto(s)
Atención Primaria de Salud , Trastornos Relacionados con Sustancias , Humanos , Reducción del Daño , Atención a la Salud , Investigación Cualitativa , Trastornos Relacionados con Sustancias/prevención & control
5.
BMC Health Serv Res ; 23(1): 87, 2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36703146

RESUMEN

INTRODUCTION: Opioid-related hospitalizations have risen dramatically, placing hospitals at the frontlines of the opioid epidemic. Medicaid expansion and 1115 waivers for substance use disorders (SUDs) are two key policies aimed at expanding access to care, including opioid use disorder (OUD) services. Yet, little is known about the relationship between these policies and the availability of hospital based OUD programs. The aim of this study is to determine whether state Medicaid expansion and adoption of 1115 waivers for SUDs are associated with hospital provision of OUD programs. METHODS: We conducted a cross-sectional study of a random sample of hospitals (n = 457) from the American Hospital Association's 2015 American Hospital Directory, compiled with the most recent publicly available community health needs assessment (2015-2018). RESULTS: Controlling for hospital characteristics, overdose burden, and socio-demographic characteristics, both Medicaid policies were associated with hospital adoption of several OUD programs. Hospitals in Medicaid expansion states had significantly higher odds of implementing any program related to SUDs (OR: 1.740; 95% CI: 1.032-2.934) as well as some specific activities such as programs for OUD treatment (OR: 1.955; 95% CI: 1.245-3.070) and efforts to address social determinants of health (OR: 6.787; 95% CI: 1.308-35.20). State 1115 waivers for SUDs were not significantly associated with any hospital-based SUD activities. CONCLUSIONS: Medicaid expansion was associated with several hospital programs for addressing OUD. The differential availability of hospital-based OUD programs may indicate an added layer of disadvantage for low-income patients with SUD living in non-expansion states.


Asunto(s)
Medicaid , Trastornos Relacionados con Opioides , Humanos , Estados Unidos/epidemiología , Estudios Transversales , Trastornos Relacionados con Opioides/terapia , Analgésicos Opioides/uso terapéutico , Hospitales
6.
BMC Health Serv Res ; 23(1): 560, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37259081

RESUMEN

BACKGROUND: There are well-established guidelines for treating hypertension (HTN), yet only half of patients with HTN meet the defined target of < 140/90. Team-based care (TBC) is an evidence-based strategy for improving blood pressure (BP) management and control. TBC is defined as the provision of health services by at least two health professionals "who work collaboratively with patients and their caregivers to accomplish shared goals to achieve coordinated, high-quality care". However, primary care practices experience challenges to implementing TBC principles and care processes; these are more pronounced in small independent practice settings (SIPs). Practice facilitation (PF) is an implementation strategy that may overcome barriers to adopting evidence-based TBC to improve HTN management in SIPs. METHODS: Using a stepped wedge randomized controlled trial design, we will test the effect of PF on the adoption of TBC to improve HTN management in small practices (< 5 FTE clinicians) in New York City, and the impact on BP control compared with usual care. We will enroll 90 SIPs and randomize them into one of three 12-month intervention waves. Practice facilitators will support SIPs to adopt TBC principles to improve implementation of five HTN management strategies (i.e., panel management, population health, measuring BP, supporting medication adherence, self-management). The primary outcome is the adoption of TBC for HTN management measured at baseline and 12 months. Secondary outcomes include the rate of BP control and sustainability of TBC and BP outcomes at 18 months. Aggregated data on BP measures are collected every 6 months in all clusters so that each cluster provides data points in both the control and intervention conditions. Using a mixed methods approach, we will also explore factors that influence the effectiveness of PF at the organization and team level. DISCUSSION: This study will provide much-needed guidance on how to optimize adoption and sustainability of TBC in independent primary care settings to reduce the burden of disease related to suboptimal BP control and advance understanding of how facilitation works to improve implementation of evidence-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05413252 .


Asunto(s)
Hipertensión , Humanos , Hipertensión/terapia , Presión Sanguínea , Calidad de la Atención de Salud , Cumplimiento de la Medicación , Personal de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Am J Drug Alcohol Abuse ; 49(2): 206-215, 2023 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-36877147

RESUMEN

Background: Hospitals are well-positioned to integrate harm reduction into their workflow. However, the extent to which hospitals across the United States are adopting these strategies remains unknown.Objectives: To assess what factors are associated with hospital adoption of harm reduction/risk education strategies, and trends of adoption across time.Methods: We constructed a dataset marking implementation of harm reduction/risk education strategies for a 20% random sample of nonprofit hospitals in the U.S (n = 489) using 2019-2021 community health needs assessments (CHNAs) and implementation strategies obtained from hospital websites. We used two-level mixed effects logistic regression to test the association between adoption of these activities and organizational and community-level variables. We also compared the proportion of hospitals that adopted these strategies in the 2019-2021 CHNAs to an earlier cohort (2015-2018.)Results: In the 2019-2021 CHNAs, 44.7% (n = 219) of hospitals implemented harm reduction/risk education programs, compared with 34.1% (n = 156) in the 2015-2018 cycle. In our multivariate model, hospitals that implemented harm reduction/risk education programs had higher odds of having adopted three or more additional substance use disorder (SUD) programs (OR: 10.5: 95% CI: 5.35-20.62), writing the CHNA with a community organization (OR: 2.14; 95% CI: 1.15-3.97), and prioritizing SUD as a top three need in the CHNA (OR: 2.63; 95% CI: 1.54-4.47.)Conclusions: Our results suggest that hospitals with an existing SUD infrastructure and with connections to community are more likely to implement harm reduction/risk education programs. Policymakers should consider these findings when developing strategies to encourage hospital implementation of harm reduction activities.


Asunto(s)
Reducción del Daño , Trastornos Relacionados con Sustancias , Estados Unidos/epidemiología , Humanos , Hospitales , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/prevención & control , Organizaciones sin Fines de Lucro , Evaluación de Necesidades
8.
Int J Mol Sci ; 24(17)2023 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-37686423

RESUMEN

The development of targeted therapies has revolutionized cancer treatment, offering improved efficacy with reduced side effects compared with traditional chemotherapy. This review highlights the current landscape of targeted therapy in lung cancer, colorectal cancer, and prostate cancer, focusing on key molecular targets. Moreover, it aligns with US Food and Drug Administration (FDA)-approved drugs and drug candidates. In lung cancer, mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene rearrangements have emerged as significant targets. FDA-approved drugs like osimertinib and crizotinib specifically inhibit these aberrant pathways, providing remarkable benefits in patients with EGFR-mutated or ALK-positive lung cancer. Colorectal cancer treatment has been shaped by targeting the vascular endothelial growth factor (VEGF) and EGFR. Bevacizumab and cetuximab are prominent FDA-approved agents that hinder VEGF and EGFR signaling, significantly enhancing outcomes in metastatic colorectal cancer patients. In prostate cancer, androgen receptor (AR) targeting is pivotal. Drugs like enzalutamide, apalutamide, and darolutamide effectively inhibit AR signaling, demonstrating efficacy in castration-resistant prostate cancer. This review further highlights promising targets like mesenchymal-epithelial transition (MET), ROS1, BRAF, and poly(ADP-ribose) polymeras (PARP) in specific cancer subsets, along with ongoing clinical trials that continue to shape the future of targeted therapy.


Asunto(s)
Neoplasias del Colon , Neoplasias Pulmonares , Neoplasias de la Próstata , Estados Unidos , Masculino , Humanos , Factor A de Crecimiento Endotelial Vascular , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Receptores ErbB
9.
J Gen Intern Med ; 37(16): 4248-4256, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36167954

RESUMEN

BACKGROUND: Studies specifically focused on patients' perspectives on telemedicine visits in primary and behavioral health care are fairly limited and have often focused on highly selected populations or used overall satisfaction surveys. OBJECTIVE: To examine patient perspectives on the shift to telemedicine, the remote delivery of health care via the use of electronic information and communications technology, in primary and behavioral health care in Federally Qualified Health Centers (FQHCs) during COVID-19. DESIGN: Semi-structured interviews were conducted using video conference with patients and caregivers between October and December 2020. PARTICIPANTS: Providers from 6 FQHCs nominated participants. Eighteen patients and caregivers were interviewed: 6 patients with only primary care visits; 5 with only behavioral health visits; 3 with both primary care and behavioral health visits; and 4 caregivers of children with pediatric visits. APPROACH: Using a protocol-driven, rapid qualitative methodology, we analyzed the interview data and assessed the quality of care, benefits and challenges of telemedicine, and use of telemedicine post-pandemic. KEY RESULTS: Respondents broadly supported the option of home-based synchronous telemedicine visits in primary and behavioral health care. Nearly all respondents appreciated remote visits, largely because such visits provided a safe option during the pandemic. Patients were generally satisfied with telemedicine and believed the quality of visits to be similar to in-person visits, especially when delivered by a provider with whom they had established rapport. Although most respondents planned to return to mostly in-person visits when considered safe to do so, they remained supportive of the continued option for remote visits as remote care addresses some of the typical barriers faced by low-income patients. CONCLUSIONS: Addressing digital literacy challenges, enhancing remote visit privacy, and improving practice workflows will help ensure equitable access to all patients as we move to a new post-COVID-19 "normal" marked by increased reliance on telemedicine and technology.


Asunto(s)
COVID-19 , Atención Primaria de Salud , Telemedicina , Niño , Humanos , COVID-19/epidemiología , Atención a la Salud , Pandemias , Telemedicina/métodos , Comunicación por Videoconferencia
10.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-34360634

RESUMEN

Autophagy is an attractive process to researchers who are seeking novel potential treatments for various diseases. Autophagy plays a critical role in degrading damaged cellular organelles, supporting normal cell development, and maintaining cellular homeostasis. Because of the various effects of autophagy, recent human genome research has focused on evaluating the relationship between autophagy and a wide variety of diseases, such as autoimmune diseases, cancers, and inflammatory diseases. The skin is the largest organ in the body and provides the first line of defense against environmental hazards, including UV damage, chemical toxins, injuries, oxidative stress, and microorganisms. Autophagy takes part in endogenous defense mechanisms by controlling skin homeostasis. In this manner, regulating autophagy might contribute to the treatment of skin barrier dysfunctions. Various studies are ongoing to elucidate the association between autophagy and skin-related diseases in order to find potential therapeutic approaches. However, little evidence has been gathered about the relationship between autophagy and the skin. In this review, we highlight the previous findings of autophagy and skin barrier disorders and suggest potential therapeutic strategies. The recent research regarding autophagy in acne and skin aging is also discussed.


Asunto(s)
Autofagia , Enfermedades de la Piel/etiología , Humanos , Terapia Molecular Dirigida , Permeabilidad , Piel/metabolismo , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/terapia
11.
Artículo en Inglés | MEDLINE | ID: mdl-34812120

RESUMEN

The performance of CATACOAT, a nano-platinum thermal catalyst system, was evaluated for the removal of chemical hazardous compounds from air. Xylene, benzene, styrene, and toluene were selected as standard volatile organic compounds (VOCs) in this study. In addition, formaldehyde was tested as a chemical hazardous compound. Each VOC, or formaldehyde, was evaporated in a 4,000 L chamber under controlled environments. At the maximum concentration point, CATACOAT was turned on and the concentrations of the chemical hazardous compounds were recorded for 5 h. The air purifier based on H-13-grade high-efficiency particulate air (HEPA) filter was tested in the same way to compare the effects of CATACOAT. Compared with the HEPA filter system, every VOC concentration was significantly decreased with the CATACOAT system only 0.025 h after turning on the air purifier (P values for xylene, benzene, styrene, and toluene are 0.00488, 0.01508, 0.00014, and 0.04690, respectively). After running the air cleaners for 5 h, every VOC and formaldehyde demonstrated significantly decreased concentrations with the CATACOAT system, compared with HEPA filter system (P values for xylene, benzene, styrene, toluene, and formaldehyde are 0.00034, 0.00009, 0.00008, 0.00001, and 0.00571, respectively). In conclusion, the CATACOAT may be a viable solution to control indoor air pollution.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Benceno/análisis , Formaldehído/análisis , Platino (Metal) , Compuestos Orgánicos Volátiles/análisis
12.
Int J Mol Sci ; 21(23)2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33255783

RESUMEN

Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.


Asunto(s)
Inflamación/tratamiento farmacológico , Metformina/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Piel/efectos de los fármacos , Acantosis Nigricans/tratamiento farmacológico , Acantosis Nigricans/genética , Acantosis Nigricans/patología , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/genética , Acné Vulgar/patología , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/genética , Dermatitis Alérgica por Contacto/patología , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/patología , Humanos , Inflamación/genética , Inflamación/patología , FN-kappa B/antagonistas & inhibidores , FN-kappa B/genética , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Psoriasis/patología , Piel/metabolismo , Enfermedades de la Piel/genética , Enfermedades de la Piel/patología
13.
Int J Mol Sci ; 19(6)2018 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-29844257

RESUMEN

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of 50 mm³) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.


Asunto(s)
Neoplasias Experimentales/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Células A549 , Animales , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Fármacos Fotosensibilizantes/química , Porfirinas/química , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Biomed Pharmacother ; 178: 117114, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39053425

RESUMEN

Bosutinib has been approved for use in patients with chronic myeloid leukemia. Information regarding the effects of bosutinib on clinically important drug transporters is limited, particularly regarding its inhibitory potency on transporters and in vivo effects. Therefore, we conducted a study investigating the in vitro and in vivo effects of bosutinib on drug transporters. Bosutinib showed moderate or strong inhibitory effects on organic cation transporter 2, multidrug and toxin extrusion protein 1, and breast cancer resistance protein with IC50 values of 0.0894, 0.598, and 10.8 µM, respectively. In vivo experiments in rats showed that bosutinib significantly inhibited organic cation transporter 2 and multidrug and toxin extrusion protein 1, leading to a marked reduction in the renal clearance of metformin and an increase in systemic exposure to metformin. Bosutinib increased systemic exposure to sulfasalazine, a probe substrate of breast cancer resistance protein, by 75 % in rats, highlighting its potential to significantly affect intestinal drug efflux. These quantitative changes suggest that bosutinib may alter the in vivo pharmacokinetics of drugs that are substrates of these transporters, potentially leading to increased drug exposure and enhanced or unexpected pharmacological effects.


Asunto(s)
Compuestos de Anilina , Nitrilos , Quinolinas , Animales , Nitrilos/farmacología , Nitrilos/farmacocinética , Quinolinas/farmacología , Quinolinas/farmacocinética , Compuestos de Anilina/farmacología , Compuestos de Anilina/farmacocinética , Masculino , Ratas , Humanos , Ratas Sprague-Dawley , Metformina/farmacología , Metformina/farmacocinética , Transporte Biológico/efectos de los fármacos
15.
Toxicol Lett ; 394: 57-65, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38423481

RESUMEN

Drug transporters are among the factors that determine the pharmacokinetic profiles after drug administration. In this study, we investigated the roles of drug transporters involved in transport of SN-38, which is an active metabolite of irinotecan, in the intestine under inflammatory conditions in vitro and determined their functional consequences. The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38. We also determined the cytotoxicity of SN-38 under inflammatory conditions. Decreased BCRP expression and increased OATP2B1 expression were observed under inflammatory conditions in vitro, which led to altered accumulation profiles of prazosin, DBF, and SN-38, and the subsequent cytotoxic profiles of SN-38. Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Transportadores de Anión Orgánico , Humanos , Femenino , Irinotecán , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Proteínas de Transporte de Membrana , Prazosina , Neoplasias de la Mama/tratamiento farmacológico
16.
PLoS One ; 19(5): e0304256, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38781234

RESUMEN

INTRODUCTION: Despite being an important determinant of health outcomes, measures of structural racism are lacking in studies examining the relationship between the social determinants of health (SDOH) and overdose deaths. The aim of this study is to examine the association between per capita revenue generated from fines and forfeitures, a novel measure of structural racism, and other SDOH with county-level overdose deaths from 2017-2020. METHODS: This longitudinal analysis of 2,846 counties from 2017-2020 used bivariate and multivariate Generalized Estimating Equations models to estimate associations between county overdose mortality rates and SDOH characteristics, including the fines and forfeitures measure. RESULTS: In our multivariate model, higher per capita fine and forfeiture revenue (5.76; CI: 4.76, 6.78), households receiving food stamps (1.15; CI: 0.77, 1.53), residents that are veterans (1.07; CI: 0.52, 1.63), substance use treatment availability (4.69; CI: 3.03, 6.33) and lower population density (-0.002; CI: -0.004, -0.001) and percent of Black residents (-0.7`; CI: -1.01, -0.42) were significantly associated with higher overdose death rates. There was a significant additive interaction between the fines and forfeitures measure (0.10; CI: 0.03, 0.17) and the percent of Black residents. CONCLUSIONS: Our findings suggest that structural racism, along with other SDOH, is associated with overdose deaths. Future research should focus on connecting individual-level data on fines and forfeitures to overdose deaths and other health outcomes, include measures of justice-related fines, such as court fees, and assess whether interventions aimed at increasing economic vitality in disadvantaged communities impact overdose deaths in a meaningful way.


Asunto(s)
Sobredosis de Droga , Racismo , Determinantes Sociales de la Salud , Humanos , Sobredosis de Droga/mortalidad , Racismo/estadística & datos numéricos , Masculino , Femenino , Estudios Longitudinales , Adulto , Estados Unidos/epidemiología
17.
Health Aff Sch ; 2(1)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38410743

RESUMEN

Telehealth utilization increased during the COVID-19 pandemic, yet few studies have documented associations of telehealth use with subsequent medical costs and health care utilization. We examined associations of telehealth use during the early COVID-19 public health emergency (March-June 2020) with subsequent total medical costs and health care utilization among people with heart disease (HD). We created a longitudinal cohort of individuals with HD using MarketScan Commercial Claims data (2018-2022). We used difference-in-differences methodology adjusting for patients' characteristics, comorbidities, COVID-19 infection status, and number of in-person visits. We found that using telehealth during the stay-at-home order period was associated with a reduction in total medical costs (by -$1814 per person), number of emergency department visits (by -88.6 per 1000 persons), and number of inpatient admissions (by -32.4 per 1000 persons). Telehealth use increased per-person per-year pharmacy prescription claims (by 0.514) and average number of days' drug supply (by 0.773 days). These associated benefits of telehealth use can inform decision makers, insurance companies, and health care professionals, especially in the context of disrupted health care access.

18.
Am J Prev Med ; 67(4): 568-580, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38844146

RESUMEN

INTRODUCTION: Discrimination in medical settings (DMS) contributes to healthcare disparities in the United States, but few studies have determined the extent of DMS in a large national sample and across different populations. This study estimated the national prevalence of DMS and described demographic and health-related characteristics associated with experiencing DMS in seven different situations. METHODS: Survey data from 41,875 adults participating in the All of Us Research Program collected in 2021-2022 and logistic regression were used to examine the association between sociodemographic and health-related characteristics and self-reported DMS among adults engaged with a healthcare provider within the past 12 months. Statistical analysis was performed in 2023-2024. RESULTS: About 36.89% of adults reported having experienced at least one DMS situation. Adults with relative social and medical disadvantages had higher prevalence of experiencing DMS. Compared to their counterparts, respondents with higher odds of experiencing DMS in at least one situation identified as female, non-Hispanic Black, having at least some college, living in the South, renter, having other living arrangement, being publicly insured, not having a usual source of care, having multiple chronic conditions, having any disability, and reporting fair or poor health, p<0.05. CONCLUSIONS: The findings indicate a high prevalence of DMS, particularly among some population groups. Characterizing DMS may be a valuable tool for identifying populations at risk within the healthcare system and optimizing the overall patient care experience. Implementing relevant policies remains an essential strategy for mitigating the prevalence of DMS and reducing healthcare disparities.


Asunto(s)
Disparidades en Atención de Salud , Humanos , Masculino , Femenino , Estados Unidos , Adulto , Persona de Mediana Edad , Disparidades en Atención de Salud/estadística & datos numéricos , Adulto Joven , Anciano , Encuestas y Cuestionarios , Adolescente , Prevalencia , Factores Socioeconómicos , Racismo/estadística & datos numéricos
20.
Mol Cell Biochem ; 375(1-2): 59-67, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23225230

RESUMEN

Striatal neuronal cell death is one of the pathological features of Huntington's disease (HD). Overexpression of some heat shock proteins (HSPs) has been reported to suppress the aggregate formation of mutant huntingtin and concurrent cell death. Heat shock transcription factor-1 (HSF 1), a major transcription factor of HSPs, has also been reported to be increased in HD models. However, the exact role of HSF 1 in the pathogenesis of HD has not been clearly elucidated. 3-Nitropropionic acid (3NP), an irreversible inhibitor of the mitochondrial complex II, induces selective damage to the striatum in animals and produces clinical features of HD. To investigate roles of HSF 1 on 3NP-induced oxidative stress, HSF 1 was transiently overexpressed in striatal cells. Expression of HSF 1 significantly attenuated 3NP-induced apoptotic striatal cell death and resulted in increased expression of HSP 70. Furthermore, expression of HSF 1 significantly attenuated 3NP-induced intracellular reactive oxygen species (ROS) generation. Taken together, the present study clearly demonstrates that HSF 1 attenuates 3NP-induced apoptotic striatal cell death and ROS generation, possibly through HSP70 expression, suggesting that HSF 1 might be a valuable therapeutic target in the treatment of HD.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Neostriado/patología , Nitrocompuestos/farmacología , Propionatos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Factores de Transcripción/metabolismo , Animales , Caspasa 3/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Proteínas de Unión al ADN/genética , Expresión Génica , Proteínas HSP70 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP70 de Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico , Humanos , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Azul de Metileno/farmacología , Ratones , Neostriado/metabolismo , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/metabolismo , Succinato Deshidrogenasa/antagonistas & inhibidores , Factores de Transcripción/genética
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