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1.
Exp Hematol ; 135: 104248, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38834136

RESUMEN

DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies, including acute myeloid leukemia. An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly comutated genes in myeloid malignancies, such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ERT2 murine model systems to study the effects of constitutively active KrasG12D-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO). Due to the rapid generation of diverse nonhematologic tumors appearing after tamoxifen induction, we employed a transplantation model. With pretransplant tamoxifen induction, most Kras mice died quickly of T-cell malignancies regardless of Dnmt3a status. Using posttransplant induction, we observed a dose-dependent effect of DNMT3A depletion that skewed the leukemic phenotype toward a myeloid lineage. Specifically, 64% of 3aKO/Kras mice had exclusively myeloid disease compared with 36% of 3aHet/Kras and only 13% of Kras mice. Here, 3aKO combined with Kras led to increased disease burden, multiorgan infiltration, and faster disease progression. DOT1L inhibition exerted profound antileukemic effects in malignant 3aKO/Kras cells, but not malignant cells with Kras mutation alone, consistent with the known sensitivity of DNMT3A-mutant leukemia to DOT1L inhibition. RNAseq from malignant myeloid cells revealed that biallelic Dnmt3a deletion was associated with loss of cell-cycle regulation, MYC activation, and TNF⍺ signaling. Overall, we developed a robust model system for mechanistic and preclinical investigations of acute myeloid leukemia with DNMT3A and Ras-pathway lesions.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasas , ADN Metiltransferasa 3A , Proteínas Proto-Oncogénicas p21(ras) , Animales , ADN Metiltransferasa 3A/genética , ADN Metiltransferasa 3A/metabolismo , Ratones , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Modelos Animales de Enfermedad , Ratones Transgénicos , Ratones Noqueados , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo
2.
Am J Public Health ; : e1-e5, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935888

RESUMEN

Since April 2019, CA Bridge has worked with emergency departments (EDs) in diverse geographic and emergency care settings across California to scale up low-threshold buprenorphine access, patient navigation programs, harm reduction services, and take-home naloxone. Between April 2019 and June 2023, 268 (81.0%) of 331 acute care hospitals in California received funding and technical assistance from CA Bridge and completed data reporting. These hospitals provided navigation services during 279 025 patient encounters and gave patients buprenorphine in 89 549 ED visits. (Am J Public Health. Published online ahead of print June 27, 2024:e1-e5. https://doi.org/10.2105/AJPH.2024.307710).

3.
J Acquir Immune Defic Syndr ; 96(4): 326-333, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38916426

RESUMEN

BACKGROUND: Associations of sleep deficiency and methamphetamine use with sexual health and HIV treatment outcomes are poorly understood. SETTING: A longitudinal cohort of men who have sex with men at risk for or living with HIV (the mSTUDY) was analyzed. This analysis included 1445 study visits among 382 participants. Data were collected from June 2018 to February 2022. METHODS: Semiannual study visits included self-interviews for sleep deficiency, sexual behaviors, substance use, and HIV treatment. Sleep deficiency was measured using the Pittsburgh Sleep Quality Index. Participants provided specimens for HIV viral load and sexually transmitted infection (STI) testing (chlamydia, gonorrhea, syphilis). Associations between sleep deficiency and STI/HIV outcomes were estimated using multiple logistic regression. RESULTS: Across visits, the prevalence of sleep deficiency was 56%, with 33% reporting methamphetamine use and 55% living with HIV. Sleep deficiency was associated with reporting at least 1 new anal sex partner (aOR = 1.62, 95% CI: 1.21 to 2.15), exchange sex (aOR = 2.71, 95% CI: 1.15 to 6.39), sex party attendance (aOR = 2.60, 95% CI: 1.68 to 4.04), and missing HIV medications (aOR = 1.91, 95% CI: 1.16 to 3.14). The association between sleep deficiency and exchange sex differed for participants who did and did not report the use of methamphetamine (P = 0.09). CONCLUSION: Sleep deficiency was associated with sexual health and HIV treatment behaviors after accounting for methamphetamine use. Sleep health should be considered in STI/HIV prevention, particularly for those who use methamphetamine.


Asunto(s)
Infecciones por VIH , Homosexualidad Masculina , Asunción de Riesgos , Conducta Sexual , Humanos , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Adulto , Estudios Longitudinales , Persona de Mediana Edad , Adulto Joven , Metanfetamina , Resultado del Tratamiento , Parejas Sexuales , Minorías Sexuales y de Género , Trastornos del Sueño-Vigilia/epidemiología
5.
JAMA Netw Open ; 7(1): e2353771, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38285444

RESUMEN

Importance: Although substantial evidence supports buprenorphine for treatment of opioid use disorder (OUD) in controlled trials, prospective study of patient outcomes in clinical implementation of emergency department (ED) buprenorphine treatment is lacking. Objective: To examine the association between buprenorphine treatment in the ED and follow-up engagement in OUD treatment 1 month later. Design, Setting, and Participants: This multisite cohort study was conducted in 7 California EDs participating in a statewide implementation project to improve access to buprenorphine treatment. The study population included ED patients aged at least 18 years identified with OUD between April 1, 2021, and June 30, 2022. Data analysis was performed in October 2023. Exposure: All participants were offered buprenorphine treatment for OUD (either in ED administration, prescription, or both), the uptake of which was examined as the exposure of interest. Main Outcomes and Measures: The primary outcome was engagement in OUD treatment 30 days after the ED visit, determined by patient report or clinical documentation. The association of ED buprenorphine treatment with subsequent OUD treatment engagement was estimated using hierarchical generalized linear models. Results: This analysis included 464 ED patients with OUD. Their median age was 36.0 (IQR, 29.0-38.7) years, and most were men (343 [73.9%]). With regard to race and ethnicity, 64 patients (13.8%) self-identified as non-Hispanic Black, 183 (39.4%) as Hispanic, and 185 as non-Hispanic White (39.9%). Most patients (396 [85.3%]) had Medicaid insurance, and more than half (262 [57.8%]) had unstable housing. Self-reported fentanyl use (242 [52.2%]) and a comorbid mental health condition (328 [71.5%]) were common. Interest in buprenorphine treatment was high: 398 patients (85.8%) received buprenorphine treatment; 269 (58.0%) were administered buprenorphine in the ED and 339 (73.1%) were prescribed buprenorphine. With regard to OUD treatment engagement at 30 days after the ED visit, 198 participants (49.7%) who received ED buprenorphine treatment remained engaged compared with 15 participants (22.7%) who did not receive ED buprenorphine treatment. An association of ED buprenorphine treatment with subsequent OUD treatment engagement at 30 days was observed (adjusted risk ratio, 1.97 [95% CI, 1.27-3.07]). Conclusions and Relevance: The findings of this cohort study suggest that among patients with OUD presenting to EDs implementing low-threshold access to medications for OUD, buprenorphine treatment was associated with a substantially higher likelihood of follow-up treatment engagement 1 month later. Future research should investigate techniques to optimize both the uptake and effectiveness of buprenorphine initiation in low-threshold settings such as the ED.


Asunto(s)
Buprenorfina , Etnicidad , Estados Unidos , Masculino , Humanos , Adolescente , Adulto , Femenino , Estudios de Cohortes , Estudios Prospectivos , Buprenorfina/uso terapéutico , Servicio de Urgencia en Hospital
6.
J Subst Use Addict Treat ; 157: 209228, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37981239

RESUMEN

INTRODUCTION: Methamphetamine use is highly prevalent among men who have sex with men (MSM), but knowledge of the long-term dynamics, and how they are affected by substance use treatment, is limited. This study aimed to describe trajectories of methamphetamine use among MSM, and to evaluate the impact of treatment for any kind of substance use on frequency of methamphetamine use. METHODS: This analysis used data from a cohort of MSM in Los Angeles, CA, who participated in semi-annual study visits from 2014 to 2022. The study characterized trajectories of methamphetamine use using a continuous time multistate Markov model with three states. States were defined using self-reported frequency of methamphetamine use in the past six months: frequent (daily), occasional (weekly or less), and never. The model estimated the association between receiving treatment for any kind of substance use and changes in state of frequency of methamphetamine use. RESULTS: This analysis included 2348 study visits among 285 individuals who were followed-up for an average of 4.4 years. Among participants who were in the frequent use state, 65 % (n = 26) of those who were receiving any kind of substance use treatment at a study visit had reduced their methamphetamine use at their next visit, compared to 33 % (n = 95) of those who were not receiving treatment. Controlling for age, race/ethnicity, and HIV-status, those who reported receiving current treatment for substance use were more likely to transition from occasional to no use (HR: 1.63, 95 % CI: 1.10-2.42) and frequent to occasional use (HR: 4.25, 95 % CI: 2.11-8.59) in comparison to those who did not report receiving current treatment for substance use. CONCLUSIONS: Findings from this dynamic modeling study provide a new method for assessing longitudinal methamphetamine use outcomes and add important evidence outside of clinical trials that substance use treatment may reduce methamphetamine use.


Asunto(s)
Metanfetamina , Minorías Sexuales y de Género , Trastornos Relacionados con Sustancias , Masculino , Humanos , Homosexualidad Masculina , Los Angeles/epidemiología , Trastornos Relacionados con Sustancias/epidemiología
7.
Am J Prev Med ; 65(1): 12-18, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37074258

RESUMEN

INTRODUCTION: Novel strategies are needed to address barriers to COVID-19 vaccination among people experiencing homelessness (PEH), a population that faces increased COVID-19 risk. Although growing evidence suggests that financial incentives for vaccination are acceptable to PEH, their impact on uptake is unknown. This study aimed to assess whether offering $50 gift cards was associated with the uptake of the first doses of COVID-19 vaccine among PEH in Los Angeles County. METHODS: Vaccination clinics began on March 15, 2021; the financial incentive program was implemented from September 26, 2021 to April 30, 2022. Interrupted time-series analysis with quasi-Poisson regression was used to evaluate the level and slope change in the number of weekly first doses administered. Time-varying confounders included the weekly number of clinics and the weekly number of new cases. Demographic characteristics were compared for PEH vaccinated before and after the implementation of the incentive program using chi-square tests. RESULTS: Offering financial incentives was associated with the administration of 2.5 times (95% CI=1.8, 3.1) more first doses than would have been expected without the program. Level (-0.184, 95% CI= -1.166, -0.467) and slope change (0.042, 95% CI=0.031, 0.053) were observed. Individuals who were unsheltered, aged <55 years, and identified as Black or African American accounted for a higher percentage of those vaccinated during the post-intervention period than during the pre-intervention period. CONCLUSIONS: Financial incentives may be an effective tool for increasing vaccine uptake among PEH, but important ethical considerations must be made to avoid coercion of vulnerable populations.


Asunto(s)
COVID-19 , Personas con Mala Vivienda , Vacunas , Humanos , Vacunas contra la COVID-19 , Motivación , COVID-19/prevención & control
8.
JMIR Res Protoc ; 12: e41831, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36951909

RESUMEN

BACKGROUND: Sexual dysfunction represents a critical aspect of quality of life for adolescent and young adult cancer survivors. Studies have consistently documented that adolescents and young adults report greater psychological and physical morbidity than older survivors and healthy peers, including elevated rates of sexual dysfunction, often accompanied by lower satisfaction with sex life and delays in meeting sexual milestones. Moreover, sexual dysfunction, body image concerns, and fertility status affect their confidence in being both physically and emotionally intimate. Despite this evidence, limited research has investigated the influence of psychosocial and interpersonal factors on sexual health outcomes reported by this group. This constitutes a significant gap in the provision of comprehensive sexual health care for adolescent- and young adult-onset cancer survivors, especially since greater emphasis has been recently placed on the biopsychosocial model of sexuality and dyadic approaches to intervention and treatment. In comparison to other cancer types, the incidence of colorectal cancer (CRC) has been increasing at an alarming rate for the adolescent and young adult group. Patients with early-onset CRC experience elevated rates of sexual dysfunction, psychological distress, and social and physical burden, often resulting from issues with bowel control, incontinence, and body image. OBJECTIVE: This study uses an explanatory sequential mixed methods approach to (1) characterize sexual function, sexual distress, dyadic coping, infertility-related distress, relationship and mental health outcomes of adolescent and young adult CRC survivors within the first 5 years post diagnosis and their partners; (2) examine the reciprocal influence of sexual function and dyadic coping behaviors on sexual distress; and (3) identify interpersonal or couple characteristics associated with coping with sexual dysfunction and its associated distress. METHODS: Participating couples (n=60) will complete a quantitative web-based survey investigating sexual function, sexual distress, dyadic coping, infertility-related distress, emotional functioning, relationship satisfaction, and body image (cancer survivors only). A subset of 20 couples will participate in an in-depth dyadic interview with 2 members of the research team to further explore couple-based strategies implemented to cope with cancer-related sexual dysfunction and distress. RESULTS: The study received institutional review board approval. Recruitment and enrollment of couples began in July 2022. CONCLUSIONS: Results will provide a deeper understanding of the challenges couples experience as they navigate sexual intimacy after CRC treatment by highlighting the role of interpersonal processes. These findings will inform a dyadic intervention for young couples at risk of greater sexual distress in the aftermath of CRC. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41831.

9.
Am J Public Health ; 113(2): 170-174, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36455191

RESUMEN

People experiencing homelessness (PEH) have been disproportionately affected by COVID-19, yet their vaccination coverage is lower than is that of the general population. We implemented a COVID-19 vaccination program that used evidence-based and culturally tailored approaches to promote vaccine uptake and equity for PEH in Los Angeles County, California. From February 2021 through February 2022, 33 977 doses of vaccine were administered at 2658 clinics, and 9275 PEH were fully vaccinated. This program may serve as a model for future service delivery in vulnerable populations. (Am J Public Health. 2023;113(2):170-174. https://doi.org/10.2105/AJPH.2022.307147).


Asunto(s)
COVID-19 , Personas con Mala Vivienda , Vacunas , Humanos , Vacunas contra la COVID-19 , Los Angeles/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación
10.
J Infect Dis ; 226(Suppl 3): S346-S352, 2022 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-36208168

RESUMEN

BACKGROUND: This study aimed to evaluate the feasibility and acceptability of engaging unhoused peer ambassadors (PAs) in coronavirus disease 2019 (COVID-19) vaccination efforts to reach people experiencing unsheltered homelessness in Los Angeles County. METHODS: From August to December 2021, vaccinated PAs aged ≥18 years who could provide informed consent were recruited during vaccination events for same-day participation. Events were held at encampments, service providers (eg, housing agencies, food lines, and mobile showers), and roving locations around Los Angeles. PAs were asked to join outreach alongside community health workers and shared their experience getting vaccinated, receiving a $25 gift card for each hour they participated. Postevent surveys evaluated how many PAs enrolled and how long they participated. In October 2021, we added a preliminary effectiveness evaluation of how many additional vaccinations were attributable to PAs. Staff who enrolled the PAs estimated the number of additional people vaccinated because of talking with the PA. RESULTS: A total of 117 PAs were enrolled at 103 events, participating for an average of 2 hours. At events with the effectiveness evaluation, 197 additional people were vaccinated over 167 PA hours ($21.19 gift card cost per additional person vaccinated), accounting for >25% of all vaccines given at these events. DISCUSSION: Recruiting same-day unhoused PAs is a feasible, acceptable, and preliminarily effective technique to increase COVID-19 vaccination in unsheltered settings. The findings can inform delivery of other health services for people experiencing homelessness.


Asunto(s)
COVID-19 , Personas con Mala Vivienda , Vacunas , Adolescente , Adulto , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios de Factibilidad , Humanos , Los Angeles/epidemiología , Vacunación
11.
J Urban Health ; 99(3): 594-602, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35639229

RESUMEN

Unhoused people have higher COVID-19 mortality and lower vaccine uptake than housed community members. Understanding vaccine hesitancy among unhoused people is key for developing programs that address their unique needs. A three-round, rapid, field-based survey was conducted to describe attitudes toward COVID-19 vaccination. Round 1 assessed vaccine brand preference, round 2 assessed intention to accept a financial incentive for vaccination, and round 3 measured vaccine uptake and assessed reasons for vaccine readiness during implementation of a financial incentive program. A total of 5177 individuals were approached at COVID-19 vaccination events for unhoused people in Los Angeles County from May through November 2021. Analyses included 4949 individuals: 3636 (73.5%) unsheltered and 1313 (26.5%) sheltered. Per self-report, 2008 (40.6%) were already vaccinated, 1732 (35%) wanted to get vaccinated, 359 (7.3%) were not yet ready, and 850 (17.2%) did not want to get vaccinated. Brand preference was evenly split among participants (Moderna 31.0%, J&J 35.5%, either 33.5%, p = 0.74). Interest in a financial incentive differed between those who were not yet ready and those who did not want to get vaccinated (43.2% vs. 16.2%, p < 0.01). After implementing a financial incentive program, 97.4% of participants who indicated interest in vaccination were vaccinated that day; the financial incentive was the most cited reason for vaccine readiness (n = 731, 56%). This study demonstrated the utility of an iterative, field-based assessment for program implementation during the rapidly evolving pandemic. Personal engagement, a variety of brand choices, and financial incentives could be important for improving vaccine uptake among unhoused people.


Asunto(s)
COVID-19 , Personas con Mala Vivienda , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Los Angeles , Motivación , Vacunación
12.
Am Econ Rev ; 112(2): 494-533, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35529584

RESUMEN

This paper develops a satellite account for the US health sector and measures productivity growth in health care for the elderly population between 1999 and 2012. We measure the change in medical spending and health outcomes for a comprehensive set of 80 conditions. Medical care has positive productivity growth over the time period, with aggregate productivity growth of 1.5% per year. However, there is significant heterogeneity in productivity growth. Care for cardiovascular disease has had very high productivity growth. In contrast, care for people with musculoskeletal conditions has been costly but has not led to improved outcomes.

13.
J Gen Intern Med ; 37(8): 2026-2032, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35411533

RESUMEN

BACKGROUND: COVID-19 vaccination is a priority for people experiencing homelessness. However, there are barriers to vaccine access driven in part by mistrust towards clinicians and healthcare. Community health workers (CHWs) and Peer Ambassadors (PAs) may be able to overcome mistrust in COVID-19 vaccine outreach. An unhoused PA program for COVID-19 vaccine outreach by CHWs was implemented in Los Angeles using a participatory academic-community partnership. OBJECTIVE: The purpose of this study was to evaluate CHW perspectives on an unhoused PA COVID-19 vaccine outreach program in Los Angeles. DESIGN: This study used a participatory community conference and qualitative focus groups to understand CHW perspectives on the PA program. The one-day conference was held in November 2021. PARTICIPANTS: Of the 42 conference participants, 19 CHWs participated in focus groups for two-way knowledge exchange between CHWs and researchers. APPROACH: Four focus groups were held during the conference, with 4-6 CHWs per group. Each group had a facilitator and two notetakers. Focus group notes were then analyzed using content analysis to derive categories of findings. CHWs reviewed the qualitative analysis to ensure that findings represented their experiences with the PA program. KEY RESULTS: The five categories of findings from focus groups were as follows: (1) PAs were effective liaisons to their peers to promote COVID-19 vaccines; (2) CHWs recognized the importance of establishing genuine trust and equitable working relationships within CHW/PA teams; (3) there were tradeoffs of integrating unhoused PAs into the existing CHW workflow; (4) CHWs had initial misgivings about the research process; and (5) there were lingering questions about the ethics of "exploiting" the invaluable trust unhoused PAs have with unhoused communities. CONCLUSIONS: CHWs were in a unique position to empower unhoused PAs to take a leadership role in reaching their peers with COVID-19 vaccines and advocate for long-term employment and housing needs.


Asunto(s)
COVID-19 , Personas con Mala Vivienda , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Agentes Comunitarios de Salud , Vivienda , Humanos , Investigación Cualitativa
14.
J Urban Health ; 99(2): 305-315, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35235134

RESUMEN

The objective was to examine the impact of the COVID-19 pandemic on mental health care, cannabis use, and behaviors that increase the risk of STIs among men living with or at high risk for HIV. Data were from mSTUDY - a cohort of men who have sex with men in Los Angeles, California. Participants who were 18 to 45 years and a half were HIV-positive. mSTUDY started in 2014, and at baseline and semiannual visits, information was collected on substance use, mental health, and sexual behaviors. We analyzed data from 737 study visits from March 2020 through August 2021. Compared to visits prior to the COVID-19 pandemic, there were significant increases in depressive symptomatology (CES-D ≥ 16) and anxiety (GAD-7 ≥ 10). These increases were highest immediately following the start of the pandemic and reverted to pre-pandemic levels within 17 months. Interruptions in mental health care were associated with higher substance use (especially cannabis) for managing anxiety/depression related to the pandemic (50% vs. 31%; p-value < .01). Cannabis use for managing pandemic-related anxiety/depression was higher among those reporting changes in sexual activity (53% vs. 36%; p-value = 0.01) and was independently associated with having more than one sex partner in the prior 2 weeks (adjusted OR = 1.5; 95% CI 1.0-2.4). Our findings indicate increases in substance use, in particular cannabis, linked directly to experiences resulting from the COVID-19 pandemic and the associated interruptions in mental health care. Strategies that deliver services without direct client contact are essential for populations at high risk for negative sexual and mental health outcomes.


Asunto(s)
COVID-19 , Cannabis , Infecciones por VIH , Minorías Sexuales y de Género , Trastornos Relacionados con Sustancias , Ansiedad/epidemiología , COVID-19/epidemiología , Depresión/epidemiología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Homosexualidad Masculina/psicología , Humanos , Los Angeles/epidemiología , Masculino , Salud Mental , Pandemias
15.
Inverse Probl ; 38(5)2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-37727531

RESUMEN

Transdermal alcohol biosensors that do not require active participation of the subject and yield near continuous measurements have the potential to significantly enhance the data collection abilities of alcohol researchers and clinicians who currently rely exclusively on breathalyzers and drinking diaries. Making these devices accessible and practical requires that transdermal alcohol concentration (TAC) be accurately and consistently transformable into the well-accepted measures of intoxication, blood/breath alcohol concentration (BAC/BrAC). A novel approach to estimating BrAC from TAC based on covariate-dependent physics-informed hidden Markov models with two emissions is developed. The hidden Markov chain serves as a forward full-body alcohol model with BrAC and TAC, the two emissions, assumed to be described by a bivariate normal which depends on the hidden Markovian states and person-level and session-level covariates via built-in regression models. An innovative extension of hidden Markov modeling is developed wherein the hidden Markov model framework is regularized by a first-principles PDE model to yield a hybrid that combines prior knowledge of the physics of transdermal ethanol transport with data-based learning. Training, or inverse filtering, is effected via the Baum-Welch algorithm and 256 sets of BrAC and TAC signals and covariate measurements collected in the laboratory. Forward filtering of TAC to obtain estimated BrAC is achieved via a new physics-informed regularized Viterbi algorithm which determines the most likely path through the hidden Markov chain using TAC alone. The Markovian states are decoded and used to yield estimates of BrAC and to quantify the uncertainty in the estimates. Numerical studies are presented and discussed. Overall good agreement between BrAC data and estimates was observed with a median relative peak error of 22% and a median relative area under the curve error of 25% on the test set. We also demonstrate that the physics-informed Viterbi algorithm eliminates non-physical artifacts in the BrAC estimates.

16.
PLoS One ; 15(8): e0237082, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32776954

RESUMEN

To understand the cost burden of medical care it is essential to partition medical spending into conditions. Two broad strategies have been used to measure disease-specific spending. The first attributes each medical claim to the condition that physicians list as its cause. The second decomposes total spending for a person over a year to their cumulative set of health conditions. Traditionally, this has been done through regression analysis. This paper has two contributions. First, we develop a new cost attribution method to attribute spending to conditions using a more flexible attribution approach, based on propensity score analysis. Second, we compare the propensity score approach to the claims-based approach and the regression approach in a common set of beneficiaries age 65 and older in the 2009 Medicare Current Beneficiary Survey. Our estimates show that the three methods have important differences in spending allocation and that the propensity score model likely offers the best theoretical and empirical combination.


Asunto(s)
Costo de Enfermedad , Costos y Análisis de Costo/métodos , Anciano , Femenino , Humanos , Revisión de Utilización de Seguros/estadística & datos numéricos , Masculino , Medicare/estadística & datos numéricos , Puntaje de Propensión , Análisis de Regresión , Estados Unidos
17.
Cornea ; 39(8): 1062-1065, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32118669

RESUMEN

PURPOSE: The trifolded, endothelium-in approach to Descemet membrane endothelial keratoplasty (DMEK) facilitates tissue insertion into the anterior chamber. We hypothesized that preloading the trifolded donor grafts in a cartridge for 48 hours before insertion would induce biomechanical changes that decrease their scrolling tendency compared with those loaded immediately before insertion. METHODS: Ten Descemet membrane donor grafts, peeled and cut to 8.0 mm, were prepared by a single eye bank technician. Each graft was trifolded and pulled into a DMEK cartridge and stored for 48 hours. They were then pulled with microforceps into a petri dish filled with balanced salt solution. A video was recorded of the graft becoming a scroll over a 2-minute period. Each graft, serving as its own control, was then trifolded, pulled into the cartridge, and the process repeated. Images from 1, 5, 10, 60, and 120 seconds were extracted from video recording of the procedures. Scroll width was analyzed by graders masked to group assignment. A paired t test was used to determine differences in scroll width at each time point between the 48-hour and instant trifolding conditions. RESULTS: All grafts scrolled after removal from the cartridge into balanced salt solution. We measured a significant difference at all time points 1 through 120 seconds (4.02 preloaded vs. 2.91-mm instant trifold, P = 0.035). CONCLUSIONS: Preloading DMEK grafts in a trifolded configuration for 48 hours reduces the scrolling tendency of Descemet membrane for at least 2 minutes.


Asunto(s)
Pérdida de Celulas Endoteliales de la Córnea/cirugía , Lámina Limitante Posterior/cirugía , Queratoplastia Endotelial de la Lámina Limitante Posterior/métodos , Bancos de Ojos , Donantes de Tejidos , Recolección de Tejidos y Órganos/métodos , Agudeza Visual , Anciano , Pérdida de Celulas Endoteliales de la Córnea/diagnóstico , Lámina Limitante Posterior/citología , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
J Surv Stat Methodol ; 9(3): 598-625, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34337089

RESUMEN

Information about an extensive set of health conditions on a well-defined sample of subjects is essential for assessing population health, gauging the impact of various policies, modeling costs, and studying health disparities. Unfortunately, there is no single data source that provides accurate information about health conditions. We combine information from several administrative and survey data sets to obtain model-based dummy variables for 107 health conditions (diseases, preventive measures, and screening for diseases) for elderly (age 65 and older) subjects in the Medicare Current Beneficiary Survey (MCBS) over the fourteen-year period, 1999-2012. The MCBS has prevalence of diseases assessed based on Medicare claims and provides detailed information on all health conditions but is prone to underestimation bias. The National Health and Nutrition Examination Survey (NHANES), on the other hand, collects self-reports and physical/laboratory measures only for a subset of the 107 health conditions. Neither source provides complete information, but we use them together to derive model-based corrected dummy variables in MCBS for the full range of existing health conditions using a missing data and measurement error model framework. We create multiply imputed dummy variables and use them to construct the prevalence rate and trend estimates. The broader goal, however, is to use these corrected or modeled dummy variables for a multitude of policy analysis, cost modeling, and analysis of other relationships either using them as predictors or as outcome variables.

19.
Prog Community Health Partnersh ; 13(5): 61-69, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31378736

RESUMEN

BACKGROUND: Women with disabilities are an unrecognized cancer disparities population who experience well-documented barriers to breast cancer screening. There is a critical need for targeted, community-directed programing to address these disparities. OBJECTIVES: To describe the trajectory of a long-term community-academic partnership aimed at understanding and addressing breast cancer screening disparities among women with disabilities. METHODS: Phase 1 was a thematic qualitative focus group study (n = 40) with women with physical disabilities to understand their breast cancer screening experiences. Phase 2 was the application of an equity-focused knowledge translation (KT) process that brought together breast cancer survivors with disabilities and graduate applied health students in KT collaboratives to create innovative, evidence-informed knowledge products. Phase 3 included the development of community-based programming. RESULTS: In phase 1, women with disabilities identified provider and patient barriers to breast cancer screening, including a lack of provider knowledge and respect for individuals with disabilities, lack of accessibility, the history of stigma and mistreatment within the health care setting, and treatment fatigue. In phase 2, KT collaboratives created the short film "ScreenABLE" to educate providers and community members about physical and attitudinal barriers to cancer screening. In phase 3, community, academic, and clinical partners collaborated to create ScreenABLE Saturday, a wellness fair and free accessible mammograms, for women with disabilities with programming developed to directly address cancer screening barriers identified from the phase 1 research. CONCLUSIONS: Long-term sustained partnerships between academic, disability, and clinical partners are needed to address the complex issues that perpetuate breast cancer screening disparities among women with disabilities.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Personas con Discapacidad , Detección Precoz del Cáncer/métodos , Educación en Salud/organización & administración , Salud de la Mujer , Relaciones Comunidad-Institución , Femenino , Accesibilidad a los Servicios de Salud , Disparidades en el Estado de Salud , Humanos , Mamografía , Factores Socioeconómicos , Universidades/organización & administración
20.
Health Aff (Millwood) ; 38(2): 222-229, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30715965

RESUMEN

We examined trends in per capita spending for Medicare beneficiaries ages sixty-five and older in the United States in the period 1999-2012 to determine why spending growth has been declining since around 2005. Decomposing spending by condition, we found that half of the spending slowdown was attributable to slower growth in spending for cardiovascular diseases. Spending growth also slowed for dementia, renal and genitourinary diseases, and aftercare for people with acute illnesses. Using estimates from the medical literature of the impact of pharmaceuticals on acute disease, we found that roughly half of the reduction in major cardiovascular events was attributable to medications controlling cardiovascular risk factors. Despite this substantial cost-saving improvement in cardiovascular health, additional opportunities remain to lower spending through disease prevention and control.


Asunto(s)
Atención a la Salud/economía , Gastos en Salud/tendencias , Medicare/estadística & datos numéricos , Anciano , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedad Crónica , Humanos , Estados Unidos
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