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1.
Risk Anal ; 43(9): 1745-1762, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36509545

RESUMO

We estimate the country-level risk of extreme wildfires defined by burned area (BA) for Mediterranean Europe and carry out a cross-country comparison. To this end, we avail of the European Forest Fire Information System (EFFIS) geospatial data from 2006 to 2019 to perform an extreme value analysis. More specifically, we apply a point process characterization of wildfire extremes using maximum likelihood estimation. By modeling covariates, we also evaluate potential trends and correlations with commonly known factors that drive or affect wildfire occurrence, such as the Fire Weather Index as a proxy for meteorological conditions, population density, land cover type, and seasonality. We find that the highest risk of extreme wildfires is in Portugal (PT), followed by Greece (GR), Spain (ES), and Italy (IT) with a 10-year BA return level of 50'338 ha, 33'242 ha, 25'165 ha, and 8'966 ha, respectively. Coupling our results with existing estimates of the monetary impact of large wildfires suggests expected losses of 162-439 million € (PT), 81-219 million € (ES), 41-290 million € (GR), and 18-78 million € (IT) for such 10-year return period events. SUMMARY: We model the risk of extreme wildfires for Italy, Greece, Portugal, and Spain in form of burned area return levels, compare them, and estimate expected losses.

2.
J Natl Compr Canc Netw ; 19(7): 829-838, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33662936

RESUMO

BACKGROUND: It is standard of care and an accreditation requirement to screen for and address distress and psychosocial needs in patients with cancer. This study assessed the availability of mental health (MH) and chemical dependency (CD) services at US cancer centers. METHODS: The 2017-2018 American Hospital Association (AHA) survey, Area Health Resource File, and Centers for Medicare & Medicaid Services Hospital Compare databases were used to assess availability of services and associations with hospital-level and health services area (HSA)-level characteristics. RESULTS: Of 1,144 cancer centers surveyed, 85.4% offered MH services and 45.5% offered CD services; only 44.1% provided both. Factors associated with increased adjusted odds of offering MH services were teaching status (odds ratio [OR], 1.76; 95% CI, 1.18-2.62), being a member of a hospital system (OR, 2.00; 95% CI, 1.31-3.07), and having more beds (OR, 1.04 per 10-bed increase; 95% CI, 1.02-1.05). Higher population estimate (OR, 0.98; 95% CI, 0.97-0.99), higher percentage uninsured (OR, 0.90; 95% CI, 0.86-0.95), and higher Mental Health Professional Shortage Area level in the HSA (OR, 0.99; 95% CI, 0.98-1.00) were associated with decreased odds of offering MH services. Government-run (OR, 2.85; 95% CI, 1.30-6.22) and nonprofit centers (OR, 3.48; 95% CI, 1.78-6.79) showed increased odds of offering CD services compared with for-profit centers. Those that were members of hospital systems (OR, 1.61; 95% CI, 1.14-2.29) and had more beds (OR, 1.02; 95% CI, 1.01-1.03) also showed increased odds of offering these services. A higher percentage of uninsured patients in the HSA (OR, 0.92; 95% CI, 0.88-0.97) was associated with decreased odds of offering CD services. CONCLUSIONS: Patients' ability to pay, membership in a hospital system, and organization size may be drivers of decisions to co-locate services within cancer centers. Larger organizations may be better able to financially support offering these services despite poor reimbursement rates. Innovations in specialty payment models highlight opportunities to drive transformation in delivering MH and CD services for high-need patients with cancer.


Assuntos
Saúde Mental , Neoplasias , Idoso , Atenção à Saúde , Pessoal de Saúde , Hospitais , Humanos , Medicare , Neoplasias/epidemiologia , Neoplasias/terapia , Estados Unidos/epidemiologia
3.
J Urol ; 198(1): 92-99, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28153509

RESUMO

PURPOSE: Robot-assisted radical prostatectomy has undergone rapid dissemination driven in part by market forces to become the most frequently used surgical approach in the management of prostate cancer. Accordingly, a critical analysis of its volume-outcome relationship has important health policy implications. Therefore, we evaluated the association of hospital robot-assisted radical prostatectomy volume with perioperative outcomes, and examined the distribution of hospital procedure volume to contextualize the volume-outcome relationship. MATERIALS AND METHODS: We identified 140,671 men who underwent robot-assisted radical prostatectomy from 2009 to 2011 in NIS (Nationwide Inpatient Sample). The associations of hospital volume with perioperative outcomes and total hospital costs were evaluated using multivariable logistic regression and generalized linear models. RESULTS: In 2011, 70% of hospitals averaged 1 robot-assisted radical prostatectomy per week or less, accounting for 28% of surgeries. Compared to patients treated at the lowest quartile hospitals, those treated at the highest quartile hospitals had significantly lower rates of intraoperative complications (0.6% vs 1.4%), postoperative complications (4.8% vs 13.9%), perioperative blood transfusion (1.5% vs 4.0%), prolonged hospitalization (4.3% vs 13.8%) and mean total hospital costs ($12,647 vs $15,394, all ptrend <0.001). When modeled as a nonlinear continuous variable, increasing hospital volume was independently associated with improved rates of each perioperative end point up to approximately 100 robot-assisted radical prostatectomies per year, beyond which there appeared to be marginal improvement. CONCLUSIONS: Increasing hospital robot-assisted radical prostatectomy volume was associated with improved perioperative outcomes up to approximately 100 surgeries per year, beyond which there appeared to be marginal improvement. A substantial proportion of these procedures is performed at low volume hospitals.


Assuntos
Hospitais/estatística & dados numéricos , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Idoso , Economia Hospitalar , Custos Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/economia , Neoplasias da Próstata/economia , Procedimentos Cirúrgicos Robóticos/economia , Resultado do Tratamento , Estados Unidos/epidemiologia
4.
Cancer Immunol Immunother ; 64(11): 1487-94, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26289091

RESUMO

The efficacy of immunotherapy in cancer patients is influenced by differences in their immune status. An evaluation of immunocompetence before therapy may help to predict therapeutic success and guide the selection of appropriate regimens. We assessed the preexisting cellular immunity against prostate-specific antigen (PSA) in untreated prostate cancer patients and healthy controls through measurement of the phenotype and function of CD8(+) T cells. Our data show that the majority of healthy men possess functional PSA-specific CD8(+) T cells in contrast to cancer patients, where <50 % showed a CD8(+) T cell response. PSA146-154-specific CD8(+) T cells of these patients had a higher expression of the activation marker CD38 and the exhaustion marker Tim-3, indicating that PSA-specific cells are exhausted. The heterogeneity of the CD8(+) T cell response against PSA in prostate cancer patients may influence their response to therapy and is a factor to be taken into account while designing and selecting treatment regimens.


Assuntos
ADP-Ribosil Ciclase 1/análise , Linfócitos T CD8-Positivos/imunologia , Glicoproteínas de Membrana/análise , Proteínas de Membrana/análise , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/imunologia , Idoso , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/química , Neoplasias da Próstata/terapia
5.
Blood ; 122(3): 405-12, 2013 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-23719298

RESUMO

CD8(+) T cells play an essential role in immunity against intracellular pathogens, with cytotoxicity being considered their major effector mechanism. However, we here demonstrate that a major part of central and effector memory CD8(+) T cells expresses CD40L, one key molecule for CD4(+) T-cell-mediated help. CD40L(+) CD8(+) T cells are detectable among human antigen-specific immune responses, including pathogens such as influenza and yellow fever virus. CD40L(+) CD8(+) T cells display potent helper functions in vitro and in vivo, such as activation of antigen-presenting cells, and exhibit a cytokine expression signature similar to CD4(+) T cells and unrelated to cytotoxic CD8(+) T cells. The broad occurrence of CD40L(+) CD8(+) T cells in cellular immunity implicates that helper functions are not only executed by major histocompatibility complex (MHC) class II-restricted CD4(+) helper T cells but are also a common feature of MHC class I-restricted CD8(+) T cell responses. Due to their versatile functional capacities, human CD40L(+) CD8(+) T cells are promising candidate cells for immune therapies, particularly when CD4(+) T-cell help or pathogen-associated molecular pattern signals are limited.


Assuntos
Ligante de CD40/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Citocinas/metabolismo , Citotoxicidade Imunológica , Epitopos/imunologia , Humanos , Memória Imunológica , Imunofenotipagem , Camundongos , Camundongos Endogâmicos C57BL
6.
J Rural Health ; 40(3): 485-490, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38693658

RESUMO

PURPOSE: By assessing longitudinal associations between COVID-19 census burdens and hospital characteristics, such as bed size and critical access status, we can explore whether pandemic-era hospital quality benchmarking requires risk-adjustment or stratification for hospital-level characteristics. METHODS: We used hospital-level data from the US Department of Health and Human Services including weekly total hospital and COVID-19 censuses from August 2020 to August 2023 and the 2021 American Hospital Association survey. We calculated weekly percentages of total adult hospital beds containing COVID-19 patients. We then calculated the number of weeks each hospital spent at Extreme (≥20% of beds occupied by COVID-19 patients), High (10%-19%), Moderate (5%-9%), and Low (<5%) COVID-19 stress. We assessed longitudinal hospital-level COVID-19 stress, stratified by 15 hospital characteristics including joint commission accreditation, bed size, teaching status, critical access hospital status, and core-based statistical area (CBSA) rurality. FINDINGS: Among n = 2582 US hospitals, the median(IQR) weekly percentage of hospital capacity occupied by COVID-19 patients was 6.7%(3.6%-13.0%). 80,268/213,383 (38%) hospital-weeks experienced Low COVID-19 census stress, 28% Moderate stress, 22% High stress, and 12% Extreme stress. COVID-19 census burdens were similar across most hospital characteristics, but were significantly greater for critical access hospitals. CONCLUSIONS: US hospitals experienced similar COVID-19 census burdens across multiple institutional characteristics. Evidence-based inclusion of pandemic-era outcomes in hospital quality reporting may not require significant hospital-level risk-adjustment or stratification, with the exception of rural or critical access hospitals, which experienced differentially greater COVID-19 census burdens and may merit hospital-level risk-adjustment considerations.


Assuntos
COVID-19 , Censos , Hospitais Rurais , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Estados Unidos/epidemiologia , Hospitais Rurais/estatística & dados numéricos , Hospitais Rurais/normas , Pandemias , Número de Leitos em Hospital/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Qualidade da Assistência à Saúde/normas , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/normas , Benchmarking
7.
Artigo em Inglês | MEDLINE | ID: mdl-36505980

RESUMO

Objective: To develop a simple, interpretable value metric (VM) to assess the value of care of hospitals for specific procedures or conditions by operationalizing the value equation: Value = Quality/Cost. Patients and Methods: The present study was conducted on a retrospective cohort from 2015 to 2018 drawn from the 100% US sample of Medicare inpatient claims. The final cohort comprised 637,341 consecutive inpatient encounters with a cancer-related Medicare Severity-Diagnosis Related Grouping and 13,307 consecutive inpatient encounters with the International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision procedure code for partial or total gastrectomy. Claims-based demographic and clinical variables were used for risk adjustment, including age, sex, year, dual eligibility, reason for Medicare entitlement, and binary indicators for each of the Elixhauser comorbidities used in the Elixhauser mortality index. Risk-adjusted 30-day mortality and risk-adjusted encounter-specific costs were combined to form the VM, which was calculated as follows: number needed to treat = 1/(Mortalitynational - Mortalityhospital), and VM = number needed to treat × risk-adjusted cost per encounter. Results: Among hospitals with better-than-average 30-day cancer mortality rates, the cost to prevent 1 excess 30-day mortality for an inpatient cancer encounter ranged from $71,000 (best value) to $1.4 billion (worst value), with a median value of $543,000. Among hospitals with better-than-average 30-day gastrectomy mortality rates, the cost to prevent 1 excess 30-day mortality for an inpatient gastrectomy encounter ranged from $710,000 (best value) to $95 million (worst value), with a median value of $1.8 million. Conclusion: This simple VM may have utility for interpretable reporting of hospitals' value of care for specific conditions or procedures. We found substantial inter- and intrahospital variation in value when defined as the costs of preventing 1 excess cancer or gastrectomy mortality compared with the national average, implying that hospitals with similar quality of care may differ widely in the value of that care.

8.
Telemed Rep ; 4(1): 100-108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283856

RESUMO

Background: A steep increase in the use of delivery of virtual care occurred during the COVID-19 public health emergency (PHE) because of easing up of payment and coverage restrictions. With the end of PHE, there is uncertainty regarding continued coverage and payment parity for the virtual care services. Methods: On November 8, 2022, The Mass General Brigham held the Third Annual Virtual Care Symposium: Demystifying Clinical Appropriateness in Virtual Care and What's Ahead for Pay Parity. Results: In one of the panels, experts from Mayo Clinic led by Dr. Bart Demaerschalk discussed key issues related to "Payment and Coverage Parity for Virtual Care and In-Person Care: How Do We Get There?" The discussions centered around current policies around payment and coverage parity for virtual care, including state licensure laws for virtual care delivery and the current evidence base regarding outcomes, costs, and resource utilization associated with virtual care. The panel discussion ended with highlighting next steps targeting policymakers, payers, and industry groups to help strengthen the case for parity. Conclusions: To ensure the continued viability of virtual care delivery, legislators and insurers must address the coverage and payment parity between telehealth and in-person visits. This will require a renewed focus on research on clinical appropriateness, parity, equity and access, and economics of virtual care.

9.
J Bone Joint Surg Am ; 104(Suppl 3): 4-8, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36260036

RESUMO

The availability of large state and federally run administrative health-care databases provides potentially comprehensive population-wide information that can dramatically impact both medical and health-policy decision-making. Specific opportunities and important limitations exist with all administrative databases based on what information is collected and how reliably specific data elements are reported. Access to patient identifiable-level information can be critical for certain long-term outcome studies but can be difficult (although not impossible) due to patient privacy protections, while more easily available de-identified information can provide important insights that may be more than sufficient for some short-term operative or in-hospital outcome questions. The first section of this paper by Sarah K. Meier and Benjamin D. Pollock discusses Medicare and the different data files available to health-care researchers. They describe what is and is not generally available from even the most granular Medicare Standard Analytic Files, and provide an analysis of the strengths and weaknesses of Medicare administrative data as well as the resulting best and inappropriate uses of these data. In the second section, the Nationwide Inpatient Sample and complementary State Inpatient Database programs are reviewed by Steven M. Kurtz and Edmund Lau, with insights into the origins of these programs, the data elements that are recorded relating to the operative procedure and hospital stay, and examples of the types of studies that optimally utilize these data sources. They also detail the limitations of these databases and identify studies that they are not well-suited for, especially those involving linkage or longitudinal studies over time. Both sections provide useful guidance on the best uses and pitfalls related to these important large representative national administrative data sources.


Assuntos
Medicare , Idoso , Humanos , Bases de Dados Factuais , Governo , Pacientes Internados , Estados Unidos
11.
PLoS One ; 16(8): e0248909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34432808

RESUMO

Brain-based deception research began only two decades ago and has since included a wide variety of contexts and response modalities for deception paradigms. Investigations of this sort serve to better our neuroscientific and legal knowledge of the ways in which individuals deceive others. To this end, we conducted activation likelihood estimation (ALE) and meta-analytic connectivity modelling (MACM) using BrainMap software to examine 45 task-based fMRI brain activation studies on deception. An activation likelihood estimation comparing activations during deceptive versus honest behavior revealed 7 significant peak activation clusters (bilateral insula, left superior frontal gyrus, bilateral supramarginal gyrus, and bilateral medial frontal gyrus). Meta-analytic connectivity modelling revealed an interconnected network amongst the 7 regions comprising both unidirectional and bidirectional connections. Together with subsequent behavioral and paradigm decoding, these findings implicate the supramarginal gyrus as a key component for the sociocognitive process of deception.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Enganação , Modelos Neurológicos , Rede Nervosa/fisiologia , Adulto , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/anatomia & histologia , Lobo Parietal/anatomia & histologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia
12.
Front Hum Neurosci ; 15: 587018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613207

RESUMO

Over 100 million Americans suffer from chronic pain (CP), which causes more disability than any other medical condition in the United States at a cost of $560-$635 billion per year (Institute of Medicine, 2011). Opioid analgesics are frequently used to treat CP. However, long term use of opioids can cause brain changes such as opioid-induced hyperalgesia that, over time, increase pain sensation. Also, opioids fail to treat complex psychological factors that worsen pain-related disability, including beliefs about and emotional responses to pain. Cognitive behavioral therapy (CBT) can be efficacious for CP. However, CBT generally does not focus on important factors needed for long-term functional improvement, including attainment of personal goals and the psychological flexibility to choose responses to pain. Acceptance and Commitment Therapy (ACT) has been recognized as an effective, non-pharmacologic treatment for a variety of CP conditions (Gutierrez et al., 2004). However, little is known about the neurologic mechanisms underlying ACT. We conducted an ACT intervention in women (n = 9) with chronic musculoskeletal pain. Functional magnetic resonance imaging (fMRI) data were collected pre- and post-ACT, and changes in functional connectivity (FC) were measured using Network-Based Statistics (NBS). Behavioral outcomes were measured using validated assessments such as the Acceptance and Action Questionnaire (AAQ-II), the Chronic Pain Acceptance Questionnaire (CPAQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and the NIH Toolbox Neuro-QoLTM (Quality of Life in Neurological Disorders) scales. Results suggest that, following the 4-week ACT intervention, participants exhibited reductions in brain activation within and between key networks including self-reflection (default mode, DMN), emotion (salience, SN), and cognitive control (frontal parietal, FPN). These changes in connectivity strength were correlated with changes in behavioral outcomes including decreased depression and pain interference, and increased participation in social roles. This study is one of the first to demonstrate that improved function across the DMN, SN, and FPN may drive the positive outcomes associated with ACT. This study contributes to the emerging evidence supporting the use of neurophysiological indices to characterize treatment effects of alternative and complementary mind-body therapies.

13.
Brain Sci ; 11(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374858

RESUMO

Chronic musculoskeletal pain is a costly and prevalent condition that affects the lives of over 50 million individuals in the United States. Chronic pain leads to functional brain changes in those suffering from the condition. Not only does the primary pain network transform as the condition changes from acute to persistent pain, a state of hyper-connectivity also exists between the default mode, frontoparietal, and salience networks. Graph theory analysis has recently been used to investigate treatment-driven brain network changes. For example, current research suggests that Acceptance and Commitment Therapy (ACT) may reduce the chronic pain associated hyper-connectivity between the default mode, frontoparietal, and salience networks, as well as within the salience network. This study extended previous work by examining the associations between the three networks above and a meta-analytically derived pain network. Results indicate decreased connectivity within the pain network (including left putamen, right insula, left insula, and right thalamus) in addition to triple network connectivity changes after the four-week Acceptance and Commitment Therapy intervention.

14.
Int J Radiat Oncol Biol Phys ; 106(5): 905-911, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32001382

RESUMO

PURPOSE: The proposed Radiation Oncology Alternative Payment Model (RO-APM) released on July 10, 2019, represents a dramatic shift from fee-for-service (FFS) reimbursement in radiation therapy (RT). This study compares historical revenue at Mayo Clinic to the RO-APM and quantifies the effect that disease characteristics may have on reimbursement. METHODS AND MATERIALS: FFS Medicare reimbursements were determined for patients undergoing RT at Mayo Clinic from 2015 to 2016. Disease categories and payment episodes were defined as per the RO-APM. Average RT episode reimbursements were reported for each disease site, except for lymphoma and metastases, and stratified by stage and disease subcategory. Comparisons with RO-APM reimbursements were made via descriptive statistics. RESULTS: A total of 2098 patients were identified, of whom 1866 (89%) were categorized per the RO-APM; 840 (45%) of those were aged >65 years. Breast (33%), head and neck (HN) (14%), and prostate (11%) cancer were most common. RO-APM base rate reimbursements and sensitivity analysis range were lower than historical reimbursement for bladder (-40%), cervical (-34%), lung (-28%), uterine (-26%), colorectal (-24%), upper gastrointestinal (-24%), HN (-23%), pancreatic (-20%), prostate (-16%), central nervous system (-13%), and anal (-10%) and higher for liver (+24%) and breast (+36%). Historical reimbursement varied with stage (stage III vs stage I) for breast (+57%, P < .01), uterine (+53%, P = .01), lung (+50%, P < .01), HN (+24%, P = .01), and prostate (+13%, P = .01). Overall, for patients older than 65 years of age, the RO-APM resulted in a -9% reduction in total RT reimbursement compared with historical FFS (-2%, -15%, and -27% for high, mid, and low adjusted RO-APM rates). CONCLUSIONS: Our findings indicate that the RO-APM will result in significant reductions in reimbursement at our center, particularly for cancers more common in underserved populations. Practices that care for socioeconomically disadvantaged populations may face significant reductions in revenue, which could further reduce access for this vulnerable population.


Assuntos
Neoplasias/patologia , Neoplasias/radioterapia , Radioterapia (Especialidade)/economia , Idoso , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias/economia , Mecanismo de Reembolso
15.
Chembiochem ; 10(1): 166-75, 2009 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-19058273

RESUMO

A systematic comparison has been performed of the morphology and stability of microtubules (MTs) induced by the potent microtubule-stabilizing agents (MSAs) taxol, epothilone B (Epo B), and discodermolide (DDM) under GTP-free conditions. DDM-induced tubulin polymerization occurred significantly faster than that induced by taxol and Epo B. At the same time, tubulin polymers assembled from soluble tubulin by DDM were morphologically distinct (shorter and less ordered) from those induced by either taxol or Epo B, as demonstrated by electron microscopy. Exposure of MSA-induced tubulin polymers to ultrasound revealed the DDM-based polymers to be less stable to this type of physical stress than those formed with either Epo B or taxol. Interestingly, MT assembly in the presence of both DDM and taxol appeared to produce a distinct new type of MT polymer with a mixed morphology between those of DDM- and taxol-induced structures. The observed differences in MT morphology and stability might be related, at least partly, to differences in intramicrotubular tubulin isotype distribution, as DDM showed a different pattern of beta-tubulin isotype usage in the assembly process.


Assuntos
Alcanos/farmacologia , Produtos Biológicos/farmacologia , Carbamatos/farmacologia , Epotilonas/farmacologia , Lactonas/farmacologia , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Paclitaxel/farmacologia , Pironas/farmacologia , Moduladores de Tubulina/farmacologia , Animais , Encéfalo/citologia , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Microscopia Eletrônica , Nefelometria e Turbidimetria , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Suínos , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo
16.
J Neurochem ; 106(6): 2322-36, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18643796

RESUMO

It has been suggested that disturbances in endocannabinoid signaling contribute to the development of depressive illness; however, at present there is insufficient evidence to allow for a full understanding of this role. To further this understanding, we performed an analysis of the endocannabinoid system in an animal model of depression. Male rats exposed to chronic, unpredictable stress (CUS) for 21 days exhibited a reduction in sexual motivation, consistent with the hypothesis that CUS in rats induces depression-like symptoms. We determined the effects of CUS, with or without concurrent treatment with the antidepressant imipramine (10 mg/kg), on CP55940 binding to the cannabinoid CB(1) receptor; whole tissue endocannabinoid content; and fatty acid amide hydrolase (FAAH) activity in the prefrontal cortex, hippocampus, hypothalamus, amygdala, midbrain and ventral striatum. Exposure to CUS resulted in a significant increase in CB(1) receptor binding site density in the prefrontal cortex and a decrease in CB(1) receptor binding site density in the hippocampus, hypothalamus and ventral striatum. Except in the hippocampus, these CUS-induced alterations in CB(1) receptor binding site density were attenuated by concurrent antidepressant treatment. CUS alone produced a significant reduction in N-arachidonylethanolamine (anandamide) content in every brain region examined, which was not reversed by antidepressant treatment. These data suggest that the endocannabinoid system in cortical and subcortical structures is differentially altered in an animal model of depression and that the effects of CUS on CB(1) receptor binding site density are attenuated by antidepressant treatment while those on endocannabinoid content are not.


Assuntos
Antidepressivos/farmacologia , Encéfalo/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Endocanabinoides , Analgésicos/farmacologia , Animais , Antidepressivos Tricíclicos/farmacologia , Ácidos Araquidônicos/metabolismo , Encéfalo/fisiopatologia , Cicloexanóis/farmacologia , Transtorno Depressivo Maior/fisiopatologia , Modelos Animais de Doenças , Imipramina/farmacologia , Masculino , Motivação , Alcamidas Poli-Insaturadas/metabolismo , Ratos , Ratos Long-Evans , Receptor CB1 de Canabinoide/efeitos dos fármacos , Receptor CB1 de Canabinoide/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Sexual Animal/fisiologia , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia
17.
Neuropharmacology ; 54(1): 108-16, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17675104

RESUMO

Endocannabinoid signaling has been implicated in habituation to repeated stress. The hypothesis that repeated exposures to stress alters endocannabinoid signaling in the limbic circuit was tested by restraining male mice for 30 min/day for 1, 7, or 10 days and measuring brain endocannabinoid content. Amygdalar N-arachidonylethanolamine was decreased after 1, 7, and 10 restraint episodes; 2-arachidonylglycerol was increased after the 10th restraint. A similar pattern occurred in the medial prefrontal cortex (mPFC): N-arachidonylethanolamine was decreased after the 7th and 10th restraints and 2-arachidonylglycerol was increased after the 10th restraint. In the ventral striatum, the pattern reversed: N-arachidonylethanolamine was increased after the 10th restraint and 2-arachidonylglycerol was decreased after the 7th restraint. Palmitoylethanolamide contents changed in parallel with N-arachidonylethanolamine in the amygdala and ventral striatum. A single restraint episode did not affect the activity of fatty acid amide hydrolase (FAAH) in any of the brain regions examined. After the 10th restraint, both V(max) and K(m) for N-arachidonylethanolamine were increased in the mPFC; while only the V(max) was increased in the amygdala. On the other hand, the V(max) of FAAH was decreased in ventral striatum after the 10th restraint. After the 10th restraint, the maximum velocity for 2-oleoylglycerol hydrolysis was increased in mPFC; no other changes in 2-oleoylglycerol hydrolysis occurred. Repeated exposure to restraint produced no changes in CB(1) receptor density in any of the areas examined. These studies are consistent with the hypothesis that stress exposure alters endocannabinoid signaling in the brain and that alterations in endocannabinoid signaling occur during habituation to stress.


Assuntos
Tonsila do Cerebelo/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Corpo Estriado/metabolismo , Endocanabinoides , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/patologia , Amidoidrolases/metabolismo , Análise de Variância , Animais , Corticosterona/sangue , Cicloexanóis/farmacocinética , Ensaio de Imunoadsorção Enzimática/métodos , Glicerídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Restrição Física/métodos , Estresse Psicológico/etiologia , Estresse Psicológico/metabolismo , Fatores de Tempo , Trítio/farmacocinética
18.
Cytometry A ; 73(11): 1035-42, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18785645

RESUMO

Recently, new methods have been introduced describing assessment of antigen-specific CD4+ T-cell immunity according to the induction of CD154 (CD40L) on CD4+ T cells during short-term activation. In our study, we have evaluated the influence of different stimulation conditions on the flow cytometric analysis of CD154 expression after antigenic in vitro activation. We used different cell preparation methods, antigen sources, and time periods of in vitro stimulation and analyzed their impact on intra and extracellular detection of antigen-induced CD154 expression on CD4+ T cells. We could demonstrate that analysis of CD4+ T-cell immunity according to CD154 expression displayed low intra-assay variability and was robust with respect to its induction in the course of a variety of stimulation conditions. For a basic quantitative evaluation of antigen-specific CD4+ T cells, surface CD154 analysis could be employed, enabling the fast analysis of live antigen-specific CD4+ T cells. Intracellular analysis of CD154 in combination with cytokines such as IL-2 and IFNgamma allowed quantitative and qualitative assessment of antigen-specific CD4+ T cells. The cytometric analysis of antigen-specific CD4+ T-cell immunity according to CD154 expression is characterized by robustness, high sensitivity, and low intra-assay variability.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Ligante de CD40/imunologia , Citometria de Fluxo/métodos , Ativação Linfocitária/imunologia , Linfócitos T CD4-Positivos/citologia , Contagem de Células , Membrana Celular/metabolismo , Humanos , Espaço Intracelular/metabolismo
19.
Popul Health Manag ; 21(5): 415-421, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29393807

RESUMO

Elderly seasonal migrators share time between homes in different states, presenting challenges for care coordination and patient attribution methods. Medicare has prioritized alternative payment models, putting health care providers at risk for quality and value of services delivered to their attributed patients, regardless of the location of care. Little research is available to guide providers and payers on the service use of seasonal migrators. The authors use claims data on fee-for-service (FFS) Medicare beneficiaries' locations throughout the year to (1) identify seasonal migrators and (2) describe the care they receive in each seasonal home, focusing on primary care and emergency department (ED) visits and the relationships between the two. In all, 5.5% of the Medicare aged FFS population were identified as seasonal migrators, with 4.1% following the traditional snowbird pattern of migration, spending warm months in the north and cold months in the south. Migrators had higher rates of ED visits and primary care treatable (PCT) ED visits than the nonmigratory groups, controlling for location, age, race, sex, Medicaid status, season, and comorbidities. They also had more visits with specialist physicians, more days with outpatient services, and more days seeing a physician in any setting. Having local primary care strongly reduced rates of both PCT ED visits and total ED visits for all migration categories, with the greatest reduction seen in PCT ED visits by migrators (local primary care was associated with a 58% reduction in PCT ED visits by snowbirds and a 65% reduction in PCT ED visits by other migrators).


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Estações do Ano , Demandas Administrativas em Assistência à Saúde , Idoso , Humanos , Medicare , Características de Residência , Medicina de Viagem , Estados Unidos
20.
Mayo Clin Proc Innov Qual Outcomes ; 2(3): 248-256, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30225458

RESUMO

BACKGROUND: The Comprehensive Care for Joint Replacement program implemented by the Centers for Medicare and Medicaid Services did not incorporate risk adjustment for lower extremity joint replacement (LEJR). Lack of adjustment places hospitals at financial risk and creates incentives for adverse patient selection. OBJECTIVE: To identify patient-level risk factors associated with health care utilization and costs of patients undergoing LEJR. METHODS: A comprehensive search of research databases from January 1, 1990, through January 31, 2016, was conducted. The databases included Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and SCOPUS and is reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The search identified 2020 studies. Eligible studies focused on primary unilateral and bilateral LEJR. Independent reviewers determined study eligibility and extracted utilization and cost data. RESULTS: Seventy-nine of 330 studies (24%) were included and were abstracted for analysis. Comorbidities, age, disease severity, and obesity were associated with increased costs. Increased number of comorbidities and age, presence of specific comorbidities, lower socioeconomic status, and female sex had evidence of increased length of stay. We found no significant association between indication for surgery and the likelihood of readmission. CONCLUSION: Developing a risk adjustment model for LEJR that incorporates clinical variables may serve to reduce the likelihood of adverse patient selection and enhance appropriate reimbursement aligned with procedural complexity.

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