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1.
JNCI Cancer Spectr ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676669

RESUMO

Social determinants of health and unmet social needs are directly related to cancer outcomes, from diagnosis to survivorship. If identified, unmet social needs can be addressed in oncology care by changing care plans in collaboration with patients' preferences and accounting for clinical practice guidelines (eg, reducing the frequency of appointments, switching treatment modalities) and connecting patients to resources within healthcare organizations (eg, social work support, patient navigation), and with community organizations (eg, food banks, housing assistance programs). Screening for social needs is the first step to identifying those who need additional support and is increasingly recognized as a necessary component of high-quality cancer care delivery. Despite evidence about the relationship between social needs and cancer outcomes and the abundance of screening tools, the implementation of social needs screening remains a challenge and little is known regarding the adoption, reach, and sustainability of social needs screening in routine clinical practice. We present data on the adoption and implementation of social needs screening at two large academic cancer centers and discuss three challenges associated with implementing evidence-based social needs screening in clinical practice: (1) identifying an optimal approach for administering social needs screening in oncology care, (2) adequately addressing identified unmet needs with resources and support, and (3) coordinating social needs screening between oncology and primary care.

2.
J Med Internet Res ; 26: e54008, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587889

RESUMO

BACKGROUND: Numerous prior opinion papers, administrative electronic health record data studies, and cross-sectional surveys of telehealth during the pandemic have been published, but none have combined assessments of video visit success monitoring with longitudinal assessments of perceived challenges to the rapid adoption of video visits during the pandemic. OBJECTIVE: This study aims to quantify (1) the use of video visits (compared with in-person and telephone visits) over time during the pandemic, (2) video visit successful connection rates, and (3) changes in perceived video visit challenges. METHODS: A web-based survey was developed for the dual purpose of monitoring and improving video visit implementation in our health care system during the COVID-19 pandemic. The survey included questions regarding rates of in-person, telephone, and video visits for clinician-patient encounters; the rate of successful connection for video visits; and perceived challenges to video visits (eg, software, hardware, bandwidth, and technology literacy). The survey was distributed via email to physicians, advanced practice professionals, and clinicians in May 2020. The survey was repeated in March 2021. Differences between the 2020 and 2021 responses were adjusted for within-respondent correlation across surveys and tested using generalized estimating equations. RESULTS: A total of 1126 surveys were completed (511 surveys in 2020 and 615 surveys in 2021). In 2020, only 21.7% (73/336) of clinicians reported no difficulty connecting with patients during video visits and 28.6% (93/325) of clinicians reported no difficulty in 2021. The distribution of the percentage of successfully connected video visits ("Over the past two weeks of scheduled visits, what percentage did you successfully connect with patients by video?") was not significantly different between 2020 and 2021 (P=.74). Challenges in conducting video visits persisted over time. Poor connectivity was the most common challenge reported by clinicians. This response increased over time, with 30.5% (156/511) selecting it as a challenge in 2020 and 37.1% (228/615) in 2021 (P=.01). Patients not having access to their electronic health record portals was also a commonly reported challenge (109/511, 21.3% in 2020 and 137/615, 22.3% in 2021, P=.73). CONCLUSIONS: During the pandemic, our health care delivery system rapidly adopted synchronous patient-clinician communication using video visits. As experience with video visits increased, the reported failure rate did not significantly decline, and clinicians continued to report challenges related to general network connectivity and patient access to technology.


Assuntos
COVID-19 , Meios de Comunicação , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Transversais , Comunicação
3.
JCO Oncol Pract ; 20(2): 239-246, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38175992

RESUMO

PURPOSE: Oncology advanced practice providers (APPs), including nurse practitioners, clinical nurse specialists, physician assistants, and clinical pharmacists, contribute significantly to quality cancer care. Understanding the research-related roles of APPs in the National Cancer Institute's (NCI) Community Oncology Research Program (NCORP) could lead to enhanced protocol development, trial conduct, and accrual. METHODS: The 2022 NCORP Landscape Assessment Survey asked two questions about the utilization and roles of APPs in the NCORP. RESULTS: A total of 271 practice groups completed the 2022 survey, with a response rate of 90%. Of the 259 nonpediatric exclusive practice groups analyzed in this study, 92% used APPs for clinical care activities and 73% used APPs for research activities. APPs most often provided clinical care for patients enrolled in trials (97%), followed by assistance with coordination (65%), presenting/explaining clinical trials (59%), screening patients (49%), ordering investigational drugs (37%), and consenting participants (24%). Some groups reported APPs as an enrolling investigator (18%) and/or participating in institutional oversight/selection of trials (15%). Only 5% of NCORP sites reported APPs as a site primary investigator for trials, and very few (3%) reported APPs participating in protocol development. CONCLUSION: Practice groups report involving APPs in clinical research within the NCORP network; however, opportunities for growth exists. As team-based care has enhanced clinical practice in oncology, this same approach can be used to enhance successful research. Suggested strategies include supporting APP research-related time, recognition, and education. The findings of this survey and subsequent recommendations may be applied to all adult oncology practices that participate in clinical research.


Assuntos
Neoplasias , Profissionais de Enfermagem , Adulto , Estados Unidos , Humanos , National Cancer Institute (U.S.) , Neoplasias/terapia , Oncologia , Qualidade da Assistência à Saúde
4.
World Neurosurg ; 181: e453-e458, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37865197

RESUMO

OBJECTIVE: Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. METHODS: A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. RESULTS: The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. CONCLUSIONS: The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression.


Assuntos
Neoplasias Encefálicas , Lesões por Radiação , Radiocirurgia , Humanos , Radiocirurgia/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Estudos Retrospectivos , Diagnóstico por Imagem , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Necrose/etiologia , Resultado do Tratamento
5.
J Bone Oncol ; 43: 100510, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38075938

RESUMO

Cancer-induced bone pain (CIBP) is the most common and devastating symptom of bone metastatic cancer that substantially disrupts patients' quality of life. Currently, there are few effective analgesic treatments for CIBP other than opioids which come with severe side effects. In order to better understand the factors and mechanisms responsible for CIBP it is essential to have clinically relevant animal models that mirror pain-related symptoms and disease progression observed in patients with bone metastatic cancer. In the current study, we characterize a syngeneic mouse model of prostate cancer induced bone pain. We transfected a prostate cancer cell line (RM1) with green fluorescent protein (GFP) and luciferase reporters in order to visualize tumor growth longitudinally in vivo and to assess the relationship between sensory neurons and tumor cells within the bone microenvironment. Following intra-femoral injection of the RM1 prostate cancer cell line into male C57BL/6 mice, we observed a progressive increase in spontaneous guarding of the inoculated limb between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. Daily running wheel performance was evaluated as a measure of functional impairment and potentially movement evoked pain. We observed a progressive reduction in the distance traveled and percentage of time at optimal velocity between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. We utilized histological, radiographic and µCT analysis to examine tumor induced bone remodeling and observed osteolytic lesions as well as extra-periosteal aberrant bone formation in the tumor bearing femur, similar to clinical findings in patients with bone metastatic prostate cancer. Within the tumor bearing femur, we observed reorganization of blood vessels, macrophage and nerve fibers within the intramedullary space and periosteum adjacent to tumor cells. Tumor bearing mice displayed significant increases in the injury marker ATF3 and upregulation of the neuropeptides SP and CGRP in the ipsilateral DRG as well as increased measures of central sensitization and glial activation in the ipsilateral spinal cord. This immunocompetent mouse model will be useful when combined with cell type selective transgenic mice to examine tumor, immune cell and sensory neuron interactions in the bone microenvironment and their role in pain and disease progression associated with bone metastatic prostate cancer.

6.
Interv Neuroradiol ; : 15910199231217144, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082554

RESUMO

BACKGROUND: Middle meningeal artery embolization (MMAE) has shown promise as an alternative treatment for chronic subdural hematoma (cSDH); however, the most effective procedural technique is debated. We sought to assess the safety and efficacy of coil embolization as a stand-alone technique for MMAE in cSDH. METHODS: A single-center retrospective analysis was performed of patients who underwent MMAE for chronic SDH with coil embolization alone. RESULTS: Forty-five patients were included in the study. All underwent successful stand-alone coil MMAE, of which 51.1% were bilateral. Indications for MMAE were varied, but 13.3% of patients required ongoing anticoagulation and another 11.1% had severe thrombocytopenia. Conscious sedation or no sedation was used in 73.2% of patients; 10 patients (22.2%) were scheduled electively and discharged same day. There were no severe or minor procedural complications identified. Of the 45 patients, only 3 (6.6%) underwent unplanned repeat surgical intervention: one patient developed a large recurrence at eight weeks after MMAE and underwent burr hole drainage; the second patient received burr hole drainage prior to MMAE but needed repeat burr hole drainage two weeks later due to residual; the third patient received two burr hole drainages at two and three weeks post MMAE due to persistent disease. CONCLUSION: Stand-alone MMAE with coiling can be performed under conscious sedation as an outpatient procedure and may be sufficient to prevent cSDH recurrence in most cases without the need for particle penetration of cSDH microvascular beds. Larger confirmatory studies are necessary.

7.
Prim Care Diabetes ; 17(2): 148-154, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36697280

RESUMO

OBJECTIVE: To examine changes in cardiovascular disease (CVD) risk outcomes of overweight/obese adults with prediabetes. METHODS: Using data from a randomized control trial of digital diabetes prevention program (d-DPP) with 599 participants. We applied the atherosclerotic CVD (ASCVD) risk calculator to predict 10-year CVD risk for d-DPP and small education (comparison) groups. Between-group risk changes at 4 and 12 months were compared using a repeated measures linear mixed-effect model. We examined within-group differences in proportion of participants over time for specific CVD risk factors using generalized estimating equations. RESULTS: We found no differences between baseline 10-year ASCVD risk. Relative to the comparison group, the d-DPP group experienced greater reductions in predicted 10-year ASCVD risk at each follow-up visit and a significant group difference at 4 months (-0.96%; 95% confidence interval: -1.58%, -0.34%) (but not at 12 months). Additionally, we observed that the d-DPP group experienced a decreased proportion of individuals with hyperlipidemia (18% and 16% from baseline to 4 and 12 months), high-risk total cholesterol (8% from baseline to 12 months), and being insufficiently active (26% and 22% from baseline to 4 and 12 months at follow-up time points. CONCLUSIONS: Our findings suggest that a digitally adapted DPP may promote the prevention of cardiometabolic disease among overweight/obese individuals with prediabetes. However, given the lack of maintenance of effect on ASCVD risk at 12 months, there may also be a need for additional interventions to sustain the effect detected at 4 months.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/complicações , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Sobrepeso , Fatores de Risco , Obesidade/complicações , Fatores de Risco de Doenças Cardíacas
8.
Am J Prev Med ; 62(4): 567-577, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35151522

RESUMO

INTRODUCTION: In light of the need to expand the reach and access of clinically proven digital Diabetes Prevention Programs (d-DPPs) and the need for rigorous evidence of effectiveness, the purpose of this study was to determine the effectiveness of a digital Diabetes Prevention Program for improving weight, HbA1c, and cardiovascular risk factors among people with prediabetes compared to enhanced standard care plus waitlist control. STUDY DESIGN: This was a single-blind RCT among participants at risk of developing type 2 diabetes and included 12 months of follow-up. SETTING/PARTICIPANTS: A total of 599 volunteer patients with prediabetes were recruited primarily through electronic medical records and primary care practices. INTERVENTION: Participants were randomized to either a d-DPP (n=299) or a single-session small-group diabetes-prevention education class (n=300) focused on action planning for weight loss. The d-DPPs consisted of 52 weekly sessions, lifestyle coaching, virtual peer support, and behavior tracking tools. MAIN OUTCOME MEASURES: The primary outcome was a change in HbA1c from baseline to 12 months using intent-to-treat analyses. On the basis of multiple comparisons of endpoints, 95% CIs are presented and 2-sided p<0.025 was required for statistical significance. Secondary outcomes included body weight and cardiovascular disease risk factors. RESULTS: Among 599 randomized participants (mean age=55.4 years, 61.4% women), 483 (80%) completed the study. The d-DPPs produced significantly greater reductions in HbA1c (0.08%, 95% CI= -0.12, -0.03) and percentage change in body weight (-5.5% vs -2.1%, p<0.001) at 12 months. A greater proportion of the d-DPPs group achieved a clinically significant weight loss ≥5% (43% vs 21%, p<0.001), and more participants shifted from prediabetes to normal HbA1c range (58% vs 48%, p=0.04). Engagement in d-DPPs was significantly related to improved HbA1c and weight loss. CONCLUSIONS: This d-DPPs demonstrated clinical effectiveness and has significant potential for widespread dissemination and impact, particularly considering the growing demand for telemedicine in preventive healthcare services. TRIAL REGISTRATION: This study is registered at www. CLINICALTRIALS: gov (ClinicalTrials.gov Identifier: NCT03312764).


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Telemedicina , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/terapia , Método Simples-Cego , Redução de Peso
9.
Neuroradiol J ; 35(2): 170-176, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34269121

RESUMO

BACKGROUND AND PURPOSE: Acute ischemic stroke has increasingly become a procedural disease following the demonstrated benefit of mechanical thrombectomy (MT) for emergent large vessel occlusion (ELVO) on clinical outcomes and tissue salvage in randomized trials. Given these data and anecdotal experience of decreased numbers of decompressive hemicraniectomies (DHCs) performed for malignant cerebral edema, we sought to correlate the numbers of strokes, thrombectomies, and DHCs performed over the timeline of the 2013 failed thrombolysis/thrombectomy trials, to the 2015 modern randomized MT trials, to post-DAWN and DEFUSE 3. MATERIALS AND METHODS: This is a multicenter retrospective compilation of patients who presented with ELVO in 11 US high-volume comprehensive stroke centers. Rates of tissue plasminogen activator (tPA), thrombectomy, and DHC were determined by current procedural terminology code, and specificity to acute ischemic stroke confirmed by each institution. Endpoints included the incidence of stroke, thrombectomy, and DHC and rates of change over time. RESULTS: Between 2013 and 2018, there were 55,247 stroke admissions across 11 participating centers. Of these, 6145 received tPA, 4122 underwent thrombectomy, and 662 patients underwent hemicraniectomy. The trajectories of procedure rates over time were modeled and there was a significant change in MT rate (p = 0.002) without a concomitant change in the total number of stroke admissions, tPA administration rate, or rate of DHC. CONCLUSIONS: This real-world study confirms an increase in thrombectomy performed for ELVO while demonstrating stable rates of stroke admission, tPA administration and DHC. Unlike prior studies, increasing thrombectomy rates were not associated with decreased utilization of hemicraniectomy.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/cirurgia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
10.
J Clin Neurosci ; 95: 88-93, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929657

RESUMO

Optimal management of metastatic lung cancer to the spine (MLCS) incorporates a multidisciplinary approach. With improvements in lung cancer screening andnonsurgical treatment, the role for surgerymay be affected. The objective of this study is to assess trends in the surgical management of MLCS using the National Inpatient Sample (NIS) database. The NIS was queried for patients with MLCS who underwent surgery from 2005 to 2014. The frequencies of spinal decompression alone, spinal stabilization with or without (+/-) decompression, and vertebral augmentation were calculated. Statistical analysis was performed to analyze the effect of patient characteristics on outcomes. The most common procedure performed was vertebral augmentation (10719, 44.3%), followed by spinal stabilization +/- decompression (8634, 35.7%) and then decompression alone (4824, 20.0%). The total number of surgeries remained stable, while the rate of spinal stabilizations increased throughout the study period (p < 0.001). Invasive procedures such as stabilization and decompression were associated with greater costs, length of stay,complications and mortality. Increasingcomorbidity was associated with increased odds of complication, especially in patients undergoing more invasive procedures. In patients with lowpre-operative comorbidity, the type of procedure did not influence the odds of complication. Graded increases in length of stay, cost and mortality were seen with increasing complication rate.The rate of spinal stabilizations increased, which may be due to either increased early detection of disease facilitating use of outpatient vertebral augmentation procedures and/or the recognition that surgical decompression and stabilization are necessary for optimal outcome in the setting of MLCS with neurological deficit.


Assuntos
Neoplasias Pulmonares , Fusão Vertebral , Descompressão Cirúrgica , Detecção Precoce de Câncer , Humanos , Pacientes Internados , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos
11.
J Clin Neurosci ; 91: 99-104, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373068

RESUMO

Management of metastatic breast cancer to the spine (MBCS) incorporates a multimodal approach. Improvement in screening and nonsurgical therapies may alter the trends in surgical management of MBCS. The objective of this study is to assess trends in surgical management of MBCS and short-term outcomes based on the National Inpatient Sample (NIS) database. The NIS database was queried for patients with MBCS who underwent surgery from 2005 to 2014. The weighted frequencies of spinal decompression alone, spinal stabilization +/- decompression, and vertebral augmentation were calculated. Multivariate analysis was performed to analyze the effect of patient characteristics on outcomes stratified by procedure. The most common procedure performed was vertebral augmentation (11,114, 53.4%), followed by stabilization +/- decompression (6,906, 33.2%) and then decompression alone (3,312, 13.4%). The total population-adjusted rate of surgical management for MBCS remained stable, while the rate of spinal stabilization increased (P < 0.001) and vertebral augmentation decreased (p < 0.003). The risk of complication increased with spinal stabilization and decompression compared to vertebral augmentation procedures in those with fewer comorbidities. This relative increase in risk abated in patients with higher numbers of pre-operative comorbidities. Any single complication was associated with increases in length of stay, cost, and mortality. The rate of in-hospital interventions remained stable over the study period. Stratified by procedure, the rate of stabilizations increased with a concomitant decrease in vertebral augmentations, which suggests that patients who require hospitalization for MBCS are becoming more likely to represent advanced cases that are not amenable to palliative vertebral augmentation procedures.


Assuntos
Neoplasias da Mama , Doenças da Coluna Vertebral/cirurgia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Descompressão Cirúrgica , Feminino , Hospitalização , Humanos , Incidência , Pacientes Internados , Complicações Pós-Operatórias , Estudos Retrospectivos , Doenças da Coluna Vertebral/etiologia , Fusão Vertebral
12.
World Neurosurg ; 153: e66-e75, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34129967

RESUMO

BACKGROUND: Citation rates are an important measure for the impact of articles. This study is the most comprehensive analysis of predictors for scientific neurosurgical research articles. METHODS: Scientific articles published in 13 neurosurgical journals in 2015 were selected. Data collected included article subject, level of evidence (LOE), journal impact factor (IF), authorship, contributing centers, and study design. Citation counts were collected for each article in Web of Science (WoS) and Google Scholar (GS) 2.5 and 5 years after publication and Scopus 5 years after publication. A generalized linear mixed-effects model using the predictors of search engine, LOE, number of centers, number of authors, and IF was constructed to predict total citation count at 5 years. RESULTS: A total of 2867 articles generated 39,190 citations in WoS, 61,682 in GS, and 43,481 in Scopus. The median number of citations per article was 10 (interquartile range [IQR], 14) in WoS, 15 (IQR, 20) in GS, and 11 (IQR, 15) in Scopus. On average, for every 1 citation in WoS, Scopus and GS identified 1.11 and 1.58 citations, respectively. Significant predictors of citation count in all databases 5 years after publication included search engine, LOE, number of centers, number of authors, number of countries, journal IF, and the month of publication (P < 0.05). The article subject (e.g., tumor or spine) did not significantly predict citation counts. CONCLUSIONS: In the most thorough analysis of citation predictors in the neurosurgical literature, search engine, LOE, number of centers, number of authors, number of countries, journal impact factor, and month of publication influenced citations 5 years after publication.


Assuntos
Pesquisa Biomédica , Fator de Impacto de Revistas , Neurocirurgia , Projetos de Pesquisa , Autoria , Bibliometria , Humanos
13.
Mol Pain ; 17: 1744806921997206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33829907

RESUMO

Beta 2 adrenergic receptor (ß2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of ß2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the ß2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. Depletion of spinal noradrenergic neurons delayed recovery of hypersensitivity following incision evident as a flattened slope compared to non-depleted rats (-1.8 g/day with 95% CI -2.4 to -1.085, p < 0.0001). Chronic administration of clenbuterol reduced mechanical hypersensitivity evident as a greater initial intercept in noradrenergic depleted (6.2 g with 95% CI 1.6 to 10.8, p = 0.013) and non-depleted rats (5.4 g with 95% CI 1.2 to 9.6, p = 0.018) with plantar incision compared to vehicle treated rats. Despite a persistent reduction in mechanical hypersensitivity, clenbuterol did not alter the slope of recovery when modeled over several days (p = 0.053) or five weeks in depleted rats (p = 0.64). Systemic clenbuterol suppressed the enhanced microglial activation in depleted rats and reduced the density of macrophage at the site of incision. Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of ß2-AR stimulation in this model are largely peripherally mediated. Lastly, we examined ß2-AR distribution in the spinal cord and skin using in-situ hybridization and IHC. These data add to our understanding of the role of ß2-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of ß2-AR agonists to models of surgical injury.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Clembuterol/uso terapêutico , Hiperalgesia/tratamento farmacológico , Imunidade/efeitos dos fármacos , Microglia/efeitos dos fármacos , Dor Pós-Operatória/tratamento farmacológico , Ferida Cirúrgica/complicações , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Clembuterol/farmacologia , Hiperalgesia/etiologia , Hiperalgesia/imunologia , Masculino , Neurônios/efeitos dos fármacos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/imunologia , Ratos , Ratos Sprague-Dawley
14.
Transl Behav Med ; 11(5): 1066-1077, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33677529

RESUMO

Population health management (PHM) strategies to address diabetes prevention have the potential to engage large numbers of at-risk individuals in a short duration. We examined a PHM approach to recruit participants to a diabetes prevention clinical trial in a metropolitan health system. We examined reach and representativeness and assessed differences from active and passive respondents to recruitment outreach, and participants enrolled through two clinical screening protocols. The PHM approach included an electronic health record (EHR) query, physician review of identified patients, letter invitation, and telephone follow-up. Data describe the reach and representativeness of potential participants at multiple stages during the recruitment process. Subgroup analyses examined proportional reach, participant differences based on passive versus active recruitment response, and clinical screening method used to determine diabetes risk status. The PHM approach identified 10,177 potential participants to receive a physician letter invitation, 60% were contacted by telephone, 2,796 (46%) completed telephone screening, 1,961 were eligible from telephone screen, and 599 were enrolled in 15 months. Accrual was unaffected by shifting clinical screening protocols despite the increase in participant burden. Relative to census data, study participants were more likely to be obese, female, older, and Caucasian. Relative to the patient population, enrolled participants were less likely to be Black and were older. Active respondents were more likely to have a higher income than passive responders. PHM strategies have the potential to reach a large number of participants in a relatively short period, though concerted efforts are needed to increase participant diversity.


Assuntos
Diabetes Mellitus , Gestão da Saúde da População , Diabetes Mellitus/prevenção & controle , Feminino , Humanos , Seleção de Pacientes , Projetos de Pesquisa , Telefone
15.
Sci Rep ; 10(1): 15195, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938997

RESUMO

Hypoxia inducible factor (HIFs) signaling contributes to malignant cell behavior in glioblastoma (GBM). We investigated a novel HIF2α inhibitor, PT2385, both in vitro, with low-passage patient-derived cell lines, and in vivo, using orthotopic models of glioblastoma. We focused on analysis of HIF2α expression in situ, cell survival/proliferation, and survival in brain tumor-bearing mice treated with PT2385 alone and in combination with standard of care chemoradiotherapy. HIF2α expression increased with glioma grade, with over half of GBM specimens HIF2α positive. Staining clustered in perivascular and perinecrotic tumor regions. Cellular phenotype including proliferation, viability, migration/invasion, and also gene expression were not altered after PT2385 treatment. In the animal model, PT2385 single-agent treatment did improve median overall survival compared to placebo (p = 0.04, n = 21) without a bioluminescence correlate (t = 0.67, p = 0.52). No difference in animal survival was seen in combination treatment with radiation (RT)/temozolomide (TMZ)/PT2385 (p = 0.44, n = 10) or mean tumor bioluminescence (t 1.13, p = 0.32). We conclude that HIF2α is a reasonable novel therapeutic target as expressed in the majority of glioblastomas in our cohort. PT2385 as a single-agent was efficacious in vivo, however, an increase in animal survival was not seen with PT2385 in combination with RT/TMZ. Further study for targeting HIF2α as a therapeutic approach in GBM is warranted.


Assuntos
Antineoplásicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Indanos/uso terapêutico , Sulfonas/uso terapêutico , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Indanos/farmacologia , Camundongos , Camundongos Nus , Terapia de Alvo Molecular , Sulfonas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
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