Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 48
Filter
Add more filters

Publication year range
1.
J Gen Intern Med ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769259

ABSTRACT

BACKGROUND: Heart failure is a leading cause of death in the USA, contributing to high expenditures near the end of life. Evidence remains lacking on whether billed advance care planning changes patterns of end-of-life healthcare utilization among patients with heart failure. Large-scale claims evaluation assessing billed advance care planning and end-of-life hospitalizations among patients with heart failure can fill evidence gaps to inform health policy and clinical practice. OBJECTIVE: Assess the association between billed advance care planning delivered and Medicare beneficiaries with heart failure upon the type and quantity of healthcare utilization in the last 30 days of life. DESIGN: This retrospective cross-sectional cohort study used Medicare fee-for-service claims from 2016 to 2020. PARTICIPANTS: A total of 48,466 deceased patients diagnosed with heart failure on Medicare. MAIN MEASURES: Billed advance care planning services between the last 12 months and last 30 days of life will serve as the exposure. The outcomes are end-of-life healthcare utilization and total expenditure in inpatient, outpatient, hospice, skilled nursing facility, and home healthcare services. KEY RESULTS: In the final cohort of 48,466 patients (median [IQR] age, 83 [76-89] years; 24,838 [51.2%] women; median [IQR] Charlson Comorbidity Index score, 4 [2-5]), 4406 patients had an advance care planning encounter. Total end-of-life expenditure among patients with billed advance care planning encounters was 19% lower (95% CI, 0.77-0.84) compared to patients without. Patients with billed advance care planning encounters had 2.65 times higher odds (95% CI, 2.47-2.83) of end-of-life outpatient utilization with a 33% higher expected total outpatient expenditure (95% CI, 1.24-1.42) compared with patients without a billed advance care planning encounter. CONCLUSIONS: Billed advance care planning delivery to individuals with heart failure occurs infrequently. Prioritizing billed advance care planning delivery to these individuals may reduce total end-of-life expenditures and end-of-life inpatient expenditures through promoting use of outpatient end-of-life services, including home healthcare and hospice.

2.
BMC Public Health ; 24(1): 1436, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811963

ABSTRACT

BACKGROUND: HIV molecular epidemiology (HIV ME) can support the early detection of emerging clusters of new HIV infections by combining HIV sequence data routinely obtained during the clinical treatment of people living with HIV with behavioral, geographic, and sociodemographic information. While information about emerging clusters promises to facilitate HIV prevention and treatment efforts, the use of this data also raises several ethical concerns. We sought to assess how those working on the frontlines of HIV ME, specifically public health practitioners (PHPs) and researchers, prioritized these issues. METHODS: Ethical issues were identified through literature review, qualitative in-depth interviews, and stakeholder engagement. PHPs and researchers using HIV ME prioritized the issues using best-worst scaling (BWS). A balanced incomplete block design was used to generate 11 choice tasks each consisting of a sub-set of 5 ethical concerns. In each task, respondents were asked to assess the most and least concerning issue. Data were analyzed using conditional logit, with a Swait-Louviere test of poolability. Latent class analysis was then used to explore preference heterogeneity. RESULTS: In total, 57 respondents completed the BWS experiment May-June 2023 with the Swait-Louviere test indicating that researchers and PHPs could be pooled (p = 0.512). Latent class analysis identified two classes, those highlighting "Harms" (n = 29) (prioritizing concerns about potential risk of legal prosecution, individual harm, and group stigma) and those highlighting "Utility" (n = 28) (prioritizing concerns about limited evidence, resource allocation, non-disclosure of data use for HIV ME, and the potential to infer the directionality of HIV transmission). There were no differences in the characteristics of members across classes. CONCLUSIONS: The ethical issues of HIV ME vary in importance among stakeholders, reflecting different perspectives on the potential impact and usefulness of the data. Knowing these differences exist can directly inform the focus of future deliberations about the policies and practices of HIV ME in the United States.


Subject(s)
HIV Infections , Molecular Epidemiology , Humans , HIV Infections/epidemiology , Male , Female , Research Personnel/psychology , Research Personnel/ethics , Adult , Public Health/ethics , Middle Aged , Qualitative Research
3.
Med Care ; 60(1): 22-28, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34670222

ABSTRACT

BACKGROUND: Before the Affordable Care Act (ACA), most women who gained pregnancy-related Medicaid were not eligible for Medicaid as parents postpartum. The ACA aimed to expand health insurance coverage, in part, by expanding Medicaid; introducing mandates; reforming regulations; and establishing exchanges with federal subsidies. Federal subsidies offer a means to coverage for individuals with income at 100%-400% of the federal poverty level who do not qualify for Medicaid. OBJECTIVE: The objective of this study was to identify the effects of the ACA's non-Medicaid provisions on women's postpartum insurance coverage and depressive symptoms in nonexpansion states with low parental Medicaid thresholds. PARTICIPANTS: Women with incomes at 100%-400% of the federal poverty level who had prenatal insurance and completed the Pregnancy Risk Assessment Monitoring System (2012-2015). SETTING: Five non-Medicaid expansion states with Medicaid parental eligibility thresholds below the federal poverty level. DESIGN: Interrupted time-series analyses were conducted to examine changes between pre-ACA (January 2012-November 2013) and post-ACA (December 2013-December 2015) trends for self-reported loss of postpartum insurance and symptoms of postpartum depression. RESULTS: The sample included 9,472 women. Results showed significant post-ACA improvements where the: (1) trend for loss of postpartum insurance reversed (change of -0.26 percentage points per month, P=0.047) and (2) level of postpartum depressive symptoms decreased (change of -3.5 percentage points, P=0.042). CONCLUSIONS: In these 5 states, the ACA's non-Medicaid provisions were associated with large increases in retention of postpartum insurance and reductions in postpartum depressive symptoms, although depressive symptoms findings are sensitive to model specification.


Subject(s)
Depression, Postpartum/economics , Insurance Coverage/standards , Medicaid/trends , Patient Protection and Affordable Care Act/statistics & numerical data , State Government , Adult , Depression, Postpartum/epidemiology , Female , Health Services Accessibility/standards , Health Services Accessibility/statistics & numerical data , Humans , Insurance Coverage/statistics & numerical data , Medicaid/economics , Medicaid/statistics & numerical data , Middle Aged , Patient Protection and Affordable Care Act/economics , Pregnancy , United States
4.
Epidemiol Infect ; 150: e105, 2022 05 18.
Article in English | MEDLINE | ID: mdl-35582988

ABSTRACT

Repeated serosurveys are an important tool for understanding trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination. During 1 September 2020-20 March 2021, the NYC Health Department conducted a population-based SARS-CoV-2 antibody prevalence survey of 2096 NYC adults who either provided a blood specimen or self-reported the results of a previous antibody test. The serosurvey, the second in a series of surveys conducted by the NYC Health Department, aimed to estimate SARS-CoV-2 antibody prevalence across the city and for different groups at higher risk for adverse health outcomes. Weighted citywide prevalence was 23.5% overall (95% confidence interval (CI) 20.1-27.4) and increased from 19.2% (95% CI 14.7-24.6) before coronavirus disease 2019 vaccines were available to 31.3% (95% CI 24.5-39.0) during the early phases of vaccine roll-out. We found no differences in antibody prevalence by age, race/ethnicity, borough, education, marital status, sex, health insurance coverage, self-reported general health or neighbourhood poverty. These results show an overall increase in population-level seropositivity in NYC following the introduction of SARS-CoV-2 vaccines and highlight the importance of repeated serosurveys in understanding the pandemic's progression.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , New York City/epidemiology , Prevalence , Vaccination
5.
BMC Med Educ ; 19(1): 261, 2019 Jul 15.
Article in English | MEDLINE | ID: mdl-31307460

ABSTRACT

BACKGROUND: Improved training approaches have the potential to overcome barriers to the use of postpartum intrauterine devices (PPIUDs) in Pakistan, including a shortage of female providers who are able to insert the device. This study assessed the effectiveness and acceptability of a competency-based onsite training approach that employed a newly developed anatomic model (the Mama-U) to train doctors and midwives on postpartum family planning (PPFP) and the insertion of PPIUDs. METHODS: An observational, mixed methods study conducted training evaluations and knowledge and skills assessments with 11 trainers and 88 doctors and midwives who participated in eight PPIUD training sessions. Two months later, follow-up interviews and clinical assessments were conducted with 20 providers, and interviews and a focus group discussion were conducted with 85 married women who received a PPIUD from a trained provider. RESULTS: The training significantly improved provider knowledge (p < 0.001), and follow-up assessments showed that clinical skills were retained for at least two months post-training. After training, 81.8% of providers were confident in their ability to provide PPIUD services, and midwives and doctors had similar PPIUD insertion skills. However, midwives were more likely than doctors to meet all 10 key requirements during PPIUD counseling sessions (63.9% versus 13.3%, p = 0.004). Providers found the Mama-U model to be a useful tool for client counseling as well as training and skills practice, and clients agreed. Trainers identified the low cost, light weight, and portability of the Mama-U model as advantages over the conventional training model and noted that its abstract shape reduced embarrassment among trainers, providers, and clients. CONCLUSIONS: Competency-based training with the Mama-U model can improve the quality of PPIUD counseling and PPIUD insertion services and has the potential to extend PPFP/PPIUD service delivery to midwives working in rural Pakistan. The portable, low-cost Mama-U permits onsite, on-the-job PPIUD insertion training that is tailored to the local setting; it is also well suited for the continuing practice that providers need to maintain their skills. Further research is needed to confirm the usefulness and cost-effectiveness of the Mama-U at scale and in other settings.


Subject(s)
Clinical Competence , Competency-Based Education/methods , Family Planning Services/education , Intrauterine Devices/statistics & numerical data , Midwifery/education , Simulation Training/economics , Adolescent , Adult , Cost Savings , Developing Countries , Female , Focus Groups , Health Personnel/education , Humans , Models, Educational , Pakistan , Postpartum Period , Pregnancy , Young Adult
6.
BMC Palliat Care ; 17(1): 54, 2018 Mar 27.
Article in English | MEDLINE | ID: mdl-29587711

ABSTRACT

BACKGROUND: Advance care planning (ACP) aids can help prepare patients, family members, and physicians for in-the-moment medical decision-making. We wished to describe the content and approach of paper-based ACP aids in order to characterize existing aids and inform the development of a new ACP aid. METHODS: Paper-based ACP aids were identified through an environmental scan and screened for eligibility. ACP conceptual frameworks and data were gathered via stakeholder engagement and used to inform the coding framework that two investigators used to independently code each aid. A directed content analysis was conducted on these eligible aids. Aids were categorized through a deliberative process with an investigator abstracting general information for each aid. RESULTS: Fifteen aids met the eligibility criteria. They ranged in length from 6 to 78 pages with the average aid written at an eighth-grade reading level. The content analysis revealed that many aids encouraged choosing a surrogate decision maker and informed users about legal medical documents. Fewer than half of the aids facilitated patient clarification of values regarding quality of life issues. The authors identified and termed the following three categories of aids: informative; semi-action oriented; and action-oriented. It was often unclear whether patients contributed to the development or testing of the ACP aids reviewed. CONCLUSIONS: Most existing paper-based ACP aids address legal matters such as completing an advance directive. Only a minority elicited patient values and it was unclear whether any were developed in partnership with patients. Future development of ACP aids should account for patient preferences with a goal of supporting in-the-moment medical decision-making.


Subject(s)
Advance Care Planning/standards , Decision Making , Pamphlets , Patient-Centered Care/standards , Advance Directives/trends , Humans , Patient Preference/psychology , Patient-Centered Care/methods , Terminal Care/methods , Terminal Care/standards
7.
Br J Cancer ; 117(6): 813-825, 2017 Sep 05.
Article in English | MEDLINE | ID: mdl-28797031

ABSTRACT

BACKGROUND: Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia and activates survival pathways. The aim of this study was to determine the role of hypoxia-induced autophagy in GBM. METHODS: Pharmacological inhibition of autophagy was applied in combination with bevacizumab in GBM patient-derived xenografts (PDXs). Sensitivity towards inhibitors was further tested in vitro under normoxia and hypoxia, followed by transcriptomic analysis. Genetic interference was done using ATG9A-depleted cells. RESULTS: We find that GBM cells activate autophagy as a survival mechanism to hypoxia, although basic autophagy appears active under normoxic conditions. Although single agent chloroquine treatment in vivo significantly increased survival of PDXs, the combination with bevacizumab resulted in a synergistic effect at low non-effective chloroquine dose. ATG9A was consistently induced by hypoxia, and silencing of ATG9A led to decreased proliferation in vitro and delayed tumour growth in vivo. Hypoxia-induced activation of autophagy was compromised upon ATG9A depletion. CONCLUSIONS: This work shows that inhibition of autophagy is a promising strategy against GBM and identifies ATG9 as a novel target in hypoxia-induced autophagy. Combination with hypoxia-inducing agents may provide benefit by allowing to decrease the effective dose of autophagy inhibitors.


Subject(s)
Autophagy-Related Proteins/physiology , Autophagy/drug effects , Bevacizumab/pharmacology , Brain Neoplasms/drug therapy , Chloroquine/pharmacology , Glioblastoma/drug therapy , Membrane Proteins/physiology , Neoplasm Proteins/physiology , Tumor Hypoxia/physiology , Vesicular Transport Proteins/physiology , Angiogenesis Inhibitors/pharmacology , Animals , Autophagy/physiology , Autophagy-Related Proteins/metabolism , Brain Neoplasms/blood supply , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Drug Synergism , Gene Expression Profiling , Gene Knockdown Techniques , Gene Silencing , Glioblastoma/blood supply , Glioblastoma/metabolism , Heterografts , Humans , Membrane Proteins/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Molecular Targeted Therapy/methods , Neoplasm Proteins/metabolism , Neoplasm Transplantation , Random Allocation , Spheroids, Cellular/pathology , Vesicular Transport Proteins/metabolism
8.
Am J Physiol Gastrointest Liver Physiol ; 310(6): G337-46, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26767983

ABSTRACT

In several gut inflammatory or cancer diseases, cell-cell interactions are compromised, and an increased cytoplasmic expression of ß-catenin is observed. Over the last decade, numerous studies provided compelling experimental evidence that the loss of cadherin-mediated cell adhesion can promote ß-catenin release and signaling without any specific activation of the canonical Wnt pathway. In the present work, we took advantage of the ability of lipofectamine-like reagent to cause a synchronous dissociation of adherent junctions in cells isolated from the rat enteric nervous system (ENS) for obtaining an in vitro model of deregulated ß-catenin signaling. Under these experimental conditions, a green fluorescent protein Wnt reporter plasmid called ΔTop_EGFP3a was successfully tested to screen ß-catenin stabilization at resting and primed conditions with exogenous Wnt3a or lipopolysaccharide (LPS). ΔTop_EGFP3a provided a reliable and strong fluorescent signal that was easily measurable and at the same time highly sensitive to modulations of Wnt signaling following Wnt3a and LPS stimulation. The reporter gene was useful to demonstrate that Wnt3a exerts a protective activity in the ENS from overstimulated Wnt signaling by promoting a downregulation of the total ß-catenin level. Based on this evidence, the use of ΔTop_EGFP3a reporter plasmid could represent a more reliable tool for the investigation of Wnt and cross-talking pathways in ENS inflammation.


Subject(s)
Enteric Nervous System , Gastroenteritis/genetics , Genes, Reporter/genetics , Plasmids/genetics , Wnt Signaling Pathway/genetics , Animals , Cell Adhesion/drug effects , Cell Membrane/pathology , Down-Regulation/drug effects , Fluorescence , Gastroenteritis/physiopathology , Green Fluorescent Proteins , Indicators and Reagents , Lipids , Lipopolysaccharides/pharmacology , Rats , Rats, Sprague-Dawley , Wnt3A Protein/pharmacology , beta Catenin/metabolism
9.
Pediatr Hematol Oncol ; 33(6): 393-407, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27690707

ABSTRACT

Cancer- and treatment-related side effects in patients with childhood cancer may cause limitations in motor performance affecting activities of daily living (ADLs). Data focusing on long-term effects are available, but little is known with regard to the short-term perspective. Therefore, the purpose of this study was to assess muscle strength performance and quality of life (QoL) in children and adolescents with cancer at the beginning of primary treatment. Forty children and adolescents aged 5-18 years (mean: 11.39 ± 4.08 years) with different types of childhood cancer were enrolled. On average 36 ± 20.5 days after diagnosis, strength performance in 7 muscle groups was assessed by handheld dynamometry. KINDL questionnaires were completed to evaluate QoL (children's self-report and parents' report). All parameters were compared with age- and gender-matched reference values. Patients with childhood cancer showed significantly lower strength values in all muscle groups (P < .01) compared with age- and gender-matched controls. Most affected were the lower extremities, with a -57.1% ± 10.4%, median: -59.2%, minimum: -75.4%, maximum: -41.4% percentage deviation in knee flexion from healthy peers. Children themselves and parents assessed total QoL significantly below age- and gender-matched reference values (P < .01). Correlation between elbow flexion and self-reported QoL was detected. Broader correlations were found for the parents' report. Muscle weakness and decreased QoL in children and adolescents seem to persist already at the beginning of anticancer treatment. This underlines the need of counteracting measures, such as exercise intervention programs, starting as early as possible during the treatment process. Efforts on this topic are currently being carried out by our group.


Subject(s)
Muscle Strength , Neoplasms/physiopathology , Neoplasms/therapy , Quality of Life , Surveys and Questionnaires , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male
10.
J Neuroinflammation ; 12: 23, 2015 Feb 03.
Article in English | MEDLINE | ID: mdl-25644719

ABSTRACT

BACKGROUND: In the last years, Wnt signaling was demonstrated to regulate inflammatory processes. In particular, an increased expression of Wnts and Frizzled receptors was reported in inflammatory bowel disease (IBD) and ulcerative colitis to exert both anti- and pro-inflammatory functions regulating the intestinal activated nuclear factor κB (NF-кB), TNFa release, and IL10 expression. METHODS: To investigate the role of Wnt pathway in the response of the enteric nervous system (ENS) to inflammation, neurons and glial cells from rat myenteric plexus were treated with exogenous Wnt3a and/or LPS with or without supporting neurotrophic factors such as basic fibroblast growth factor (bFGF), epithelial growth factor (EGF), and glial cell-derived neurotrophic factor (GDNF). The immunophenotypical characterization by flow cytometry and the protein and gene expression analysis by qPCR and Western blotting were carried out. RESULTS: Flow cytometry and immunofluorescence staining evidenced that enteric neurons coexpressed Frizzled 9 and toll-like receptor 4 (TLR4) while glial cells were immunoreactive to TLR4 and Wnt3a suggesting that canonical Wnt signaling is active in ENS. Under in vitro LPS treatment, Western blot analysis demonstrated an active cross talk between canonical Wnt signaling and NF-кB pathway that is essential to negatively control enteric neuronal response to inflammatory stimuli. Upon costimulation with LPS and Wnt3a, a significant anti-inflammatory activity was detected by RT-PCR based on an increased IL10 expression and a downregulation of pro-inflammatory cytokines TNFa, IL1B, and interleukin 6 (IL6). When the availability of neurotrophic factors in ENS cultures was abolished, a changed cell reactivity by Wnt signaling was observed at basal conditions and after LPS treatment. CONCLUSIONS: The results of this study suggested the existence of neuronal surveillance through FZD9 and Wnt3a in enteric myenteric plexus. Moreover, experimental evidences were provided to clarify the correlation among soluble trophic factors, Wnt signaling, and anti-inflammatory protection of ENS.


Subject(s)
Cytokines/metabolism , Myenteric Plexus/cytology , Neurons/metabolism , Signal Transduction/physiology , Wnt Proteins/metabolism , Animals , Animals, Newborn , Cells, Cultured , Cytokines/genetics , Fibroblast Growth Factor 2/pharmacology , Frizzled Receptors/genetics , Frizzled Receptors/metabolism , Gene Expression Regulation/drug effects , Lipopolysaccharides/pharmacology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neuroglia/drug effects , Neuroglia/metabolism , Neurons/drug effects , Protein Binding/drug effects , Rats , Rats, Sprague-Dawley , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Signal Transduction/drug effects , Time Factors , Wnt3A Protein/pharmacology
11.
Histochem Cell Biol ; 143(4): 397-410, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25371326

ABSTRACT

Enteric neurons and blood vessels form intricate networks throughout the gastrointestinal tract. To support the hypothesis of a possible interaction of both networks, we investigated whether primary mesenteric vascular cells (MVCs) and enteric nervous system (ENS)-derived cells (ENSc) depend on each other using two- and three-dimensional in vitro assays. In a confrontation assay, both cell types migrated in a target-oriented manner towards each other. The migration of MVCs was significantly increased when cultured in ENSc-conditioned medium. Co-cultures of ENSc with MVCs resulted in an improved ENSc proliferation and differentiation. Moreover, we analysed the formation of the vascular and nervous system in developing mice guts. It was found that the patterning of newly formed microvessels and neural stem cells, as confirmed by nestin and SOX2 stainings, is highly correlated in all parts of the developing gut. In particular in the distal colon, nestin/SOX2-positive cells were found in the tissues adjacent to the capillaries and in the capillaries themselves. Finally, in order to provide evidences for a mutual interaction between endothelial and neural cells, the vascular patterns of a RET((-/-)) knockout mouse model as well as human Hirschsprung's cases were analysed. In the distal colon of postnatal RET((-/-)) knockout mice, the vascular and neural networks were similarly disrupted. In aganglionic zones of Hirschsprung's patients, the microvascular density was significantly increased compared with the ganglionic zone within the submucosa. Taken together, these findings indicate a strong interaction between the enteric nervous and vascular system.


Subject(s)
Cell Communication , Enteric Nervous System/physiology , Intestines/blood supply , Intestines/innervation , Microvessels/physiology , Neural Stem Cells/physiology , Animals , Cell Proliferation , Cells, Cultured , Chemotaxis , Coculture Techniques , Culture Media, Conditioned/metabolism , Enteric Nervous System/cytology , Enteric Nervous System/metabolism , Female , Gene Expression Regulation, Developmental , Green Fluorescent Proteins/biosynthesis , Green Fluorescent Proteins/genetics , Hirschsprung Disease/pathology , Hirschsprung Disease/physiopathology , Humans , Infant , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Microvessels/cytology , Microvessels/metabolism , Neovascularization, Physiologic , Nestin/genetics , Nestin/metabolism , Neural Stem Cells/metabolism , Neurogenesis , Paracrine Communication , Proto-Oncogene Proteins c-ret/deficiency , Proto-Oncogene Proteins c-ret/genetics , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism
12.
J Cell Mol Med ; 18(7): 1429-43, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24780093

ABSTRACT

The enteric nervous system (ENS) has to respond to continuously changing microenvironmental challenges within the gut and is therefore dependent on a neural stem cell niche to keep the ENS functional throughout life. In this study, we hypothesize that this stem cell niche is also affected during inflammation and therefore investigated lipopolysaccharides (LPS) effects on enteric neural stem/progenitor cells (NSPCs). NSPCs were derived from the ENS and cultured under the influence of different LPS concentrations. LPS effects upon proliferation and differentiation of enteric NSPC cultures were assessed using immunochemistry, flow cytometry, western blot, Multiplex ELISA and real-time PCR. LPS enhances the proliferation of enteric NSPCs in a dose-dependent manner. It delays and modifies the differentiation of these cells. The expression of the LPS receptor toll-like receptor 4 on NSPCs could be demonstrated. Moreover, LPS induces the secretion of several cytokines. Flow cytometry data gives evidence for individual subgroups within the NSPC population. ENS-derived NSPCs respond to LPS in maintaining at least partially their stem cell character. In the case of inflammatory disease or trauma where the liberation and exposure to LPS will be increased, the expansion of NSPCs could be a first step towards regeneration of the ENS. The reduced and altered differentiation, as well as the induction of cytokine signalling, demonstrates that the stem cell niche may take part in the LPS-transmitted inflammatory processes in a direct and defined way.


Subject(s)
Cell Differentiation , Enteric Nervous System/cytology , Lipopolysaccharides/pharmacology , Neural Stem Cells/cytology , Stem Cell Niche/drug effects , Animals , Bacteria , Blotting, Western , Cell Proliferation , Cells, Cultured , Enteric Nervous System/drug effects , Enteric Nervous System/metabolism , Flow Cytometry , Fluorescent Antibody Technique , Immunoenzyme Techniques , Mice , Mice, Inbred BALB C , Nestin/genetics , Nestin/metabolism , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Neurogenesis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism
13.
Cell Tissue Res ; 355(1): 35-48, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24253464

ABSTRACT

The enteric nervous system (ENS) controls and modulates gut motility and responds to food intake and to internal and external stimuli such as toxins or inflammation. Its plasticity is maintained throughout life by neural progenitor cells within the enteric stem cell niche. Granulocyte-colony stimulating factor (G-CSF) is known to act not only on cells of the immune system but also on neurons and neural progenitors in the central nervous system (CNS). Here, we demonstrate, for the first time, that G-CSF receptor is present on enteric neurons and progenitors and that G-CSF plays a role in the expansion and differentiation of enteric neural progenitor cells. Cultured mouse ENS-neurospheres show increased expansion with increased G-CSF concentrations, in contrast to CNS-derived spheres. In cultures from differentiated ENS- and CNS-neurospheres, neurite outgrowth density is enhanced depending on the amount of G-CSF in the culture. G-CSF might be an important factor in the regeneration and differentiation of the ENS and might be a useful tool for the investigation and treatment of ENS disorders.


Subject(s)
Enteric Nervous System/cytology , Enteric Nervous System/metabolism , Granulocyte Colony-Stimulating Factor/metabolism , Neural Stem Cells/cytology , Neurogenesis , Neurons/cytology , Animals , Cells, Cultured , Female , Granulocyte Colony-Stimulating Factor/analysis , Granulocytes/pathology , Hirschsprung Disease/pathology , Humans , Male , Mice , Neural Stem Cells/metabolism , Neurons/metabolism , Receptors, Granulocyte Colony-Stimulating Factor/analysis , Receptors, Granulocyte Colony-Stimulating Factor/metabolism
14.
BMC Palliat Care ; 13: 32, 2014.
Article in English | MEDLINE | ID: mdl-25067908

ABSTRACT

BACKGROUND: High-risk surgery patients may lose decision-making capacity as a result of surgical complications. Advance care planning prior to surgery may be beneficial, but remains controversial and is hindered by a lack of appropriate decision aids. This study sought to examine stakeholders' views on the appropriateness of using decision aids, in general, to support advance care planning among high-risk surgery populations and the design of such a decision aid. METHODS: Key informants were recruited through purposive and snowball sampling. Semi-structured interviews were conducted by phone until data collected reached theoretical saturation. Key informants were asked to discuss their thoughts about advance care planning and interventions to support advance care planning, particularly for this population. Researchers took de-identified notes that were analyzed for emerging concordant, discordant, and recurrent themes using interpretative phenomenological analysis. RESULTS: Key informants described the importance of initiating advance care planning preoperatively, despite potential challenges present in surgical settings. In general, decision aids were viewed as an appropriate approach to support advance care planning for this population. A recipe emerged from the data that outlines tools, ingredients, and tips for success that are needed to design an advance care planning decision aid for high-risk surgical settings. CONCLUSIONS: Stakeholders supported incorporating advance care planning in high-risk surgical settings and endorsed the appropriateness of using decision aids to do so. Findings will inform the next stages of developing the first advance care planning decision aid for high-risk surgery patients.

15.
PLoS One ; 19(1): e0296062, 2024.
Article in English | MEDLINE | ID: mdl-38180988

ABSTRACT

BACKGROUND: There is a paucity of evidence on the association between satisfaction with quality of care and adherence to antidepressants. OBJECTIVES: To examine the association between patient satisfaction with healthcare and adherence to antidepressants. METHODS: A cohort study design was used to identify antidepressant users from the 2010-2016Medical Expenditure Panel Survey data, a national longitudinal complex survey study design on the cost and healthcare utilization of the noninstitutionalized population in the United States. The Consumer Assessment of Healthcare Providers and Systems were used to measure participants' satisfaction with access and quality of care, patient-provider communication and shared decision-making (SDM). Patients were considered satisfied if they ranked the quality of care at ≥9 (range: 0[worst]- 10[best]). Antidepressant adherence was measured based on medication refill and complete discontinuation. MEPS sampling survey-weighted multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between satisfaction and adherence to antidepressants. We tested for the potential presence of reverse associations by restricting the analysis to new users of antidepressants. The roles of patient-provider communication and SDM on the satisfaction-adherence association were examined through structural equation models (SEM). RESULTS: Among 4,990 (weighted counts = 8,661,953) antidepressant users, 36% were adherent while 39% discontinued antidepressants therapy. Half of antidepressant users were satisfied with the healthcare received. Satisfied patients were 26% (OR = 1.26, 95%CI: 1.08, 1.47) more likely to adhere and 17% (OR = 0.83, 95%CI: 0.71, 0.96) less likely to discontinue, compared to unsatisfied antidepressant users. Patient satisfaction was also associated with higher odds (OR = 1.41, 95%CI: 1.06, 1.88) of adherence among a subgroup of new users of antidepressants. The SEM analysis revealed that satisfaction was a manifestation of patient-provider communication (ß = 2.03, P-value<0.001) and SDM (ß = 1.14, P-value<0.001). CONCLUSIONS: Patient satisfaction is a potential predictor of antidepressant adherence. If our findings are confirmed through intervention studies, improving patient-provider communication and SDM could likely drive both patient satisfaction and adherence to antidepressants.


Subject(s)
Antidepressive Agents , Patient Satisfaction , Humans , Cohort Studies , Antidepressive Agents/therapeutic use , Communication , Decision Making, Shared
16.
Curr Med Res Opin ; : 1-11, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39250177

ABSTRACT

OBJECTIVE: HIV molecular epidemiology (HIV ME) is a tool that aims to improve HIV research, surveillance, and cluster detection and response. HIV ME is a core pillar of the U.S. initiative to End the HIV Epidemic but faces some challenges and criticisms from stakeholders. We sought to assess user experience to identify the current needs for HIV ME. METHODS: Users of HIV ME, including researchers and public health practitioners, were engaged via a structured survey. Needs were assessed via open-ended questions about HIV ME. Data were analyzed using reflexive thematic analysis; the concordance of results was assessed semi-quantitatively. RESULTS: Of 90 possible HIV-ME end-users, 57 completed the survey (response rate = 63%), which included users engaged in research (n = 29) and public health (n = 28). Respondents identified current imperatives, challenges, and strategies to improve HIV ME. Imperatives included characterization of the virus, identification of HIV hotspots, and tailoring of HIV interventions. Challenges encompassed technological issues, ethical concerns, and implementation difficulties. Strategies to improve HIV ME involved improving data access and analysis, enhancing implementation guidance and resources, and fostering community engagement and support. Researchers and public health practitioners prioritized different imperatives, but similarly emphasized the ethical concerns with HIV ME. CONCLUSION: The imperatives identified by users underscore the necessity of HIV ME, while the challenges highlight the hurdles to be overcome, including ethical concerns which emerged as a shared emphasis across user groups. The strategies outlined offer a roadmap for overcoming these challenges. These insights, drawn from user experience, present a valuable opportunity to inform the development of guidelines for the ethical application of HIV ME in research, surveillance, and cluster detection and response.

17.
Am Soc Clin Oncol Educ Book ; 43: e390678, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37290027

ABSTRACT

The theme of the 2023 American Society of Clinical Oncology Annual Meeting is Partnering With Patients: The Cornerstone of Cancer Care and Research. As we aim to partner with patients to improve their health care, digital tools have the potential to enhance patient-centered cancer care and make clinical research more accessible and generalizable. Using electronic patient-reported outcomes (ePROs) to collect patients' reports of symptoms, functioning, and well-being facilitates patient-clinician communication and improves care and outcomes. Early studies suggest that racial and ethnic minority populations, older patients, and patients with less education may benefit even more from ePRO implementation. Clinical practices looking to implement ePROs can refer to the resources of the PROTEUS Consortium (Patient-Reported Outcomes Tools: Engaging Users & Stakeholders). Beyond ePROs, in response to the COVID-19 pandemic, cancer practices have rapidly adopted other digital tools (eg, telemedicine, remote patient monitoring). As implementation grows, we must be aware of the limitations of these tools and implement them in ways to promote optimal function, access, and ease of use. Infrastructure, patient, provider, and system-level barriers need to be addressed. Partnerships across all levels can inform development and implementation of digital tools to meet the needs of diverse groups. In this article, we describe how we use ePROs and other digital health tools in cancer care, how digital tools can expand access to and generalizability of oncology care and research, and prospects for broader implementation and use.


Subject(s)
COVID-19 , Health Equity , Neoplasms , Humans , Ethnicity , Pandemics , Minority Groups , COVID-19/epidemiology , Patient Reported Outcome Measures , Neoplasms/epidemiology , Neoplasms/therapy
18.
PLoS One ; 18(6): e0287730, 2023.
Article in English | MEDLINE | ID: mdl-37390051

ABSTRACT

BACKGROUND: The impacts of socioeconomic status (SES) on COVID-19-related changes in cancer prevention behavior have not been thoroughly investigated. We conducted a cohort study to examine the effects of SES on changes in cancer prevention behaviors during the COVID-19 pandemic. METHODS: We invited adult participants from previous studies conducted at Ohio State University to participate in a study assessing the impact of COVID-19 on various behaviors. Post-COVID-19 cancer prevention behaviors, including physical activity, daily intake of fruits and vegetables, alcohol and tobacco consumption, and qualitative changes in post-COVID-19 behaviors relative to pre-COVID levels, were used to construct a prevention behavior change index that captures the adherence status and COVID-related changes in each behavior, with higher index scores indicating desirable changes in prevention behaviors. Participants were classified into low, middle, or high SES based on household income, education, and employment status. Adjusted regression models were used to examine the effects of SES on changes in cancer prevention behaviors during the COVID-19 pandemic. RESULTS: The study included 6,136 eligible participants. The average age was 57 years, 67% were women, 89% were non-Hispanic Whites, and 33% lived in non-metro counties. Relative to participants with high SES, those with low SES had a 24% [adjusted relative ratio, aRR = 0.76 (95%CI 0.72-0.80)], 11% [aRR = 0.89 (95%CI 0.86-0.92)], and 5% [aRR = 0.95 (95%CI 0.93-0.96)], lower desirable changes in prevention behaviors for physical activity, fruit and vegetable intake, and tobacco use, respectively. Low SES had a higher desirable change in alcohol consumption prevention behaviors, 16% [aRR = 1.16 (95%CI 1.13-1.19)] relative to high SES. The adjusted odds of an overall poor change in prevention behavior were adjusted odds ratio (aOR) 1.55 (95%CI 1.27 to 1.89) and aOR 1.40 (95%CI 1.19 to 1.66), respectively, higher for those with low and middle SES relative to those with high SES. CONCLUSION: The adverse impacts of COVID-19 on cancer prevention behaviors were seen most in those with lower SES. Public health efforts are currently needed to promote cancer prevention behaviors, especially amongst lower SES adults.


Subject(s)
COVID-19 , Neoplasms , Adult , Female , Humans , Middle Aged , Male , Cohort Studies , Pandemics , COVID-19/epidemiology , COVID-19/prevention & control , Neoplasms/epidemiology , Neoplasms/prevention & control , Social Class
19.
Front Genet ; 14: 1053613, 2023.
Article in English | MEDLINE | ID: mdl-36741312

ABSTRACT

Background: A national priority in the United States is to promote patient engagement in cancer genomics research, especially among diverse and understudied populations. Several cancer genomics research programs have emerged to accomplish this priority, yet questions remain about the meaning and methods of patient engagement. This study explored how cancer genomics research programs define engagement and what strategies they use to engage patients across stages in the conduct of research. Methods: An environmental scan was conducted of cancer genomics research programs focused on patient engagement. Research programs were identified and characterized using materials identified from publicly available sources (e.g., websites), a targeted literature review, and interviews with key informants. Descriptive information about the programs and their definitions of engagement, were synthesized using thematic analysis. The engagement strategies were synthesized and mapped to different stages in the conduct of research, including recruitment, consent, data collection, sharing results, and retention. Results: Ten research programs were identified, examples of which include the Cancer Moonshot Biobank, the MyPART Network, NCI-CONNECT, and the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. All programs aimed to include understudied or underrepresented populations. Based on publicly available information, four programs explicitly defined engagement. These definitions similarly characterized engagement as being interpersonal, reciprocal, and continuous. Five general strategies of engagement were identified across the programs: 1) digital (such as websites) and 2) non-digital communications (such as radio broadcasts, or printed brochures); 3) partnering with community organizations; 4) providing incentives; and 5) affiliating with non-academic medical centers. Digital communications were the only strategy used across all stages of the conduct of research. Programs tailored these strategies to their study goals, including overcoming barriers to research participation among diverse populations. Conclusion: Programs studying cancer genomics are deeply committed to increasing research participation among diverse populations through patient engagement. Yet, the field needs to reach a consensus on the meaning of patient engagement, develop a taxonomy of patient engagement measures in cancer genomics research, and identify optimal strategies to engage patients in cancer genomics. Addressing these needs could enable patient engagement to fulfill its potential and accelerate the pace of cancer genomic discoveries.

20.
Cell Rep ; 42(9): 113034, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37651228

ABSTRACT

Metabolic rewiring is essential for cancer onset and progression. We previously showed that one-carbon metabolism-dependent formate production often exceeds the anabolic demand of cancer cells, resulting in formate overflow. Furthermore, we showed that increased extracellular formate concentrations promote the in vitro invasiveness of glioblastoma cells. Here, we substantiate these initial observations with ex vivo and in vivo experiments. We also show that exposure to exogeneous formate can prime cancer cells toward a pro-invasive phenotype leading to increased metastasis formation in vivo. Our results suggest that the increased local formate concentration within the tumor microenvironment can be one factor to promote metastases. Additionally, we describe a mechanistic interplay between formate-dependent increased invasiveness and adaptations of lipid metabolism and matrix metalloproteinase activity. Our findings consolidate the role of formate as pro-invasive metabolite and warrant further research to better understand the interplay between formate and lipid metabolism.


Subject(s)
Glioblastoma , Lipid Metabolism , Humans , Formates , Neoplasm Invasiveness , Tumor Microenvironment
SELECTION OF CITATIONS
SEARCH DETAIL