PubMed Health⌕ Search

Biomedical subjects

Jeffrey Smith

Publications and source records attributed to Jeffrey Smith.

16 recordsLinked to original sources
PubMed2006

Models, strategies, and tools. Theory in implementing evidence-based findings into health care practice.

This paper presents a case for careful consideration of theory in planning to implement evidence-based practices into clinical care. As described, theory should be tightly linked to strategic planning through careful choice or creation of an implementation framework. Strategies should be linked to specific interventions and/or intervention components to be implemented, and the choice of tools should match the interventions and overall strategy, linking back to the original theory and framework. The thesis advanced is that in most studies where there is an attempt to implement planned change in clinical processes, theory is used loosely. An example of linking theory to intervention design is presented from a Mental Health Quality Enhancement Research Initiative effort to increase appropriate use of antipsychotic medication among patients with schizophrenia in the Veterans Health Administration.

Antipsychotic Agents↗
PubMed2005

Hantaan/Andes virus DNA vaccine elicits a broadly cross-reactive neutralizing antibody response in nonhuman primates.

At least four hantavirus species cause disease with prominent renal involvement-hemorrhagic fever with renal syndrome (HFRS); and several hantavirus strains cause disease with significant pulmonary involvement-hantavirus pulmonary syndrome (HPS). The most prevalent and lethal hantaviruses associated with HFRS and HPS are Hantaan virus (HTNV) and Andes virus (ANDV), respectively. Here, we constructed a DNA vaccine plasmid (pWRG/HA-M) that contains both the HTNV and ANDV M gene segments. Rhesus macaques vaccinated with pWRG/HA-M produced antibodies that bound the M gene products (i.e., G1 and G2 glycoproteins), and neutralized both HTNV and ANDV. Neutralizing antibody titers elicited by the dual-immunogen pWRG/HA-M, or single-immunogen plasmids expressing only the HTNV or ANDV glycoproteins, increased rapidly to high levels after a booster vaccination administered 1-2 years after the initial vaccination series. Memory responses elicited by this long-range boost exhibited an increased breadth of cross-neutralizing activity relative to the primary response. This is the first time that hantavirus M gene-based DNA vaccines have been shown to elicit a potent memory response, and to elicit antibody responses that neutralize viruses that cause both HFRS and HPS.

Animals↗
PubMed2005

Funding emergency medicine development in low- and middle-income countries.

The specialty of EM is developing rapidly throughout the world. This growth is relatively lacking in the LICs, however. The lack of resources and financing capabilities in these regions may hinder specialty development. Further growth of the specialty in these countries requires an understanding of their health priorities and the global health and development agencies that often assist these countries in supporting the health sector. Identifying health priorities in these regions that intersect with EM is crucial and may form the basis for further expansion of EM. Many potential funding opportunities exist within the governmental and private sector, but all require some familiarity with application mechanisms and project cycles. Building relationships with personnel within these agencies and countries of interest is often fundamental to successful programmatic funding.

Developing Countries↗
PubMed2005

Priorities in global emergency medicine development.

EM initiatives are gaining global acceptance as a result of emergency physicians; local advocates; national, transnational, and international EM organizations; and governmental leadership, organizations, and agencies involved in international health and an evolving global health agenda. Spanning the spectrum from basic initiatives to improve acute care services to mature EM specialty development, all countries acknowledge the need for emergency care. The level of EM development in a country is fluid and depends on many variables, including status of health development, burden of disease,resources, advocacy, available expertise, and public demand. Emergency physicians should support the promotion of EM in the context of essential public health and primary care initiatives in these developing countries. Additionally, emergency physicians should work closely with stakeholders, health policy experts, health economics, and international organizations involved in health care to promote the advancement of EM worldwide.

Developing Countries↗
PubMed2005

One size fits some: the impact of patient treatment attitudes on the cost-effectiveness of a depression primary-care intervention.

BACKGROUND: Despite their impact on outcomes, the effect of patient treatment attitudes on the cost-effectiveness of health-care interventions is not widely studied. This study estimated the impact of patient receptivity to antidepressant medication on the cost-effectiveness of an evidence-based primary-care depression intervention. METHOD: Twelve community primary-care practices were stratified and then randomized to enhanced (intervention) or usual care. Subjects included 211 patients beginning a new treatment episode for major depression. At baseline, 111 (52.6%) and 145 (68.7%) reported receptivity to antidepressant medication and counseling respectively. The intervention trained the primary-care teams to assess, educate, and monitor depressed patients. Twelve-month incremental (enhanced minus usual care) total costs and quality-adjusted life years (QALYs) were calculated. RESULTS: Among patients receptive to antidepressants, the mean incremental cost-effectiveness ratio was dollar 5,864 per QALY (sensitivity analyses up to dollar 14,689 per QALY). For patients not receptive to antidepressants, the mean incremental QALY score was negative (for both main and sensitivity analyses), or the intervention was at least no more effective than usual care. CONCLUSIONS: These findings suggest a re-thinking of the 'one size fits all' depression intervention, given that half of depressed primary-care patients may be non-receptive to antidepressant medication treatment. A brief assessment of treatment receptivity should occur early in the treatment process to identify patients most likely to benefit from primary-care quality improvement efforts for depression treatment. Patient treatment preferences are also important for the development, design, and analysis of depression interventions.

Adult↗
PubMed2005

The cortex as a central pattern generator.

Vertebrate spinal cord and brainstem central pattern generator (CPG) circuits share profound similarities with neocortical circuits. CPGs can produce meaningful functional output in the absence of sensory inputs. Neocortical circuits could be considered analogous to CPGs as they have rich spontaneous dynamics that, similar to CPGs, are powerfully modulated or engaged by sensory inputs, but can also generate output in their absence. We find compelling evidence for this argument at the anatomical, biophysical, developmental, dynamic and pathological levels of analysis. Although it is possible that cortical circuits are particularly plastic types of CPG ('learning CPGs'), we argue that present knowledge about CPGs is likely to foretell the basic principles of the organization and dynamic function of cortical circuits.

Animals↗
PubMed2004

Topical application of dimethylbenz[a]anthracene results in the generation of multiple melanocytic nevi in C3H/HeN mice.

Melanocytic nevi are a common dermatological problem for which there are few in vivo models. It has been postulated that environmental factors contribute to their development. Experiments were therefore conducted to determine whether application of dimethylbenz[a]anthracene (DMBA) to the skin of mice would result in the development of melanocytic nevi. One hundred microliters of a 0.1%, 0.5%, or 1.0% solution of DMBA was applied to the dorsal skin of C3H/HeN mice. The mice were then observed for the appearance of pigmented lesions. Histological examination revealed perifollicular accumulations of nevus cells, which were S-100-protein and HMB-45-positive, confirming their melanocytic origin. Pigmented lesions did not occur in animals treated with vehicle alone. Dose response studies revealed both greater numbers of nevi and lesions with larger diameters as the dose of DMBA was increased from 0.1% to 0.5%. In no instance was an invasive melanoma observed even after 40 weeks. The fact that melanocytic nevi can be produced by topical application of DMBA suggests that xenobiotics may play a previously unrecognized role in the development of this common benign neoplasm. Because this is one of the only animal models for melanocytic nevi, further examination of this model may facilitate identification of the molecular and biochemical mechanisms that lead to the development of pigmented nevi and the factors that promote their evolution into invasive melanomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer.

Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) is involved in catalyzing estrogen, the hormone that plays a central role in the etiology of breast cancer. A common polymorphism [A(TA)6TAA (allele *1) to A(TA)7TAA change (allele *28)] in the TATA-box of the promoter region of the UGT1A1 gene has been reported to be associated with a reduced transcription of this gene. We investigated the association of this polymorphism with the risk of breast cancer among 1047 breast cancer cases and 1083 community controls in the Shanghai Breast Cancer Study, a population-based case-control study. Approximately same proportion of cases (12.5%) and controls (13.0%) carried the variant allele *28 in the Chinese population (p = 0.32). When stratified by age, carrying the *28 allele was associated with an increased risk of breast cancer among women aged less than 40 years (odds ratio [OR] = 1.7; 95% CI = 1.0-2.7) but not among women 40 years old and over (OR = 0.8; 0.7-1.1). Only a few women were homozygous for the *28 allele, precluding a detailed gene-dose association analysis. Additional analyses showed that, the elevated risk associated with the UGT1A1 *28 allele among young women was primarily seen in women who had a later menarche, short menstrual years, absence of family history of breast cancer, low waist-to-hip ratio, or low body-mass index. These results suggested that the *28 allele in the UGT1A1 gene may be associated with an increased risk for breast cancer among Chinese women under age 40. No significant associations were observed with *28 allele and breast cancer risk by estrogen receptor/progesterone receptor status.

Adult↗
PubMed2003

Cost-effectiveness of a primary care intervention for depressed females.

BACKGROUND: To date, there is little information about the differential impact of primary care interventions by gender. We conducted an exploratory cost-effectiveness analysis by gender of an intervention to improve recognition and guideline-concordant treatment of depression in primary care. METHODS: Primary care practices that did not employ an onsite mental healthcare specialist were randomized to enhanced (intervention) versus usual care. All subjects met study criteria for current major depression. Medical Outcomes Study SF-36 scores were converted into quality-adjusted life years (QALYs) to compare the 1-year effectiveness of enhanced versus usual care by gender. Based on results of previous studies, antidepressant acceptors beginning a new depression treatment episode were the focus of the analysis. Statistical analyses included multivariate regression models controlling for sociodemographic and clinical covariates. RESULTS: In the main analysis, enhanced care for females was more expensive and more effective than usual care, at an additional cost of $5244 per QALY. For males, enhanced care was essentially cost and outcome neutral compared to usual care. The cost-effectiveness ratio estimates were robust to sensitivity analyses. Psychological side effects to the intervention may partially explain the limited effect of the intervention on outcomes for males. LIMITATIONS: We consider these results exploratory because the SF-36 to quality-adjusted life year conversion formula is preliminary and because of the relatively small sample size. CONCLUSIONS: The estimated cost-effectiveness ratio of this depression intervention is within the acceptable range for females, but not males. If replicated, these exploratory findings suggest that interventions to improve primary care depression treatment may need to be modified to improve their effectiveness in males while maintaining their effectiveness in females.

Adult↗
PubMed2003

Cost-effectiveness of a primary care depression intervention.

OBJECTIVE: To determine the incremental cost-effectiveness of a quality improvement depression intervention (enhanced care) in primary care settings relative to usual care. DESIGN: Following stratification, we randomized 12 primary care practices to enhanced or usual care conditions and followed patients for 12 months. SETTING: Primary care practices located in 10 states across the United States. PATIENTS/PARTICIPANTS: Two hundred eleven patients beginning a new treatment episode for major depression. INTERVENTIONS: Training the primary care team to assess, educate, and monitor depressed patients during the acute and continuation stages of their depression treatment episode over 1 year. MEASUREMENTS AND MAIN RESULTS: Cost-effectiveness was measured by calculating incremental (enhanced minus usual care) costs and quality-adjusted life years (QALYs) derived from SF-36 data. The mean incremental cost-effectiveness ratio in the main analysis was US dollars 15463 per QALY. The mean incremental cost-effectiveness ratios for the sensitivity analyses ranged from US dollars 11341 (using geographic block variables to control for pre-intervention service utilization) to US dollars 19976 (increasing the cost estimates by 50%) per QALY. CONCLUSIONS: This quality improvement depression intervention was cost-effective relative to usual care compared to cost-effectiveness ratios for common primary care interventions and commonly cited cost-effectiveness ratio thresholds for intervention implementation.

Cost-Benefit Analysis↗
PubMed2002

Comparison of the functional properties of murine dendritic cells generated in vivo with Flt3 ligand, GM-CSF and Flt3 ligand plus GM-SCF.

Flt3 ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important growth factors for dendritic cells (DC). Substantial numbers of DC can be generated in vivo following the administration of either factor. We sought to extend our knowledge of the functional properties of these cells including their ability to prime naïve CD8(+) T cells. In addition, we compared the nature of the DC generated in vivo with the single cytokines to those generated with the combination of FL+polyethylene glycol-modified GM-CSF (pGM-CSF). Treatment with FL+pGM-CSF yielded greater numbers of both CD11b(low) and CD11b(high) DC than with either cytokine alone, and these DC were more efficient at antigen (Ag) capture. The FL+pGM-CSF-generated CD11b(low) DC lacked expression of CD8alpha. Following treatment with LPS in vivo, all DC subsets upregulated CD40, CD80, CD86, and MHC class II expression, but surprisingly Ag capture was not downregulated and some DC subsets retained expression of intracellular MHC class II vesicles. Thus, even after activation in vivo with LPS, DC retained Ag capture properties of immature DC, and Ag presentation/costimulation properties of mature DC. Though all DC subsets stimulated CD4(+) T cell proliferation equivalently, FL-generated DC were more efficient at priming Ag-specific CD8(+) cytolytic T cells than DC generated with either pGM-CSF alone or FL+pGM-CSF, and CD11b(high) DC were more efficient at priming CD8(+) T cells than CD11b(low) DC.

Adjuvants, Immunologic↗
PubMed2002

Ox40 costimulation enhances the development of T cell responses induced by dendritic cells in vivo.

Dendritic cells (DCs) are bone marrow-derived APCs that display unique properties aimed at stimulating naive T cells. Several members of the TNF/TNFR families have been implicated in T cell functions. In this study, we examined the role that Ox40 costimulation might play on the ability of DCs to regulate CD4(+) and CD8(+) T cell responses in vivo. Administration of anti-mouse Ox40 mAb enhanced the Th response induced by immunization with Ag-pulsed DCs, and introduced a bias toward a Th1 immune response. However, anti-Ox40 treatment enhanced the production of Th2 cytokines in IFN-gamma(-/-) mice after immunization with Ag-pulsed DCs, suggesting that the production of IFN-gamma during the immune response could interfere with the development of Th2 lymphocytes induced by DCs. Coadministration of anti-Ox40 with DCs during Ag rechallenge enhanced both Th1 and Th2 responses induced during a primary immunization with DCs, and did not reverse an existing Th2 response. This suggests that Ox40 costimulation amplifies an ongoing immune response, regardless of Th differentiation potential. In an OVA-TCR class II-restricted adoptive transfer system, anti-Ox40 treatment greatly enhanced the level of cytokine secretion per Ag-specific CD4(+) T cell induced by immunization with DCs. In an OVA-TCR class I-restricted adoptive transfer system, administration of anti-Ox40 strongly enhanced expansion, IFN-gamma secretion, and cytotoxic activity of Ag-specific CD8(+) T cells induced by immunization with DCs. Thus, by enhancing immune responses induced by DCs in vivo, the Ox40 pathway might be a target for immune intervention in therapeutic settings that use DCs as Ag-delivery vehicles.

Adjuvants, Immunologic↗
PubMed2002

Human Sir2 and the 'silencing' of p53 activity.

Members of the evolutionarily conserved silent information regulator 2 (Sir2) protein family are nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylases. In yeast, the founding Sir2 protein is known to function in transcriptional silencing processes through the deacetylation of histones H3 and H4, thus setting up a repressive chromatin structure. Yeast and Caenorhabditis elegans Sir2 are also involved in regulating the life span of these organisms. Until recently, the function of mammalian Sir2 family members was completely unknown. However, several recent studies have now determined a remarkable function for the human SIRT1 protein, which is the closest human homolog of yeast Sir2. SIRT1 specifically associates with the p53 tumor suppressor protein and deacetylates it, resulting in negative regulation of p53-mediated transcriptional activation. Importantly, p53 deacetylation by SIRT1 also prevents cellular senescence and apoptosis induced by DNA damage and stress.

Animals↗
PubMed2002

Gamma scintigraphic evaluation of a novel budesonide dry powder inhaler using a validated radiolabeling technique.

A scintigraphic study was carried out to compare the lung deposition of budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in healthy volunteers. Validation of Technetium-99m ((99m)Tc) radiolabeling of the budesonide/lactose blend used in the Clickhaler and excipient-free budesonide used in the Turbuhaler was carried out using a multistage liquid impinger, and compared with reference unlabeled devices. Budesonide was quantified using high-performance liquid chromatography and (99m)Tc by scintillation counting. The percentages (SD) of fine particles (<5.5 microm diameter) from radiolabeled and unlabeled devices were not significantly different (p > 0.05). Mean values for drug and radiolabel, respectively, were 34.6% (2.5) and 31.6% (3.8) for the Clickhaler, and 29.8% (5.5) and 31.4% (5 6) for the Turbuhaler. Fifteen healthy male volunteers received a single dose (2 x 200 microg actuations) from both devices in a double-blinded, double dummy, crossover study. During dosing, each inhalation maneuver was recorded using a computer-linked pressure transducer. To permit accurate determination of radiolabeled drug deposition, the lung margins of each volunteer were determined by Krypton-81m ((81m)Kr) gas imaging. Mean [SD] lung deposition for the Clickhaler (26.8% [6.8], RSD 25.2) was significantly greater (p < 0.001) than for the Turbuhaler (15.8% [6.6], RSD 42.2). Inspiratory flow rate parameters were similar for both devices with peak and mean values of 73 and 51 L/min for the Clickhaler, and 73 and 47 L/min for the Turbuhaler, respectively. These results indicate that, in healthy volunteers, budesonide lung deposition was higher and more consistent with the Clickhaler than with the Turbuhaler.

Adult↗
PubMed2002

Use, quality, and outcomes of care for mental health: the rural perspective.

This review synthesizes empirical research in rural mental health services to identify current research priorities to improve the mental health of rural Americans. Using a conceptual framework of the multiple determinants of use, quality, and outcomes, the authors address (1) how key constructs are operationalized, (2) their theoretical influence on the care process, (3) reported differences for nonmetropolitan and metropolitan individuals or within nonmetropolitan individuals, (4) salient issues rural advocates have raised, and (5) key research questions. While the authors recognize that rurality is a useful political umbrella to organize advocacy efforts, they propose that investigators no longer employ any of the multiple definitions of the term in the literature as even intrarural comparisons have not provided compelling evidence about the underlying causes of observed outcomes differences. Until these underlying causes have been identified, it is difficult to determine which components of the nonmetropolitan service system need to be improved.

Humans↗