Toward a VA women’s health research agenda: Setting evidence-based priorities to improve the health and health care of women veterans

The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the changing demographics and special health care needs of women, the VA Office of Research & Development recently sponsored the first national VA Women’s Health Research Agenda-setting conference to map research priorities to the needs of women veterans and position VA as a national leader in Women’s Health Research. This paper summarizes the process and outcomes of this effort, outlining VA’s research priorities for biomedical, clinical, rehabilitation, and health services research.     

Distance-adjusted motor threshold for transcranial magnetic stimulation.

OBJECTIVE: To examine the relationship between coil-cortex distance and effective cortical stimulation using transcranial magnetic stimulation (TMS) in the left and right motor cortex. We also compare the effect of coil-cortex distance using 50 and 70 mm figure-eight stimulating coils. METHODS: Coil-cortex distance was manipulated within each participant using 5 and 10 mm acrylic separators placed between the coil and scalp surface. The effect of cortical stimulation was indexed by resting motor threshold (MT). RESULTS: Increasing distance between the coil and underlying cortex was associated with a steep linear increase in MT. For each additional millimetre separating the stimulating coil from the scalp surface, an additional approximately 2.8% of absolute stimulator output (approximately 0.062 T) was required to reach MT. The gradient of the observed distance effect did not differ between hemispheres, and no differences were observed between the 50 and 70 mm TMS coils. CONCLUSIONS: Coil-cortex distance directly influences the magnitude of cortical stimulation in TMS. The relationship between TMS efficacy and coil-cortex distance is well characterised by a linear function, providing a simple and effective method for scaling stimulator output to a distance adjusted MT. SIGNIFICANCE: MT measured at the scalp-surface is dependent on the underlying scalp-cortex distance, and therefore does not provide an accurate index of cortical excitability. Distance-adjusted MT provides a more accurate index of cortical excitability, and improves the safety and efficacy of MT-calibrated TMS.     

Development of a new Adolescent Patient-Provider Interaction Scale (APPIS) for youth at risk for STDs/HIV

PurposeAlthough an adult model of patient-provider mutual exchange of information has been proposed, there is no guiding model for adolescents or measurement methodology. Our purpose was to develop a new scale of patient-provider interaction for adolescents accessing reproductive health care and at risk for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV), and assess the reliability and validity of the scale.MethodsThe Adolescent Patient-Provider Interaction Scale (APPIS) was developed from the Roter and Hall theory of doctor-patient relationships, previously validated adolescent satisfaction and communication scales, and focus group and individual elicitation interviews. To assess construct validity, the new nine-item APPIS was compared with the satisfaction scale used by the Young Adult Health Care Survey (YAHCS), and Kahn’s Provider Communication Scale. Pearson correlation coefficients were used to examine convergence across scales, and factor analysis of the APPIS was performed.ResultsThe study recruited 192 African American girls aged 17.9 ± 1.7 years (range 15–21 years) from three sites: a county STD clinic (n = 51), urban adolescent clinic (n = 99), and a family planning clinic (n = 42). Most participants (85%) rated their overall health care highly (≥ 7 on a 10-point scale); 49% felt that both the provider and patient were “in charge” of the visit, and 88% “strongly agreed” or “agreed” that there was an equal “exchange of information” during the visit. The APPIS showed good internal consistency (Cronbach alpha = .75), and moderate convergence with the six-item YAHCS scale (r = .57, p < .001) and seven-item Kahn scale (r = .48, p < .001). Three factors emerged from exploratory factor analyses, supporting our conceptualization of patient-provider interaction as being multi-dimensional.ConclusionsA new theory-based scale of adolescent patient-provider interaction compares favorably with previous scales of health care satisfaction and communication. The new APPIS may be useful for evaluating approaches to improve health care outcomes for adolescents at-risk for STDs and HIV.     

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.     

Acute pain management services have progressed, albeit insufficiently in Canadian academic hospitals

PURPOSE: Acute pain management services (APMS) evolved in response to the desire for improved management of postoperative pain. The management of postoperative pain received formal support from international organizations over the past decade and by 1993 half of the Canadian university-affiliated teaching hospitals had implemented an APMS. The purpose of this survey was to describe APMSs in Canadian academic institutions, with specific emphasis on postoperative analgesics, new analgesic methods, training and research. METHODS: Between June 2000 and January 2001, 62 Canadian hospitals affiliated with the 16 Canadian university anesthesiology departments were sent a postal questionnaire. RESULTS: Fifty of the 62 respondents returned a completed questionnaire representing a response rate of 81%. Eighty percent of the hospitals surveyed had at least 200 beds, 90% (45) had implemented an APMS. Anesthesiology was primarily responsible in all 45 hospitals with an APMS. The results presented are based on the 45 centres with an APMS. CONCLUSION: Since the early 1990s the percent of Canadian academic hospitals with an APMS has increased from 53% to 92%. These figures are comparable to the United States. Greater collaboration from nursing and pharmacy, mandatory training for medical and nursing students and residents, and a standardized approach to continuous quality improvement remain necessary.     

Depressive symptom deterioration in a large primary care-based elderly cohort.

OBJECTIVE: The purpose of this study is to examine the incidence and clinical predictors of symptom deterioration in depressed elderly patients who have responded to treatment in primary care. METHOD: A cohort study of 901 older adults from 18 primary care clinics in five states who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression and/or dysthymia at baseline interview, had participated in a trial of collaborative care for depression compared to usual care, and had improved to the point of no longer meeting criteria for major depression at 12 months were observed for one year (18 and 24 months) after enrolling in the original study. RESULTS: A total of 40% of patients met criteria for significant depressive symptom deterioration over the 12- to 24-month observational period. Among usual-care patients, higher initial severity of depression and a higher number of residual DSM-IV depressive symptoms at 12 months were significant predictors of symptom deterioration. No variables predicted symptom deterioration in intervention patients. CONCLUSIONS: There is a high rate of symptom deterioration among elderly patients in primary care who are treated for depression. Efforts to improve long-term outcomes of older patients with major depression and/or dysthymia should focus on providing more intensive treatment and follow up for patients with residual depressive symptoms.     

Reduction of scar formation in full-thickness wounds with topical celecoxib treatment

Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.     

A potentially deleterious role of IGFBP-2 on bone density in aging men and women.

The role of the IGFs and IGFBPs on age-related changes in BMD in adult men and women is not well understood. Studying an age-stratified community based sample of 344 men and 276 women, we found higher IGFBP-2 levels to be associated with lower BMD. IGFBP-2, which increases with age in both men and women, was the strongest, most consistent predictor of BMD among the IGF/IGFBPs studied. INTRODUCTION: Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of tissue growth and metabolism, but their association with BMD in adult men and women is controversial. MATERIALS AND METHODS: In an age-stratified, random sample of the community population, we examined the role of serum levels of IGF-I, IGF-II, and IGFBP-1, -2, and -3 on BMD of the proximal femur (total hip), lateral spine, midshaft, and ultradistal radius as measured by DXA. We explored the association before and after adjustment for potential confounders, including age, bioavailable estradiol and testosterone, sex hormone binding globulin (SHBG), and measures of total fat and skeletal muscle mass. RESULTS: We studied 344 men (age, 23-90 years) and 276 women (age, 21-93 years; 166 postmenopausal) not on hormone replacement or oral contraceptives. In both men and women, IGF-I and IGFBP-3 levels fell with advancing age, whereas IGFBP-2 levels tended to rise with age. There was an inverse association of IGFBP-2 with BMD at most skeletal sites in men and both premenopausal and postmenopausal women, whereas lower IGF-I and IGFBP-3 were associated with lower BMD in men and postmenopausal women only. Lower IGF-II was associated with lower BMD in men only. There were no associations between IGFBP-1 and BMD in either sex. After adjustment for age, in most cases, we found no further associations between IGF-I, IGF-II, or IGFBP-3 and BMD. In contrast, after age adjustment, higher IGFBP-2 remained a predictor of lower BMD in men and postmenopausal women at all sites except for the lateral spine (for men: r = -0.21, -0.20, and -0.19, all p < 0.001; and for postmenopausal women: r = -0.34, -0.24, and -0.25, all p < 0.01, for the total hip, midshaft, and ultradistal radius, respectively). IGFBP-2 remained an independent negative predictor of BMD in men, postmenopausal women, and all women combined after additional adjustment for bioavailable sex steroids, but not at all sites after adjustment for SHBG and muscle mass. In premenopausal women, IGFBP-2 had similar associations as seen in postmenopausal women, but they were weaker and not statistically robust. CONCLUSIONS: Among the IGF/IGFBPs in our study, IGFBP-2 was a key negative predictor of BMD among men and women, particularly postmenopausal women. Our findings suggest a potential role of the IGF/IGFBP system in regulating bone loss in aging men and women and identify a previously under-recognized, potentially deleterious role for IGFBP-2, a known inhibitor of IGF action that increases with age in both sexes. Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study.     

Sequences in the proximal 5′ flanking region of the rat neuron-specific enolase (NSE) gene are sufficient for cell type-specific reporter gene expression

We investigated the regulation of the rat neuron-specific enolase gene using a transient transfection approach. Recent transgenic mouse studies have shown that a 1.8-kb segment of the ratNSE gene 5′ flanking region, including the first (noncoding) exon but not the first intron, is able to drive expression of a reporter gene in parallel with endogenousNSE. These data suggest thatcis-acting elements responsible for the spatial and temporal pattern ofNSE gene expression are located within the proximal 1.8 kb of the 5′ flanking sequence. To further investigate this region, we joined the 1.8-kb regulatory cassette to thecat reporter gene and generated a number of constructs in which the flanking sequence was progressively deleted from the 5′ end. These constructs were tested by transient transfection into neuronal and nonneuronal cells, followed by an assay for CAT activity. We found that as little as 255 bp of 5′ flanking sequence was able to confer cell type-specificity on the reporter gene. Further truncation to 120 bp of 5′ sequence resulted in a sharp downregulation of reporter activity in PC12 cells but a significant rise in both Neuro-2A neuroblastoma cells and nonneuronal Ltk- cells, indicating thatcis-acting elements controlling the regulation ofNSE in Ltk-, Neuro-2A, and PC12 cells may lie within the 135 bp region covered by this deletion. This region contains an AP-2 site and an element similar in sequence and position to a motif identified in the proximal promoter region of the neuron-specific peripherin gene. Reduction to 95 bp of 5′ sequence resulted in a slight downregulation of CAT activity in all cell lines tested, and further truncation to 65 bp of 5′ sequence caused a universal reduction to background levels of CAT activity, concomitant with the disruption of the basalNSE promoter. Our results show that the 5′ flanking region of theNSE gene is capable of conferring cell type-specificity on a heterologous gene in transfected cells and that elements responsible for this are located within the proximal 255 bp.