The cost of a patient activation intervention for achieving successful outcomes: results from the PAADRN randomized controlled trial.

In a large, pragmatic clinical trial, we calculated the costs of achieving four successful patient-centered outcomes using a tailored patient activation DXA result letter accompanied by a bone health brochure. The cost to achieve one successful outcome (e.g., a 0.5 standard deviation improvement in care satisfaction) ranged from $127.41 to $222.75. INTRODUCTION: Pragmatic randomized controlled trials (RCTs) should focus on patient-centered outcomes and report the costs for achieving those outcomes. We calculated per person incremental intervention costs, the number-needed-to-treat (NNT), and incremental per patient costs (cost per NNT) for four patient-centered outcomes in a direct-to-patient bone healthcare intervention. METHODS: The Patient Activation after DXA Result Notification (PAADRN) pragmatic RCT enrolled 7749 patients presenting for DXA at three health centers between February 2012 and August 2014. Interviews occurred at baseline and 52 weeks post-DXA. Intervention subjects received an individually tailored DXA result letter accompanied by an educational bone health brochure 4 weeks post-DXA, while the usual care subjects did not. Outcomes focused on patients (a) correctly identifying their results, (b) contacting their providers, (c) discussing their results with their providers, and (d) satisfaction with their bone healthcare. NNTs were determined using intention-to-treat linear probability models, per person incremental intervention costs were calculated, and costs per NNT were computed. RESULTS: Mean age was 66.6 years old, 83.8% were women, and 75.3% were non-Hispanic whites. The incremental per patient cost (costs per NNT) to increase the ability of a patient to (a) correctly identify their DXA result was $171.07; (b) contact their provider about their DXA result was $222.75; (c) discuss their DXA result with their provider was $193.55; and (d) achieve a 0.5 SD improvement in satisfaction with their bone healthcare was $127.41. CONCLUSION: An individually tailored DXA result letter accompanied by an educational brochure can improve four patient-centered outcomes at a modest cost. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01507662.

Prospective study of postpartum blues. Biologic and psychosocial factors.

Potential biologic and psychosocial causative factors for the postpartum blues were tested in a prospective study of 182 women followed up from the second trimester of pregnancy until postpartum week 9. Personal and family history of depression, depressive symptoms, stressful life events, and social adjustment were all assessed during the second trimester. Levels of progesterone, prolactin, estradiol, free and total estriol, and free and total cortisol were measured on several occasions during late pregnancy and early puerperium. Obstetric and child-care stressors and the postpartum blues were assessed after delivery. Predictors of the postpartum blues were personal and family history of depression, social adjustment, stressful life events, and levels of free and total estriol. Our results support the hypothesis that the postpartum blues is within the spectrum of affective disorders.

[3H]cortivazol: a unique high affinity ligand for the glucocorticoid receptor.

Cortivazol (CVZ) and deacylcortivazol (DAC) are pyrazolosteroids with potent glucocorticoid activity. In previous work we showed that DAC is 40-fold more potent than dexamethasone (DEX) in lysing leukemic lymphoblasts. To assess the interaction between these atypical steroids and the glucocorticoid receptor, we examined the binding of [3H]CVZ to cytosol from glucocorticoid-sensitive and -resistant variants of the human leukemic cell line CEM C7. In glucocorticoid-sensitive cells [3H]CVZ causes a 2-fold induction of glutamine synthetase and binds to a protein in the 4.6 S region of high salt sucrose gradients. On DEAE-cellulose chromatography, [3H]CVZ-receptor complexes show a shift from high (0.25 M KP) to low salt (0.09 M KP) eluting forms upon activation. CVZ competes for a 97,000-dalton protein labeled by [3H]dexamethasone mesylate. Scatchard analysis of the binding of [3H]CVZ in glucocorticoid-sensitive cells revealed a curvilinear plot which resolved into high (0.4 nM) and low (11 nM) affinity components. The receptor concentration of the low affinity site (0.30 pmol/mg protein) was approximately twice that of the high affinity site (0.14 pmol/mg protein). Dissociation experiments with dilution and/or excess unlabeled CVZ supported the presence of independent sites. In contrast, the binding of [3H]DEX to C7 cytosol revealed a single class of binding sites (Kd = 1.9 nM; receptor concentration, 0.46 pmol/mg protein). Examination of the binding of [3H]CVZ using 10(-5) M DEX as the competing ligand showed that DEX binds only to the low affinity site detected by [3H]CVZ. In cytosol from a glucocorticoid-resistant cell line with virtually no [3H]DEX binding, [3H]CVZ detected a single high affinity binding site that was similar in dissociation constant (0.8 nM) and receptor concentration (0.13 pmol/mg protein) to the high affinity site detected in the glucocorticoid-sensitive cell line C7.

Use of [3H]cortivazol to characterize glucocorticoid receptors in a dexamethasone-resistant human leukemic cell line.

ICR 27 is a mutant derived from the glucocorticoid-sensitive human leukemic cell line CEM C7 that has been characterized as glucocorticoid receptor negative based on its ability to specifically bind [3H]dexamethasone ([3H]DEX). We used the pyrazolosteroid [3H]cortivazol ([3H]CVZ) to determine whether ICR 27 cells actually contain glucocorticoid receptors and, if so, whether these receptors can mediate physiological effects. Scatchard analysis of the binding of [3H]CVZ to cytosol from ICR 27 cells was consistent with a single class of receptors of uniform affinity (0.7 nM). Cytosolic [3H]CVZ complexes had a sedimentation coefficient of 4.6S on linear sucrose gradients and eluted from DEAE-cellulose columns at a potassium phosphate concentration of 250 mM. CVZ also competed with [3H]DEX mesylate for binding to a 96,000 mol wt protein. Incubation of ICR 27 cells with CVZ caused 50% growth inhibition and 50% maximal induction of glutamine synthetase activity at concentrations of 20 and 35 nM, respectively. Elution profiles of [3H]CVZ complexes from DEAE-cellulose columns showed that complexes formed upon thermal activation were relatively unstable, and little or no increase in binding of [3H]CVZ-receptor complexes to DNA-cellulose was observed. Thus, [3H]CVZ identifies functional glucocorticoid receptors in a cell line previously described as DEX resistant. Although the binding of [3H]CVZ to activated receptors in vitro appears unstable, high concentrations of CVZ may facilitate stabilization of activated complexes that can mediate both anabolic and catabolic effects.

Decreased glucocorticoid receptor binding in adrenal insufficiency.

To examine the effect of glucocorticoid deficiency on the glucocorticoid receptor, we examine the binding of [3H] dexamethasone to lymphocytes in normal subjects and patients with adrenal insufficiency before and after glucocorticoid replacement therapy. Using a whole cell competitive binding assay, normal human lymphocytes had 5977 +/- 1487 (mean +/- SD) binding sites/cell and a dissociation constant of 10 +/- 2 nM. Lymphocytes from patients with untreated adrenal insufficiency had fewer binding sites (3364 +/-322) and a 2-fold increase in binding affinity (5.4 +/- 0.9 mM). The administration of conventional replacement doses of cortisone acetate for 6 months caused no change in receptor number, but was associated with a decrease in binding affinity toward normal. After long term glucocorticoid replacement therapy, binding parameters were similar to those in patients before treatment. The physiological implications of the decreased receptor number and increased binding affinity in adrenal insufficiency remain to be elucidated.

Bone density in amenorrheic women with and without hyperprolactinemia.

To determine whether decreased bone density in patients with PRL-secreting pituitary tumors is specifically related to hyperprolactinemia or is a consequence of disordered pituitary-gonadal function common to all amenorrheic states, we measured the bone mineral content of the radius by photon absorptiometry in normal subjects, in women with amenorrhea and normal serum PRL levels, and in women with PRL-secreting pituitary tumors. The women did not differ significantly in mean age, height, weight, or serum calcium, phosphorous, gonadotropin, testosterone, vitamin D, or PTH concentrations, and all had normal renal and thyroid function. The bone mineral content in women with amenorrhea and normal serum PRL levels (0.91 +/- 0.02 g/cm) was not significantly different from that in control subjects (0.88 +/- 0.01 g/cm). Patients with PRL-secreting tumors studied 2-5 yr after transsphenoidal surgery had significantly diminished bone mineral content whether they were cured (0.82 +/- 0.02 g/cm) or had persistent amenorrhea and hyperprolactinemia (0.81 +/- 0.02 g/cm). Serum estradiol concentrations did not differ significantly in the four groups, and there was no correlation between estradiol concentration and bone mineral content or between PRL concentration and bone mineral content in the amenorrheic women. The presence of decreased bone mineral content in hyperprolactinemic patients suggests that PRL may have a direct effect on bone and may be another indication for early treatment of PRL-secreting pituitary tumors.

Long term follow-up of women with surgically treated prolactin-secreting pituitary tumors.

To examine the long term effectiveness of transsphenoidal microsurgery for patients with PRL-secreting pituitary tumors, we studied 54 women at yearly intervals after transsphenoidal surgery. Five years after surgery, 19 women (35%) had normal serum PRL concentrations, and 23 (43%) had persistent hyperprolactinemia. Hyperprolactinemia recurred in 12 of 31 patients (39%) who had normal PRL concentration 6 weeks after surgery. None of the patients with recurrent hyperprolactinemia had radiographic evidence of tumor regrowth, and only 3 of 12 had amenorrhea. A serum PRL level below 6 ng/ml 6 weeks after surgery occurred more frequently in cured patients than in those who had a recurrence. PRL responses to TRH were normal in cured patients 1 and 5 yr after surgery and abnormal in those who had recurrent hyperprolactinemia. The PRL responses to chlorpromazine- and insulin-induced hypoglycemia were blunted in patients with normal as well as elevated PRL levels. Patients with recurrent, as well as those with persistent, hyperprolactinemia had no nocturnal rise in serum PRL 5 yr after surgery. The 39% recurrence rate of hyperprolactinemia and persistent abnormalities in pituitary-hypothalamic regulation of PRL secretion after transsphenoidal surgery raise important questions about the choice of primary therapy for patients with PRL-secreting tumors.

Potentiation of glucocorticoid-induced cytolysis in sensitive human leukemic cells by an inhibitor of ADP-ribosylation.

3-Aminobenzamide, a general inhibitor of poly(ADP-ribose)polymerase, potentiated the triamcinolone acetonide-mediated growth inhibition and lysis of the glucocorticoid-sensitive CEM-C7 human leukemic cell line. This potentiation was dose-dependent with maximal response being detected at 3 mM 3-aminobenzamide, and was completely blocked by the glucocorticoid receptor antagonist RU 38486. Scatchard analysis of whole cell specific [3H]triamcinolone acetonide binding data did not reveal any effect of 3-aminobenzamide on either the number of intracellular receptor binding sites or their affinity for the agonist. Treatment of the ICR-27 cell line, which is a glucocorticoid resistant mutant isolated from CEM-C7, with 3-aminobenzamide did not restore triamcinolone acetonide sensitivity. Similarly, 3-aminobenzamide treatment of several other lymphoid cell lines (human HL60 and IM-9 and murine L1210 cells) which contain functional receptors but are not normally lysed by glucocorticoid agonists, failed to induce sensitivity to triamcinolone acetonide. Since treatment of sensitive lymphoid cells with glucocorticoid agonists results in DNA fragmentation prior to cell death, these data suggest that 3-aminobenzamide potentiates the cytolytic response of sensitive cells to glucocorticoid agonists by inhibiting DNA excision repair mechanisms.

Lymphocyte glucocorticoid receptor binding in depressed patients with hypercortisolemia.

Despite elevated levels of serum and urinary cortisol, patients with depressive illness manifest none of the clinical stigmata of glucocorticoid excess. This hypercortisolemia in the absence of clinical effects suggests a state of hormone resistance and could be mediated by alterations in the glucocorticoid receptor. Earlier studies have shown that small doses of glucocorticoids cause a decrease in glucocorticoid receptor binding in normal human lymphocytes. White cells from depressed patients with significant hypercortisolemia would be expected to show a similar change in receptor concentration if peripheral tissues are adequately exposed to and sensitive to the hormone. In this study we compared the binding of [3H]dexamethasone to lymphocytes from normal subjects and depressed patients with hypercortisolemia. Lymphocytes from normal subjects had a mean receptor concentration of 10.2 +/- 0.66 fm/10(6) cells (S.E.M.) and a dissociation constant of 4.8 +/- 0.47 nM. Lymphocytes from depressed patients with abnormal 0800 h serum cortisol after dexamethasone had a mean receptor concentration of 8.8 +/- 0.75 fm/10(6) cells, which was not significantly different from that in lymphocytes from normal subjects or from depressed subjects with normal post-dexamethasone cortisol levels (9.4 +/- 0.95 fm/10(6) cells). Lymphocytes from depressed patients with elevated urinary free cortisol excretion (UFC) also had normal receptor concentration and binding affinity for dexamethasone. The lack of a change in lymphocyte glucocorticoid receptor concentration in the presence of cortisol excess suggests the possibility that hypercortisolemia in depressive illness represents a state of peripheral glucocorticoid resistance.

Factors influencing choice of academic or practice careers in radiology.

Factors, both personal and job-related in nature, that influence career choice among radiology residents are identified. Twenty-six third and fourth year radiology residents at two separate locations, and 17 age-matched and sex-matched internal medicine residents completed a 30-minutes interview and rated themselves on a series of job-related competencies. Data were collected on five groups of variables: demographic data, residency-related variables, factors that influence career choice, self-descriptions, and personal competencies. The results indicate that residents who choose academic careers and those who plan to have private practice careers differ substantially in their reasons for career choice. An academic career is chosen because of its atmosphere, emphasis on research and specialized techniques, and opportunity for teaching. In contrast, private practice careers are selected because of the autonomy they allow, the accompanying lifestyle, and financial reimbursement.

Effects of prolactin in stimulating disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a chronic autoimmune illness, is influenced by hormones. High prolactin concentrations were associated with early death from autoimmune renal disease in NZB/NZW mice, an animal model of severe SLE. NZB/NZW mice that delivered and nursed pups and those that underwent pseudopregnancy had changes in serum IgG and autoantibodies. NZB/NZW mice treated with the prolactin-suppressing drug bromocriptine had prolonged lives. Elevated serum prolactin concentrations are reported in SLE patients of both sexes. We found four women with long-standing hyper-prolactinemia who developed SLE. A survey of premenopausal women whose sera were submitted for autoantibody testing showed that 20% with anti-ds-DNA antibodies also had high prolactin levels. Many hyperprolactinemic patients whose sera were referred to an endocrinology laboratory had positive FANA tests (women 33%, men 53%) but did not have SLE. Disease activity was suppressed in six of seven SLE patients treated with bromocriptine. All had elevated disease activity and five became unexpectedly hyperprolactinemic after treatment stopped. Manipulating serum prolactin affords a means of treating clinical SLE activity.

The relationship between the density of the alveolar processes and that of post-cranial bone.

Skeletal mass declines in all populations with age, and the literature suggests that changes in oral bone may be linked to the status of the post-cranial (systemic) skeleton. However, there is a lack of information defining the relationship between alveolar process bone and the post-cranial skeleton in healthy individuals. The purpose of this study was to determine: (1) if the bone densities of the maxillary and mandibular alveolar processes are related to the bone density of the spine, hip, or radius in healthy women; and (2) if the alveolar process densities decline with age. Forty-one dentate Caucasian women aged 20 to 78 years underwent assessment of post-cranial (systemic) and alveolar process bone. D-speed vertical bitewing and periapical radiographs incorporating aluminum stepwedges, controlled exposure and processing conditions, and a density correction algorithm were used to make alveolar process density assessments with regions of interest (ROIs) apical to crestal bone and intrabony defects. Anteroposterior lumbar (L1 to L4) and lateral lumbar (L2 to L4) spine, total hip (and subregions), and radius bone densities were determined by dual-energy x-ray absorptiometry (DEXA). Correlation analysis revealed significant relationships between maxillary alveolar process bone density and the density of the mandibular alveolar process (r = 0.57, p < or = 0.001), anteroposterior lumbar spine (r = 0.53, p < or = 0.001), lateral lumbar spine (r = 0.52, p < or = 0.001), total hip (r = 0.39, p = 0.01), total radius (r = 0.39, p = 0.01), and age (r = -0.38, p = 0.01). A two-tailed t test comparison revealed significantly greater maxillary alveolar process bone density in women younger than 50 years of age than in those 50 and older (p < or = 0.01). We conclude that the density of maxillary alveolar process bone is significantly related to the density of the mandibular alveolar process, lumbar spine, hip, and radius in healthy women and that maxillary alveolar process bone density declines with age.

Sequential MR enhancement pattern in normal pituitary gland and in pituitary adenoma.

PURPOSE: To measure and evaluate the temporal enhancement characteristics of the normal pituitary gland and pituitary adenoma. METHODS: Thirty healthy subjects and 10 patients with sellar pituitary adenomas were studied prospectively using dynamic MR imaging with a 5- or 10-sec temporal resolution during a bolus injection of gadolinium. RESULTS: Qualitative visual analysis demonstrated a consistent sequential pattern of pituitary enhancement in which the posterior lobe enhanced earlier than the anterior lobe by approximately 35 sec. Quantitative analysis revealed that posterior lobe enhancement occurred 9.8 +/- 1.5 sec (mean +/- SEM) before the anterior lobe in healthy subjects, whereas tumor enhancement occurred significantly before the anterior lobe but only slightly before the posterior lobe in patients with adenomas. CONCLUSION: The sequential enhancement pattern of the normal pituitary gland was found to be consistent with its vascular anatomy. In contrast to previous reports, pituitary adenomas were found to enhance earlier than the anterior lobe. These results suggest that pituitary adenomas have a direct arterial blood supply, similar to that of the posterior pituitary lobe.

Neurologic complications of thyroid and parathyroid disease.

Common thyroid and parathyroid disorders present with reversible neurologic signs and symptoms affecting the central and peripheral nervous system, musculature, and mental function. Patients with thyrotoxicosis may have myopathy, spasticity, seizures, and multiple psychiatric symptoms. A deficiency of thyroid hormone also causes muscle weakness and may be accompanied by reversible muscle hypertrophy or movement disorders. The chronic hypercalcemia that develops secondary to hyperparathyroidism produces many psychiatric and cognitive symptoms, as well as a reversible myopathy. Calcium deficiency leads to neuromuscular irritability, paresthesias, and tetany. Psychiatric disorders are also common in this disorder.

Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables.

Demographic, psychiatric, social, cognitive, and life stress variables were used to determine the etiology of depression in childbearing (CB; n = 182) and nonchildbearing (NCB; n = 179) women. Hormonal variables in postpartum depression were also evaluated. In the CB group predictors of depression diagnosis were previous depression, depression during pregnancy, and a Vulnerability (V) x Life Stress (LS) interaction; predictors of depressive symptomatology were previous depression, depressive symptoms during pregnancy, life events, and V x LS. Only estradiol was associated with postpartum depression diagnosis. In the NCB group V X LS was the only predictor of depression diagnosis; depressive symptoms during pregnancy and life events were predictors of depressive symptomatology. Previous findings about depression vulnerability were replicated. The significant V x LS interactions support the vulnerability-stress model of postpartum depression.

Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women.

To investigate possible effects of chronic marijuana use on reproductive and stress hormones, we assayed testosterone, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol in 93 men and 56 women with a mean (+/- S.E.) age of 23.5 +/- 0.4 years. Hormone values were compared among groups of subjects stratified according to frequency of marijuana use (frequent, moderate and infrequent; N = 27, 18, and 30, respectively) and non-using controls (N = 74). Chronic marijuana use showed no significant effect on hormone concentrations in either men or women.

Effect of the antiprogesterone RU-38486 on meningioma implanted into nude mice.

Meningiomas have been shown to have steroid-binding proteins. In vitro, estradiol, progesterone, and the antiestrogen tamoxifen stimulate tumor growth. However, incubation of tumor cells with an antiprogesterone agent results in tumor inhibition. In this investigation, a human meningioma was implanted subcutaneously in athymic nude mice. Two treatment groups were established, one receiving the antiprogesterone agent RU-38486 (10 mg/kg/day in suspension) and the other receiving only vehicle. After 3 months, the tumor growth index (defined as the tumor volume at 3 months divided by the initial tumor volume) was 0.25 +/- 0.46 (mean +/- standard deviation) in the group receiving antiprogesterone and was 1.54 +/- 0.58 in the control group (p = 0.041). Further investigation of the effect of antiprogestational agents on the growth and hormone-binding proteins of other meningiomas will better define the mechanism of their effects.

Factors associated with primary care residents' satisfaction with their training.

BACKGROUND AND OBJECTIVES: Satisfaction is known to impact work performance, learning, recruitment, and retention. This study identifies the factors associated with primary care residents' satisfaction with their training. METHODS: We used a cross-sectional survey based on the Price-Mueller model of job satisfaction. The model included 14 job characteristics, four personal characteristics, and four demographic factors. Data were collected in February and March 1996 from residents in three primary care training programs (family practice, pediatrics, and internal medicine) at a large academic medical center. The same standardized, self-administered questionnaires were used in all three departments. RESULTS: Seventy-five percent (n = 119) of the residents returned questionnaires. Five job characteristics were positively associated with resident satisfaction: continuity of care, autonomy, collegiality, work that encourages professional growth, and work group loyalty. Role conflict, a sixth job characteristic, was negatively associated with satisfaction. The personal characteristic of having an optimistic outlook on life was also positively associated with satisfaction. The model explained 66% of the variation in self-reported satisfaction. CONCLUSIONS: The satisfaction of the residents was significantly associated with six job characteristics and one personal factor. Interventions based on these job characteristics may increase resident satisfaction and may lead to better patient outcomes, better work performance, greater patient satisfaction, and more success in recruiting top students into a residency.