Psychometric validation of the Weiss Functional Impairment Rating Scale-Parent Report Form in children and adolescents with attention-deficit/hyperactivity disorder.

BACKGROUND: Measurement properties of the Weiss Functional Impairment Rating Scale-Parent Report Form (WFIRS-P), which assesses attention-deficit/hyperactivity disorder (ADHD)-related functional impairment in children/adolescents (6-17 years), were examined. METHODS: Data from seven randomized, controlled trials were pooled. Analyses were conducted in two random half-samples. WFIRS-P conceptual framework was evaluated using confirmatory factor analyses (CFA). Reliability was estimated using internal consistency (Cronbach's alpha) and test-retest reliability methods. Convergent validity was assessed using correlations between WFIRS-P domain scores and the ADHD-RS-IV and Clinical Global Impression-Severity (CGI-S) scales. Responsiveness was tested by comparing mean changes in WFIRS-P domain scores between responders and non-responders based on clinical criteria. RESULTS: CFA adequately confirmed the item-to-scale relationships defined in the WFIRS-P conceptual framework. Cronbach's alpha coefficient exceeded 0.7 for all domains and test-retest reliability exceeded 0.7 for all but Risky Activities. With few exceptions, WFIRS-P domains correlated significantly (p < 0.05) with ADHD-RS-IV Total, Inattention and Hyperactivity-Impulsivity scores and CGI-S at baseline and follow-up in both random half-samples. Mean changes in WFIRS-P domain scores differed significantly between responder and non-responder groups in the expected direction (p < 0.001). CONCLUSIONS: Study results support the reliability, validity and responsiveness of the WFIRS-P. Findings were replicated between two random samples, further demonstrating the robustness of results.

A retrospective chart review of heart rate and blood pressure abnormalities in veterans with spinal cord injury.

OBJECTIVE: Autonomic impairment may lead to increased prevalence of heart rate (HR) and blood pressure (BP) abnormalities in veterans with spinal cord injury (SCI). In addition, comorbid medical conditions and prescription medication use may influence these abnormalities, including bradycardia, and tachycardia, hypotension, hypertension as well as autonomic dysreflexia (AD), and orthostatic hypotension (OH). DESIGN: A retrospective review of clinical and administrative datasets in veterans with SCI and compared the prevalence rates between clinical values and ICD-9 diagnostic codes in individuals with tetraplegia (T: C1-C8), high paraplegia (HP: T1-T6), and low paraplegia (LP: T7 and below). RESULTS: The prevalence of clinical values indicative of a HR ≥ 80 beats per minute was higher in the HP compared to the LP and T groups. A systolic BP (SBP) ≤ 110 mmHg was more common in the T compared to the HP and LP groups, whereas the prevalence of a SBP ≥ 140 mmHg was increased in the LP compared to the HP and T groups. Diagnosis of hypertension was 39-60% whereas the diagnosis of hypotension was less than 1%. Diagnosis of AD and OH was highest in the T group, but remained below 10%, regardless of categorical lesion level. Antihypertensive medications were commonly prescribed (55%), and patients on these medications were less likely to have high BP. The odds ratio of higher SBP and DBP increased with age and body mass index (BMI). CONCLUSION: In veterans with SCI, the prevalence of HR and BP abnormalities varied depending on level of lesion, age, BMI, and prescription medication use.

Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer's disease.

OBJECTIVES: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time. METHODS: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores ≥ 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score ≤ 10) and functional (Blessed Dementia Rating Scale score ≥ 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval. RESULTS: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points. CONCLUSIONS: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects.

Pharmacist- versus physician-initiated admission medication reconciliation: impact on adverse drug events.

BACKGROUND: Medication reconciliation (MR) has proven to be a problematic task for many hospitals to accomplish. It is important to know the clinical impact of physician- versus pharmacist-initiated MR in the resource-limited hospital environment. METHODS: This quasi-experimental study took place from December 2005 to February 2006 at an urban US Veterans Affairs hospital. MR was implemented on 2 similar general medical units: one received physician-initiated MR and the other received pharmacist-initiated MR. Adverse drug events (ADEs) and a 72-hour medication-prescribing risk score were ascertained by research pharmacists for all admitted patients by structured record review. Multivariable models were tested for intervention effect, accounting for quasi-experimental design and clustered observations, and were adjusted for patient and encounter covariates. RESULTS: Pharmacists completed the MR process in 102 admissions and physicians completed the process in 116 admissions. In completing the MR process, pharmacists documented statistically more admission medication changes than physicians (3.6 vs 0.8; P < 0.001). The adjusted odds of an ADE caused by an admission prescribing change with pharmacist-initiated MR compared with a physician-initiated MR were 1.04 with a 95% CI of 0.53 to 2.0. The adjusted odds of an ADE caused by an admission prescribing change that was a prescribing error with pharmacist-initiated MR compared with a physician-initiated MR were 0.38 with a confidence interval of 0.14 to 1.05. No difference was observed in 72-hour prescribing risk score (coefficient = 0.10; 95% CI, -0.54 to 0.75). CONCLUSION: MR performed by pharmacists versus physicians was more comprehensive and was followed by lower odds of ADEs from admission prescribing errors but with similar odds of all types of ADEs. Further research is warranted to examine how MR tasks may be optimally divided among clinicians and the mechanisms by which MR affects the likelihood of subsequent ADEs.

Health care workforce development in rural america: when geriatrics expertise is 100 miles away.

The Geriatric Scholar Program (GSP) is a Department of Veterans Affairs' (VA) workforce development program to infuse geriatrics competencies in primary care. This multimodal educational program is targeted to primary care providers and ancillary staff who work in VA's rural clinics. GSP consists of didactic education and training in geriatrics and gerontology and in quality improvement (QI) and support to implement a local QI project; in addition, elective options include webinars, audio conferences, clinical practica, and mentoring. The program is effective in improving core competencies in geriatrics and in improving clinical care for older Veterans who receive health care in rural clinics.

Meeting standards of high-quality intensive care unit palliative care: clinical performance and predictors.

OBJECTIVES: High-quality care for intensive care unit patients and families includes palliative care. To promote performance improvement, the Agency for Healthcare Research and Quality's National Quality Measures Clearinghouse identified nine evidence-based processes of intensive care unit palliative care (Care and Communication Bundle) that are measured through review of medical record documentation. We conducted this study to examine how frequently the Care and Communication Bundle processes were performed in diverse intensive care units and to understand patient factors that are associated with such performance. DESIGN: Prospective, multisite, observational study of performance of key intensive care unit palliative care processes. SETTINGS: A surgical intensive care unit and a medical intensive care unit in two different large academic health centers and a medical-surgical intensive care unit in a medium-sized community hospital. PATIENTS: Consecutive adult patients with length of intensive care unit stay ≥5 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between November 2007 and December 2009, we measured performance by specified day after intensive care unit admission on nine care process measures: Identify medical decision-maker, advance directive and resuscitation preference, distribute family information leaflet, assess and manage pain, offer social work and spiritual support, and conduct interdisciplinary family meeting. Multivariable regression analysis was used to determine predictors of performance of five care processes. We enrolled 518 (94.9%) patients and 336 (83.6%) family members. Performances on pain assessment and management measures were high. In contrast, interdisciplinary family meetings were documented for <20% of patients by intensive care unit day 5. Performance on other measures ranged from 8% to 43%, with substantial variation across and within sites. Chronic comorbidity burden and site were the most consistent predictors of care process performance. CONCLUSIONS: Across three intensive care units in this study, performance of key palliative care processes (other than pain assessment and management) was inconsistent and infrequent. Available resources and strategies should be utilized for performance improvement in this area of high importance to patients, families, and providers.

Training nurses for interdisciplinary communication with families in the intensive care unit: an intervention.

BACKGROUND: Critical care nurse communication training has largely been limited to didactic materials, interactive training for nurse supervisors, or brief participatory learning programs within the context of comprehensive end-of-life care educational seminars. Preliminary evidence suggests that an interactive approach can also be effective in communication skills training for intensive care unit (ICU) nurses. METHODS: We implemented a 1-day educational intervention in five acute care hospitals within Veterans Integrated Service Network (VISN) 3 (New York-New Jersey region) of the Department of Veterans Affairs and focused solely on communication skills and targeted specifically to nurses providing bedside care for critically ill patients. A "learner centered" approach to skills training that has several integral components was employed. AMONG THESE ARE: a cognitive, evidence-based foundation upon which to build new skills; a method such as role-play that allows participants to practice newly learned skills; and an affective component, during which trainees can freely discuss their impressions of the exercise or explore difficulties that may have been encountered. Before and after the program we conducted a detailed assessment of participants' self-rated communication skills and of the techniques and materials we used. RESULTS AND CONCLUSIONS: Post-program responses documented significant improvement in self-evaluated skills for each of the core tasks we assessed. Evidence suggests that communication with patients and families in the ICU can be most effectively approached in an interdisciplinary way. For nurses to fully realize their potential for optimal communication as members of the multidisciplinary team, they must be equipped with the necessary skills. We believe this new program helps to expand the range of approaches for training nurses in essential communication skills.

Implementation and evaluation of a network-based pilot program to improve palliative care in the intensive care unit.

BACKGROUND: Intensive care unit (ICU) care could be improved by implementation of time-triggered evidence-based interventions including identification of a patient/family medical decision maker, the patient's advance directive status, and cardiopulmonary resuscitation preferences by Day 1; offer of social work and spiritual support by Day 3; and a family meeting establishing goals of care by Day 5. We implemented a program to improve care for ICU patients in five Department of Veterans Affairs' ICUs. MEASURES: We measured the percent of ICU patients with lengths of stay of five or more days that received the care processes by the appropriate day. INTERVENTION: Critical care and palliative care providers trained ICU nurse teams to improve care through auditing, performance feedback, improvement tools, education, and monthly team meetings. OUTCOMES: Pre- and postintervention care were compared. Offering social work and spiritual support, identification of the medical decision maker, and documentation of family meetings significantly improved. CONCLUSIONS/LESSONS LEARNED: ICU nurse teams can be engaged to improve care under the aegis of a collaborative quality improvement project.

Utilization of antihypertensives, antidepressants, antipsychotics, and hormones in Alzheimer disease.

This study explores the longitudinal relationship between patient characteristics and use of 4 drug classes (antihypertensives, antidepressants, antipsychotics, and hormones) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient/caregiver-reported prescription medication usage was categorized by drug class for 201 patients from the Predictors Study. Patient characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation, baseline age, and sex. Assessment interval, year of study entry, and site were controlled for. Before adjusting for covariates, useage increased for antihypertensives (47.8% to 62.2%), antipsychotics (3.5% to 27.0%), and antidepressants (32.3% to 40.5%); use of hormones decreased (19.4% to 5.4%). After controlling for patient characteristics, effects of time on the use of antidepressants were no longer significant. Antihypertensive use was associated with poorer functioning, concurrent use of memantine, and older age. Antipsychotic use was associated with poorer functioning and poorer cognition. Antidepressant use was associated with younger age, poorer functioning, and concurrent use of cholinesterase inhibitors and memantine. Hormone use was associated with being female and younger age. Findings suggest accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine.

Development of and recovery from difficulty with activities of daily living: an analysis of national data.

BACKGROUND: National-level data are needed on predictors of mild physical impairment among older adults to assist policy makers with resource allocation. METHOD: We analyzed data on adults above age 64 from the Medicare Current Beneficiary Survey (MCBS) with no activity of daily living (ADL) difficulties at baseline ( n = 14,226). Five ADLs were measured annually and recovery was defined as regaining complete ADL function at follow-up. RESULTS: The strongest correlates of ADL difficulty were use of antipsychotic medications (adjusted odds ratio [AOR] = 1.93, 95% confidence interval [CI] = 1.44 to 2.58), instrumental ADL difficulty (AOR = 1.90, 95% CI = 1.74 to 2.07), and fair-poor general health (AOR = 1.59, 95% CI = 1.42 to 1.78). Only the number of incident ADL difficulties was associated with recovery (AOR = 0.02, 95% CI = 0.01 to 0.02). CONCLUSION: Identifying factors associated with development of mild physical impairment could help direct patients toward preventive care programs to preempt decline in physical function.

Longitudinal medication usage in Alzheimer disease patients.

This study examined in detail patterns of cholinesterase inhibitors (ChEIs) and memantine use and explored the relationship between patient characteristics and such use. Patients with probable Alzheimer disease AD (n=201) were recruited from the Predictors Study in 3 academic AD centers and followed from early disease stages for up to 6 years. Random effects logistic regressions were used to examine effects of patient characteristics on ChEIs/memantine use over time. Independent variables included measures of function, cognition, comorbidities, the presence of extrapyramidal signs, psychotic symptoms, age, sex, and patient's living situation at each interval. Control variables included assessment interval, year of study entry, and site. During a 6-year study period, rate of ChEIs use decreased (80.6% to 73.0%) whereas memantine use increased (2.0% to 45.9%). Random effects logistic regression analyses showed that ChEI use was associated with better function, no psychotic symptoms, and younger age. Memantine use was associated with better function, poorer cognition, living at home, later assessment interval, and later year of study entry. Results suggest that high rate of ChEI use and increasing memantine use over time are consistent with current practice guidelines of initiation of ChEIs in mild-to-moderate AD patients and initiation of memantine in moderate-to-severe patients.

A random effects multinomial logit analysis of using Medicare and VA healthcare among veterans with dementia.

This study aimed to examine longitudinal patterns of VA-only use, dual VA and Medicare use, or Medicare-only use among veterans with dementia. Data on VA and Medicare use (1998-2001) were obtained from VA administrative datasets and Medicare claims for 2,137 male veterans with a formal diagnosis of Alzheimer's disease or vascular dementia enrolled in the National Longitudinal Caregiver Study. A random effects multinomial logit model accounting for unobserved individual heterogeneity was used to estimate the effects of patient and caregiver characteristics on use group over time. Compared to VA-only use, dual VA and Medicare use was associated with being white, married, higher education, having private insurance, Medicaid, low VA priority level, more functional limitations, and having lived in a nursing home or died in that year. Medicare-only use was associated with older age, being married, higher education, having private insurance, low VA priority level, living further from a VA Medical Center, having more comorbidities, functional limitations, and having lived in a nursing home or died. Veterans whose caregivers reported better health were more likely to be dual users, but those whose caregivers reported more comorbidities were more likely to use Medicare only. Different aspects of veterans' needs and caregiver characteristics have differential effect on where veterans seek care. Efforts to coordinate care between VA and Medicare providers are necessary to ensure patients receive high quality care.

Hospital-based palliative care consultation: effects on hospital cost.

CONTEXT: Palliative care consultation teams in hospitals are becoming increasingly more common. Palliative care improves the quality of hospital care for patients with advanced disease. Less is known about its effects on hospital costs. OBJECTIVE: To evaluate the relationship between palliative care consultation and hospital costs in patients with advanced disease. DESIGN, SETTING, AND PATIENTS: An observational study of 3321 veterans hospitalized with advanced disease between October 1, 2004 and September 30, 2006. The sample includes 606 (18%) veterans who received palliative care and 2715 (82%) who received usual hospital care. October 1, 2004 and September 30, 2006. MAIN OUTCOME MEASURES: We studied the costs and intensive care unit (ICU) use of palliative versus usual care for patients in five Veterans Affairs hospitals over a 2-year period. We used an instrumental variable approach to control for unmeasured characteristics that affect both treatment and outcome. RESULTS: The average daily total direct hospital costs were $464 a day lower for the 606 patients receiving palliative compared to the 2715 receiving usual care (p < 0.001). Palliative care patients were 43.7 percentage points less likely to be admitted to ICU during the hospitalization than usual care patients (p < 0.001). COMMENTS: Palliative care for patients hospitalized with advanced disease results in lower costs of care and less utilization of intensive care compared to similar patients receiving usual care. Selection on unobserved characteristics plays an important role in the determination of costs of care.

Emergency department patient volume and troponin laboratory turnaround time.

OBJECTIVES: Increases in emergency department (ED) visits may place a substantial burden on both the ED and hospital-based laboratories. Studies have identified laboratory turnaround time (TAT) as a barrier to patient process times and lengths of stay. Prolonged laboratory study results may also result in delayed recognition of critically ill patients and initiation of appropriate therapies. The objective of this study was to determine how ED patient volume itself is associated with laboratory TAT. METHODS: This was a retrospective cohort review of patients at five academic, tertiary care EDs in the United States. Data were collected on all adult patients seen in each ED with troponin laboratory testing during the months of January, April, July, and October 2007. Primary predictor variables were two ED patient volume measures at the time the troponin test was ordered: 1) number of all patients in the ED/number of beds (occupancy) and 2) number of admitted patients waiting for beds/beds (boarder occupancy). The outcome variable was troponin turnaround time (TTAT). Adjusted covariates included patient characteristics, triage severity, season (month of the laboratory test), and site. Multivariable adjusted quantile regression was carried out to assess the association of ED volume measures with TTAT. RESULTS: At total of 9,492 troponin tests were reviewed. Median TTAT for this cohort was 107 minutes (interquartile range [IQR] = 73-148 minutes). Median occupancy for this cohort was 1.05 patients (IQR = 0.78-1.38 patients) and median boarder occupancy was 0.21 (IQR = 0.11-0.32). Adjusted quantile regression demonstrated a significant association between increased ED patient volume and longer times to TTAT. For every 100% increase in census, or number of boarders over the number of ED beds, respectively, there was a 12 (95% confidence interval [CI] = 9 to 14) or 33 (95% CI = 24 to 42)-minute increase in TTAT. CONCLUSIONS: Increased ED patient volume is associated with longer hospital laboratory processing times. Prolonged laboratory TAT may delay recognition of conditions in the acutely ill, potentially affecting clinician decision-making and the initiation of timely treatment. Use of laboratory TAT as a patient throughput measure and the study of factors associated with its prolonging should be further investigated.

Brief communication: Management of implantable cardioverter-defibrillators in hospice: A nationwide survey.

BACKGROUND: Communication about the deactivation of implantable cardioverter-defibrillators (ICDs) in patients near the end of life is rare. OBJECTIVE: To determine whether hospices are admitting patients with ICDs, whether such patients are receiving shocks, and how hospices manage ICDs. DESIGN: Cross-sectional survey. SETTING: Randomly selected hospice facilities. PARTICIPANTS: 900 hospices, 414 of which responded fully. MEASUREMENTS: Frequency of admission of patients with ICDs, frequency with which patients received shocks, existence of ICD deactivation policies, and frequency of deactivation. RESULTS: 97% of hospices admitted patients with ICDs, and 58% reported that in the past year, a patient had been shocked. Only 10% of hospices had a policy that addressed deactivation. On average, 42% (95% CI, 37% to 48%) of patients with ICDs had the shocking function deactivated. LIMITATION: The study relied on the knowledge of hospice administrators. CONCLUSION: Hospices are admitting patients with ICDs, and patients are being shocked at the end of life. Ensuring that hospices have policies in place to address deactivation may improve the care for patients with these devices. The authors provide a sample deactivation policy. PRIMARY FUNDING SOURCE: National Institute of Aging and National Institute of Nursing Research.

Tumor necrosis factor-alpha gene polymorphisms are associated with severity of acute graft-versus-host disease following matched unrelated donor bone marrow transplantation in children: a Pediatric Blood and Marrow Transplant Consortium study.

Tumor necrosis factor (TNF)-alpha plays a significant role in conditioning related toxicities and the development of acute graft-versus-host disease (aGVHD). TNF-alpha gene polymorphisms are associated with rejection after organ transplantation and aGVHD in matched related donor blood and marrow transplantation (BMT) recipients. Few studies have been published on unrelated donor BMT in the pediatric age group. In this study, we examined the relationship between specific polymorphisms in TNF pathway genes and the occurrence and severity of aGVHD. Recipient single-nucleotide polymorphisms (SNPs) in TNF-alpha and TNF receptor superfamily members 1A (TNFRSF1A) and 1B (TNFRSF1B) were investigated. In a multi-institutional Pediatric Blood and Marrow Transplant Consortium trial, a total of 180 pediatric patients (mean age, 11.0 years) were prospectively evaluated for clinical outcomes after matched unrelated donor BMT. All patients received myeloablative conditioning and two-drug GVHD prophylaxis with cyclosporine or tacrolimus, with methotrexate in the majority of patients. TNF-alpha genotypes were not correlated with the overall incidence of aGVHD. Significant associations were seen between TNF-alpha variant alleles and the severity of aGVHD (grade II-IV and grade III-IV), especially when analyzed in whites only (n = 165). Grade II-IV aGVHD was correlated with recipient -857T allele (hazard ratio [HR], 0.47; P = .04), -238A allele (HR, 1.76; P = .002), and d3/d3 genotype (HR, 0.64; P = .03). Severe (grade III-IV) aGVHD was associated with TNF-alpha -1031C allele (HR, 2.38; P = .03), -863A allele (HR, 3.18; P = .003), and d4/d4 genotype (HR, 2.82; P = .01). After adjusting for clinical factors, the association of -1031C, -863A, -238A, and d4/d4 genotypes with severity of aGVHD remained statistically significant. No correlation between selected SNPs in TNFRSF1A or TNFRSF1B and the incidence or severity of aGVHD was found. Our findings indicate clinically important relationships between genetic polymorphisms in TNF-alpha and the severity of aGVHD in this cohort. Improved understanding of this relationship may allow for a risk-adjusted approach to GVHD prevention in pediatric BMT.

Continuous lumbar plexus block for postoperative pain control after total hip arthroplasty. A randomized controlled trial.

BACKGROUND: Continuous femoral or lumbar plexus blocks have been demonstrated to provide effective postoperative analgesia of the lower extremity following total joint arthroplasty. The purpose of this study was to compare these two techniques when used with intravenous patient-controlled analgesia and the use of patient-controlled analgesia alone for postoperative pain management following unilateral primary hip arthroplasty. METHODS: Two hundred and twenty-five patients undergoing unilateral total hip arthroplasty for a diagnosis of osteoarthritis were randomly allocated into one of three postoperative treatment groups: continuous lumbar plexus block with patient-controlled analgesia, continuous femoral block with patient-controlled analgesia, and patient-controlled analgesia alone. Scores on a visual analog pain scale administered during physiotherapy twenty-four hours postoperatively were used as the primary outcome measured. Secondary outcomes included scores on a visual analog pain scale at rest, hydromorphone consumption, opioid-related side effects, complications, sensory and motor blockade, and patient satisfaction. RESULTS: Continuous lumbar plexus block significantly reduced pain scores during physiotherapy on postoperative day 1 (p < 0.0001) and day 2 (p < 0.0001) compared with either continuous femoral block or patient-controlled analgesia alone. There were no significant differences for pain at rest between the two regional analgesic techniques. Both regional anesthesia techniques significantly reduced total hydromorphone consumption (p < 0.05) and delirium (disorientation to time and/or place) compared with patient-controlled analgesia alone (p < 0.023). In addition, the use of continuous lumbar plexus block was associated with fewer patients with opioid-related side effects (p < 0.05), greater distances walked (p < 0.05), and enhanced patient satisfaction (p < 0.05) compared with the use of a continuous femoral nerve block with patient-controlled analgesia or with patient-controlled analgesia alone. CONCLUSIONS: Continuous lumbar plexus and femoral blocks significantly reduce the need for opioids and decrease related side effects. Continuous lumbar plexus block is a more effective analgesic modality than is a continuous femoral block or patient-controlled intravenous administration of hydromorphone alone during physical therapy following primary unilateral total hip arthroplasty.

Chemoprevention of colorectal neoplasia by estrogen: potential role of vitamin D activity.

Postmenopausal hormone replacement therapy lowers colon cancer incidence. In humans, the mechanism is unknown, but animal models suggest that it may involve activation of the vitamin D receptor (VDR) pathway. The aims of our study were to determine whether estrogen intervention affects global gene expression in rectal mucosal biopsies and whether vitamin D-related genes are affected. Estradiol was given to raise serum estradiol to premenopausal levels in 10 postmenopausal women under close nutritional control. Primary end points were expression of VDR, CYP24A1, CYP27B1, and E-cadherin in rectal mucosa by reverse transcription-PCR and examining response to estradiol by genome-wide arrays. Responses in gene expression in rectal biopsies to estrogen were determined in each subject individually and compared with a human estrogen response gene array database and a custom array in vitro-generated database. Cluster analysis showed that subjects maintained their overall gene expression profile and that interindividual differences were greater than intraindividual differences after intervention. Eight of 10 subjects showed significant enrichment in estrogen-responsive genes. Gene array group analysis showed activation of the VDR pathway and down-regulation of inflammatory and immune signaling pathways. Reverse transcription-PCR analysis showed significant up-regulation of VDR and E-cadherin, a downstream target of vitamin D action. These data suggest that the chemopreventive action of hormone replacement therapy on colon neoplasia results, at least in part, from changes in vitamin D activity. Evaluation of gene arrays is useful in chemopreventive intervention studies in small groups of subjects.