Clinical aspects of ALS in Gulf War veterans.

The increased incidence of ALS in military veterans of the first Persian Gulf War raised speculation that they may have a 'Persian Gulf' variant of ALS with atypical clinical features. Medical records of military veterans with ALS, previously identified in our epidemiological study, were evaluated for clinical features (age and site of onset, race, unexplained atypical findings) and ventilator-free survival. Comparisons between deployed versus non-deployed cohorts were made with deployment status based on designation by the Department of Defense Manpower Data Center (DMDC) or by self-report. Other than the young age of onset in both cohorts (40.8 years overall mean; 40.1 years for DMDC deployed, 41.2 years for DMDC non-deployed), review of the medical records failed to document any atypical features. After adjusting for bulbar onset, median survival from symptom onset in those > or =40 years of age was 35.5 months (2.96 years) compared to 64.7 months (5.39 years) in the group <40 years of age (hazard ratio (HR)=0.47, 95% CI 0.30-0.73, p=0.0006). After adjusting for age, median survival was 45.4 months (3.78 years) and 54.8 months (4.57 years) in bulbar- versus non-bulbar onset groups, respectively (HR=1.41, 95% CI 0.83-2.39, p=0.20). After adjusting for age and site of onset, deployed veterans had significantly shorter survival than non-deployed (40.2 vs. 57.0 months, HR=0.62, 95% CI 0.40-0.96, p=0.03) using DMDC data. In conclusion, although veterans developing ALS after deployment to the Persian Gulf in 1990-1991 exhibited otherwise typical clinical features, they experienced shorter ventilator-free survival than non-deployed veterans.

A controlled trial of inpatient and outpatient geriatric evaluation and management.

BACKGROUND: Over the past 20 years, both inpatient units and outpatient clinics have developed programs for geriatric evaluation and management. However, the effects of these interventions on survival and functional status remain uncertain. METHODS: We conducted a randomized trial involving frail patients 65 years of age or older who were hospitalized at 11 Veterans Affairs medical centers. After their condition had been stabilized, patients were randomly assigned, according to a two-by-two factorial design, to receive either care in an inpatient geriatric unit or usual inpatient care, followed by either care at an outpatient geriatric clinic or usual outpatient care. The interventions involved teams that provided geriatric assessment and management according to Veterans Affairs standards and published guidelines. The primary outcomes were survival and health-related quality of life, measured with the use of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), one year after randomization. Secondary outcomes were the ability to perform activities of daily living, physical performance, utilization of health services, and costs. RESULTS: A total of 1388 patients were enrolled and followed. Neither the inpatient nor the outpatient intervention had a significant effect on mortality (21 percent at one year overall), nor were there any synergistic effects between the two interventions. At discharge, patients assigned to the inpatient geriatric units had significantly greater improvements in the scores for four of the eight SF-36 subscales, activities of daily living, and physical performance than did those assigned to usual inpatient care. At one year, patients assigned to the outpatient geriatric clinics had better scores on the SF-36 mental health subscale, even after adjustment for the score at discharge, than those assigned to usual outpatient care. Total costs at one year were similar for the intervention and usual-care groups. CONCLUSIONS: In this controlled trial, care provided in inpatient geriatric units and outpatient geriatric clinics had no significant effects on survival. There were significant reductions in functional decline with inpatient geriatric evaluation and management and improvements in mental health with outpatient geriatric evaluation and management, with no increase in costs.

Change, Challenge and Opportunity: Departments of Medicine and Their Leaders.

Academic Health Centers are evolving to larger and more complex Academic Health Systems (AHS), reflecting financial stresses requiring them to become nimble, efficient, and patient (consumer) and faculty (employee) focused. The evolving AHS organization includes many positive attributes: unity of purpose, structural integration, collaboration and teamwork, alignment of goals with resource allocation, and increased financial success. The organization, leadership, and business acumen of the AHS influence directly opportunities for Departments of Medicine. Just as leadership capabilities of the AHS affect its future success, the same is true for departmental leadership. The Department of Medicine is no longer a quasi- autonomous entity, and the chairperson is no longer an independent decision-maker. Departments of Medicine will be most successful if they maintain internal unity and cohesion by not fragmenting along specialty lines. Departments with larger endowments or those with public financial support have more flexibility when investing in the academic missions. The chairpersons of the future should serve as change agents while simultaneously adopting a "servant leadership" model. Chairpersons with executive and team building skills, and business acumen and experience, are more likely to succeed in managing productive and lean departments. Quality of patient care and service delivery enhance the department's effectiveness and credibility and assure access to additional financial resources to subsidize the academic missions. Moreover, the drive for excellence, high performance and growth will fuel financial solvency.

Geriatric evaluation and management units in the care of the frail elderly cancer patient.

BACKGROUND: Geriatric assessment has been suggested as a possibly useful approach in dealing with frail elderly cancer patients. METHODS: This was a secondary subset analysis from a randomized 2 x 2 factorial trial in 11 Department of Veterans Affairs medical centers. Hospitalized, frail patients at least 65 years old, after stabilization of their acute illness, were randomized to receive care in a geriatric inpatient unit, a geriatric outpatient clinic, both, or neither. The interventions involved core teams that provided geriatric assessment and patient management. We identified 99 patients with a diagnosis of cancer by The International Classification of Diseases, 9th Revision (ICD-9) codes, excluding all nonmelanoma skin cancers. Outcomes collected at discharge, 6 months, and 1 year after randomization were survival, changes in health-related quality of life (using the Medical Outcomes Study 36-Item Short-Form general health survey [SF-36]), activities of daily living, physical performance, health service utilization, and costs. RESULTS: There was no effect on mortality (1-year survival 59.6%). The changes in the SF-36 scores from randomization for emotional limitation, mental health and bodily pain (also sustained at 1 year) on the SF-36 were better for geriatric inpatient care cancer patients at discharge. There was no difference in SF-36 scores between geriatric outpatient and usual outpatient care. Days of hospitalization and overall costs were equivalent for the interventions and usual care over the 1-year study. CONCLUSIONS: This study suggests that inpatient geriatric assessment and management may be an effective approach to the management of pain and psychological status in the elderly cancer inpatient at no greater length of hospitalization or extra cost than usual care.

Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. OBJECTIVE: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. DESIGN: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. SETTING: 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. PARTICIPANTS: 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. INTERVENTION: Doxycycline, 200 mg, or matching placebo daily for 12 months. MEASUREMENTS: The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. RESULTS: No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. LIMITATIONS: Adherence to treatment after 6 months was poor. CONCLUSION: Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.

Communicating and advocating for science and medicine: beyond the basics.

I have discussed several advocacy strategies to improve effective communications for those motivated to do the necessary work to make a difference in policy decisions involving science and health care. I encourage you to get involved personally with members of Congress, their key "staffers," and to contribute financially to their election efforts. Other suggestions are self-evident, for example, think strategically, only advocate for important policies and do not "over promise" or "under deliver." If you "get to yes," stop negotiating and leave gratefully. Remember, you are operating in a high stakes arena and while you understand the intended consequences, you may misjudge unintended consequences that could diminish success. But if you want to make a difference, you must become a "player in the policy and political game." And if you "get in the game," you should play to win!

Potential cost savings of erythropoietin administration in end-stage renal disease.

BACKGROUND: In a Department of Veterans Affairs randomized controlled trial, a lower dose of recombinant human erythropoietin (epoetin) was shown to attain target hematocrit levels when administered subcutaneously compared with intravenously. Since epoetin is expensive, optimizing the therapeutic effect of epoetin using a strategy that includes subcutaneous administration could lead to substantial cost savings. METHODS: We used an economic cost projection model to estimate potential savings to the Medicare End-Stage Renal Disease Program that could occur during a transition from intravenous to subcutaneous administration of epoetin among hemodialysis patients. Data included clinical results from the Department of Veterans Affairs randomized controlled trial, the 1998 Centers for Medicare and Medicaid Services' End-Stage Renal Disease Core Indicators Survey, and the 1997-1998 Medicare claims files. In sensitivity analyses, we varied the expected dose reductions (10% to 50%) and the proportion of patients (25% to 100%) who switched to subcutaneous administration. RESULTS: Medicare cost savings were estimated at $47 to $142 million annually as 25% to 75% of hemodialysis patients who received epoetin intravenously switched to subcutaneous administration while reducing the dose by 32%. A minimal reduction (10%) in epoetin dose would result in Medicare cost savings of an estimated $15 to $44 million annually. CONCLUSION: Administering epoetin subcutaneously would provide substantial cost savings to Medicare. For the transition to occur, consensus among stakeholders is needed, especially among patients whose treatment satisfaction and health-related quality of life would be most affected.

Effects of geriatric evaluation and management on adverse drug reactions and suboptimal prescribing in the frail elderly.

PURPOSE: To determine if inpatient or outpatient geriatric evaluation and management, as compared with usual care, reduces adverse drug reactions and suboptimal prescribing in frail elderly patients. METHODS: The study employed a randomized 2 x 2 factorial controlled design. Subjects were patients in 11 Veterans Affairs (VA) hospitals who were > or =65 years old and met criteria for frailty (n = 834). Inpatient geriatric unit and outpatient geriatric clinic teams evaluated and managed patients according to published guidelines and VA standards. Patients were followed for 12 months. Blinded physician-pharmacist pairs rated adverse drug reactions for causality (using Naranjo's algorithm) and seriousness. Suboptimal prescribing measures included unnecessary and inappropriate drug use (Medication Appropriateness Index), inappropriate drug use (Beers criteria), and underuse. RESULTS: For serious adverse drug reactions, there were no inpatient geriatric unit effects during the inpatient or outpatient follow-up periods. Outpatient geriatric clinic care resulted in a 35% reduction in the risk of a serious adverse drug reaction compared with usual care (adjusted relative risk = 0.65; 95% confidence interval: 0.45 to 0.93). Inpatient geriatric unit care reduced unnecessary and inappropriate drug use and underuse significantly during the inpatient period (P <0.05). Outpatient geriatric clinic care reduced the number of conditions with omitted drugs significantly during the outpatient period (P <0.05). CONCLUSION: Compared with usual care, outpatient geriatric evaluation and management reduces serious adverse drug reactions, and inpatient and outpatient geriatric evaluation and management reduces suboptimal prescribing, in frail elderly patients.

An overview of variance inflation factors for sample-size calculation.

For power and sample-size calculations, most practicing researchers rely on power and sample-size software programs to design their studies. There are many factors that affect the statistical power that, in many situations, go beyond the coverage of commercial software programs. Factors commonly known as design effects influence statistical power by inflating the variance of the test statistics. The authors quantify how these factors affect the variances so that researchers can adjust the statistical power or sample size accordingly. The authors review design effects for factorial design, crossover design, cluster randomization, unequal sample-size design, multiarm design, logistic regression, Cox regression, and the linear mixed model, as well as missing data in various designs. To design a study, researchers can apply these design effects, also known as variance inflation factors to adjust the power or sample size calculated from a two-group parallel design using standard formulas and software.

The effect of geriatrics evaluation and management on nursing home use and health care costs: results from a randomized trial.

BACKGROUND: The Geriatric Evaluation and Management study was developed to assess the impact of a comprehensive geriatric assessment service on the care of the elderly. OBJECTIVES: We sought to evaluate the cost and clinical impact of inpatient units and outpatient clinics for geriatric evaluation and management. RESEARCH DESIGN: We undertook a prospective, randomized, controlled trial using a 2x2 factorial design, with 1-year follow-up. SUBJECTS: A total of 1388 participants hospitalized on either a medical or surgical ward at 11 participating Veterans Affairs medical centers were randomized to receive either inpatient geriatric unit (GEMU) or usual inpatient care (UCIP), followed by either outpatient care from a geriatric clinic (GEMC) versus usual outpatient care (UCOP). MEASURES: We measured health care utilization and costs. RESULTS: Patients assigned to the GEMU had a significantly decreased rate of nursing home placement (odds ratio=0.65; P=0.001). Neither the GEMU nor GEMC had any statistically significant improvement effects on survival and only modest effects on health status. There were statistically insignificant mean cost savings of $1027 (P=0.29) per patient for the GEMU and $1665 (P=0.69) per patient for the GEMC. CONCLUSIONS: Inpatient or outpatient geriatric evaluation and management units didn't increase the costs of care. Although there was no effect on survival and only modest effects on SF-36 scores at 1-year follow-up, there was a statistically significant reduction in nursing home admissions for patients treated in the GEMU.