Efficacy and safety of Sandoz biosimilar rituximab for active rheumatoid arthritis: 52-week results from the randomized controlled ASSIST-RA trial.

OBJECTIVES: This report provides data for the extent of B cell depletion and recovery, efficacy, safety and immunogenicity of Sandoz rituximab (SDZ-RTX; GP2013; Rixathon®) compared with reference rituximab (Ref-RTX) up to week 52 of the ASSIST-RA study. METHODS: Patients were randomized to SDZ-RTX or Ref-RTX in combination with methotrexate according to the RTX label. The primary endpoint was analysed at week 24. Responders (28-joint DAS [DAS28] decrease from baseline >1.2) at week 24 with residual disease activity (DAS28 ≥2.6) were eligible for a second treatment course between week 24 and 52. Endpoints after week 24 included change from baseline in peripheral B cells, DAS28, ACR 20% response rate (ACR20), Clinical and Simplified Disease Activity Indexes (CDAI, SDAI) and HAQ disability index (HAQ-DI). Safety and immunogenicity were assessed by the incidence of adverse events and antidrug antibodies. RESULTS: Primary and secondary endpoints up to week 24 were met. Overall, 260/312 randomized patients completed treatment up to week 52. SDZ-RTX resulted in B cell concentrations over time similar to Ref-RTX. The efficacy of SDZ-RTX was similar to Ref-RTX up to week 52, as measured by DAS28, ACR20/50/70, CDAI, SDAI and HAQ-DI. Safety of SDZ-RTX was similar to Ref-RTX regarding frequency, type and severity of adverse events, which were consistent with the known Ref-RTX safety profile. The incidence of antidrug antibodies was low and transient similarly across treatment groups. CONCLUSION: SDZ-RTX demonstrated similar B cell concentrations over time, efficacy, safety and immunogenicity to Ref-RTX over 52 weeks of the ASSIST-RA study.

Brief Report: Safety and Immunogenicity of Rituximab Biosimilar GP 2013 After Switch From Reference Rituximab in Patients With Active Rheumatoid Arthritis.

OBJECTIVE: Comparable clinical efficacy of the rituximab (RTX) biosimilar GP2013 and reference RTX has been established in blinded randomized trials. However, when switching from a reference biologic to a biosimilar, potential safety implications are often an important consideration. Therefore, the aim of this study was to evaluate the safety of switching from reference RTX to RTX biosimilar GP2013 compared with treatment continuation with reference RTX in patients with rheumatoid arthritis (RA). METHODS: In this multinational, randomized, double-blind, parallel-group safety study, 107 patients with RA who had previously received treatment (of any duration) with reference RTX as part of routine practice and who required continuation of treatment were randomized to receive either GP2013 or to continue treatment with reference RTX. All patients received a stable dosage of methotrexate and folic acid during the study. Study assessments included the incidence of hypersensitivity, infusion-related and anaphylactic reactions, immunogenicity (antidrug antibodies), and general safety. RESULTS: Regardless of whether patients switched to GP2013 or continued treatment with reference RTX, the incidences of hypersensitivity (9.4% and 11.1%, respectively) and infusion-related reactions (11.3% and 18.5%, respectively) were similarly low. Only 1 patient (in the reference RTX group) developed antidrug antibodies to RTX after starting study treatment. No neutralizing antidrug antibodies were observed. Antidrug antibodies were not associated with adverse events (AEs). No clinically meaningful differences in the rate of AEs were observed between treatment groups. CONCLUSION: No safety risks were detected when patients switched from reference RTX to GP2013. The safety profiles of patients in both treatment groups were similar, although the study was not powered for statistical testing of equivalence in safety.

A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis.

OBJECTIVES: The aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment. METHODS: In this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid. The primary endpoint was the area under the serum concentration-time curve from study drug infusion to infinity (AUC0-inf). Additional PK and PD parameters, along with efficacy, immunogenicity and safety outcomes were also assessed up to week 24. RESULTS: The 90% CI of the geometric mean ratio of the AUCs were within the bioequivalence limits of 80% to 125% for all three comparisons; GP2013 versus RTX-EU: 1.106 (90% CI 1.010 to 1.210); GP2013 versus RTX-US: 1.012 (90% CI 0.925 to 1.108); and RTX-EU versus RTX-US: 1.093 (90% CI 0.989 to 1.208). Three-way PD equivalence of B cell depletion was also demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX. CONCLUSIONS: Three-way PK/PD equivalence of GP2013, RTX-EU and RTX-US was demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX. TRIAL REGISTRATION NUMBER: NCT01274182; Results.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Pain and physical and psychological symptoms in ambulatory HIV patients in the current treatment era.

CONTEXT: HIV infection has become a manageable chronic disease. There are few studies of pain and symptoms in the current treatment era. OBJECTIVES: Our primary objective was to determine the prevalence of and risk factors for pain and physical and psychological symptoms in a population of ambulatory HIV patients. METHODS: We performed a cross-sectional study using the Brief Pain Inventory and the Memorial Symptom Assessment Scale-Short Form (MSAS). RESULTS: We evaluated 156 individuals with a median age of 47.5 years (range 21-71), median time since HIV diagnosis of 11 years (range <1 to 25), and median CD4+ cell count of 502 cells/mm(3) (interquartile range [IQR] 308-683). Most (125, 80.6%) of the patients had an undetectable viral load. Seventy-six (48.7%) patients reported pain, of whom 39 (51.3%) had moderate to severe pain, and 43 (57.3%) had pain that caused moderate to severe interference with their lives. The median number of symptoms was eight (IQR 5-14.5) of 32 queried. In multivariable analyses, patients with psychiatric illness were 39.8% more likely to have pain (P<0.001). Psychiatric illness was associated with 0.7 and 1.2 point higher MSAS subscale scores, and IV drug use was associated with 0.4 and 0.5 higher subscale scores (out of four). CONCLUSION: Pain and other physical and psychological symptoms were common among ambulatory HIV patients. Pain and symptoms were strongly associated with psychiatric illness and IV drug use. Future investigation should evaluate interventions that include psychiatric and substance abuse components for HIV patients with pain.

Early termination of a trial of mycophenolate mofetil for treatment of interstitial cystitis/painful bladder syndrome: lessons learned.

PURPOSE: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries. RESULTS: Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls. CONCLUSIONS: In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.

Good intentions: risk factors for unintended pregnancies in the US cohort of a microbicide trial.

BACKGROUND: The study was conducted to assess socio-behavioral and biological factors associated with unplanned pregnancy in the US cohort of a microbicide trial. STUDY DESIGN: We conducted a mixed-method, nested case-control study of risk factors for pregnancy within the US cohort of the microbicide trial HPTN 035. We developed an instrument to assess attitudes and beliefs about fertility control/contraceptive utilization among 122 women. Cases were HPTN 035 participants who became pregnant while enrolled, matched by time on study 1:4 with controls. Univariable and multivariable analysis were performed with pregnancy as the outcome of interest. RESULTS: Contraceptive method change during the trial was associated with unplanned pregnancy (OR=1.76). Participant desire/partners' desire for future children (OR=4.95) and young age (OR=0.88 annually above age 19 years) were independently associated with unintended pregnancy. CONCLUSION: Within a trial that enroll heterosexually active women, there may be ways to identify those at highest risk of becoming pregnant a priori.

Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial.

BACKGROUND: Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic. METHODS: This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006-2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed. RESULTS: Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIH-CPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and subscores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups. CONCLUSION: Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00371033.

Effect of amitriptyline on symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome.

PURPOSE: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports. MATERIALS AND METHODS: We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment. RESULTS: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01). CONCLUSIONS: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.

Red blood cell transfusion is associated with infection and extracerebral complications after subarachnoid hemorrhage.

OBJECTIVE: Red blood cell transfusion (RBCT) is associated with medical complications in general medical and surgical patients. We examined the hypothesis that RBCT during intensive care unit (ICU) care is associated with medical complications after subarachnoid hemorrhage (SAH). METHODS: We retrospectively analyzed a prospective observational database containing 421 patients with SAH (mean age, 51.5 years; standard deviation, 14.6 years). Logistic regression models were used to adjust for age, admission hemoglobin (Hgb), clinical grade, average ICU Hgb, and symptomatic vasospasm. RESULTS: Two hundred fourteen patients received an RBCT during their ICU stay. Medical complications were identified in 156 patients and were more common in those who received blood (46%) than in those who did not (29.8%) (P < .001). Major medical complications (cardiac, pulmonary, renal, or hepatic) occurred in 111 patients, and minor complications (eg, skin rash, deep vein thrombosis) occurred in 45 patients. Any non-central nervous system infection (n = 183; P < .001), including pneumonia (n = 103; P < .001) or septicemia (n = 36; P = .02), was more common with RBCT. Central nervous system infections (meningitis, cranial wound, n = 15) also were associated with RBCT (P = .03). Mechanically ventilated patients (n = 259) were more likely to have received an RBCT than those who did not (P < .001). When logistic regression was used to control for age, admission clinical grade and Hgb, average ICU Hgb, symptomatic vasospasm, and other admission variables associated with outcome, the following factors (odds ratio; 95% confidence interval) were associated with RBCT: any medical complication (1.8; 1.1-3.0), major medical complications (2.1; 1.2-3.7), any infection (2.8; 1.7-4.5), pneumonia (2.6; 1.5-4.7), septicemia (2.9; 1.2-6.8), and need for mechanical ventilation (2.8; 1.5-5.1). CONCLUSION: These data suggest that RBCTs are associated with medical complications after SAH. However, the data do not infer causation, and further study is necessary to better define the indications for transfusion after SAH.

Association of a younger age with an increased risk of angiographic and symptomatic vasospasms following subarachnoid hemorrhage.

OBJECT: Vasospasm is a leading cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). It is important to predict which patients are at risk for vasospasm so that interventions can be made. There are several potential risk factors for vasospasm, one of which is age. However, the effect of age on vasospasm, particularly symptomatic vasospasm, remains controversial. METHODS: Three hundred ninety-one patients were retrospectively identified from a prospective observational database of patients with SAH who had been admitted to a single center. Demographic and clinical data were recorded, and cerebral angiograms obtained at admission and between 5 and 10 days later were compared. The relationship between age and angiographic and symptomatic vasospasms was examined using logistic regression techniques. RESULTS: Mild (86 patients), moderate (69 patients), severe (56 patients), and no angiographic vasospasms (180 patients) were documented by comparing admission and follow-up angiograms in each patient. Symptomatic vasospasm was identified in 69 patients (17.6%). Angiographic vasospasm was more frequent as age decreased. Except in patients < 30 years old, the frequency of symptomatic vasospasm also increased with decreasing age (p = 0.0001). After adjusting for variables known to be associated with vasospasm, an advanced age was associated with a reduced incidence of any angiographic vasospasm (OR 0.96, 95% CI 0.94-0.97), severe angiographic vasospasm (OR 0.96, 95% CI 0.95-0.98), and symptomatic vasospasm (OR 0.98, 95% CI 0.96-0.99). CONCLUSIONS: Results in this study show that a younger age is associated with an increased incidence of angiographic and symptomatic vasospasm.

Prolonged hospital stay and the resident duty hour rules of 2003.

BACKGROUND: Resident duty hour reforms of 2003 had the potential to create a major impact on the delivery of inpatient care. OBJECTIVE: We examine whether the reforms influenced the probability of a patient experiencing a prolonged hospital length of stay (PLOS), a measure reflecting either inefficiency of care or the development of complications that may slow the rate of discharge. RESEARCH DESIGN: Conditional logistic models to compare PLOS in more versus less teaching-intensive hospitals before and after the reform, adjusting for patient comorbidities, common time trends, and hospital site. SUBJECTS: Medicare (N = 6,059,015) and Veterans Affairs (VA) (N = 210,276) patients admitted for medical conditions (acute myocardial infarction, heart failure, stroke, or gastrointestinal bleeding) or surgical procedures (general, orthopedic, and vascular) from July 2000 to June 2005. MEASURES: Prolonged length of stay. RESULTS: Modeling all medical conditions together, the odds of prolonged stay in the first year post reform at more versus less teaching intensive hospitals was 1.01 (95% CI: 0.97-1.05) for Medicare and 1.07 (0.94-1.20) for the VA. Results were similarly negative in the second year post reform. For "combined surgery" the post year 1 odds ratios were 1.04 (0.98-1.09) and 0.94 (0.78-1.14) for Medicare and the VA respectively, and similarly unchanged in post year 2. Isolated increases in the probability of prolonged stay did occur for some vascular surgery procedures. CONCLUSIONS: Hospitals generally found ways to cope with duty hour reform without increasing the prevalence of prolonged hospital stays, a marker of either inefficient care or complications.

The health effects of Medicare for the near-elderly uninsured.

OBJECTIVE: To determine whether Medicare enrollment at age 65 has an effect on the health trajectory of the near-elderly uninsured. DATA SOURCES: Eight biennial waves (1992-2006) of the Health and Retirement Study, a nationally representative panel survey of noninstitutionalized 51-61 year olds and their spouses. STUDY DESIGN: We use a quasi-experimental approach to compare the health effects of insurance for the near-elderly uninsured with previously insured contemporaneous controls. The primary outcome measure is overall self-reported health status combined with mortality (i.e., excellent to very good, good, fair to poor, dead). RESULTS: The change in the trajectory of overall health status for the previously uninsured that can be attributed to Medicare is small and not statistically significant. For every 100 persons in the previously uninsured group, joining Medicare is associated with 0.6 fewer in excellent or very good health (95 percent CI: -4.8, 3.3), 0.3 more in good health (95 percent CI: -3.8, 4.1), 2.5 fewer in fair or poor health (95 percent CI: -7.4, 2.3), and 2.8 more dead (-4.0, 10.0) by age 73. The health trajectory patterns from physician objective health measures are similarly small and not statistically significant. CONCLUSIONS: Medicare coverage at age 65 for the previously uninsured is not linked to improvements in overall health status.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Did duty hour reform lead to better outcomes among the highest risk patients?

BACKGROUND: Earlier work demonstrated that ACGME duty hour reform did not adversely affect mortality, with slight improvement noted among specific subgroups. OBJECTIVE: To determine whether resident duty hour reform differentially affected the mortality risk of high severity patients or patients who experienced post-operative complications (failure-to-rescue). DESIGN: Observational study using interrupted time series analysis with data from July 1, 2000 - June 30, 2005. Fixed effects logistic regression was used to examine the change in the odds of mortality or failure-to-rescue (FTR) in more versus less teaching-intensive hospitals before and after duty hour reform. PARTICIPANTS: All unique Medicare patients (n = 8,529,595) admitted to short-term acute care non-federal hospitals and all unique VA patients (n = 318,636 patients) with principal diagnoses of acute myocardial infarction, congestive heart failure, gastrointestinal bleeding, stroke or a DRG classification of general, orthopedic or vascular surgery. MEASUREMENTS AND MAIN RESULTS: We measured mortality within 30 days of hospital admission and FTR, measured by death among patients who experienced a surgical complication. The odds of mortality and FTR generally changed at similar rates for higher and lower risk patients in more vs. less teaching intensive hospitals. For example, comparing the mortality risk for the 10% of Medicare patients with highest risk to the other 90% of patients in post-reform year 1 for combined medical an OR of 1.01 [95% CI 0.90, 1.13], for combined surgical an OR of 0.91 [95% CI 0.80, 1.04], and for FTR an OR of 0.94 [95% CI 0.80, 1.09]. Findings were similar in year 2 for both Medicare and VA. The two exceptions were a relative increase in mortality for the highest risk medical (OR 1.63 [95% CI 1.08, 2.46]) and a relative decrease in the high risk surgical patients within VA in post-reform year 1 (OR 0.52 [95% CI 0.29, 0.96]). CONCLUSIONS: ACGME duty hour reform was not associated with any consistent improvements or worsening in mortality or failure-to-rescue rates for high risk medical or surgical patients.

Depression and retirement in late middle-aged U.S. workers.

OBJECTIVE: To determine whether late middle-aged U.S. workers with depression are at an increased risk for retirement. DATA SOURCE: Six biennial waves (1992-2002) of the Health and Retirement Study, a nationally representative panel survey of noninstitutionalized 51-61-year-olds and their spouses started in 1992. STUDY DESIGN: Workers aged 53-58 years in 1994 were followed every 2 years thereafter, through 2002. Depression was coded as lagged time-dependent variables measuring active depression and severity of depression. The main outcome variable was a transition to retirement which was measured using two distinct definitions to capture different stages in the retirement process: (1) Retirement was defined as a transition out of the labor force in the sample of all labor force participants (N=2,853); (2) In addition a transition out of full time work was used as the retirement definition in the subset of labor force participants who were full time workers (N=2,288). PRINCIPAL FINDINGS: In the sample of all labor force participants, the presence of active depression significantly increased the hazard of retirement in both late middle-aged men (adjusted OR: 1.37 [95 percent CI 1.05, 1.80]) and women (adjusted OR: 1.40 [95 percent CI 1.10, 1.78]). For women, subthreshold depression was also a significant predictor of retirement. In the sample of full time workers, the relationship between depression and retirement was considerably weaker for women yet remained strong for men. CONCLUSIONS: Depression and depressive symptoms were significantly associated with retirement in late middle-aged U.S. workers. Policymakers must consider the potentially adverse impact of these labor market outcomes when estimating the cost of untreated depression and evaluating the value of interventions to improve the diagnosis and treatment of depression.

Short- and long-term mortality after an acute illness for elderly whites and blacks.

OBJECTIVE: To estimate racial differences in mortality at 30 days and up to 2 years following a hospital admission for the elderly with common medical conditions. DATA SOURCES: The Medicare Provider Analysis and Review File and the VA Patient Treatment File from 1998 to 2002 were used to extract patients 65 or older admitted with a principal diagnosis of acute myocardial infarction, stroke, hip fracture, gastrointestinal bleeding, congestive heart failure, or pneumonia. STUDY DESIGN: A retrospective analysis of risk-adjusted mortality after hospital admission for blacks and whites by medical condition and in different hospital settings. PRINCIPAL FINDINGS: Black Medicare patients had consistently lower adjusted 30-day mortality than white Medicare patients, but the initial survival advantage observed among blacks dissipated beyond 30 days and reversed by 2 years. For VA hospitalizations similar patterns were observed, but the initial survival advantage for blacks dissipated at a slower rate. CONCLUSIONS: Racial disparities in health are more likely to be generated in the posthospital phase of the process of care delivery rather than during the hospital stay. The slower rate of increase in relative mortality among black VA patients suggests an integrated health care delivery system like the VA may attenuate racial disparities in health.

Survival from in-hospital cardiac arrest during nights and weekends.

CONTEXT: Occurrence of in-hospital cardiac arrest and survival patterns have not been characterized by time of day or day of week. Patient physiology and process of care for in-hospital cardiac arrest may be different at night and on weekends because of hospital factors unrelated to patient, event, or location variables. OBJECTIVE: To determine whether outcomes after in-hospital cardiac arrest differ during nights and weekends compared with days/evenings and weekdays. DESIGN AND SETTING: We examined survival from cardiac arrest in hourly time segments, defining day/evening as 7:00 am to 10:59 pm, night as 11:00 pm to 6:59 am, and weekend as 11:00 pm on Friday to 6:59 am on Monday, in 86,748 adult, consecutive in-hospital cardiac arrest events in the National Registry of Cardiopulmonary Resuscitation obtained from 507 medical/surgical participating hospitals from January 1, 2000, through February 1, 2007. MAIN OUTCOME MEASURES: The primary outcome of survival to discharge and secondary outcomes of survival of the event, 24-hour survival, and favorable neurological outcome were compared using odds ratios and multivariable logistic regression analysis. Point estimates of survival outcomes are reported as percentages with 95% confidence intervals (95% CIs). RESULTS: A total of 58,593 cases of in-hospital cardiac arrest occurred during day/evening hours (including 43,483 on weekdays and 15,110 on weekends), and 28,155 cases occurred during night hours (including 20,365 on weekdays and 7790 on weekends). Rates of survival to discharge (14.7% [95% CI, 14.3%-15.1%] vs 19.8% [95% CI, 19.5%-20.1%], return of spontaneous circulation for longer than 20 minutes (44.7% [95% CI, 44.1%-45.3%] vs 51.1% [95% CI, 50.7%-51.5%]), survival at 24 hours (28.9% [95% CI, 28.4%-29.4%] vs 35.4% [95% CI, 35.0%-35.8%]), and favorable neurological outcomes (11.0% [95% CI, 10.6%-11.4%] vs 15.2% [95% CI, 14.9%-15.5%]) were substantially lower during the night compared with day/evening (all P values < .001). The first documented rhythm at night was more frequently asystole (39.6% [95% CI, 39.0%-40.2%] vs 33.5% [95% CI, 33.2%-33.9%], P < .001) and less frequently ventricular fibrillation (19.8% [95% CI, 19.3%-20.2%] vs 22.9% [95% CI, 22.6%-23.2%], P < .001). Among in-hospital cardiac arrests occurring during day/evening hours, survival was higher on weekdays (20.6% [95% CI, 20.3%-21%]) than on weekends (17.4% [95% CI, 16.8%-18%]; odds ratio, 1.15 [95% CI, 1.09-1.22]), whereas among in-hospital cardiac arrests occurring during night hours, survival to discharge was similar on weekdays (14.6% [95% CI, 14.1%-15.2%]) and on weekends (14.8% [95% CI, 14.1%-15.2%]; odds ratio, 1.02 [95% CI, 0.94-1.11]). CONCLUSION: Survival rates from in-hospital cardiac arrest are lower during nights and weekends, even when adjusted for potentially confounding patient, event, and hospital characteristics.

Is lower 30-day mortality posthospital admission among blacks unique to the Veterans Affairs health care system?

BACKGROUND: Several studies have reported lower risk-adjusted mortality for blacks than whites within the Veterans Affairs (VA) health care system, particularly for those age 65 and older. This finding may be a result of the VA's integrated health care system, which reduces barriers to care through subsidized comprehensive health care services. However, no studies have directly compared racial differences in mortality within 30 days of hospitalization between the VA and non-VA facilities in the US health care system. OBJECTIVE: To compare risk-adjusted 30-day mortality for black and white males after hospital admission to VA and non-VA hospitals, with separate comparisons for patients younger than age 65 and those age 65 and older. RESEARCH DESIGN: Retrospective observational study using hospital claims data from the national VA system and all non-VA hospitals in Pennsylvania and California. SUBJECTS: A total of 369,155 VA and 1,509,891 non-VA hospitalizations for a principal diagnosis of pneumonia, congestive heart failure, gastrointestinal bleeding, hip fracture, stroke, or acute myocardial infarction between 1996 and 2001. MEASURES: Mortality within 30 days of hospital admission. RESULTS: Among those under age 65, blacks in VA and non-VA hospitals had similar odds ratios of 30-day mortality relative to whites for gastrointestinal bleeding, hip fracture, stroke, and acute myocardial infarction. Among those age 65 and older, blacks in both VA and non-VA hospitals had significantly reduced odds of 30-day mortality compared with whites for all conditions except pneumonia in the VA. The differences in mortality by race are remarkably similar in VA and non-VA settings. CONCLUSIONS: These findings suggest that factors associated with better short-term outcomes for blacks are not unique to the VA.

Is thirty-day hospital mortality really lower for black veterans compared with white veterans?

OBJECTIVE: To examine the source of observed lower risk-adjusted mortality for blacks than whites within the Veterans Affairs (VA) system by accounting for hospital site where treated, potential under-reporting of black deaths, discretion on hospital admission, quality improvement efforts, and interactions by age group. DATA SOURCES: Data are from the VA Patient Treatment File on 406,550 hospitalizations of veterans admitted with a principal diagnosis of acute myocardial infarction, stroke, hip fracture, gastrointestinal bleeding, congestive heart failure, or pneumonia between 1996 and 2002. Information on deaths was obtained from the VA Beneficiary Identification Record Locator System and the National Death Index. STUDY DESIGN: This was a retrospective observational study of hospitalizations throughout the VA system nationally. The primary outcome studied was all-location mortality within 30 days of hospital admission. The key study variable was whether a patient was black or white. PRINCIPAL FINDINGS: For each of the six study conditions, unadjusted 30-day mortality rates were significantly lower for blacks than for whites (p<.01). These results did not vary after adjusting for hospital site where treated, more complete ascertainment of deaths, and in comparing results for conditions for which hospital admission is discretionary versus non-discretionary. There were also no significant changes in the degree of difference by race in mortality by race following quality improvement efforts within VA. Risk-adjusted mortality was consistently lower for blacks than for whites only within the population of veterans over age 65. CONCLUSIONS: Black veterans have significantly lower 30-day mortality than white veterans for six common, high severity conditions, but this is generally limited to veterans over age 65. This differential by age suggests that it is unlikely that lower 30-day mortality rates among blacks within VA are driven by treatment differences by race.