Patrick J. Blatchford

Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial.

IMPORTANCE For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy. OBJECTIVE To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach. INTERVENTIONS Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins. MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings. RESULTS A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, -3.5% to 10.5%; P=.36) and did not meet the noninferiority end point. Total QOL was better for the group discontinuing statin therapy (mean McGill QOL score, 7.11 vs 6.85; P=.04). Few participants experienced cardiovascular events (13 in the discontinuation group vs 11 in the continuation group). Mean cost savings were

Mortality After Prison Release: Opioid Overdose and Other Causes of Death, Risk Factors, and Time Trends From 1999 to 2009

3.37 per day and

Oral Iloprost Improves Endobronchial Dysplasia in Former Smokers

716 per patient. CONCLUSIONS AND RELEVANCE This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL, use of fewer nonstatin medications, and a corresponding reduction in medication costs. Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01415934.

Risk factors for all-cause, overdose and early deaths after release from prison in Washington state

BACKGROUND Among former prisoners, a high rate of death has been documented in the early postrelease period, particularly from drug-related causes. Little is known about risk factors and trends in postrelease mortality in the past decade, especially given general population increases in overdose deaths from pharmaceutical opioids. OBJECTIVE To determine postrelease mortality between 1999 and 2009; cause-specific mortality rates; and whether sex, calendar year, and custody factors were risk factors for all-cause, overdose, and opioid-related deaths. DESIGN Cohort study. SETTING Prison system of the Washington State Department of Corrections. PARTICIPANTS 76 208 persons released from prison. MEASUREMENTS Identities were linked probabilistically to the National Death Index to identify deaths and causes of death, and mortality rates were calculated. Cox proportional hazards regression estimated the effect of age, sex, race or ethnicity, whether the incarceration resulted from a violation of terms of the persons community supervision, length of incarceration, release type, and calendar year on the hazard ratio (HR) for death. RESULTS The all-cause mortality rate was 737 per 100 000 person-years (95% CI, 708 to 766) (n = 2462 deaths). Opioids were involved in 14.8% of all deaths. Overdose was the leading cause of death (167 per 100 000 person-years [CI, 153 to 181]), and overdose deaths in former prisoners accounted for 8.3% of the overdose deaths among persons aged 15 to 84 years in Washington from 2000 to 2009. Women were at increased risk for overdose (HR, 1.38 [CI, 1.12 to 1.69]) and opioid-related deaths (HR, 1.39 [CI, 1.09 to 1.79]). LIMITATION The study was done in only 1 state. CONCLUSION Innovation is needed to reduce the risk for overdose among former prisoners. PRIMARY FUNDING SOURCE National Institute on Drug Abuse and the Robert Wood Johnson Foundation.

Bronchial Epithelial Ki-67 Index Is Related to Histology, Smoking, and Gender, but Not Lung Cancer or Chronic Obstructive Pulmonary Disease

There are no established chemopreventive agents for lung cancer, the leading cause of cancer death in the United States. Prostacyclin levels are low in lung cancer and supplementation prevents lung cancer in preclinical models. We carried out a multicenter double-blind, randomized, phase II placebo-controlled trial of oral iloprost in current or former smokers with sputum cytologic atypia or endobronchial dysplasia. Bronchoscopy was performed at study entry and after completion of six months of therapy. Within each subject, the results were calculated by using the average score of all biopsies (Avg), the worst biopsy score (Max), and the dysplasia index (DI). Change in Avg was the primary end point, evaluated in all subjects, as well as in current and former smokers. The accrual goal of 152 subjects was reached and 125 completed both bronchoscopies (60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age, tobacco exposure, and baseline histology. Baseline histology was significantly worse for current smokers (Avg 3.0) than former smokers (Avg 2.1). When compared with placebo, former smokers receiving oral iloprost exhibited a significantly greater improvement in Avg (0.41 units better, P = 0.010), in Max (1.10 units better, P = 0.002), and in DI (12.45%, P = 0.006). No histologic improvement occurred in current smokers. Oral iloprost significantly improves endobronchial histology in former smokers and deserves further study to determine if it can prevent the development of lung cancer. Cancer Prev Res; 4(6); 793–802. ©2011 AACR.

High-Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long-Term Care Residents: A Randomized Clinical Trial

BACKGROUND High mortality rates after release from prison have been well-documented, particularly from overdose. However, little is known about the risk factors for death after release from prison. Therefore, the objective of this study was to determine the demographic and incarceration-related risk factors for all-cause, overdose and early mortality after release from prison. METHODS We conducted a retrospective cohort study of inmates released from a state prison system from 1999 through 2003. The cohort included 30,237 who had a total of 38,809 releases from prison. Potential risk factors included gender, race/ethnicity, age, length of incarceration, and community supervision. Cox proportional hazards regression was used to determine risk factors for all-cause, overdose and early (within 30 days of release) death after release from prison. RESULTS Age over 50 was associated with an increased risk for all-cause mortality (hazard ratio [HR] 2.67 for each decade increase, 95% confidence interval [CI] 2.23, 3.20) but not for overdose deaths or early deaths. Latinos were at decreased risk of death compared to Whites only for all-cause mortality (HR 0.61, 95% CI 0.42, 0.87). Increasing years of incarceration were associated with a decreased risk of all-cause mortality (HR 0.95, 95% CI 0.91, 0.99) and overdose deaths (HR 0.80, 95% CI 0.68, 0.95), but not early deaths. Gender and type of release were not significantly associated with all-cause, overdose or early deaths. CONCLUSIONS Age, ethnicity and length of incarceration were associated with mortality after release from prison. Interventions to reduce mortality among former inmates are needed.

Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

Purpose: To determine whether increased bronchial epithelial proliferation is associated with histology, smoking status, gender, age, chronic obstructive pulmonary disease (COPD), or lung cancer. Experimental Design: Cross-sectional study of 113 subjects undergoing white light and autofluorescence bronchoscopy: 27 never smokers; 27 current or ex-smokers with normal spirometry; 31 current or ex-smokers with COPD; and 28 current, ex-, or never smokers with lung cancer. Ki-67 expresssion was determined by immunohistochemistry on all evaluable biopsy sites without carcinoma. Relationships between Ki-67 index (percentage of epithelial cells expressing Ki-67), demographic variables, smoking, histology, and the presence of COPD and/or lung cancer were determined. Results: Results for both maximal and mean Ki-67 index are similar, so only the former are reported. Average maximal Ki-67 index was higher in current smokers than either ex-smokers or never smokers (48.0% versus 30.6% versus 22.6%; P < 0.001). Males had higher Ki-67 index than females (39.9% versus 23.6%; P < 0.001). Compared with subjects without disease (Ki-67 index = 30.0%), maximal Ki-67 index was not significantly elevated (P = 0.44) in subjects with either lung cancer (Ki-67 = 39.1%) or COPD (Ki-67 = 38.9%). Conclusions: Smoking status, bronchial histology, and gender were significantly associated with Ki-67 index. No increase in Ki-67 index was found in the nonmalignant epithelium of patients with lung cancer or COPD. Although Ki-67 index may provide insight into the short-term effects of chemoprevention agents on cell proliferation, its lack of association with lung cancer or COPD raises question regarding its utility as a lung cancer risk biomarker. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2425–31)

Psychostimulant-related deaths among former inmates.

To determine the efficacy and safety of high‐dose vitamin D supplementation for prevention of acute respiratory infection (ARI) in older long‐term care residents.

High Symptom Burden and Low Functional Status in the Setting of Multimorbidity

ABSTRACT The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed—chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase–associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)—measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 – 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.

Patterns of fractionation for patients with T2N0M0 glottic larynx cancer undergoing definitive radiotherapy in the United States

Objectives:Psychostimulants are highly addictive and their use is increasing. Little is known about psychostimulant-related deaths. This study identified characteristics, risk factors, and contributing substances reported upon death among former prison inmates who died from a psychostimulant-related death. Methods:This retrospective cohort study of released inmates from 1999 to 2003 (N = 30,237) linked data from the Washington State Department of Corrections with the National Death Index. We examined characteristics of individuals who died with psychostimulants listed among their causes of death. These were categorized into 3 groups: (1) noncocaine psychostimulants, (2) cocaine only, and (3) all psychostimulants. Cox proportional hazards regression determined risk factors for death in each group, and the risk of death in the first 2 weeks after release from prison Results:Of the 443 inmates who died, 25 (6%) had noncocaine psychostimulants listed among their causes of death. Six of these 25 deaths had both noncocaine psychostimulants and cocaine listed among their causes-of-death. Most of the former inmates who died with noncocaine psychostimulants were male (n = 21, 84%) and non-Hispanic white (88%, n = 22). Cocaine only was listed among the causes-of-death for 49 former inmates; most were male (n = 35, 71%) and non-Hispanic white (n = 27, 55%). Longer length of incarceration was associated with a reduced risk of death from any psychostimulant use (hazard ratio = 0.76, confidence interval = 0.63–0.920 for each additional year of incarceration) and from use of noncocaine psychostimulants (hazard ratio = 0.42, 95% CI = 0.22–0.80). Risk of death was highest during the first 2 weeks postrelease for cocaine only–related deaths (incidence mortality ratio = 1224.0, confidence interval = 583–1865). Conclusions:Former prisoners have a significant risk of death from psychostimulants, especially within the first 2 weeks postrelease.