A Comparison of Liver Disease Mortality With HIV and Overdose Mortality Among Georgia Prisoners and Releasees: A 2-Decade Cohort Study of Prisoners Incarcerated in 1991

Objectives. We investigated whether eventual causes of death among a cohort of inmates imprisoned in the southeastern United States differed from those in previous prisoner studies.Methods. We matched 23 510 prisoners in Georgia, a state with historically low levels of heroin consumption but moderate amounts of injection drug use, who were incarcerated on June 30, 1991, to death registries through 2010. Main exposure was 4-year time intervals over 2 decades of observation; main outcome was mortality from liver disease, HIV, and overdose.Results. Although the HIV-related mortality rate exceeded that from liver-related conditions before 2003, liver disease subsequently surpassed HIV as a cause of death. Among 3863 deaths, 22 (0.6%) occurred within 2 weeks after release from prison. Of these, only 2 were caused by accidental poisoning (likely drug overdose). Cardiovascular disease and cancer were the most frequent causes of death in this aging cohort.Conclusions. Our study design deemphasized immediate deaths but highlighted long-term sequelae of exposure to viral hepatitis and alcohol. Treating hepatitis C and implementing interventions to manage alcohol use disorders may improve survival among prisoners in the Southeast.Drug use, incarceration, and mortality are intertwined: the use of illicit drugs can result in both incarceration and premature death. A 2010 international meta-analysis of prisoners'' survival after their release into the community emphasized mortality from overdose in the 2 weeks following discharge, possibly attributable to loss of opiate tolerance after forced sobriety in prison,1 but a more recent publication illustrates how this pattern may vary among subpopulations.2Long-term consequences of injection drug use include hepatitis C and HIV infection. In the United States, sexual exposure is the most common mode of HIV transmission, but the hepatitis C epidemic is mainly driven by the injection of drugs, even if the drug use is not sustained.3 HIV prevalence is 3 times as common among prisoners as among the general population,4 but hepatitis C prevalence is 13 times as high.5,6 Sequelae that could lead to death from hepatitis C typically occur 2 to 4 decades after injection drug use was initiated. Little is known about the long-term survival of inmates, particularly in the southeastern United States, where historical and recent patterns of drug use may differ from those in other regions.In contrast with other studies that have examined cohorts of released inmates, we sought to assess long-term prisoner survival by retrospectively following a cohort composed of a cross section of all imprisoned persons in the state of Georgia on a single day in 1991. In a previous study, we did not observe significantly higher mortality among members of this cohort immediately after release from prison than in the subsequent postrelease period.7 Multiple sources suggest that heroin use is less common in Georgia than in other states. Between 2002 and 2012, consistently fewer than 6.5% of men jailed in Atlanta, the capital of and largest city in Georgia, had evidence of heroin in their urine samples.8,9 The prevalence of opiate use in Atlanta was among the lowest for any city studied in the past decade by the Office of the National Drug Control Policy.8–10 In particular, heroin use was lower than in Washington State, site of a previous study of former inmate mortality.11 According to the Treatment Episode Data Set–Admissions for 1992 to 2010 from the Substance Abuse and Mental Health Services Administration, heroin addiction accounted for only 1.6% of admissions for drug rehabilitation in Georgia, but 9.7% in Washington State and 14.2% nationally.12In assessment of risk for hepatitis C, needle use—whether for heroin, cocaine, or another drug—is more important than what is injected. Needle use in Georgia is not uncommon. According to population-wide National Survey on Drug Use and Health data for 2002 to 2009, 1.1% of Georgians have ever used a needle to inject drugs, including cocaine—a moderate rate compared with the frequency in Washington State, where lifetime prevalence is 2.7%, and nationally, where prevalence is 1.6%.13 State-level data on needle use prior to 2002 are not publically available from the Substance Abuse and Mental Health Services Administration.The prevalence of hepatitis C in the Georgia general population is moderately high, especially in Atlanta. At Grady Memorial Hospital, the safety net charity hospital for Atlanta, the prevalence of hepatitis C among ambulatory primary care patients is 7%. A liver clinic established at this hospital saw 807 unique patients in its first 5 years of existence and was still receiving 60 new patient referrals each month through 2010.14 Three quarters of the patients were African American, and most patients were born between 1945 and 1965; 64% were former drug users, and only 4% were currently using.14 High prevalence of hepatitis C in this baby boomer birth cohort probably reflects time-limited parenteral drug use decades ago, perhaps as early as the Vietnam war era.15 Despite relatively low levels of heroin use in the state, we hypothesized that the prevalence of hepatitis C would be high among inmates in the Georgia prison system who were born between 1945 and 1965.We sought to describe the leading causes of death over 2 decades in a large cohort of all Georgians who were in state prisons on June 30, 1991, and to evaluate whether the immediate mortality following prison discharge was low, because Georgia is a state with low heroin use. In light of the moderate background rates of injection drug use in Georgia, we hypothesized that mortality from liver-related causes would rise over time as the cohort aged. Our first aim was to rank the causes of death and categorize which deaths occurred in prison, immediately after release, and subsequently. Second, we compared deaths from liver disease to those from HIV in 4-year intervals between 1991 and 2010.     

Analytical and between-subject variation of thrombin generation measured by calibrated automated thrombography on plasma samples*

Background: The Calibrated Automated Thrombography (CAT) is an in vitro thrombin generation (TG) assay that holds promise as a valuable tool within clinical diagnostics. However, the technique has a considerable analytical variation, and we therefore, investigated the analytical and between-subject variation of CAT systematically. Moreover, we assess the application of an internal standard for normalization to diminish variation.

Methods: 20 healthy volunteers donated one blood sample which was subsequently centrifuged, aliquoted and stored at ?80?°C prior to analysis. The analytical variation was determined on eight runs, where plasma from the same seven volunteers was processed in triplicates, and for the between-subject variation, TG analysis was performed on plasma from all 20 volunteers. The trigger reagents used for the TG assays included both PPP reagent containing 5?pM tissue factor (TF) and PPPlow with 1?pM TF. Plasma, drawn from a single donor, was applied to all plates as an internal standard for each TG analysis, which subsequently was used for normalization.

Results: The total analytical variation for TG analysis performed with PPPlow reagent is 3–14% and 9–13% for PPP reagent. This variation can be minimally reduced by using an internal standard but mainly for ETP (endogenous thrombin potential). The between-subject variation is higher when using PPPlow than PPP and this variation is considerable higher than the analytical variation.

Conclusion: TG has a rather high inherent analytical variation but considerable lower than the between-subject variation when using PPPlow as reagent.     

Medical Rehabilitation: Guidelines to Advance the Field With High-Impact Clinical Trials

The purpose of this Special Communication is to summarize guidelines and recommendations stemming from an expert panel convened by the National Institutes of Health, National Center for Medical Rehabilitation Research (NCMRR) for a workshop entitled The Future of Medical Rehabilitation Clinical Trials, held September 29-30, 2016, at the NCMRR offices in Bethesda, Maryland. The ultimate goal of both the workshop and this summary is to offer guidance on clinical trials design and operations to the medical rehabilitation research community, with the intent of maximizing the effect of future trials.