A Retrospective 4-year Outcome Study of Veterans Admitted to an Acute Inpatient Detoxification Unit for Opioid Use Disorder.

BACKGROUND AND OBJECTIVES: With 47 600 opioid-related deaths in 2017, the yearly deaths have surpassed the HIV/AIDS peak yearly death rates. Residential rehabilitation (RR) and medication-assisted treatments (MAT) are commonly utilized treatments for opioid use disorder (OUD). METHODS: All patients (n = 182) who were admitted to the Boston Veterans Health Administration for inpatient admission for medically supervised opioid withdrawal in 2015 were included. Deceased patients were matched 1:1, based on age and sex to living patients from the 182-patient cohort. Nationwide electronic medical records were analyzed from 2015 through 2018. Via multilinear regression, risk factor correlation to all-cause mortality (the dependent variable) was our main outcome. Primary risk factors included recurrent admissions for medically supervised withdrawals and exposure to RR or MAT. Secondary risk factors were opioid use traits, nonopioid drug use, partner support, education level, homelessness, and employment. RESULTS: 18.4% (n = 34) were deceased by the time of follow-up-equivalent to 4760 deaths per 100 000 person-years. A total of 61.8% (n = 21) of these deaths were directly related to opioid use. Completion of RR correlated with lower predicted mortality (ß = -8.21, P = 0.03). In contrast, attending RR but not completing correlated with higher predicted mortality rate (ß = 6.51, P = 0.046). Concurrent benzodiazepine use (ß = 8.99, P = 0.047), generalized anxiety disorder (ß = 7.13, P = 0.03) and major depressive disorder (ß = 5.44, P = 0.04) increased risk of death. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: OUD carries a shockingly high lethality in Veterans requiring inpatient admission for opioid withdrawal, particularly when there are untreated comorbid psychiatric conditions. RR and MAT are correlated to lower all-cause mortality in this population and should be highly utilized. Given the extremely high mortality, intensive system-wide interventions are needed for the care of Veterans with OUD. On the basis of the reduced predicted mortality with RR and MAT, further research into novel MATs as well as refining RR programs should be a major focus. (Am J Addict 2019;28:318-323).

Cerebral bioenergetic differences measured by phosphorus-31 magnetic resonance spectroscopy between bipolar disorder and healthy subjects living in two different regions suggesting possible effects of altitude.

AIM: Increased oxidative stress in cerebral mitochondria may follow exposure to the systemic hypobaric hypoxia associated with residing at higher altitudes. Because mitochondrial dysfunction is implicated in bipolar disorder (BD) pathophysiology, this may impact the cerebral bioenergetics in BD. In this study, we evaluated the cerebral bioenergetics of BD and healthy control (HC) subjects at two sites, located at sea level and at moderate altitude. METHODS: Forty-three veterans with BD and 33 HC veterans were recruited in Boston (n = 22) and Salt Lake City (SLC; n = 54). Levels of phosphocreatine, ß nucleoside triphosphate (ßNTP), inorganic phosphate, and pH over total phosphate (TP) were measured using phosphorus-31 magnetic resonance spectroscopy in the following brain regions: anterior cingulate cortex and posterior occipital cortex, as well as bilateral prefrontal and occipitoparietal (OP) white matter (WM). RESULTS: A significant main effect of site was found in ßNTP/TP (Boston > SLC) and phosphocreatine/TP (Boston < SLC) in most cortical and WM regions, and inorganic phosphate/TP (Boston < SLC) in OP regions. A main effect analysis of BD diagnosis demonstrated a lower pH in posterior occipital cortex and right OP WM and a lower ßNTP/TP in right prefrontal WM in BD subjects, compared to HC subjects. CONCLUSION: The study showed that there were cerebral bioenergetic differences in both BD and HC veteran participants at two different sites, which may be partly explained by altitude difference. Future studies are needed to replicate these results in order to elucidate the dysfunctional mitochondrial changes that occur in response to hypobaric hypoxia.

Can multisite clinical trial results change clinical practice? Use of long-acting injectable risperidone nationally in the Veterans Health Administration.

BACKGROUND: Multisite practical clinical trials evaluate treatments in real-world practice. A multisite randomized Veterans Health Administration (VHA) cooperative study (CSP#555) published in 2011 compared the first long-acting injectable (LAI) second-generation antipsychotic (SGA), Risperidone Consta®, in veterans with a diagnosis of schizophrenia or schizoaffective disorder, to oral antipsychotics, with unexpected null results for effectiveness and cost-effectiveness. Whether null results of this type could change VHA practice has not been studied. METHODS: A longitudinal observational analysis was used to evaluate the impact of the trial findings on VHA clinical practices. National administrative data compared new starts on LAI risperidone during the 4 years before the publication of CSP#555 in 2011 to new starts on LAI risperidone during the 4 years after. RESULTS: Among 119,565 Veterans with the indicated diagnoses treated with antipsychotics from 2007 to 2015, the number and proportion of new starts on LAI risperidone declined significantly following the study publication, as did the total number of annual users and drug expenditures. However, data from 2007 to 2010 showed the decline in new starts actually preceded the publication of CSP#555. This change was likely explained by the increase in new starts, total use, and expenditures on a newer medicine, LAI paliperidone, a 4-week LAI treatment, in the 2 years prior to the publication of CSP#555. CONCLUSIONS: The declining use of LAI risperidone likely primarily reflects the substitution of a longer-acting LAI SGA, paliperidone, that came to market 2 years before the study publication, a substitution that may have been reinforced by null CSP#555 study results for LAI risperidone.

Impact of multi-site clinical trial results on clinical practice: Use of risperidone to treat PTSD nationally in the veterans health administration.

Multi-site randomized effectiveness trials evaluate treatments under real-world conditions. Whether results change practice is under-studied. A 6-month 26-site Veterans Health Administration (VHA) cooperative study published in 2011 compared an oral second-generation antipsychotic, risperidone, to placebo for refractory PTSD with null results. National VHA administrative data compared new starts on risperidone during the 5 years before and after the year of publication. Among the 450,000-841,000 Veterans diagnosed with PTSD annually from 2006 to 2016 the proportion with new starts on risperidone declined every year before and after publication. No evidence of an effect of null study results on VHA clinical practice was observed.

Familial risk for psychiatric disorders in military veterans who have post-traumatic stress disorder with psychosis: a retrospective electronic record review.

AIMS/OBJECTIVES/BACKGROUND: Post-traumatic stress disorder (PTSD) is a leading cause of morbidity among military veterans, with up to one-in-five individuals with PTSD also having psychotic symptoms. The current study was designed to determine the association between a known family history of psychiatric illness and risk of developing psychosis in patients with PTSD. METHODS: Retrospective medical record review was performed on a cohort study of 414 consecutive individuals admitted to the Veteran Administration in 2014 with a diagnosis of military-related PTSD, but without a prior diagnosis of a psychotic disorder. PTSD with psychotic features was defined as the presence of hallucinations, paranoia, other delusions, thought insertion, withdrawal, broadcasting, and/or dissociative episodes. RESULTS: Overall, 22.9% of individuals with PTSD had psychotic symptoms. Having a first-degree relative with bipolar affective and with anxiety disorders was associated with an increased risk of PTSD with psychosis (odds ratio=2.01, 95% confidence interval: 1.01-4.45 and odds ratio=2.72, 95% confidence interval: 1.16-6.41, respectively). A family history of schizophrenia or depression was not associated with risk of developing psychotic features in patients with PTSD. In veterans with military-related PTSD, a familial vulnerability for bipolar disorder and anxiety disorders was associated with an increased risk of developing PTSD with psychotic features. These are preliminary data, given the limitations of a retrospective record review design. These results await replication in future prospective direct family interview studies.