Lithium continuation therapy following ketamine in patients with treatment resistant unipolar depression: a randomized controlled trial.

The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is associated with rapid but transient antidepressant effects in patients with treatment resistant unipolar depression (TRD). Based on work suggesting that ketamine and lithium may share overlapping mechanisms of action, we tested lithium compared to placebo as a continuation strategy following ketamine in subjects with TRD. Participants who met all eligibility criteria and showed at least an initial partial response to a single intravenous infusion of ketamine 0.5 mg/kg were randomized under double-blind conditions to lithium or matching placebo before receiving an additional three infusions of ketamine. Subsequent to the ketamine treatments, participants remained on lithium or placebo during a double-blind continuation phase. The primary study outcome was depression severity as measured by the Montgomery-Åsberg Depression Rating Scale compared between the two groups at Study Day 28, which occurred ~2 weeks following the final ketamine of four infusions. Forty-seven participants with TRD were enrolled in the study and underwent an initial ketamine infusion, of whom 34 participants were deemed to have at least a partial antidepressant response and were eligible for randomization. Comparison between treatment with daily oral lithium (n = 18) or matching placebo (n = 16) at the primary outcome showed no difference in depression severity between groups (t32 = 0.11, p = 0.91, 95% CI [-7.87, 8.76]). There was no difference between lithium and placebo in continuing the acute antidepressant response to ketamine. The identification of a safe and effective strategy for preventing depression relapse following an acute course of ketamine treatment remains an important goal for future studies.

Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.

BACKGROUND: At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. METHODS: The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. RESULTS: There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t19=5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t19=4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. LIMITATIONS: Open-label, proof-of-concept design. CONCLUSIONS: Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted.

Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature.

BACKGROUND/OBJECTIVES: Nitrous oxide (N2 O) is known to have abuse potential, although debate regarding the toxic effects of such abuse continues. Our objective was to review the case literature and present the neurologic, psychiatric and medical consequences of N2 O abuse. METHODS: A systematic literature review was completed for case reports using keywords "nitrous oxide" with "abuse/abusing" or "misuse/misusing" or "overuse/overusing" or "addiction." Non-English-language cases and cases not involving direct toxic effects of N2 O were excluded as were commentaries or personal essays. Clinical presentation, frequency of N2 O abuse, laboratory studies, imaging, ancillary tests, treatments and outcomes were collected from case reports. RESULTS: Our review returned 335 Pubmed, 204 Web of Science, 73 PsycINFO, 6 CINAHL, 55 EMBASE and 0 Grey Literature results, and after exclusion and removal of duplicates, 91 individual cases across 77 publications were included. There were also 11 publications reporting 29 cases of death related to N2 O abuse. The majority of cases (N = 72) reported neurologic sequelae including myeloneuropathy and subacute combined degeneration, commonly (N = 39) with neuroimaging changes. Psychiatric (N = 11) effects included psychosis while other medical effects (N = 8) included pneumomediastinum and frostbite. Across all cases N2 O abuse was correlated with low or low-normal Vitamin B12 (cyanocobalamin) levels (N = 52) and occasionally elevated homocysteine and methylmalonic acid. CONCLUSIONS/SCIENTIFIC SIGNIFICANCE: N2 O abuse represents a significant problem because of the difficulty involved with identification and the toxicity related to chronic abuse including possible death. Health professionals should be aware of the toxic effects of N2 O and be able to identify potential N2 O abuse. (Am J Addict 2016;25:358-369).

Association Between Occupational Exposures and Sarcoidosis: An Analysis From Death Certificates in the United States, 1988-1999.

BACKGROUND: Sarcoidosis is a disease that is associated with occupational and environmental antigens, in the setting of a susceptible host. The aim of this study was to examine the association between sarcoidosis mortality and previously reported occupational exposures based on sex and race. METHODS: The decedents enrolled in this study were derived from United States death certificates from 1988-1999. Cause of death was coded according to ICD-9 and ICD-10. The usual occupation was coded with Bureau of the Census Occupation Codes. Mortality odds ratio (MOR) were determined and multiple Poisson regression were performed to evaluate the independent exposure effects after adjustment for age, sex, race and other occupational exposures. RESULTS: Of the 7,118,535 decedents in our study, 3,393 were identified as sarcoidosis-related, including 1,579 identified as sarcoidosis being the underlying cause of death. The sarcoidosis-related MOR of any occupational exposure was 1.52 (95% CI, 1.35-1.71). Women with any exposure demonstrated an increased MOR compared to women without (MOR 1.65, 95% CI, 1.45-1.89). The mortality risk was significantly elevated in those with employment involving metal working, health care, teaching, sales, banking, and administration. Higher sarcoidosis-related mortality risks associated with specific exposures were noted in women vs men and blacks vs whites. CONCLUSIONS: Findings of prior occupations and risk of sarcoidosis were verified using sarcoidosis mortality rates. There were significant differences in risk for sarcoidosis mortality by occupational exposures based on sex and race.

Lead and other heavy metals in dust fall from single-family housing demolition.

OBJECTIVE: We measured lead and other heavy metals in dust during older housing demolition and effectiveness of dust suppression. METHODS: We used American Public Housing Association Method 502 and U.S. Environmental Protection Agency Methods SW3050B and SW6020 at 97 single-family housing demolition events with intermittent (or no) use of water to suppress dust at perimeter, non-perimeter, and locations without demolition, with nested mixed modeling and tobit modeling with left censoring. RESULTS: The geometric mean (GM) lead dust fall during demolition was 6.01 micrograms of lead per square foot per hour (µg Pb/ft(2)/hour). GM lead dust fall was 14.18 µg Pb/ft(2)/hour without dust suppression, but declined to 5.48 µg Pb/ft(2)/hour (p=0.057) when buildings and debris were wetted. Significant predictors included distance, wind direction, and main street location. At 400 feet, lead dust fall was not significantly different from background. GM lead concentration at demolition (2,406 parts per million [ppm]) was significantly greater than background (GM=579 ppm, p=0.05). Arsenic, chromium, copper, iron, and manganese demolition dust fall was significantly higher than background (p<0.001). Demolition of approximately 400 old housing units elsewhere with more dust suppression was only 0.25 µg Pb/ft(2)/hour. CONCLUSIONS: Lead dust suppression is feasible and important in single-family housing demolition where distances between houses are smaller and community exposures are higher. Neighbor notification should be expanded to at least 400 feet away from single-family housing demolition, not just adjacent properties. Further research is needed on effects of distance, potential water contamination, occupational exposures, and water application.

An evaluation framework for faculty practice.

Faculty practice is promoted in schools of nursing for the purposes of strengthening the clinical expertise of faculty, maintaining clinically relevant curricula, fostering student learning, and generating revenue. For clinical faculty, this practice often provides the foundation for academic scholarship. The integration of this scholarship into the traditional academic triad of education, research, and service has proved difficult. Pohl et al notes, "In promotion and tenure decisions, 68 percent of faculty reported that practice was weighted less than teaching and research in their institutions." There appears to be an inherent tension between the requirements for scholarly faculty practice and the academic missions of schools of nursing. The purpose of this article is to describe a framework for the evaluation of faculty practice at the Johns Hopkins University School Nursing (JHUSON) and the actions taken to align the scholarship of faculty practice with the academic research mission of the School.