Effect of Locally Delivered Nimodipine Microparticles on Spreading Depolarization in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Recurrent spreading depolarizations (SDs) occur in patients after aneurysmal subarachnoid hemorrhage (aSAH), resulting in metabolic stress to brain. These events are closely associated with delayed cerebral ischemia. Preclinical data suggest that the beneficial effect of nimodipine demonstrated in clinical trials may be related to inhibition of SD rather than limitation of large artery vasospasm. METHODS: Subjects enrolled in a phase 3 trial of intraventricularly delivered, sustained-release nimodipine (EG-1962) versus standard of care oral nimodipine (NEWTON 2) who required surgical clipping had subdural strip electrodes implanted for monitoring of SD. SD was then scored blinded to NEWTON 2 allocation. RESULTS: Five subjects underwent electrocorticography monitoring of SD. Three of five patients had SD. There were fewer SDs, a lower rate of SD, and shorter depression durations in subjects treated with EG-1962 compared to standard of care. Outcomes were worse in the standard of care group, though there were baseline imbalances. CONCLUSIONS: These results are consistent with a beneficial effect of locally delivered nimodipine (EG-1962) on SD after aSAH in more severely injured patients who are at risk of delayed cerebral ischemia related to SD. Larger studies are warranted to test this effect.

Co-prescription of naloxone as a Universal Precautions model for patients on chronic opioid therapy-Observational study.

BACKGROUND: The epidemic of lethal prescription opioid overdose is one of the most pressing public health problems in the United States. In an ambulatory clinic setting, current practice guidelines suggest that health care providers should screen patient's aberrant drug-related behaviors. Given the difficulty of predicting which patients on chronic opioid therapy (COT) will experience opioid overdose, a new paradigm of harm reduction is called for. In previous studies, naloxone, an opioid antagonist, was given only to high-risk patients. However, if naloxone is co-prescribed in a Universal Precautions manner for all patients receiving COT, this may have a significant impact on intentional and unintentional opioid overdose deaths. METHODS: Adult patients treated with COT for chronic noncancer pain are eligible study participants at the University of New Mexico Pain Center. The primary goal of this 1-year study was to develop an efficient Universal Precautions model for co-prescribing of naloxone with COT in the ambulatory clinic setting. Outcome measures included demographic data, detailed medical and substance use history, current morphine equivalent dose (MED), other "high-risk" medications used, and opioid misuse risk. RESULTS: One hundred and sixty-four patients were enrolled in this study. All subjects were educated about the risks of opioid overdose and provided naloxone rescue kits. No overdoses occurred in the study population. Follow-up data illustrated that approximately 57% of the cohort had depressive disorder, the median MED was 90 mg/day, and the median Current Opioid Misuse Measure score (COMM) was 5.0. CONCLUSIONS: The ambulatory co-prescribing of naloxone in a Universal Precautions model for all patients prescribed COT can be adopted as a useful public health intervention. This study illustrates a model that can be used to educate patients, caregivers, and an interdisciplinary team of health care professionals in an academic medical center.

Association of Take-Home Naloxone and Opioid Overdose Reversals Performed by Patients in an Opioid Treatment Program.

Importance: The US opioid crisis was deemed a public health emergency in 2017. More than 130 individuals in the US die daily as a result of unintentional opioid overdose deaths. Objective: To measure use of take-home naloxone for overdose reversals performed by study participants with opioid use disorder receiving treatment at an opioid treatment program. Design, Setting, and Participants: In a year-long cohort study, between April 4, 2016, and May 16, 2017, 395 study participants enrolled at the University of New Mexico Addiction and Substance Abuse Opioid Treatment Program, an outpatient clinic treating substance use disorders. Inclusion criteria included all patients enrolled at University of New Mexico Addiction and Substance Abuse Opioid Treatment Program during the study enrollment period; positive history of opioid use disorder treated with methadone, buprenorphine, or naltrexone; and age 18 years or older. Exclusion criteria included allergy to naloxone and age younger than 18 years. The study closed 1 year after enrollment, on May 17, 2018. Data analysis was performed from May 2018 to July 2019. Exposure: Two doses of take-home naloxone combined with opioid overdose education were provided to study participants. Main Outcomes and Measures: The primary outcome was to measure the association of take-home naloxone with overdose reversals performed by patients with opioid use disorder enrolled in an opioid treatment program. Results: We enrolled 395 study participants (270 female [68.4%]; mean [SD] age, 35.4 [12.6] years; 260 [65.8%] with Hispanic white race/ethnicity) in the 1-year prospective trial. Sixty-eight female participants (25.2% of all female participants) were pregnant at the time of enrollment. Seventy-three of the 395 study participants (18.0%) performed 114 overdose reversals in the community. All community reversals were heroin related. Most study participants (86.8%) stated that the person on whom they performed an overdose reversal was a friend, relative, acquaintance, or significant other. In the year before enrollment, only 18 study participants (4.5%) had been prescribed naloxone. Conclusions and Relevance: Take-home naloxone as part of overdose education and naloxone distribution provided to patients in an opioid treatment program may be associated with a strategic targeted harm reduction response for reversing opioid overdose-related deaths. Policy makers may consider regulations to mandate overdose education and naloxone distribution in opioid treatment programs.