Publications

AIRE is a well-established master regulator of central tolerance. It plays an essential role in driving expression of tissue-specific antigens in the thymus and shaping the development of positively selected T-cells. Humans and mice with compromised or absent AIRE function have markedly variable phenotypes that include a range of autoimmune manifestations. Recent evidence suggests that this variability stems from cooperation of autoimmune susceptibilities involving both central and peripheral tolerance checkpoints. Here we discuss the broadening understanding of the factors that influence Aire expression, modify AIRE function, and the impact and intersection of AIRE with peripheral immunity. This rapidly expanding body of knowledge will force a reexamination of the definition and clinical management of APS-1 patients as well as provide a foundation for the development of immunomodulatory strategies targeting central tolerance.

OBJECTIVE

The United States is amidst an opioid epidemic, including synthetic opioids that may result in rapid death, leaving minimal opportunity for bystander rescue. We pilot tested a behavioral intervention to reduce the occurrence of opioid overdose among opioid dependent persons at high-risk for subsequent overdose.

MATERIALS AND METHODS

We conducted a single-blinded randomized-controlled trial of a repeated dose motivational interviewing intervention (REBOOT) to reduce overdose versus treatment as usual, defined as information and referrals, over 16 months at the San Francisco Department of Public Health from 2014-2016. Participants were 18-65 years of age, had opioid use disorder by Structured Clinical Interview, active opioid use, opioid overdose within 5 years, and prior receipt of naloxone kits. The intervention was administered at months 0, 4, 8, and 12, preceded by the assessment which was also administered at month 16. Dual primary outcomes were any overdose event and number of events, collected by computer-assisted personal interview, as well as any fatal overdose events per vital records.

RESULTS

A total of 78 persons were screened and 63 enrolled. Mean age was 43 years, 67% were born male, 65% White, 17% African-American, and 14% Latino. Ninety-two percent of visits and 93% of counseling sessions were completed. At baseline, 33.3% of participants had experienced an overdose in the past four months, with a similar mean number of overdoses in both arms (p = 0.95); 29% overdosed during follow-up. By intention-to-treat, participants assigned to REBOOT were less likely to experience any overdose (incidence rate ratio [IRR] 0.62 [95%CI 0.41-0.92, p = 0.019) and experienced fewer overdose events (IRR 0.46, 95%CI 0.24-0.90, p = 0.023), findings that were robust to sensitivity analyses. There were no differences between arms in days of opioid use, substance use treatment, or naloxone carriage.

CONCLUSIONS

REBOOT reduced the occurrence of any opioid overdose and the number of overdoses.

TRIAL REGISTRATION

clinicaltrials.gov NCT02093559.

BACKGROUND

Chemical irritants used in crowd control, such as tear gases and pepper sprays, are generally considered to be safe and to cause only transient pain and lacrimation. However, there are numerous reports that use and misuse of these chemicals may cause serious injuries. We aimed to review documented injuries from chemical irritants to better understand the morbidity and mortality associated with these weapons.

METHODS

We conducted a systematic review using PRISMA guidelines to identify injuries, permanent disabilities, and deaths from chemical irritants worldwide between January 1, 1990 and March 15, 2015. We reviewed injuries to different body systems, injury severity, and potential risk factors for injury severity. We also assessed region, context and quality of each included article.

RESULTS

We identified 31 studies from 11 countries. These reported on 5131 people who suffered injuries, two of whom died and 58 of whom suffered permanent disabilities. Out of 9261 total injuries, 8.7% were severe and required professional medical management, while 17% were moderate and 74.3% were minor. Severe injuries occurred to all body systems, with the majority of injuries impacting the skin and eyes. Projectile munition trauma caused 231 projectile injuries, with 63 (27%) severe injuries, including major head injury and vision loss. Potentiating factors for more severe injury included environmental conditions, prolonged exposure time, and higher quantities of chemical agent in enclosed spaces.

CONCLUSIONS

Although chemical weapons may have a limited role in crowd control, our findings demonstrate that they have significant potential for misuse, leading to unnecessary morbidity and mortality. A nuanced understanding of the health impacts of chemical weapons and mitigating factors is imperative to avoiding indiscriminate use of chemical weapons and associated health consequences.