Continuous IV infusion of anakinra.

Objective: A review of the use of continuous IV infusion of anakinra; a description of the protocol for continuous IV infusion of anakinra in the treatment of cytokine storm developed over the past 4 years at a tertiary level academic medical center in the United States. Methods: We reviewed published reports of continuous IV infusion of anakinra in cytokine storm and summarize this method of treatment in other diseases. As well, over the past 4 years, continuous IV infusions of anakinra were administered at our tertiary level academic medical center in the United States (Regions Hospital, St. Paul, Minnesota) for approximately 400 patient days of treatment primarily for the cytokine storm associated with macrophage activation syndrome (MAS) in adults. This updated protocol is presented. While this a single center protocol, it may serve as an initial guide for further refinement of protocols in MAS and other conditions. Conclusion:Continuous IV infusion of anakinra has advantages over subcutaneous infusions and may be important in controlling severe life-threatening cytokine storm as seen in macrophage activation syndrome. This has the potential to be an important therapy for other syndromes including Cytokine Release Syndrome related to CAR T-cell therapy. Close collaboration between Rheumatology, Pharmacy and Nursing allows this treatment to be delivered rapidly and efficiently.

Missed opportunities: Arrest and court touchpoints for individuals who fatally overdosed in Philadelphia in 2016.

BACKGROUND: Many studies document high risk of fatal overdose after incarceration. Few explore earlier touchpoints in criminal justice processes, like arrests and court hearings. Understanding these touchpoints is important for several reasons. Arrest and adjudicatory processes are harmful even when not resulting in incarceration. Arrests and criminal hearings also may reflect changes in overdose-related risk factors like transitions in employment and housing stability. Moreover, knowledge about these touchpoints contextualizes debate about the implementation of court-based programs like Drug Treatment Courts. This study described the incidence and accumulation of touchpoints for people who fatally overdosed in Philadelphia in 2016, and depicted how touchpoint incidence and characteristics interface with court-program eligibility. METHODS: Criminal court documents were obtained for all individuals who fatally overdosed in Philadelphia in 2016 from the Philadelphia Medical Examiner's Office. The characteristics of arrests and court hearings were abstracted to compile lifetime criminal histories. Latent class analysis was performed to identify whether these histories followed observably distinct patterns. RESULTS: In 2016, 907 people fatally overdosed in Philadelphia. Of these, 605 had at least one or more of 3,926 arrests and 3,822 hearings over their lifetime. There were 488 arrests and 533 hearings in the two years before death, with public disorder charges especially common closer to death. Less than 20% of these hearings resulted in custodial sentences. Of individuals with touchpoints, only nine participated in Drug Treatment Court, consistent with findings that most individuals were ineligible. Latent class analysis suggested five distinguishable patterns in age, timing, and characteristics of touchpoints. CONCLUSIONS: The type and frequency of touchpoints preceding fatal overdose reflect a period of complex vulnerability. Few individuals qualified for court-based programming, underscoring the limitations of supporting this population in specialized court settings. Reducing incidence and improving the health impact of criminal justice touchpoints remain important public health priorities.

Missed opportunities to advance knowledge on traffic safety: Accessibility of driver licensing and crash data for scientific research.

OBJECTIVE: Identifiable individual-level driver licensing and motor vehicle crash data are essential to advancing transportation safety research. However, epidemiologic studies using such data are rare, which may reflect their inaccessibility. We conducted a legal mapping study to evaluate US state laws regulating access to driver licensing and motor vehicle crash data for use in scientific research. METHODS: Legal statutes regulating the release of driver licensing and motor vehicle crash data for all 50 US states and the District of Columbia (D.C.) were retrieved. Legal text was evaluated to determine whether these jurisdictions authorize release of identifiable individual-level licensing and crash data for use in non-governmental research. RESULTS: Thirty-six states and D.C. explicitly authorize release of identifiable individual-level licensing data to researchers. Only five states and D.C. authorize release of identifiable individual-level crash records. No states explicitly prohibit the release of individual-level data about licensing records and only three states prohibit release of individual-level crash record data, meaning that in many states it is ambiguous whether and when releasing such data to researchers is permitted. CONCLUSIONS: It is important to understand why licensing data are not used more frequently in transportation safety research given that many state laws permit access for non-governmental researchers. Reforming state laws to clarify and increase access to identifiable individual-level crash report data is an important priority for transportation safety advocates and researchers.

Molecular effects of autoimmune-risk promoter polymorphisms on expression, exon choice, and translational efficiency of interferon regulatory factor 5.

The rs2004640 single nucleotide polymorphism and the CGGGG copy-number variant (rs77571059) are promoter polymorphisms within interferon regulatory factor 5 (IRF5). They have been implicated as susceptibility factors for several autoimmune diseases. IRF5 uses alternative promoter splicing, where any of 4 first exons begin the mRNA. The CGGGG indel is in exon 1A's promoter; the rs2004640 allele creates a splicing recognition site, enabling usage of exon 1B. This study aimed at characterizing alterations in IRF5 mRNA due to these polymorphisms. Cells with risk polymorphisms exhibited ~2-fold higher levels of IRF5 mRNA and protein, but demonstrated no change in mRNA stability. Quantitative PCR demonstrated decreased usage of exons 1C and 1D in cell lines with the risk polymorphisms. RNA folding analysis revealed a hairpin in exon 1B; mutational analysis showed that the hairpin shape decreased translation 5-fold. Although translation of mRNA that uses exon 1B is low due to a hairpin, increased IRF5 mRNA levels in individuals with the rs2004640 risk allele lead to higher overall protein expression. In addition, several new splice variants of IRF5 were sequenced. IRF5's promoter polymorphisms alter first exon usage and increase transcription levels. High levels of IRF5 may bias the immune system toward autoimmunity.