Dispensing Methadone at Hospital Discharge: One Hospital's Approach to Implementing the "72-hour Rule" Change.

OBJECTIVES: Methadone for opioid use disorder treatment in ambulatory settings is restricted to federally licensed opioid treatment programs (OTPs) in the United States. However, these restrictions do not apply during hospitalization. A recent change to the rule governing methadone in non-OTP settings created an opportunity to dispense methadone at hospital discharge for up to 72 hours. METHODS: Here, we describe one hospital's approach to dispensing methadone at discharge in alignment with the "72-hour rule," including implementation challenges and considerations for other hospitals planning on adopting this practice. Implementation included creating a workflow and detailed documents outlining dispensing procedure, educating interprofessional staff, and coordinating with local OTPs. RESULTS: Our experiences highlight the importance of pharmacy champions to support implementation and interdisciplinary staff education, the need to consider electronic health record capabilities, and the importance of having policies and practices that support appropriate interpretation of the "72-hour rule" renewal timeline. CONCLUSIONS: Exceptions to federal regulations allow greater flexibility in discharge planning for patients with opioid use disorder; however, dispensation workflow falls outside standard hospital care and may be challenging to implement.

Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease.

Nearly all human genetic disorders result from a limited repertoire of mutations in an associated gene or its regulatory elements. We recently described an individual with an inherited form of anemia (alpha-thalassemia) who has a deletion that results in a truncated, widely expressed gene (LUC7L) becoming juxtaposed to a structurally normal alpha-globin gene (HBA2). Although it retains all of its local and remote cis-regulatory elements, expression of HBA2 is silenced and its CpG island becomes completely methylated early during development. Here we show that in the affected individual, in a transgenic model and in differentiating embryonic stem cells, transcription of antisense RNA mediates silencing and methylation of the associated CpG island. These findings identify a new mechanism underlying human genetic disease.

Implementation of a Nurse-Driven Medication Ordering Protocol to Improve Clinician and Nursing Experiences.

ABSTRACT: Paging and text messaging to request new orders remain common means of communication between clinicians and nurses in the hospital setting. However, sending and triaging multiple pages can lead to interruptions in other clinical duties. A medication order delegation protocol allowing for nurse-driven ordering of low-risk medications was developed with an objective of decreasing potentially avoidable pages. The aim of this study was to evaluate the impact of implementing this protocol on nurse and clinician perceptions of clerical burden and satisfaction. A survey assessing satisfaction with the process of obtaining medications in this protocol and the perception of clerical burden associated with ordering them before and after delegation protocol implementation was completed by over 160 clinicians and nurses. Survey respondents reported increased satisfaction and decreased clerical burden associated with the implementation of the delegation protocol. These results suggest the potential for delegation protocols to limit clerical burden associated with paging.

In Pursuit of the Quadruple Aim: A Geriatric Prescribing Context's Impact on Clinician Workflows and Alert Fatigue.

The impact of a novel Geriatric Prescribing Context (GPC) on hospital clinicians' prescribing workflows is still unknown. A cross-sectional survey was distributed to 346 inpatient pharmacists, physicians, and advance practice providers employed at three pilot site hospitals affected by the GPC to assess awareness and impact to usual workflow. The GPC, a set of medication default doses and frequencies for patients 75 years and older, was unnoticed by 74% of survey respondents (n = 119) with pharmacists more likely to be aware of the context than prescribers. The impact of the GPC on clinicians' workflow differed by setting, with academic respondents reporting no change or decreased time to write or verify orders, and community respondents reporting no change or increased time to write or verify orders. The GPC has smoothly integrated into usual prescribing workflows for both prescribers and pharmacists and both overall reported positive responses to the implementation.

Safer Prescribing for Hospitalized Older Adults with an Electronic Health Records-Based Prescribing Context.

BACKGROUND/OBJECTIVES: Hospitalized older adults are at risk of receiving potentially inappropriate medication (PIM) doses, driven in part by age-independent dose defaults used by electronic health records (EHRs), leading providers to prescribe for older adults as they do for younger adults. We studied whether an automated EHR-based medication support tool would reduce PIM dosing for hospitalized older adults. DESIGN: Pre-post study design. SETTING: Tertiary care, level 1 trauma, academic medical center in Oregon. PARTICIPANTS: Hospitalized adults 75 years and older in the inpatient, nonemergency setting prescribed medications with geriatric-specific dose considerations. INTERVENTION: An EHR-based, automated set of evidence-based, age-specific dose and frequency defaults called the Geriatric Prescribing Context (GPC). MEASUREMENTS: The process measure is percentage of orders consistent with geriatric dose recommendations, and outcome measures are average dose (AD) in milligrams and total daily dose (TDD) in milligrams in the 12 months before and after implementation. RESULTS: Use of recommended geriatric doses with the context improved for all 10 of the most commonly ordered medications. In the year after implementation, there was a trend toward decreasing TDD and AD across all drug classes. CONCLUSION: The GPC is a simple, elegant, and effective means to align prescribing practices with safety standards for older adults, improving prescribing safety for all. It works within the current prescriber workflow without triggering alert fatigue and requires minimal resources for development and maintenance.

Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues.

ATRX is an X-encoded member of the SNF2 family of ATPase/helicase proteins thought to regulate gene expression by modifying chromatin at target loci. Mutations in ATRX provided the first example of a human genetic disease associated with defects in such proteins. To better understand the role of ATRX in development and the associated abnormalities in the ATR-X (alpha thalassemia mental retardation, X-linked) syndrome, we conditionally inactivated the homolog in mice, Atrx, at the 8- to 16-cell stage of development. The protein, Atrx, was ubiquitously expressed, and male embryos null for Atrx implanted and gastrulated normally but did not survive beyond 9.5 days postcoitus due to a defect in formation of the extraembryonic trophoblast, one of the first terminally differentiated lineages in the developing embryo. Carrier female mice that inherit a maternal null allele should be affected, since the paternal X chromosome is normally inactivated in extraembryonic tissues. Surprisingly, however, some carrier females established a normal placenta and appeared to escape the usual pattern of imprinted X-inactivation in these tissues. Together these findings demonstrate an unexpected, specific, and essential role for Atrx in the development of the murine trophoblast and present an example of escape from imprinted X chromosome inactivation.

Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence.

We have devised a strategy (called recombinase-mediated genomic replacement, RMGR) to allow the replacement of large segments (>100 kb) of the mouse genome with the equivalent human syntenic region. The technique involves modifying a mouse ES cell chromosome and a human BAC by inserting heterotypic lox sites to flank the proposed exchange interval and then using Cre recombinase to achieve segmental exchange. We have demonstrated the feasibility of this approach by replacing the mouse alpha globin regulatory domain with the human syntenic region and generating homozygous mice that produce only human alpha globin chains. Furthermore, modified ES cells can be used iteratively for functional studies, and here, as an example, we have used RMGR to produce an accurate mouse model of human alpha thalassemia. RMGR has general applicability and will overcome limitations inherent in current transgenic technology when studying the expression of human genes and modeling human genetic diseases.