Cluster randomized adaptive implementation trial comparing a standard versus enhanced implementation intervention to improve uptake of an effective re-engagement program for patients with serious mental illness

Background

Persons with serious mental illness (SMI) are disproportionately burdened by premature mortality. This disparity is exacerbated by poor continuity of care with the health system. The Veterans Health Administration (VA) developed Re-Engage, an effective population-based outreach program to identify veterans with SMI lost to care and to reconnect them with VA services. However, such programs often encounter barriers getting implemented into routine care. Adaptive designs are needed when the implementation intervention requires augmentation within sites that do not initially respond to an initial implementation intervention. This protocol describes the methods used in an adaptive implementation design study that aims to compare the effectiveness of a standard implementation strategy (Replicating Effective Programs, or REP) with REP enhanced with External Facilitation (enhanced REP) to promote the uptake of Re-Engage.

Methods/Design

This study employs a four-phase, two-arm, longitudinal, clustered randomized trial design. VA sites (n?=?158) across the United States with a designated Re-Engage provider, at least one Veteran with SMI lost to care, and who received standard REP during a six-month run-in phase. Subsequently, 88 sites with inadequate uptake were stratified at the cluster level by geographic region (n?=?4) and VA regional service network (n?=?20) and randomized to REP (n?=?49) vs. enhanced REP (n?=?39) in phase two. The primary outcome was the percentage of veterans on each facility outreach list documented on an electronic web registry. The intervention was at the site and network level and consisted of standard REP versus REP enhanced by external phone facilitation consults. At 12 months, enhanced REP sites returned to standard REP and 36 sites with inadequate participation received enhanced REP for six months in phase three. Secondary implementation outcomes included the percentage of veterans contacted directly by site providers and the percentage re-engaged in VA health services.

Discussion

Adaptive implementation designs consisting of a sequence of decision rules that are tailored based on a site’s uptake of an effective program may produce more relevant, rapid, and generalizable results by more quickly validating or rejecting new implementation strategies, thus enhancing the efficiency and sustainability of implementation research and potentially leading to the rollout of more cost-efficient implementation strategies.

Trial registration

Current Controlled TrialsISRCTN21059161.

     

NMR methods for structural studies of large monomeric and multimeric proteins

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Epigenetic control of plant development by Polycomb-group proteins

Recent genetic studies indicate that the plant Polycomb-group genes play much broader roles in development than was initially apparent from their single mutant phenotypes. At the mechanistic level, evidence is accumulating that their protein products act together in complexes that direct changes in histone methylation patterns. We discuss recent studies that give clues as to how these epigenetic changes are propagated through mitosis, how they are interpreted, and how they might be reset.     

Antagonistic roles of SEPALLATA3, FT and FLC genes as targets of the polycomb group gene CURLY LEAF

In Arabidopsis, mutations in the Pc-G gene CURLY LEAF (CLF) give early flowering plants with curled leaves. This phenotype is caused by mis-expression of the floral homeotic gene AGAMOUS (AG) in leaves, so that ag mutations largely suppress the clf phenotype. Here, we identify three mutations that suppress clf despite maintaining high AG expression. We show that the suppressors correspond to mutations in FPA and FT, two genes promoting flowering, and in SEPALLATA3 (SEP3) which encodes a co-factor for AG protein. The suppression of the clf phenotype is correlated with low SEP3 expression in all case and reveals that SEP3 has a role in promoting flowering in addition to its role in controlling floral organ identity. Genetic analysis of clf ft mutants indicates that CLF promotes flowering by reducing expression of FLC, a repressor of flowering. We conclude that SEP3 is the key target mediating the clf phenotype, and that the antagonistic effects of CLF target genes masks a role for CLF in promoting flowering.