Focused Ethnographic Examination of Barriers to Use of Long-Acting Injectable Antipsychotics.

OBJECTIVE: The authors designed this project to identify barriers to using long-acting formulations of antipsychotics. METHODS: The authors used a focused ethnographic approach. Patients, psychiatrists, nurses, therapists and administrators were interviewed about barriers to use of long-acting injectable (LAI) antipsychotics at six facilities in New York State, as were representatives from insurance firms, a pharmaceutical company, and a national professional organization. Interviews were conducted and analyzed by a central team not affiliated with the institutions. RESULTS: Interviews were obtained with 23 patients, 16 psychiatrists, three nurses, 23 therapists, 14 administrators, four insurers, one representative from a pharmaceutical industry, and one representative from a national organization. Major barriers identified from the interviews included restricting discussions about LAI medication to only patients with nonadherence or repeated hospitalizations; inadequate education efforts with patients about LAI antipsychotics; inadequate support for patients making medication decisions; lack of communication within the treatment team about issues relevant to use of LAI formulations by patients; therapists' limited knowledge about LAI antipsychotics, which restricted their role in supporting patients making treatment decisions; psychiatrist concerns about the pharmacologic properties of LAI formulations; lack of clinic infrastructure to support LAI prescriptions; and payer concerns about whether the immediate costs of LAI administration would translate into later potential cost benefits. CONCLUSIONS: Effective shared decision making about use of LAI antipsychotics requires that patients receive accurate information and support for their decision making. The training needs and administrative support requirements of all team members should be considered to provide patients with the information and support required.

Arabidopsis chlorophyll biosynthesis: an essential balance between the methylerythritol phosphate and tetrapyrrole pathways.

Chlorophyll, essential for photosynthesis, is composed of a chlorin ring and a geranylgeranyl diphosphate (GGPP)-derived isoprenoid, which are generated by the tetrapyrrole and methylerythritol phosphate (MEP) biosynthesis pathways, respectively. Although a functional MEP pathway is essential for plant viability, the underlying basis of the requirement has been unclear. We hypothesized that MEP pathway inhibition is lethal because a reduction in GGPP availability results in a stoichiometric imbalance in tetrapyrrolic chlorophyll precursors, which can cause deadly photooxidative stress. Consistent with this hypothesis, lethality of MEP pathway inhibition in Arabidopsis thaliana by fosmidomycin (FSM) is light dependent, and toxicity of MEP pathway inhibition is reduced by genetic and chemical impairment of the tetrapyrrole pathway. In addition, FSM treatment causes a transient accumulation of chlorophyllide and transcripts associated with singlet oxygen-induced stress. Furthermore, exogenous provision of the phytol molecule reduces FSM toxicity when the phytol can be modified for chlorophyll incorporation. These data provide an explanation for FSM toxicity and thereby provide enhanced understanding of the mechanisms of FSM resistance. This insight into MEP pathway inhibition consequences underlines the risk plants undertake to synthesize chlorophyll and suggests the existence of regulation, possibly involving chloroplast-to-nucleus retrograde signaling, that may monitor and maintain balance of chlorophyll precursor synthesis.