Interpersonal communication-, education- and counselling-based interventions to support adherence to oral anticancer therapy: a systematic review.

Background. Many factors contribute to oral anti-cancer therapy adherence, including counselling and educational support. Objective. We systematically review the literature evaluating the effectiveness of interpersonal communication-, counselling- and education-based interventions on patient adherence to oral anticancer therapy. Methods. Using search terms pertaining to medication adherence, oral anticancer therapy, and communication, education, and counselling, we conducted a systematic search for full-text, original research articles prior to 3/13/20. Two reviewers independently reviewed each paper for inclusion and charted study information. Results. Twenty-four articles were included. All considered the use of oral anticancer therapy between two defined time points. Four studies also considered the length of time a patient persisted on therapy. Half (n = 12) of the studies reported a statistically significant relationship between the intervention and medication adherence, with no consistent pattern among intervention structure/content and effectiveness. Programmes offering in-person counselling and those targeting patients with chronic myeloid leukemia (CML), tended to report positive findings. Most studies faced substantial risk of bias, and only two reported using a behavioural theory to guide interventional content. Conclusions. Findings highlight the infancy of evidence base and need for rigorous and large-scale studies grounded in established behavioural theories to advance patient-targeted educational and counselling practices supporting adherence to oral anti-cancer therapy.

Subretinal gene therapy of mice with Bardet-Biedl syndrome type 1.

PURPOSE: To study safety and efficacy of subretinal adeno-associated virus (AAV) vector AAV-Bbs1 injection for treatment of a mouse model of Bardet-Biedl syndrome type 1 (BBS1). METHODS: Constructs containing a wild-type (WT) Bbs1 gene with and without a FLAG tag in AAV2/5 vectors were generated. Viral genomes were delivered by subretinal injection to right eyes and sham injections to left eyes at postnatal day 30 (P30) to P60. Transgene expression and BBSome reconstitution were evaluated by immunohistochemistry and Western blotting following sucrose gradient ultracentrifugation. Retinal function was analyzed by electroretinogram (ERG) and structure by optical coherence tomography (OCT). Histology and immunohistochemistry were performed on selected eyes. RESULTS: Expression of FLAG-tagged Bbs1 was demonstrated in photoreceptor cells using antibody directed against the FLAG tag. Coinjection of AAV-GFP demonstrated transduction of 24% to 32% of the retina. Western blotting demonstrated BBS1 protein expression and reconstitution of the BBSome. ERG dark-adapted bright flash b-wave amplitudes were higher in AAV-Bbs1-injected eyes than in sham-injected fellow eyes in more than 50% of 19 animals. Anti-rhodopsin staining demonstrated improved localization of rhodopsin in AAV-Bbs1-treated eyes. WT retinas injected with AAV-Bbs1 with or without a FLAG tag showed outer retinal degeneration on ERG, OCT, and histology. CONCLUSIONS: In a knock-in model of BBS1, subretinal delivery of AAV-Bbs1 rescues BBSome formation and rhodopsin localization, and shows a trend toward improved ERG. BBS is challenging to treat with gene therapy due to the stoichiometry of the BBSome protein complex and overexpression toxicity.