Developing a tailored implementation action plan for a suicide prevention clinical intervention in an Australian mental health service: A qualitative study using the EPIS framework.

Background: Tailoring implementation strategies to local contexts is a promising approach to supporting implementation and sustainment of evidence-based practices in health settings. While there is increasing research on tailored implementation of mental health interventions, implementation research on suicide prevention interventions is limited. This study aimed to evaluate implementation and subsequently develop a tailored action plan to support sustainment of an evidence-based suicide prevention intervention; Collaborative Assessment and Management of Suicidality (CAMS) in an Australian public mental health service. Methods: Approximately 150 mental health staff working within a regional and remote Local Health District in Australia were trained in CAMS. Semi-structured interviews and focus groups with frontline staff and clinical leaders were conducted to examine barriers and facilitators to using CAMS. Data were analysed using a reflexive thematic analysis approach and mapped to the Exploration, Preparation, Implementation and Sustainment (EPIS) framework and followed by stakeholder engagement to design a tailored implementation action plan based on a 'tailored blueprint' methodology. Results: A total of 22 barriers to implementing CAMS were identified. Based on the perceived impact on implementation fidelity and the feasibility of addressing identified barriers, six barriers were prioritised for addressing through an implementation action plan. These barriers were mapped to evidence-based implementation strategies and, in collaboration with local health district staff, goals and actionable steps for each strategy were generated. This information was combined into a tailored implementation plan to support the sustainable use of CAMS as part of routine care within this mental health service. Conclusions: This study provides an example of a collaborative approach to tailoring strategies for implementation on a large scale. Novel insights were obtained into the challenges of evaluating the implementation process and barriers to implementing an evidence-based suicide prevention treatment approach within a geographically large and varied mental health service in Australia. Plain language abstract: This study outlines the process of using a collaborative stakeholder engagement approach to develop tailored implementation plans. Using the Exploration Preparation Implementation Sustainment Framework, findings identify the barriers to and strategies for implementing a clinical suicide prevention intervention in an Australian community mental health setting. This is the first known study to use an implementation science framework to investigate the implementation of the clinical suicide prevention intervention (Collaborative Assessment and Management of Suicidality) within a community mental health setting. This work highlights the challenges of conducting implementation research in a dynamic public health service.

Internet-delivered cognitive behavioral therapy for panic disorder with or without agoraphobia: a systematic review and meta-analysis.

The current systematic review and meta-analysis examined the efficacy and effectiveness of internet-delivered cognitive behavioral therapy (iCBT) on panic disorder and agoraphobia symptom severity. Twenty-seven studies were identified. Results from nine randomised controlled trials (RCTs) showed that iCBT outperformed waiting list and information controls for panic (g = 1.22) and agoraphobia (g = .91) symptoms, but the quality of RCTs varied and heterogeneity was high. Results from three RCTs suggested iCBT may have similar outcomes to face-to-face CBT in reducing panic and agoraphobia symptoms. Within-group effect sizes between baseline and post-treatment were large for panic (n = 29, g = 1.16) and medium for agoraphobia symptom severity (n = 18, g = .73). Subgroup analyses of within-group pre/post treatment effect sizes showed larger within-group effect sizes for efficacy studies (n = 15) compared to effectiveness studies (n = 14) for panic severity (g = 1.38 vs. g = .98) but not agoraphobia severity. There was no impact of program length, inclusion or arousal reduction techniques, or degree of clinician support. Within-group effects of iCBT suggest the reduction in panic and agoraphobia symptom severity is maintained at 3-6 month follow-up (n = 12).

Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes.

Inherited cardiac conditions (ICCs) are characterised by marked genetic and allelic heterogeneity and require extensive sequencing for genetic characterisation. We iteratively optimised a targeted gene capture panel for ICCs that includes disease-causing, putatively pathogenic, research and phenocopy genes (n = 174 genes). We achieved high coverage of the target region on both MiSeq (>99.8% at ≥ 20× read depth, n = 12) and NextSeq (>99.9% at ≥ 20×, n = 48) platforms with 100% sensitivity and precision for single nucleotide variants and indels across the protein-coding target on the MiSeq. In the final assay, 40 out of 43 established ICC genes informative in clinical practice achieved complete coverage (100 % at ≥ 20×). By comparison, whole exome sequencing (WES; ∼ 80×), deep WES (∼ 500×) and whole genome sequencing (WGS; ∼ 70×) had poorer performance (88.1, 99.2 and 99.3% respectively at ≥ 20×) across the ICC target. The assay described here delivers highly accurate and affordable sequencing of ICC genes, complemented by accessible cloud-based computation and informatics. See Editorial in this issue (DOI: 10.1007/s12265-015-9667-8 ).

The transcriptional regulator lola is required for stem cell maintenance and germ cell differentiation in the Drosophila testis.

Stem cell behavior is regulated by extrinsic signals from specialized microenvironments, or niches, and intrinsic factors required for execution of context-appropriate responses to niche signals. Here we show that function of the transcriptional regulator longitudinals lacking (lola) is required cell autonomously for germline stem cell and somatic cyst stem cell maintenance in the Drosophila testis. In addition, lola is also required for proper execution of key developmental transitions during male germ cell differentiation, including the switch from transit amplifying progenitor to spermatocyte growth and differentiation, as well as meiotic cell cycle progression and spermiogenesis. Different lola isoforms, each having unique C-termini and zinc finger domains, may control different aspects of proliferation and differentiation in the male germline and somatic cyst stem cell lineages.

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes.

Adult stem cells are believed to be maintained by a specialized microenvironment, the niche, which provides short-range signals that either instruct stem cells to self-renew or inhibit execution of preprogrammed differentiation pathways. In Drosophila testes, somatic cyst stem cells (CySCs) and the apical hub form the niche for neighboring germline stem cells (GSCs), with CySCs as the proposed source of instructive self-renewal signals [Leatherman JL, Dinardo S (2010) Nat Cell Biol 12(8):806-811]. In contrast to this model, we show that early germ cells with GSC characteristics can be maintained over time after ablation of CySCs and their cyst cell progeny. Without CySCs and cyst cells, early germ cells away from the hub failed to initiate differentiation. Our results suggest that CySCs do not have a necessary instructive role in specifying GSC self-renewal and that the differentiated progeny of CySCs provide an environment necessary to trigger GSC differentiation. This work highlights the complex interaction between different stem cell populations in the same niche and how the state of one stem cell population can influence the fate of the other.

Domain-specific regulation of recombination in Caenorhabditis elegans in response to temperature, age and sex.

It is generally considered that meiotic recombination rates increase with temperature, decrease with age, and differ between the sexes. We have reexamined the effects of these factors on meiotic recombination in the nematode Caenorhabditis elegans using physical markers that encompass >96% of chromosome III. The only difference in overall crossover frequency between oocytes and male sperm was observed at 16 degrees . In addition, crossover interference (CI) differs between the germ lines, with oocytes displaying higher CI than male sperm. Unexpectedly, our analyses reveal significant changes in crossover distribution in the hermaphrodite oocyte in response to temperature. This feature appears to be a general feature of C. elegans chromosomes as similar changes in response to temperature are seen for the X chromosome. We also find that the distribution of crossovers changes with age in both hermaphrodites and females. Our observations indicate that it is the oocytes from the youngest mothers-and not the oldest-that showed a different pattern of crossovers. Our data enhance the emerging hypothesis that recombination in C. elegans, as in humans, is regulated in large chromosomal domains.