A mixed methods pilot study with a cluster randomized control trial to evaluate the impact of a leadership intervention on guideline implementation in home care nursing

Abstract Background Foot ulcers are a significant problem for people with diabetes. Comprehensive assessments of risk factors associated with diabetic foot ulcer are recommended in clinical guidelines to decrease complications such as prolonged healing, gangrene and amputations, and to promote effective management. However, the translation of clinical guidelines into nursing practice remains fragmented and inconsistent, and a recent homecare chart audit showed less than half the recommended risk factors for diabetic foot ulcers were assessed, and peripheral neuropathy (the most significant predictor of complications) was not assessed at all. Strong leadership is consistently described as significant to successfully transfer guidelines into practice. Limited research exists however regarding which leadership behaviours facilitate and support implementation in nursing. The purpose of this pilot study is to evaluate the impact of a leadership intervention in community nursing on implementing recommendations from a clinical guideline on the nursing assessment and management of diabetic foot ulcers. Methods Two phase mixed methods design is proposed (ISRCTN 12345678). Phase I: Descriptive qualitative to understand barriers to implementing the guideline recommendations, and to inform the intervention. Phase II: Matched pair cluster randomized controlled trial (n = 4 centers) will evaluate differences in outcomes between two implementation strategies. Primary outcome: Nursing assessments of client risk factors, a composite score of 8 items based on Diabetes/Foot Ulcer guideline recommendations. Intervention: In addition to the organization's 'usual' implementation strategy, a 12 week leadership strategy will be offered to managerial and clinical leaders consisting of: a) printed materials, b) one day interactive workshop to develop a leadership action plan tailored to barriers to support implementation; c) three post-workshop teleconferences. Discussion This study will provide vital information on which leadership strategies are well received to facilitate and support guideline implementation. The anticipated outcomes will provide information to assist with effective management of foot ulcers for people with diabetes. By tracking clinical outcomes associated with guideline implementation, health care administrators will be better informed to influence organizational and policy decision-making to support evidence-based quality care. Findings will be useful to inform the design of future multi-centered trials on various clinical topics to enhance knowledge translation for positive outcomes. Trial Registration Current Control Trials ISRCTN0691089

Core domain interactions in full-length p53 in solution

The tumor suppressor p53 consists of four 393-residue chains, each of which has two natively unfolded (N- and C-terminal) and two folded (core and tetramerization) domains. Their structural organization is poorly characterized as the protein tends to aggregate, has defied crystallization, and is at the limits of NMR studies. We first stabilized the protein by mutation to make it more suitable for extended study and then acquired NMR spectra on full-length protein and various combinations of shorter domain constructs. The NMR spectrum ((15)N,(1)H transverse relaxation optimized spectroscopy) of full-length p53 was close to that expected from the sum of the spectra of isolated individual domains. However, patterns of changes in chemical shifts revealed unexpected interactions between the core domains. We used the NMR data as constraints in docking algorithms and found a previously uncharacterized self-complementary surface for the association of core domains into dimers within the tetrameric complex. Binding to DNA requires about a 70° rotation to break those subunit interactions and form the known protein:protein interface in the p53–DNA complex. We verified the interactions by the effects of mutation on DNA binding. Spectroscopic, biophysical, and mutational data conspired to give a picture of the p53 tetramer as a dimer of loosely tethered core dimers of appropriate symmetry to be poised to bind target DNA