Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to safely reduce unnecessary hospital admissions: a pilot randomised controlled trial

Background Observational studies suggest that the Manchester Acute Coronary Syndromes (MACS) decision rule can effectively rule out' and rule in' acute coronary syndromes (ACS) following a single blood test. In a pilot randomised controlled trial, we aimed to determine whether a large trial is feasible. Methods Patients presenting to two EDs with suspected cardiac chest pain were randomised to receive care guided by the MACS decision rule (intervention group) or standard care (controls). The primary efficacy outcome was a successful discharge from the ED, defined as a decision to discharge within 4 hours of arrival providing that the patient did not have a missed acute myocardial infarction (AMI) or develop a major adverse cardiac event (MACE: death, AMI or coronary revascularisation) within 30 days. Feasibility outcomes included recruitment and attrition rates. Results In total, 138 patients were included between October 2013 and October 2014, of whom 131 (95%) were randomised (66 to intervention and 65 controls). Nine (7%) patients had prevalent AMI and six (5%) had incident MACE within 30 days. All 131 patients completed 30-day follow-up and were included in the final analysis with no missing data for the primary analyses. Compared with standard care, a significantly greater proportion of patients whose care was guided by the MACS rule were successfully discharged within 4 hours (26% vs 8%, adjusted OR 5.45, 95% CI 1.73 to 17.11, p=0.004). No patients in either group who were discharged within 4 hours had a diagnosis of AMI or incident MACE within 30 days (0.0%, 95% CI 0% to 20.0% in the intervention group). Conclusions In this pilot trial, use of the MACS rule led to a significant increase in safe discharges from the ED but a larger, fully powered trial remains necessary. Our findings seem to support the feasibility of that trial. Trial registration number ISRCTN 86818215. Research Ethics Committee reference 13/NW/0081. UKCRN registration ID 14334

Phase 2 randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis

Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase 2 multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. Methods: The REPARO phase 2 study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Main Outcome Measures: Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining). Results: At week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 μg/ml (+35.3%; 97.06% confidence interval [CI], 15.88–54.71; P < 0.001) and 58.0% receiving rhNGF 20 μg/ml (+38.4%; 97.06% CI, 18.96–57.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 μg/ml (+31.4%; 97.06% CI, 11.25–51.49; P = 0.001) and 74.0% receiving rhNGF 20 μg/ml (+30.9%; 97.06% CI, 10.60–51.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient. Conclusions: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK

Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis

Neurotrophic keratitis/keratopathy (NK), a rare degenerative corneal disease, lacks effective pharmacologic therapies.1 Because NK pathology involves trigeminal nerve damage and loss of corneal innervation, nerve growth factor (NGF) is surmised to promote healing of NK.2 Preliminary studies with murine NGF demonstrated efficacy for treating corneal neurotrophic ulcers;3 however, the complex tertiary structure of NGF has complicated the production of recombinant human NGF (rhNGF) suitable for clinical development. To this end, we developed an Escherichia coli–derived rhNGF formulation that demonstrated to be well tolerated and safe for topical ophthalmic use in a phase I study in healthy volunteers.4 We report phase I results of topical rhNGF for patients with moderate-to-severe NK

Examining the impact of virtual reality on clinical decision making – An integrative review

Background: Clinical decision making is an essential cognitive skill in nursing. It is a process undertaken daily by nurses as they make judgements about patient care and manage complex issues as they arise. Virtual reality is an emerging technology that is increasingly being used pedagogically to teach non-technical skills including CDM, communication, situational awareness, stress management, leadership, and teamwork. Objective: The objective of this integrative review are to synthesise the research findings regarding the impact of virtual reality on clinical decision making in undergraduate nurses. Design: An integrative review using Whittemore and Knafl\u27s framework for integrated reviews. Data sources: An extensive search was conducted of healthcare databases including CINAHL, Medline and Web of Science between 2010 and 2021 using the terms virtual reality, clinical decision and undergraduate nursing. Review methods: The initial search located 98 articles. After screening and checking for eligibility, 70 articles were critically reviewed. Eighteen studies were included in the review and were critically appraised using the Critical Appraisal Skills Program checklist for qualitative papers and McMaster\u27s Critical appraisal form for quantitative papers. Results: Research in the use of VR has demonstrated its potential to improve undergraduate nurses\u27 critical thinking, clinical reasoning, clinical judgement and clinical decision-making skills. Students perceive these teaching modalities to be beneficial to the development of their clinical decision-making ability. There is lack of research related to the use of immersive virtual reality in developing and enhancing undergraduate nursing students\u27 clinical decision-making skills. Conclusion: Current research on the impact of virtual reality on the development of nursing CDM has demonstrated positive results. VR is one pedagogical approach that could further assist, however, there are no identified studies that focus on its impact in developing CDM, therefore further studies are required to address this gap in the literature