A Newly Licensed Nurse Orientation Program Evaluation: Focus on Outcomes.

The aim of this project was to evaluate the effectiveness and outcomes of a redesigned newly licensed nurse orientation program. A unique aspect of this program was an end-of-orientation simulated four-patient assignment that was designed to assess five categories of critical thinking: prioritization and delegation, problem recognition, clinical decision making, clinical implementation, and reflection. Newly licensed nurses' critical thinking was measured by the Advisory Board's Critical Thinking Diagnostic tool at 10 weeks, 6 months, and 12 months. Findings showed that in all five categories of critical thinking, a significant increase was found between the 10-week and 6-month evaluation. Two of the categories-prioritization and delegation, and problem recognition-were found to have a significant increase from the 6-month evaluation to the 12-month evaluation. In addition, newly licensed nurses reported improvement in their confidence and in their preparation to work independently. J Contin Educ Nurs. 2017;48(1):22-28.

Cognitive-behavioural therapy-based intervention to reduce fear of falling in older people: therapy development and randomised controlled trial - the Strategies for Increasing Independence, Confidence and Energy (STRIDE) study.

BACKGROUND: Falls cause fear, anxiety and loss of confidence, resulting in activity avoidance, social isolation and increasing frailty. The umbrella term for these problems is 'fear of falling', seen in up to 85% of older adults who fall. Evidence of effectiveness of physical and psychological interventions is limited, with no previous studies examining the role of an individually delivered cognitive-behavioural therapy (CBT) approach. OBJECTIVES: Primary objective To develop and then determine the effectiveness of a new CBT intervention (CBTi) delivered by health-care assistants (HCAs) plus usual care compared with usual care alone in reducing fear of falling. Secondary objectives To measure the impact of the intervention on falls, injuries, functional abilities, anxiety/depression, quality of life, social participation and loneliness; investigate the acceptability of the intervention for patients, family members and professionals and factors that promote or inhibit its implementation; and measure the costs and benefits of the intervention. DESIGN: Phase I CBTi development. Phase II Parallel-group patient randomised controlled trial (RCT) of the new CBTi plus usual care compared with usual care alone. SETTING: Multidisciplinary falls services. PARTICIPANTS: Consecutive community-dwelling older adults, both sexes, aged ≥ 60 years, with excessive or undue fear of falling per Falls Efficacy Scale-International (FES-I) score of > 23. INTERVENTIONS: Phase I Development of the CBTi. The CBTi was developed following patient interviews and taught to HCAs to maximise the potential for uptake and generalisability to a UK NHS setting. Phase II RCT. The CBTi was delivered by HCAs weekly for 8 weeks, with a 6-month booster session plus usual care. MAIN OUTCOME MEASURES: These were assessed at baseline, 8 weeks, 6 months and 12 months. Primary outcome measure Fear of falling measured by change in FES-I scores at 12 months. Secondary outcome measures These comprised falls, injuries, anxiety/depression [Hospital Anxiety and Depression Scale (HADS)], quality of life, social participation, loneliness and measures of physical function. There were process and health-economic evaluations alongside the trial. RESULTS: Four hundred and fifteen patients were recruited, with 210 patients randomised to CBTi group and 205 to the control group. There were significant reductions in mean FES-I [-4.02; 95% confidence interval (CI) -5.95 to -2.1], single-item numerical fear of falling scale (-1.42; 95% CI -1.87 to 1.07) and HADS (-1; 95% CI -1.6 to -0.3) scores at 12 months in the CBTi group compared with the usual care group. There were no differences in the other secondary outcome measures. Most patients found the CBTi acceptable. Factors affecting the delivery of the CBTi as part of routine practice were identified. There was no evidence that the intervention was cost-effective. CONCLUSIONS: Our new CBTi delivered by HCAs significantly improved fear of falling and depression scores in older adults who were attending falls services. There was no impact on other measures. FURTHER WORK: Further work should focus on a joint CBTi and physical training approach to fear of falling, more rational targeting of CBTi, the possibility of mixed group and individual CBTi, and the cost-effectiveness of provision of CBTi by non-specialists. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78396615. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 56. See the NIHR Journals Library website for further project information.

Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial.

BACKGROUND: We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2). METHODS: ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fisher's exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms. RESULTS: Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3-5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured. CONCLUSIONS: We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality.

The STRIDE (Strategies to Increase confidence, InDependence and Energy) study: cognitive behavioural therapy-based intervention to reduce fear of falling in older fallers living in the community - study protocol for a randomised controlled trial.

BACKGROUND: Around 30% to 62% of older individuals fall each year, with adverse consequences of falls being by no means limited to physical injury and escalating levels of dependence. Many older individuals suffer from a variety of adverse psychosocial difficulties related to falling including fear, anxiety, loss of confidence and subsequent increasing activity avoidance, social isolation and frailty. Such 'fear of falling' is common and disabling, but definitive studies examining the effective management of the syndrome are lacking. Cognitive behavioural therapy has been trialed with some success in a group setting, but there is no adequately powered randomised controlled study of an individually based cognitive behavioural therapy intervention, and none using non-mental health professionals to deliver the intervention. METHODS/DESIGN: We are conducting a two-phase study examining the role of individual cognitive behavioural therapy delivered by healthcare assistants in improving fear of falling in older adults. In Phase I, the intervention was developed and taught to healthcare assistants, while Phase II is the pragmatic randomised controlled study examining the efficacy of the intervention in improving fear of falling in community-dwelling elders attending falls services. A qualitative process evaluation study informed by Normalization Process Theory is being conducted throughout to examine the potential promoters and inhibitors of introducing such an intervention into routine clinical practice, while a health economic sub-study running alongside the trial is examining the costs and benefits of such an approach to the wider health economy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78396615.

Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain.

OBJECTIVE: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system associated with pathogenic autoantibodies against the astrocyte water channel protein aquaporin-4 (AQP4). The presence of neutrophils is a characteristic feature in NMO lesions in humans. Neutrophils are not generally found in multiple sclerosis lesions. We evaluated the role of neutrophils in a mouse NMO model. METHODS: NMO lesions were produced in mice by intracerebral injection of immunoglobulin G (IgG) isolated from NMO patient serum and human complement. We previously reported that this mouse model produces the characteristic histological features of NMO, including perivascular complement activation, inflammatory cell infiltration, and loss of myelin, AQP4, and glial fibrillary acidic protein. Lesions are absent when AQP4 null mice are used or when IgG from non-NMO patients is injected. RESULTS: We found remarkably reduced neuroinflammation, myelin loss, and AQP4 loss in brains of neutropenic mice at 24 hours and 7 days, and increased severity of NMO lesions in mice made neutrophilic by granulocyte colony stimulating factor. NMO lesions were greatly reduced by intracerebral administration of the neutrophil protease inhibitors Sivelestat and cathepsin G inhibitor I or by intraperitoneal injection of Sivelestat alone. Immunostaining of human NMO lesions for neutrophil elastase revealed many degranulating perivascular neutrophils, with no equivalent perivascular neutrophils in human multiple sclerosis lesions. INTERPRETATION: Our data implicate a central role of neutrophils in the pathogenesis of early NMO lesions and suggest the potential utility of neutrophil protease inhibitors such as Sivelestat in NMO therapy.

T cell deficiency does not reduce lesions in mice produced by intracerebral injection of NMO-IgG and complement.

We reported recently that intracerebral administration of NMO-IgG with human complement produces neuromyelitis optica (NMO) lesions in mice. We examined the role of T cells in the formation of NMO lesions by comparing brain histopathology in wildtype and nude mice. Brains were co-injected with IgG from NMO patients and human complement. At 24h and 5days, wildtype vs. nude mouse brains had comparable inflammation (CD45 immunoreactivity), loss of myelin (Luxol Fast Blue staining) and loss of AQP4 immunoreactivity. We conclude that T cells are not required for the formation of NMO lesions in this mouse model.

Dangers of bone graft substitutes: lessons from using GeneX.

BACKGROUND: Bone graft substitutes are widely used in spinal surgery. Here, serious complications associated with the bone graft substitute GeneX are presented. GeneX contains tri-calcium phosphate and calcium sulphate. METHODS: GeneX was used in three patients who had spinal decompression and fusion. Mice were also injected with GeneX, demineralised bone matrix (DBX) or saline subcutaneously. After 24 h the extent of tissue damage and inflammation in tissue sections was quantified. To understand the licensing process for bone graft substitutes, the U.S. Food and Drug Administration (FDA) and the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) websites were accessed. RESULTS: All patients developed sterile pus in soft tissues adjacent to the GeneX followed by skin breakdown in two and pharyngeal perforation in one. In mice, GeneX produced moderate or severe skin damage compared with no or mild skin damage after DBX (p<0.05) or saline (p<0.05) injection. GeneX caused more inflammation in mouse dermis (1704±193 leucocytes/mm2, mean ± SE) than DBX (537 ± 266, p<0.01) or saline (136 ± 19, p<0.01). The FDA and MHRA classify bone graft substitutes as medical devices. In contrast with drugs, medical devices do not need to undergo clinical safety tests before obtaining FDA 510(k) clearance for use in patients. CONCLUSION: GeneX may cause soft tissue inflammation and destruction and should not be placed next to thin walled structures, such as skin or pharynx, because it may erode through these tissues. Bone graft substitutes should undergo mandatory detailed safety testing prior to approval. This could be achieved by reclassifying them as drugs.

Post-marketing safety monitoring of a new group B meningococcal vaccine in New Zealand, 2004-2006.

New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine's safety.

Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood.

BACKGROUND: The "hygiene hypothesis" postulates that infections during infancy may protect against asthma and atopy. There is also some evidence that antibiotic and/or paracetamol use may increase the risk of asthma. METHODS: The study measured the association between infections, and medication use early in life and the risk of asthma at age 6-7 years. It involved 1584 children who had been notified to public health services with serious infections at age 0-4 years, and 2539 children sampled from the general population. For both groups, postal questionnaires were completed by parents. RESULTS: There was little difference in the prevalence of current wheezing between the childhood infections group (prevalence = 23.5%) and the general population group (prevalence = 24.3%). There was also little difference whether the major site of infection was gastrointestinal (prevalence = 24.1%), invasive (prevalence = 24.6%) or respiratory (prevalence = 21.1%). However, in both groups, there were associations with antibiotic (OR = 1.78, 95% CI 1.49 to 2.14) or paracetamol (OR = 1.38, 95% CI 1.04 to 1.83) use in the first year of life or recent paracetamol use (OR = 2.10, 95% CI 1.78 to 2.49) and current wheezing. There was a weak protective effect of childhood infections in children who had not used antibiotics in the first year of life (OR = 0.78, 95% CI 0.55 to 1.10). CONCLUSIONS: These findings are consistent with other evidence that antibiotic use early in life may increase the risk of asthma. They are also consistent with some preliminary evidence associating paracetamol use with an increased risk of asthma. Any protective effect of notifiable childhood infections was weak.

The expression of ER beta cx in human breast cancer and the relationship to endocrine therapy and survival.

PURPOSE: Estrogen receptor (ER) alpha-positive breast cancer is often treated with endocrine therapy using either antiestrogens or aromatase inhibitors. However, 30% of patients who receive endocrine therapy will derive no benefit from such treatments and may indeed suffer adverse effects. Currently, there are no ways to predict response to such treatments. ER beta cx, a variant of ER beta, has a dominant-negative effect over ER alpha, and its expression thought to modulate response to endocrine treatment may represent a predictor of response to endocrine therapy. EXPERIMENTAL DESIGN: We investigated the expression of the ER beta cx in 82 frozen breast samples (8 benign, 1 ductal carcinoma in situ, and 73 malignant) by Western blot analysis. The relationship between the expression of ER beta cx variants with prognosis and outcome of endocrine therapy was examined. RESULTS: There was a statistically significant association between the presence of ER beta cx and the response to endocrine therapy (Fisher's exact test, P = 0.04). We also examined the influence of the ER beta cx status of a tumor on time to progression and death. There was a relationship between the presence of ER beta cx and survival, with patients whose tumors express ER beta cx having a longer survival rate (P = 0.05). Cell-type specificity of expression was assessed by immunohistochemistry on a selection of histological samples. CONCLUSIONS: On the basis of this small group of patients, we conclude that the expression of ER beta cx correlated with favorable response to endocrine therapy. A larger study involving the staining of archival material is currently underway to confirm these preliminary results.