A novel framework for reflecting on the functioning of research ethics review panels

In the past decade structures and processes for the ethical review of UK health care research have undergone rapid change. Although this has focused users' attention on the functioning of review committees, it remains rare to read a substantive view from the inside. This article presents details of processes and findings resulting from a novel structured reflective exercise undertaken by a newly formed research ethics review panel in a university school of nursing and midwifery. By adopting and adapting some of the knowledge to be found in the art and science of malt whisky tasting, a framework for critical reflection is presented and applied. This enables analysis of the main contemporary issues for a review panel that is primarily concerned with research into nursing education and practice. In addition to structuring the panel's own literary narrative, the framework also generates useful visual representation for further reflection. Both the analysis of issues and the framework itself are presented as of potential value to all nurses, health care professionals and educationalists with an interest in ethical review.     

Racial variation in the prevalence of atrial fibrillation among patients with heart failure: the Epidemiology, Practice, Outcomes, and Costs of Heart Failure (EPOCH) study

OBJECTIVES: This study was designed to determine the association between race and atrial fibrillation (AF) among patients with heart failure (HF). BACKGROUND: Atrial fibrillation is known to complicate HF, but whether its prevalence varies by race, and the reasons why, are not well understood. METHODS: We identified adults hospitalized with confirmed HF within a large integrated healthcare delivery system. We obtained information on demographics, comorbidity, vital signs, medications, and left ventricular systolic function status. "Atrial fibrillation" was defined as AF or atrial flutter documented by electrocardiogram or prior physician-assigned diagnoses. We evaluated the independent relationship between race and AF using multivariable logistic regression. RESULTS: Among 1,373 HF patients (223 African Americans, 1,150 Caucasians), the prevalence of AF was 36.9% (95% confidence interval [CI] 34.3% to 39.5%). Compared with Caucasians, African Americans were younger (mean age 67 vs. 74 years, p < 0.001) and more likely to have hypertension (86.6% vs. 77.7%, p < 0.01) and prior diagnosed HF (79.4% vs. 70.7%, p < 0.01). African Americans had less prior diagnosed coronary disease, revascularization, hypothyroidism, or valve replacement. Atrial fibrillation was much less prevalent in African Americans (19.7%) than Caucasians (38.3%, p < 0.001). After adjustment for risk factors for AF and other potential confounders, African Americans had 49% lower odds of AF (adjusted odds ratio 0.51, 95% CI 0.35 to 0.76). CONCLUSIONS: In a contemporary HF cohort, AF was significantly less common among African Americans than among Caucasians. This variation was not explained by differences in traditional risk factors for AF, HF etiology and severity, and treatment.     

Clinical outcomes of patients with rheumatoid arthritis after switching from infliximab to etanercept

OBJECTIVE: To assess the efficacy and monitor serious adverse events in patients with rheumatoid arthritis (RA) switching treatment from infliximab to etanercept. METHODS: Adult patients with active RA who were discontinuing treatment with infliximab were eligible to enroll in this prospective, 12-week, open label, single-arm, observational study. Four to 10 weeks after their last infusion of infliximab, patients began treatment with etanercept (twice weekly subcutaneous injections of 25 mg). Clinical assessments using the American College of Rheumatology (ACR) criteria for improvement were performed at baseline and at Weeks 6 and 12, and serious adverse events were monitored throughout the study. RESULTS: Twenty-five patients were enrolled, 18 of whom had discontinued infliximab because of lack of efficacy, and 22 completed 12 weeks of etanercept treatment. After 12 weeks, 14 of 22 patients (64%) achieved at least a 20% improvement in ACR criteria (ACR20), 13 (59%) experienced improvements in physical function that were considered clinically important (> or = 0.22 point decrease in overall Health Assessment Questionnaire score), and mean values of all individual components of the ACR criteria had improved. No serious adverse events were reported during the study and no patient discontinued because of lack of efficacy. CONCLUSION: Etanercept, a soluble tumor necrosis factor (TNF) receptor, provided a well tolerated and effective treatment option for some patients even when infliximab, a monoclonal antibody to TNF, had been ineffective.     

Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleotides and IL-15

Patients with advanced cutaneous T-cell lymphoma (CTCL) exhibit profound defects in cell-mediated immunity. Host immune functions appear to play an integral role in mediating disease-controlling responses in CTCL, therefore we investigated the effects of synthetic oligode-oxynucleotides with CpG motifs (CpG ODN), which have been recognized as immune stimulatory by virtue of activation of dendritic cells (DCs) following binding to Toll-like receptor (TLR) 9. Peripheral blood mononuclear cells (PBMCs) from patients with advanced CTCL (erythroderma with circulating malignant T cells) and healthy volunteers were cultured with either CpG-A or CpG-B ODN. Patients' PBMCs exhibited marked induction of interferon-alpha (IFN-alpha) release following culture with CpG-A. Similarly significant activation of NK cells and CD8 T cells occurred as assessed by up-modulation of CD69 expression and by natural killer lytic activity. Nevertheless, the PBMCs of patients exhibited blunted responses to CpG-A compared to healthy volunteers. In such cases, IL-15 was capable of producing levels of NK activation that were superior to CpG-A, while the combined effects of CpG-A plus IL-15 induced maximal activation of NK cells and further enhanced activation of CD8 T cells. These findings have important implications for the potential enhancement of antitumor immunity among patients with advanced CTCL.     

Long-term influence of duration and intensity of treatment on previously untreated individuals with alcohol use disorders

Aims This study examined the influence of the duration and intensity of the first episode of treatment for previously untreated individuals with alcohol use disorders on short‐term and long‐term outcomes, and the effect of additional treatment and delayed treatment on outcomes. Design, setting, participants A sample of alcoholic individuals (n = 473) was recruited at alcoholism information and referral centers and detoxification units and was surveyed at baseline and 1 year, 3 years and 8 years later. Measurements At each contact point, participants completed an inventory that assessed their treatment utilization since the last assessment and their current alcohol‐related, psychological and social problems. Findings Compared with individuals who remained untreated, individuals who entered treatment relatively quickly and who obtained a longer duration of treatment had better short‐ and long‐term alcohol‐related outcomes and better short‐term social functioning. Individuals who obtained a longer duration of additional treatment had better alcohol‐related outcomes than individuals who obtained no additional treatment but, among individuals who delayed treatment entry, the duration of treatment was not associated with treatment outcomes. In general, the intensity of treatment was not related to better outcomes. Conclusions Rapid entry into treatment and the duration of treatment for alcohol use disorders may be more important than the intensity of treatment. Treatment providers should consider structuring their programs to emphasize continuity, rather than intensity of care.     

A Simple Auditory Oddball Task in Young Adult Males at High Risk for Alcoholism

The reduction in the amplitude of the auditory P300 in young adult males at high risk for alcoholism has not been as consistently replicated as has been the reduction in the visual P300 amplitude in the same group. The easier nature of the auditory task was thought to be responsible for the inconsistency. We examined the auditory P300 amplitude in a group that has not yet been studied, young adult sons of alcoholics (mean age = 24.9 years, n = 48), and compared them with age and sex-matched controls (mean age = 27.8 years, n = 23). We found the auditory P300 amplitude to be reduced in the high-risk group and this reduction to be the greatest over the posterior centro-parietal and occipital areas when individual leads were examined. We further analyzed the data using current source density, a mathematical transformation that circumvents some of the errors inherent in measuring scalp-evoked potentials, and found reduced current source density in the high-risk group in the posterior central and parietal areas. Thus, we found that a simple auditory oddball task was effective in eliciting P300 differences in groups at high and low risk for alcoholism. The clinical significance of the P300 is discussed, as well as the relevance of task difficulty in eliciting auditory P300 differences in young males at high risk for alcoholism.     

Homozygosity For HLA-B27

The effect of homozygosity for HLA-B27 on the clinical expression of rheumatic disease was studied in two families. The 1 homozygous patient in each of two families demonstrated extraordinarily severe peripheral and axial arthritis compared to other affected heterozygous relatives. In addition, predominant peripheral or axial disease appeared to segregate with different B27 haplotypes. The 2 homozygous patients were not homozygous at the HLA-A, C, or D loci.