Can student mental health nurses be prepared for medicines management?

Aim This paper reports on an evaluation of the Medicines with Respect project, which implemented a stepped approach to education and training in medicines management (MM) for mental health nurses (MHNs). Method In the retrospective qualitative study, nine MHNs were interviewed to gain their perceptions of the MM training they received at university and to find out if it still had relevance. Results Content analysis of the interview data revealed that overall the participants valued the theoretical and practical learning strategies they experienced, although criticisms relating to all aspects of the education and training were reported. The participants also reported that the approach prepared them for clinical practice as registered nurses. Such an approach may also build the capacity of MHNs to develop as prescribers

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization.

Background: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances.Methods: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography.Results: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction - the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93) - and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend = 0.002).Conclusions: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes. (N Engl J Med 2001;344:645-54.) Copyright (C) 2001 Massachusetts Medical Society

Identification and analysis of Single Nucleotide Polymorphisms (SNPs) in the mosquito Anopheles funestus, malaria vector

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common source of genetic variation in eukaryotic species and have become an important marker for genetic studies. The mosquito Anopheles funestus is one of the major malaria vectors in Africa and yet, prior to this study, no SNPs have been described for this species. Here we report a genome-wide set of SNP markers for use in genetic studies on this important human disease vector. RESULTS: DNA fragments from 50 genes were amplified and sequenced from 21 specimens of An. funestus. A third of specimens were field collected in Malawi, a third from a colony of Mozambican origin and a third form a colony of Angolan origin. A total of 494 SNPs including 303 within the coding regions of genes and 5 indels were identified. The physical positions of these SNPs in the genome are known. There were on average 7 SNPs per kilobase similar to that observed in An. gambiae and Drosophila melanogaster. Transitions outnumbered transversions, at a ratio of 2:1. The increased frequency of transition substitutions in coding regions is likely due to the structure of the genetic code and selective constraints. Synonymous sites within coding regions showed a higher polymorphism rate than non-coding introns or 3' and 5'flanking DNA with most of the substitutions in coding regions being observed at the 3(rd )codon position. A positive correlation in the level of polymorphism was observed between coding and non-coding regions within a gene. By genotyping a subset of 30 SNPs, we confirmed the validity of the SNPs identified during this study. CONCLUSION: This set of SNP markers represents a useful tool for genetic studies in An. funestus, and will be useful in identifying candidate genes that affect diverse ranges of phenotypes that impact on vector control, such as resistance insecticide, mosquito behavior and vector competence

An Operational evaluation of head up displays for civil transport operations. NASA/FAA phase 3 report

The advantages and disadvantages of head-up displays (HUDs) in commercial jet transport approach and landing operations was evaluated. Ten airline captains currently qualified in the B-727 aircraft flew a series of instrument landing system (ILS) and nonprecision approaches in a motion base simulator using both a flight director HUD concept and a flightpath HUD concept as well as conventional head-down instruments under a variety of environmental and operational conditions to assess: (1) the potential benefits of these HUDs in airline operations; (2) problems which might be associated with their use; and (3) flight crew training requirements and flight crew operating procedures suitable for use with the HUDs. Results are presented in terms of objective simulator based performance measures, subject pilot opinion and rating data, and observer data

White cell count in the normal range and short-term and long-term mortality: international comparisons of electronic health record cohorts in England and New Zealand

OBJECTIVES: Electronic health records offer the opportunity to discover new clinical implications for established blood tests, but international comparisons have been lacking. We tested the association of total white cell count (WBC) with all-cause mortality in England and New Zealand. SETTING: Primary care practices in England (ClinicAl research using LInked Bespoke studies and Electronic health Records (CALIBER)) and New Zealand (PREDICT). DESIGN: Analysis of linked electronic health record data sets: CALIBER (primary care, hospitalisation, mortality and acute coronary syndrome registry) and PREDICT (cardiovascular risk assessments in primary care, hospitalisations, mortality, dispensed medication and laboratory results). PARTICIPANTS: People aged 30-75 years with no prior cardiovascular disease (CALIBER: N=686 475, 92.0% white; PREDICT: N=194 513, 53.5% European, 14.7% Pacific, 13.4% Maori), followed until death, transfer out of practice (in CALIBER) or study end. PRIMARY OUTCOME MEASURE: HRs for mortality were estimated using Cox models adjusted for age, sex, smoking, diabetes, systolic blood pressure, ethnicity and total:high-density lipoprotein (HDL) cholesterol ratio. RESULTS: We found 'J'-shaped associations between WBC and mortality; the second quintile was associated with lowest risk in both cohorts. High WBC within the reference range (8.65-10.05×10(9)/L) was associated with significantly increased mortality compared to the middle quintile (6.25-7.25×10(9)/L); adjusted HR 1.51 (95% CI 1.43 to 1.59) in CALIBER and 1.33 (95% CI 1.06 to 1.65) in PREDICT. WBC outside the reference range was associated with even greater mortality. The association was stronger over the first 6 months of follow-up, but similar across ethnic groups. CONCLUSIONS: Clinically recorded WBC within the range considered 'normal' is associated with mortality in ethnically different populations from two countries, particularly within the first 6 months. Large-scale international comparisons of electronic health record cohorts might yield new insights from widely performed clinical tests. TRIAL REGISTRATION NUMBER: NCT02014610

Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases: A CALIBER Cohort Study

BACKGROUND: Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints. OBJECTIVES: This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs. METHODS: We used linked primary care, hospitalization, disease registry, and mortality data in England. We included people 30 years or older with complete blood counts performed in usual clinical care and no history of CVD. We used Cox models to estimate cause-specific hazard ratios (HRs) for 12 CVDs, adjusted for cardiovascular risk factors and acute conditions affecting neutrophil counts (such as infections and cancer). RESULTS: Among 775,231 individuals in the cohort, 154,179 had complete blood counts performed under acute conditions and 621,052 when they were stable. Over a median 3.8 years of follow-up, 55,004 individuals developed CVD. Adjusted HRs comparing neutrophil counts 6 to 7 versus 2 to 3 × 10(9)/l (both within the 'normal' range) showed strong associations with heart failure (HR: 2.04; 95% confidence interval [CI]: 1.82 to 2.29), peripheral arterial disease (HR: 1.95; 95% CI: 1.72 to 2.21), unheralded coronary death (HR: 1.78; 95% CI: 1.51 to 2.10), abdominal aortic aneurysm (HR: 1.72; 95% CI: 1.34 to 2.21), and nonfatal myocardial infarction (HR: 1.58; 95% CI: 1.42 to 1.76). These associations were linear, with greater risk even among individuals with neutrophil counts of 3 to 4 versus 2 to 3 × 10(9)/l. There was a weak association with ischemic stroke (HR: 1.36; 95% CI: 1.17 to 1.57), but no association with stable angina or intracerebral hemorrhage. CONCLUSIONS: Neutrophil counts were strongly associated with the incidence of some CVDs, but not others, even within the normal range, consistent with underlying disease mechanisms differing across CVDs. (White Blood Cell Counts and Onset of Cardiovascular Diseases: a CALIBER Study [CALIBER]; NCT02014610)

Low eosinophil and low lymphocyte counts and the incidence of 12 cardiovascular diseases: a CALIBER cohort study

BACKGROUND: Eosinophil and lymphocyte counts are commonly performed in clinical practice. Previous studies provide conflicting evidence of association with cardiovascular diseases. METHODS: We used linked primary care, hospitalisation, disease registry and mortality data in England (the CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records) programme). We included people aged 30 or older without cardiovascular disease at baseline, and used Cox models to estimate cause-specific HRs for the association of eosinophil or lymphocyte counts with the first occurrence of cardiovascular disease. RESULTS: The cohort comprised 775 231 individuals, of whom 55 004 presented with cardiovascular disease over median follow-up 3.8 years. Over the first 6 months, there was a strong association of low eosinophil counts (<0.05 compared with 0.15-0.25×10(9)/L) with heart failure (adjusted HR 2.05; 95% CI 1.72 to 2.43), unheralded coronary death (HR 1.94, 95% CI 1.40 to 2.69), ventricular arrhythmia/sudden cardiac death and subarachnoid haemorrhage, but not angina, non-fatal myocardial infarction, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, subarachnoid haemorrhage or abdominal aortic aneurysm. Low eosinophil count was inversely associated with peripheral arterial disease (HR 0.63, 95% CI 0.44 to 0.89). There were similar associations with low lymphocyte counts (<1.45 vs 1.85-2.15×10(9)/L); adjusted HR over the first 6 months for heart failure was 2.25 (95% CI 1.90 to 2.67). Associations beyond the first 6 months were weaker. CONCLUSIONS: Low eosinophil counts and low lymphocyte counts in the general population are associated with increased short-term incidence of heart failure and coronary death. TRIAL REGISTRATION NUMBER: NCT02014610; results

Treatment Strategies for Central Nervous System Effects in Primary and Secondary Haemophagocytic Lymphohistiocytosis in Children

Purpose of Review: This review presents an appraisal of current therapeutic options for the treatment of central nervous system haemophagocytic lymphohistiocytosis (CNS-HLH) in the context of systemic disease, as well as when CNS features occur in isolation. We present the reader with a diagnostic approach to CNS-HLH and commonly used treatment protocols. We discuss and evaluate newer treatments on the horizon. Recent Findings: Mortality is high in patients who do not undergo HSCT, and while larger studies are required to establish benefit in many treatments, a number of new treatments are currently being evaluated. Alemtuzumab is being used as a first-line treatment for CNS-HLH in a phase I/II multicentre prospective clinical trial as an alternative to traditional HLH-1994 and 2004 protocols. It has also been used successfully as a second-line agent for the treatment of isolated CNS-HLH that is refractory to standard treatment. Ruxolitinib and emapalumab are new immunotherapies that block the Janus kinase—Signal Transducer and Activator of Transcription (JAK-STAT) pathway that have shown efficacy in refractory HLH, including for CNS-HLH disease. Summary: Treatment of CNS-HLH often requires HLH-94 or 2004 protocols followed by haematopoietic stem cell transplantation (HSCT) to maintain remission, although relapse can occur, particularly with reduced intensity conditioning if donor chimerism falls. CNS features have been shown to improve or stabilise following HSCT in CNS-HLH in the context of systemic disease and in isolated CNS-HLH. Encouraging reports of early cohort studies suggest alemtuzumab and the Janus kinase (JAK) inhibitor ruxolitinib offer potential salvage therapy for relapsed and refractory CNS-HLH. Newer immunotherapies such as tocilizumab and natalizumab have been shown to be beneficial in sporadic cases. CNS-HLH due to primary gene defects may be amenable to gene therapy in the future