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Purpose: Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison. Methods: Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar‐based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1‐year cohort window were included. DOAC, vitamin K antagonist and aspirin treatment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual‐level baseline characteristics. Results: In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017. Conclusions: Stroke prevention therapy improved from 2012 to 2017 with a corresponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database. [ABSTRACT FROM AUTHOR]

The United States Navy uses a visual feedback system for pilots, named 'the Greenie Board', to improve flight manoeuvres on aircraft carriers. Given that increased compliance with enhanced recovery after surgery protocols reduces postoperative complications, we decided to apply a similar feedback system to our institutional enhanced recovery programme. We undertook a prospective 12-month audit of 194 patients assigned to our enhanced recovery programme and evaluated adherence to the anaesthesia-related components of our protocol, before and after implementing a Greenie Board. A compliance score was calculated by summing points for adherence to: intra-operative antibiotic prophylaxis; temperature management; goal-directed intravenous fluid therapy; postoperative nausea and vomiting prophylaxis; and postoperative fluid restriction. The score for each patient was then colour-coded and anonymously displayed for each anaesthetist on a Greenie Board within the operating theatre suite. Protocol adherence improved significantly following introduction, with 'Green' scores (acceptable compliance) increasing from 33% to 72% of patients (p < 0.0001). The greatest improvement was seen with anti-emetic prophylaxis (49% to 70%, p = 0.004) with a consequent reduction in postoperative nausea and vomiting (OR 0.42, 95% CI 0.19-0.88, p = 0.021). We did not observe a decrease in other postoperative complications nor hospital length of stay. We conclude that this US Navy-inspired feedback system is an easily implemented, low-cost quality improvement tool that significantly improved adherence to intra-operative components of our enhanced recovery protocol. The system lends itself to global scaling to drive quality improvement in healthcare delivery and would be suited to institutions without electronic medical records, including low-resource countries. [ABSTRACT FROM AUTHOR]

Background The potential tissue replication sites and specific cell types that support in vivo virus survival beyond the acute phase of bovine ephemeral fever virus ( BEFV) infection have not been fully defined in cattle. To clarify the knowledge gap, tissue specimens were tested after collection from an adult steer necropsied 1 week after acute BEF. Case report Significant necropsy findings included fibrinoproliferative synovitis in the stifle joints and fibrin clot-laden fluid in serous body cavities. Moderate numbers of infiltrating neutrophils were demonstrated in sections of the prefemoral lymph nodes and haemal node, and lymphoid hyperplasia in the spleen, haemal node and prefemoral lymph nodes. Viral RNA was detected by qRT-PCR in fresh spleen, haemal node, prefemoral lymph node, synovial fluid and in several spleen-derived cell cultures. BEFV was isolated from autogenously derived splenic primary cell cultures 6 days after cessation of viraemia, and characteristic bullet-shaped virions were confirmed by electron microscopy of an ultrathin haemal node section. In sections of the spleen, haemal node and other tissues, immunohistochemistry demonstrated BEFV antigens that were intracellularly associated with probable histiocytic cells. Conclusion BEFV has preferential tropism for bovine lymphoid tissues and the spleen and haemal node may be potential sites for post-viraemic virus replication. [ABSTRACT FROM AUTHOR]

Objective This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Methods Four paralysed and six asymptomatic but virusinfected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. Results The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. Conclusion The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. [ABSTRACT FROM AUTHOR]

Background: CD40 and OX40 Ligand (OX40L) are cell-surface molecules expressed on airway smooth muscle (ASM) that can enhance inflammatory cell activation and survival. The aim of this study was to examine the effect of tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) on ASM CD40 and OX40L expression. Methods: CD40 and OX40L expression on human ASM cells from asthmatic and nonasthmatic donors following stimulation with TNF-α and/or IFN-γ was measured using cell-surface enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Involvement of signalling pathway was investigated with pharmacological inhibitors. Soluble TNF receptor levels were quantified by ELISA. Results: Interferon-γ and TNF-α synergistically increased CD40 expression to a greater extent on asthmatic than on nonasthmatic ASM. In contrast, IFN-γ reduced TNF-α-induced OX40L expression to a similar extent in both cell types. TNF-α and IFN-γ induced CD40 via nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 in both cell types and modulated OX40L via NF-κB and c-Jun N terminal kinase in nonasthmatic cells. Similar effects on the induction of OX40L in asthmatic cells were seen with NF-κB, but these were not statistically significant. The reduced OX40L expression with TNF-α and IFN-γ involved extracellular regulated kinase 1/2 activation. Conclusion: Asthmatic ASM may modulate airway inflammation locally by increasing CD40 and OX40L expression in response to cytokines. IFN-γ may regulate ASM pro-inflammatory actions by differentially modulating ASM CD40 and OX40L expression. [ABSTRACT FROM AUTHOR]

Previous studies have shown that IFN-γ is essential for the pathogenesis of cerebral malaria (CM) induced by Plasmodium berghei ANKA (PbA) in mice. However, the exact role of IFN-γ in the pathway (s) leading to CM has not yet been described. Here, we used 129P2Sv/ev mice which develop CM between 7 and 14 days post-infection with PbA. In this strain, both CD4+ and CD8+ T cells were involved in the effector phase of CM. When 129P2Sv/ev mice deficient in the IFN-γ receptor α chain (IFN-γR1) were infected with PbA, CM did not occur. Migration of leucocytes to the brain at the time of CM was observed in wild type (WT) but not in deficient mice. However, in the latter, there was an accumulation of T cells in the lungs. Analysis of chemokines and their receptors in WT and in deficient mice revealed a complex, organ-specific pattern of expression. Up-regulation of RANTES/CCL5, IP-10/CCL3 and CCR2 was associated with leucocyte migration to the brain and increased expression of MCP-1/CCL2, IP-10/CCL3 and CCR5 with leucocyte migration to the lung. This shows that IFN-γ controls trafficking of pathogenic T cells in the brain, thus providing an explanation for the organ-specific pathology induced by PbA infection. [ABSTRACT FROM AUTHOR]

Background Obese children are at high risk of developing co-morbidities, with a prevalence of abnormal tests ranging from 30 to 58%. Recent guidance recommends that all children with a body mass index (BMI) above the 95th centile be investigated. This study aimed to determine the prevalence of abnormal results in an urban paediatric population and to compare local practice against these recommendations. Methods Patient records of children attending either a community or hospital-based obesity clinic were analysed retrospectively to obtain anthropometric data and laboratory results; from this, the frequency of investigation and the prevalence of abnormal results were calculated. Investigations considered were alanine aminotransferase, thyroid-stimulating hormone (TSH), and fasting glucose, insulin and lipid profiles. Results One hundred thirty-six children (75 girls, 61 boys) were identified, with mean BMI z-score of 3.27 and mean age of 11.4 years (range 1.4-20.4). Children with BMI z-score >3 were more likely to be investigated, but otherwise, the frequency was similar for both sex and age. The prevalence of abnormal results was liver function tests, 14.3%; TSH, 0.0%; glucose, 0.0%; insulin, 31.6%; triglycerides, 10.0%; cholesterol, 15.6%. The sample size was small, but there did not appear to be a significant difference in the percentage abnormal results found for sex, age, or BMI z-score. Conclusion The prevalence of abnormal results was less than that identified in another UK study carried out in a tertiary centre, suggesting that the true population-based prevalence is lower than believed. This might be especially so because fewer tests were performed in these clinics than currently recommended and children at highest risk were more likely to be investigated. Therefore, further research is indicated to determine the true figure as well as to identify risk factors for co-morbidity, before costly recommendations to test all children with a BMI above the 95th centile are implemented. [ABSTRACT FROM AUTHOR]

Immunohistochemistry staining for β-amyloid precursor protein (β-APP) is a sensitive method to detect early axonal damage in traumatic brain injury, which was previously estimated to be of minimum 60–90 min after head injury. We present seven cases of well-documented posttraumatic survival of 35–60 min where β-APP detects early axonal damage. Cases were selected from routine work where documentation about survival is judged to be accurate. These are divided into three groups: group 1: severe head injury ( n = 7) with documented survival between 35 and 60 min. Group 2: severe head injury ( n = 4) with documented survival of less than 30 min. Group 3: cases ( n = 4) where death was not due to head injury but survival is documented between 45 and 109 min. The brains were fixed in formalin for 4 weeks and six regions (frontal lobe with anterior corpus callosum, parietal lobe with deep white matter, basal ganglia with posterior limb of internal capsule, cerebellum with white matter and middle cerebellar peduncle and pons with basis pontis and superior cerebellar peduncle) were sampled. All blocks were stained for haematoxylin and eosin and β-APP and selected ones for CD68, using antigen retrieval method. In group 1 sections revealed β-APP immunoreactivity in forms of small globules and granules and occasionally as thin and short filaments. These were detected in the pons, corpus callosum, internal capsule and cerebral white matter, with some variation in localization and intensity. In groups 2 and 3 all the sections were negative for β-APP staining. None of the cases showed evidence of severe brain swelling, increased intracranial pressure, ischaemia or infection. Using the antigen retrieval method, β-APP immunohistochemistry can detect axonal damage within 35 min after severe head injury. These results may have an implication in the consideration of minimal survival time after traumatic head injury in medico-legal practice. [ABSTRACT FROM AUTHOR]

This study describes the context for the development of a tool to formatively assess information technology skills of students. The tool provides a reliable and valid assessment of word processing competency, utilizing automation to apply the test instrument via the Microsoft Office package. Tests can be designed directly by tutors, and delivered via a network. Evaluation of the tests suggests that immediate automated testing is preferred by students compared to a traditional written test. There is evidence that the tool improves the IT skills of its users, whereas a traditional written test has no such beneficial effect. [ABSTRACT FROM AUTHOR]

Successful adaptation of craniofacial skeletal muscle is dependent upon the connective tissue component of the muscle. This is exemplified by procedures such as distraction histo/osteogenesis. The mechanisms underlying remodelling of intramuscular connective tissue are complex and multifactorial and involve extracellular matrix (ECM) molecules, receptors for the ECM (integrins) and enzymes that remodel the ECM (MMPs). This review discusses the current state of knowledge and clinical implications of connective tissue biology as applied to craniofacial skeletal muscle. [ABSTRACT FROM AUTHOR]

This study focused on the knowledge of front line staff, as individuals and in groups, in relation to the sexual abuse of adults with learning disabilities and was designed to inform staff training and policy initiatives and to explore gender dynamics. It showed that front line staff were alert to the possibility of sexual abuse but unclear about their roles and responsibilities making this an area of great concern to them. One third knew of people who had been abused but these had been dealt with haphazardly, leaving front line staff holding disproportionate anxiety on behalf of the service as a whole. [ABSTRACT FROM AUTHOR]

- The aim of this study was to determine the prevalence of traumatised permanent teeth among sensory (visual (VI) and hearing (HI)) impaired children attending special schools in Riyadh, Saudi Arabia. All the dental injuries involved incisor teeth, and trauma was noted in 33 (6.7%) children attending government schools (control group) compared to 7 (9%) VI children and 24 (11.4%) HI children. Differences in the dental trauma only reached statistical significance between the HI and control group (P < 0.05). Gender differences were only apparent in the HI group, with males having higher levels of traumatised teeth. In addition, HI children aged 11-12 years were more prone to trauma than children in the control group of the same age (P < 0.05). In conclusion, sensory impaired children do have a tendency for more dental trauma. However, this was only statistically significant for HI children. Whereas a gender difference was most noticeable for the HI group, with males having higher levels of trauma, this was noticeable by its absence among VI children. [ABSTRACT FROM AUTHOR]

This article gives a flavour of the CHIME materials on data handling in Microsoft Excel. It demonstrates the facilities for data validation within Excel. [ABSTRACT FROM AUTHOR]

Presents an abstract of the article “Murine Cerebral Malaria Studied With Monastral Blue (MB),” by A. L. Neill and N. H. Hunt, published in the December 2, 1990 issue of the journal “Immunology & Cell Biology.”

Presents an abstract of the article “Cytotoxic Effects of Oxidative Compounds on Normal and Malignant Cells,” by E. P. Cook and N. H. Hunt, published in the December 2, 1990 issue of the journal “Immunology & Cell Biology.”

Background Of the more than 250 000 emergency medical services-treated out-of-hospital cardiac arrests that occur each year in the United States, only about 8% survive to hospital discharge with good neurologic function. Treatment for out-of-hospital cardiac arrest involves a system of care that includes complex interactions among multiple stakeholders. Understanding the factors inhibiting optimal care is fundamental to improving outcomes. Methods and Results We conducted group interviews with emergency responders including 911 telecommunicators, law enforcement officers, firefighters, and transporting emergency medical services personnel (ie, emergency medical technicians and paramedics) who responded to the same out-of-hospital cardiac arrest incident. We used the American Heart Association System of Care as the framework for our analysis to identify themes and their contributory factors from these interviews. We identified 5 themes under the structure domain, which included workload, equipment, prehospital communication structure, education and competency, and patient attitudes. In the process domain, 5 themes were identified focusing on preparedness, field response and access to patient, on-scene logistics, background information acquisition, and clinical interventions. We identified 3 system themes including emergency responder culture; community support, education, and engagement; and stakeholder relationships. Three continuous quality improvement themes were identified, which included feedback provision, change management, and documentation. Conclusions We identified structure, process, system, and continuous quality improvement themes that may be leveraged to improve outcomes for out-of-hospital cardiac arrest. Interventions or programs amenable to rapid implementation include improving prearrival communication between agencies, appointing patient care and logistical leadership on-scene, interstakeholder team training, and providing more standardized feedback to all responder groups.

Aims: To identify factors that might influence cessation of groin injecting (GI) among patients receiving oral opioid substitution treatment (OST)., Design: A cross-sectional survey., Setting: Drug treatment centres in South East England., Participants: Groin injectors (GIs) attending an ultrasound 'health-check' clinic., Measurements: Clinical data and ultrasound images; comparing 65 patients who had injected drugs in the femoral vein (fv) in the previous month (current GIs) with 49 former groin injectors (former GIs)., Findings: Most of the 114 clinic attendees were men (69.3%) and white European (95.6%). Mean age, duration of GI and time in treatment were 36.4 years, 54.8 months and 20.5 months, respectively. Former GIs were significantly older (P < 0.001) and had been injecting (P < 0.05) and in treatment (P < 0.05) for longer than current GIs. History of deep vein thrombosis (DVT, P < 0.05) and septicaemia (P < 0.05); moderate/severe chronic venous disease (CVD, P < 0.01); and 'very severe' fv damage on ultrasonography (P < 0.05) were more common among former GIs. A logistic regression model correcting for the effects of covariants revealed age (B 0.08; Wald 7.1; P < 0.01) and severity of venous disease (B 1.1; Wald 4.1; P < 0.05) as the strongest predictors of behaviour change., Conclusions: GI cessation is associated with longer time in treatment, increasing age and the presence of CVD and severely damaged fv. GI appears to be an intractable behaviour that often persists despite OST and severe health complications. Persistent GI should prompt a review of whether OST is optimized and whether other interventions are needed to promote behaviour change prior to the development of serious harm., (© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.)

Objectives: To describe the circumstances and draft a typology of drug-related overdose deaths., Setting: London, 2003., Methods: An audit of 148 drug overdose deaths (involving heroin, methadone, dihydrocodeine, cocaine, amphetamine or MDMA) investigated by coroners during 2003. Information extracted on toxicology, pathology and circumstances were used to identify drug(s) implicated in the death., Results: Poly- or multiple drug use was detected in the majority of deaths with at least 69 different combinations, including 66% for heroin and 42% for cocaine. Six categories of death were identified involving an opiate (100, 68%); cocaine (14, 9%); other controlled drug (five, 3%); mixed drug overdose (18, 12%); other prescribed drug (five, 3%); and other causes (seven, 5%). A witness was present and the death was not instantaneous in 92 (61%) cases, although evidence in the coronial file suggested that in the majority of cases the overdose went unnoticed until too late to intervene. In all, 15 (one in 10) of the deceased were released from prison within 3 months of death; and 37 (one in four) were reported as in receipt of a methadone prescription., Conclusions: Perhaps for the first time in the United Kingdom cocaine was detected in more drug overdose deaths than methadone. However, reducing heroin use is central to the prevention of drug-related deaths. We recommend that overdose prevention encompasses strategies to encourage a 'mutual duty of care' among problem drug users, and in the United Kingdom further investigation of the relationship of methadone treatment failures on overall trends in drug-related deaths is merited.

Aims: To investigate whether a stimulant- and alcohol-focused brief motivational intervention induces positive behaviour change among young, regular users of MDMA ('ecstasy'), cocaine powder and crack cocaine., Design and Measurements: A randomized trial of the intervention versus a control group who received written health risk information materials only. All participants completed a baseline self-assessment questionnaire before randomization. Outcome measures were self-reported period prevalence abstinence from ecstasy, cocaine powder and crack cocaine and the frequency and amount of stimulant and alcohol use in the previous 90 days, recorded at 6-month follow-up via self-completion questionnaire and personal interview., Participants and Setting: A total of 342 adolescent and young adult stimulant users (aged 16-22 years) were recruited and 87% were followed-up. The intervention was delivered by a team of 12 agency youth drug workers and two researchers at five locations in Greater London and south-east England., Findings: There were no significant differences in abstinence for ecstasy, cocaine powder or crack cocaine use between the experimental and control groups. Contrasting follow-up with baseline self-reports, there were no between-group effects for changes in the frequency or amount of stimulant or alcohol use. Participant follow-up data suggested that the baseline assessment was a contributing factor in within-group behaviour change among experimental and control condition participants., Conclusions: Our brief motivational intervention was no more effective at inducing behaviour change than the provision of information alone. We hypothesize that research recruitment, baseline self-assessment and contact with study personnel are influences that induce positive reactive effects on stimulant use.

Viagra use among British nightclubbers, a sentinel population of illicit drug users, was first reported in 1999. There has since been little attention paid to the evolution of patterns of non-prescribed use, apart from among men who have sex with men. Beginning in 1999 an annual survey has been conducted with a specialist dance music magazine, permitting cross-sectional comparisons over time. Rising levels of lifetime and current use prevalence and data on patterns of both male and female use are reported, along with elevated prevalence levels among both gay men and women. Experimentation with Viagra appears increasingly to have become established among British nightclubbers who use recreational drugs. Ethnographic and epidemiological study and monitoring of adverse consequences is now needed to fully appreciate reasons for use and the extent of possible harms.

Aims: To describe and evaluate trends in the use of stimulant drugs over a 5-year period using an under-studied data collection method., Design: Repeated-measures cross-sectional survey., Setting and Participants: Annual magazine-based survey targeting people who use stimulant drugs in dance contexts., Measurements: Life-time use prevalence (ever used), age of first use, current use prevalence (any use within the last month) and extent of use within the last month (number of days used) for a range of stimulant drugs. Additional measures of quantity of ecstasy used were also collected., Findings: Trends in life-time and current prevalence over time have been detected and comparisons made between different stimulant drugs. Evidence is obtained of broad stability in patterns of stimulant use in respect of age of first use and frequency of use among ongoing users. Despite an apparent reduction in the current prevalence of ecstasy use, the proportion of heavy users (usually >4 pills per session) has more than doubled between 1999 and 2003., Conclusions: This purposively sampled population study has yielded time trend data broadly consistent with other indicators, where they exist, and also has demonstrable potential to identify new drug trends. Further comparisons of purposive samples and randomly formed samples are needed.