Inequalities in life expectancy in Australia according to education level: a whole-of-population record linkage study.

BACKGROUND: Life expectancy in Australia is amongst the highest globally, but national estimates mask within-country inequalities. To monitor socioeconomic inequalities in health, many high-income countries routinely report life expectancy by education level. However in Australia, education-related gaps in life expectancy are not routinely reported because, until recently, the data required to produce these estimates have not been available. Using newly linked, whole-of-population data, we estimated education-related inequalities in adult life expectancy in Australia. METHODS: Using data from 2016 Australian Census linked to 2016-17 Death Registrations, we estimated age-sex-education-specific mortality rates and used standard life table methodology to calculate life expectancy. For men and women separately, we estimated absolute (in years) and relative (ratios) differences in life expectancy at ages 25, 45, 65 and 85 years according to education level (measured in five categories, from university qualification [highest] to no formal qualifications [lowest]). RESULTS: Data came from 14,565,910 Australian residents aged 25 years and older. At each age, those with lower levels of education had lower life expectancies. For men, the gap (highest vs. lowest level of education) was 9.1 (95 %CI: 8.8, 9.4) years at age 25, 7.3 (7.1, 7.5) years at age 45, 4.9 (4.7, 5.1) years at age 65 and 1.9 (1.8, 2.1) years at age 85. For women, the gap was 5.5 (5.1, 5.9) years at age 25, 4.7 (4.4, 5.0) years at age 45, 3.3 (3.1, 3.5) years at 65 and 1.6 (1.4, 1.8) years at age 85. Relative differences (comparing highest education level with each of the other levels) were larger for men than women and increased with age, but overall, revealed a 10-25 % reduction in life expectancy for those with the lowest compared to the highest education level. CONCLUSIONS: Education-related inequalities in life expectancy from age 25 years in Australia are substantial, particularly for men. Those with the lowest education level have a life expectancy equivalent to the national average 15-20 years ago. These vast gaps indicate large potential for further gains in life expectancy at the national level and continuing opportunities to improve health equity.

New product, old problem(s): multistate outbreak of Salmonella Paratyphi B variant L(+) tartrate(+) infections linked to raw sprouted nut butters, October 2015.

A cluster of Salmonella Paratyphi B variant L(+) tartrate(+) infections with indistinguishable pulsed-field gel electrophoresis patterns was detected in October 2015. Interviews initially identified nut butters, kale, kombucha, chia seeds and nutrition bars as common exposures. Epidemiologic, environmental and traceback investigations were conducted. Thirteen ill people infected with the outbreak strain were identified in 10 states with illness onset during 18 July-22 November 2015. Eight of 10 (80%) ill people reported eating Brand A raw sprouted nut butters. Brand A conducted a voluntary recall. Raw sprouted nut butters are a novel outbreak vehicle, though contaminated raw nuts, nut butters and sprouted seeds have all caused outbreaks previously. Firms producing raw sprouted products, including nut butters, should consider a kill step to reduce the risk of contamination. People at greater risk for foodborne illness may wish to consider avoiding raw products containing raw sprouted ingredients.

Are healthcare costs from obesity associated with body mass index, comorbidity or depression? Cohort study using electronic health records.

The objective of this study was to evaluate the association between body mass index (BMI) and healthcare costs in relation to obesity-related comorbidity and depression. A population-based cohort study was undertaken in the UK Clinical Practice Research Datalink (CPRD). A stratified random sample was taken of participants registered with general practices in England in 2008 and 2013. Person time was classified by BMI category and morbidity status using first diagnosis of diabetes (T2DM), coronary heart disease (CHD), stroke or malignant neoplasms. Participants were classified annually as depressed or not depressed. Costs of healthcare utilization were calculated from primary care records with linked hospital episode statistics. A two-part model estimated predicted mean annual costs by age, gender and morbidity status. Linear regression was used to estimate the effects of BMI category, comorbidity and depression on healthcare costs. The analysis included 873 809 person-years (62% female) from 250 046 participants. Annual healthcare costs increased with BMI, to a mean of £456 (95% CI 344-568) higher for BMI ≥40 kg m(-2) than for normal weight based on a general linear model. After adjusting for BMI, the additional cost of comorbidity was £1366 (£1269-£1463) and depression £1044 (£973-£1115). There was evidence of interaction so that as the BMI category increased, additional costs of comorbidity (£199, £74-£325) or depression (£116, £16-£216) were greater. High healthcare costs in obesity may be driven by the presence of comorbidity and depression. Prioritizing primary prevention of cardiovascular disease and diabetes in the obese population may contribute to reducing obesity-related healthcare costs.

Severity of obesity and management of hypertension, hypercholesterolaemia and smoking in primary care: population-based cohort study.

Obesity and obesity-associated cardiovascular risk are increasing worldwide. This study aimed to determine how different levels of obesity are associated with the management of smoking, hypertension and hypercholesterolaemia in primary care. We conducted a cohort study of adults aged 30-100 years in England, sampled from the primary care electronic health records in the Clinical Practice Research Datalink. Prevalence, treatment and control were estimated for each risk factor by body mass index (BMI) category. Adjusted odds ratios (AOR) were estimated, allowing for age, gender, comorbidity and socioeconomic status, with normal weight as reference category. Data were analysed for 247,653 patients including 153,308 (62%) with BMI recorded, of whom 46,149 (30%) were obese. Participants were classified into simple (29,257), severe (11,059) and morbid obesity (5833) categories. Smoking declined with the increasing BMI category, but smoking cessation treatment increased. Age-standardised hypertension prevalence was twice as high in morbid obesity (men 78.6%; women 66.0%) compared with normal weight (men 37.3%; women 29.4%). Hypertension treatment was more frequent (AOR 1.75, 1.59-1.92) but hypertension control less frequent (AOR 0.63, 0.59-0.69) in morbid obesity, with similar findings for severe obesity. Hypercholesterolaemia was more frequent in morbid obesity (men 48.2%; women 36.3%) than normal weight (men 25.0%; women 20.0%). Lipid lowering therapy was more frequent in morbid obesity (AOR 1.83, 1.61-2.07) as was cholesterol control (AOR 1.19, 1.06-1.34). Increasing obesity category is associated with elevated risks from hypertension and hypercholesterolaemia. Inadequate hypertension control in obesity emerges as an important target for future interventions.

A practical approach to evidence-based dentistry: How to search for evidence to inform clinical decisions.

BACKGROUND AND OVERVIEW: Knowing how to search for evidence that can inform clinical decisions is a fundamental skill for the practice of evidence-based dentistry. There are many available types of evidence-based resources, characterized by their degrees of coverage of preappraised or summarized evidence at varying levels of processing, from primary studies to systematic reviews and clinical guidelines. The practice of evidence-based dentistry requires familiarity with these resources. In this article, the authors describe the process of searching for evidence: defining the question, identifying the question's nature and main components, and selecting the study design that best addresses the question.

What is the role for Xpert® MTB/RIF in high-resource settings? Experience from a central London hospital.

The role of Xpert(®) MTB/RIF for tuberculosis (TB) diagnosis remains to be clearly delineated in high-resource settings. At a London hospital, we evaluated a policy of selective assay use, with testing restricted to defined sub-groups of patients. Management was directly influenced in 30% of patients studied, including 'ruling-in' a TB diagnosis (leading to initiation of treatment for TB or for potential multidrug-resistant TB); negative assay results also helped support decisions for cessation of empirical anti-tuberculosis treatment or the safe initiation of other treatments such as immunosuppressant drugs. The benefits and pitfalls of this assay's use within high-resource settings are discussed.

Risks associated with preweaning mortality in 855 litters on 39 commercial outdoor pig farms in England.

A prospective longitudinal study was carried out on 39 outdoor breeding pig farms in England in 2003 and 2004 to investigate the risks associated with mortality in liveborn preweaning piglets. Researchers visited each farm and completed a questionnaire with the farmer and made observations of the paddocks, huts and pigs. The farmer recorded the number of piglets born alive and stillborn, fostered on and off and the number of piglets that died before weaning for 20 litters born after the visit. Data were analysed from a cohort of 9424 liveborn piglets from 855 litters. Overall 1274 liveborn piglets (13.5%) died before weaning. A mixed effect binomial model was used to investigate the associations between preweaning mortality and farm and litter level factors, controlling for litter size and number of piglets stillborn and fostered. Increased risk of mortality was associated with fostering piglets over 24h of age, organic certification or membership of an assurance scheme with higher welfare standards, farmer's perception that there was a problem with pest birds, use of medication to treat coccidiosis and presence of lame sows on the farm. Reduced mortality was associated with insulated farrowing huts and door flaps, women working on the farm and the farmer reporting a problem with foxes.

Using the unbiased perspectives of people living with a spinal cord injury in assessments of mobility.

STUDY DESIGN: Clinometrics study. OBJECTIVE: To devise a way of capturing the unbiased perspectives of people living with a spinal cord injury (SCI) in assessments of mobility. SETTING: SCI unit and community. METHODS: Three groups of raters used the Global Impression of Change Scale (GICS) to rate change in mobility of a cohort of patients with a recent SCI. The three groups of raters were as follows: 10 people with a recent SCI, 10 people with an established SCI and 10 physiotherapists. The ratings were done after viewing 51 pairs of videos depicting one of three motor tasks: sitting unsupported, transferring and walking. Each pair of videos showed the same person performing the same motor task on two occasions. The videos were taken between 1 h and 5 months apart and presented side by side, randomly left or right, on the screen. Raters were asked to score the amount of change in performance between the two videos on a 7-point Global Impression of Change Scale (GICS). Intra-rater reliability for the three motor tasks and three groups of raters was determined using intra-class correlation coefficients. RESULTS: People with an SCI were reliable at rating change in patients' abilities to transfer and walk with ICC's ranging from 0.66 to 0.81 (95% Confidence interval bounds ranging from 0.51 to 0.94). Physiotherapists were consistently but only marginally more reliable at rating than people with an SCI. CONCLUSIONS: Videos and the GICS may provide a way of using the unbiased perspectives of people living with spinal cord injury in assessments of mobility.

Immediate post-anaesthesia recovery 2013: Association of Anaesthetists of Great Britain and Ireland.

1. After general, epidural or spinal anaesthesia, all patients should be recovered in a specially designated area (henceforth 'post-anaesthesia care unit', PACU) that complies with the standards and recommendations described in this document. 2. The anaesthetist must formally hand over the care of a patient to an appropriately trained and registered PACU practitioner. 3. Agreed, written criteria for discharge of patients from the PACU to the ward should be in place in all units. 4. An effective emergency call system must be in place in every PACU and tested regularly. 5. No fewer than two staff (of whom at least one must be a registered practitioner) should be present when there is a patient in a PACU who does not fulfil the criteria for discharge to the ward. 6. All registered practitioners should be appropriately trained in accordance with the standards and competencies detailed in the UK National Core Competencies for Post Anaesthesia Care. 7. All patients must be observed on a one-to-one basis by an anaesthetist or registered PACU practitioner until they have regained control of their airway, have stable cardiovascular and respiratory systems and are awake and able to communicate. 8. All patients with tracheal tubes in place in a PACU should be monitored with continuous capnography. The removal of tracheal tubes is the responsibility of the anaesthetist. 9. There should be a specially designated area for the recovery of children that is appropriately equipped and staffed. 10. All standards and recommendations described in this document should be applied to all areas in which patients recover after anaesthesia, to include those anaesthetics given for obstetric, cardiology, imaging and dental procedures, and in psychiatric units and community hospitals. Only registered PACU practitioners who are familiar with these areas should be allocated to recover patients in them as and when required. 11. Patients' dignity and privacy should be respected at all times but patients' safety must always be the primary concern. When critically ill patients are managed in a PACU because of bed shortages, the primary responsibility for the patient lies with the hospital's critical care team. The standard of nursing and medical care should be equal to that in the hospital's critical care units. Audit and critical incident reporting systems should be in place in all PACUs.

Mass casualty incidents: are NHS staff prepared? An audit of one NHS foundation trust.

BACKGROUND: Lack of knowledge of an NHS trust's major incident policies by clinical staff may result in poorly coordinated responses during a mass casualty incident (MCI). AIM: To audit knowledge of the major incident policy by clinical staff working in a central London major acute NHS trust designated to receive casualties on a 24-h basis during a MCI. METHODS: A 12-question proforma was distributed to 307 nursing and medical staff in the hospital, designed to assess their knowledge of the major incident policy. Completed proformas were collected over a 2-month period between December 2006 and February 2007. RESULTS: A reply rate of 34% was obtained, with a reasonable representation from all disciplines ranging from nurses to consultants. Despite only 41% having read the policy in full, 70% knew the correct immediate action to take if informed of major incident activation. 76% knew the correct stand-down procedure. 56% knew the correct reporting point but less than 25% knew that an action card system was utilised. Nurses had significantly (p<0.01) more awareness of the policy than doctors. CONCLUSION: In view of the heightened terrorist threat in London, knowledge of major incident policy is essential. The high percentage of positive responses relating to immediate and stand-down actions reflects the rolling trust-wide MCI education programme and the organisational memory of the trust following several previous MCI in the capital. There is still scope for an improvement in awareness, however, particularly concerning knowledge of action cards, which are now displayed routinely throughout clinical areas and will be incorporated into induction packs.

Classification and nomenclature of all human homeobox genes.

BACKGROUND: The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described. RESULTS: We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'. CONCLUSION: We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.

Interpretation of Mycobacterium tuberculosis antigen-specific IFN-gamma release assays (T-SPOT.TB) and factors that may modulate test results.

BACKGROUND: Data about T cell antigen-specific (ESAT-6 and CFP-10) IFN-gamma release assays (IGRAs) during and after completion of anti-tuberculous (TB) treatment are limited and highly discordant. Thus, the utility of IGRAs as a surrogate marker of mycobacterial burden remain unclear. METHODS: To investigate factors that modulate IGRA responses during anti-TB treatment we used a standardised assay (T-SPOT.TB) in 33 patients with culture positive tuberculosis. RESULTS: Significantly more patients in the early (< or = 4 months of anti-TB treatment) rather than the late phase (> 4 months or completed anti-TB treatment) had positive IGRA responses [10/12 (83%) vs 4/21 (19%); p < or = 0.01]. Thus, 17/21 (81%) in the late phase or who had completed treatment (mean duration of treatment = 8.7 months) were IGRA negative, despite having robust antigen-specific recall proliferative responses. In these 17 patients prolonged incubation (5 days vs overnight), use of different antigen preparations (protein vs peptide) and addition of endotoxin, failed to elicit positive responses. CONCLUSIONS: In treated TB patients the discordant IGRA data remain unexplained by variation in laboratory protocols and are more likely due to host or environmental factors. In a low burden setting IGRAs may be a promising surrogate marker of mycobacterial disease burden.

The impact of social factors on tuberculosis management.

AIM: This paper is a report of a study to examine the impact of social factors on the management of tuberculosis including engagement with services, hospitalization and extended treatment. BACKGROUND: Rates of tuberculosis in major European cities have increased greatly in the last 10 years. The changing epidemiology of the disease, concentrated in marginalized groups, presents new challenges to the control of tuberculosis. METHODS: A prospective cohort study of 250 newly diagnosed tuberculosis patients was conducted in London between January 2003 and January 2005. Data were collected by means of a risk assessment tool and from medical records. Outcome measures included missed appointments, frequency and duration of hospitalization and length of treatment. RESULTS: The median age of the study sample was 33.82 (range 16.4-92.5) and 56.8% were male. Thirty-two per cent were hostel/street homeless or temporarily sharing accommodation with friends or relatives. Thirty-nine per cent were in receipt of welfare benefits and 13.2% had no income. Over a third anticipated difficulties taking their medicines and 30.3% had noone to remind them of this. Increased hospitalization was associated with hostel/street homelessness, drug or alcohol use and having noone to remind them to take their medicines (all P

Annotation, nomenclature and evolution of four novel homeobox genes expressed in the human germ line.

The homeobox genes comprise a large gene superfamily characterised by a conserved DNA motif encoding the homeodomain. Most homeodomain proteins function as transcription factors, and many have important roles in embryonic development and cell differentiation. Here we describe, annotate and name four novel homeobox genes in the human genome: ARGFX, DPRX, TPRX1 and DUXA. Each has generated multiple retrotransposed (processed) pseudogenes; these are reliable indicators of germ-line expression because only in germ-line cells can retrotransposition result in inheritance to the next generation. The retrotransposed sequences were exploited here as a novel means to deduce exon-intron boundaries. All four novel genes show accelerated rates of protein sequence evolution. This fast rate of sequence change may be connected with roles in human reproductive biology. Deducing the evolutionary origins of these genes is not straightforward, but we propose that TPRX1, DPRX and DUXA are highly divergent derivatives of the CRX gene, itself a member of the Otx homeobox gene family.

Deletion of the nuclear receptor Nr2e1 impairs synaptic plasticity and dendritic structure in the mouse dentate gyrus.

The spontaneous or targeted deletion of the nuclear receptor transcription factor Nr2e1 produces a mouse that shows hypoplasia of the hippocampal formation and reduced neurogenesis in adult mice. In these studies we show that hippocampal synaptic transmission appears normal in the dentate gyrus and cornu ammonis 1 subfields of adult mice that lack Nr2e1 (Nr2e1-/-), and that fEPSP shape, paired-pulse responses, and short-term plasticity are not substantially altered in either subfield. In contrast, the expression of long-term potentiation is selectively impaired in the dentate gyrus, and not in the cornu ammonis 1 subfield. Golgi analysis revealed that there was a significant reduction in both dendritic branching and dendritic length that was specific to dentate gyrus granule cells in the Nr2e1-/- mice. These results indicate that Nr2e1 deletion can significantly alter both synaptic plasticity and dendritic structure in the dentate gyrus.

Hearing half the message? A re-audit of the care of patients with acute asthma by emergency ambulance crews in London.

PROBLEM: An initial audit of the care provided to emergency asthma patients by the ambulance service was carried out in 1996. Some under-recognition and under-treatment of severe asthma was found as well as a lack of documentation of patient condition on scene. A re-audit was undertaken in 1999. DESIGN: A multidisciplinary advisory group was reconvened. The same method was adopted as for the first audit. Patients included were those administered nebulised salbutamol by crews in the catchment areas of four hospitals and those diagnosed with asthma at the Accident & Emergency (A&E) departments of those hospitals between January and March 1999. SETTING: London Ambulance Service. KEY MEASURES FOR IMPROVEMENT: (1) Accuracy of diagnosis and appropriateness of treatment, and (2) adherence to protocol. STRATEGIES FOR CHANGE: Following the first audit, treatment protocols were widened and brought into line with the British Thoracic Society guidelines for care of acute asthma patients. The results were widely disseminated within the service and training was initiated for all operational staff. EFFECTS OF CHANGE: The number of patients included in the re-audit more than doubled (audit 1: n = 252, audit 2: n = 532). The increase occurred exclusively in those administered nebulised salbutamol by ambulance crews but diagnosed with conditions other than asthma in A&E (audit 1: n = 15, audit 2: n = 161). The proportion of patients diagnosed with asthma in A&E who were administered nebulised salbutamol by their attending crew rose from 58% to 75%. However, 43 asthma patients were not treated; several of these were not recognised as suffering from asthma and others fell within the changed protocols for treatment. Adherence to protocol for administration of salbutamol remained high. Pre-hospital documentation of key observations did not improve. LESSONS LEARNT: Messages from the first audit seem to have been acted upon selectively. Implementing change is complex, and re-audit is necessary to understand the effects of the changes made.

Eleven daughters of NANOG.

Nanog is a recently discovered ANTP class homeobox gene. Mouse Nanog is expressed in the inner cell mass and in embryonic stem cells and has roles in self-renewal and maintenance of pluripotency. Here we describe the location, genomic organization, and relative ages of all human NANOG pseudogenes, comprising ten processed pseudogenes and one tandem duplicate. These are compared to the original, intact human NANOG gene. Eleven is an unusually high number of pseudogenes for a homeobox gene and must reflect expression in the human germ line. A pseudogene orthologous to NANOGP4 was found in chimpanzee and an expressed pseudogene in macaque. Examining pseudogenes of differing ages gives insight into pseudogene decay, which involves an excess of deletion mutations over insertions. The mouse genome has two processed pseudogenes, which are not clear orthologues of the primate pseudogenes.