Cardiovascular risk assessments at occupational health services: employee experiences.

BACKGROUND: Across England in the UK, population screening for cardiovascular disease (CVD) primarily takes place within general practice in the form of the National Health Service Health Check. Additional screening sites such as occupational health are advocated to improve the population impact. AIMS: To investigate participant experiences with cardiovascular and type 2 diabetes risk assessment (RA) at occupational health and subsequent support-seeking at general practice. METHODS: Face-to-face interviews were conducted for this qualitative study. Participants were recruited at three workplaces; a steel works and two hospital sites. Using interpretive phenomenological analyses, themes were drawn from salient narratives and categorically organized. RESULTS: There were 29 participants. Themes (n = 16) were organized into two domains; factors that facilitated (n = 9) or thwarted (n = 7) participant engagement with the RA and general practice. All participants described the RA as worthwhile and strongly valued RA at occupational health. Those with obesity and high CVD risk highlighted their difficulties in making lifestyle changes. Participants reported confusion and anxiety when GP advice about medication appeared to contradict what participants had interpreted during RA at occupational health. CONCLUSIONS: This study highlights factors that facilitate or thwart engagement in cardiovascular RA at occupational health services and general practice follow-up. Stakeholders can integrate these factors into standard operating procedures to enhance participant engagement and enable safeguards that minimize potential harm to participants.

Cardiorespiratory fitness testing and cardiovascular disease risk in male steelworkers.

BACKGROUND: The workplace has been advocated as a setting to perform cardiovascular disease (CVD) risk assessments. These risk assessments usually focus on traditional risk factors rather than cardiorespiratory fitness (CRF) despite established associations between CRF and CVD. The lack of guidance on interpreting health-related CRF values has been suggested as a barrier to utilizing CRF in practice. AIMS: To assess the merits of CRF testing in the workplace and explore whether a CRF value identified male individuals above the recommended threshold for further clinical investigation. METHODS: Cross-sectional analysis of male steelworkers from Carmarthenshire, South Wales, UK who completed a workplace-based CVD risk assessment with an added CRF protocol based on heart rate responses (Chester Step Test). Receiver operating characteristic (ROC) analysis was undertaken to explore the possibility of a CRF value to identify individuals at an increased 10-year risk of CVD (QRISK2 ≥ 10%). RESULTS: There were 81 participants. ROC analysis revealed that a CRF level of 34.5ml/kg/min identified those individuals above the ≥10% QRISK2 threshold with the best sensitivity (0.800) and specificity (0.687) to discriminate against true- and false-positive rates. Further analysis revealed that individuals with either 'Average' or 'Below Average' CRF would be five times more likely to have a 10-year CVD risk above the ≥10% QRISK2 threshold than individuals with an 'Excellent' or 'Good' level of fitness [OR 5.10 (95% CI 1.60-16.3)]. CONCLUSIONS: This study suggests CRF assessments are a useful addition to a workplace CVD assessment and could identify male individuals at increased predicted risk of the condition.

An analysis of the fate of 917 manuscripts rejected from Clinical Otolaryngology.

OBJECTIVES: The fate of all manuscripts rejected from the journal Clinical Otolaryngology (CO) over a three-year period was investigated. The aim was to review publication rate, delay and the impact factors of the journals that the papers went on to be published in. DESIGN: In total, 917 papers were rejected from CO between 2011 and 2013. The fate of these manuscripts was determined by searching for the corresponding author's surname, and if necessary keywords from the manuscript title, in both PubMed and Google Scholar. MAIN OUTCOME MEASURES: The main outcome measures recorded were as follows: the subsequent publication of the article, delay to publication and journal of publication. RESULTS: In all, 511 papers were subsequently published in journals, representing 55.7% of all rejected manuscripts. The average delay was 15.1 months (standard deviation [sd] = 8.8). The impact factor of CO was found to be higher than the average of the journals that accepted the rejected manuscripts in all 3 years. Only 41 (8%) papers were published in journals with a higher impact factor than CO. Of all subsequently accepted manuscripts, 60 (11.7%) were found only on Google Scholar (and not on PubMed). CONCLUSIONS: Rejection from CO certainly does not prevent subsequent publication, although the papers tend to be published after a lengthy delay and in journals with a lower impact factor than CO. When performing literature searches, it is important to search more than one database to ensure as many of the relevant articles are found as possible.

A re-appraisal of publication rates of scientific papers presented at the Otorhinolaryngology Research Society meetings.

OBJECTIVES: To review the rate of publication of papers in peer-reviewed journals after oral presentations at the Otorhinolaryngology Research Society meetings between 1996 and 2013 and to compare trends with the previous review (1979-1995). DESIGN: Literature review. SETTING: Merseyside ENT Research Collaborative. PARTICIPANTS: The abstracts of presentations at Otorhinolaryngology Research Society meetings are published in Clinical Otolaryngology. A structured search of PubMed was undertaken to identify published Otorhinolaryngology Research Society presentations. MAIN OUTCOME MEASURES: Publication rates. RESULTS: A total of 460 abstracts were identified. The interobserver reliability among reviewers was 98%. Of the total, 259 (56.3%) abstracts were published in peer-reviewed journals. The average time from Otorhinolaryngology Research Society presentation to publication was 27.7 months (median 23), which was not significantly different from the previous review. Publication by subspeciality was as follows: head and neck (45.6%), otology (30.5%), rhinology (22%) and others (1.9%). Most published Otorhinolaryngology Research Society presentations were published in Clinical Otolaryngology (22.4%), followed by the Journal of Laryngology and Otology (8.1%) and the Laryngoscope (7.3%). Clinical research was the most common category of abstracts being presented at Otorhinolaryngology Research Society meetings, followed by laboratory-based research. Over half (56.5%) of laboratory research presented were head and neck themed, while otology and rhinology predominated clinical research presentations. Over half (52.1%) of Otorhinolaryngology Research Society abstracts originated from units in the North of England. Bristol presented the most abstracts (30.1%), followed by Newcastle (25.1%). CONCLUSIONS: The publication rate of Otorhinolaryngology Research Society presentations remains high and many are subsequently published in high-impact factor otolaryngology journals. More Otorhinolaryngology Research Society presentations are now published in American and European journals.

'Prosiect Sir Gâr': workplace-based cardiovascular disease and diabetes risk assessments.

BACKGROUND: Cardiovascular disease (CVD) and diabetes remain two of the greatest health challenges in the UK. Government guidelines recommend screening for both of these conditions to identify individuals at high risk. Assessing individuals in the work environment for these two conditions as part of routine annual medicals could have benefits for both the employee and employer. AIMS: To introduce the Prosiect Sir Gâr workplace-based initiative for CVD and diabetes prevention and report some of the baseline measurements in regards to CVD and diabetes risk. METHODS: Individuals from two workplaces (local health board and steelworks) attended a medical health check with an added CVD and diabetes risk assessment component. Demographic and anthropometric data, systolic and diastolic blood pressure, smoking status and family and medical histories were recorded. Blood samples were analysed for total and high-density lipoprotein cholesterol and HbA1c. Ten year risk of CVD and diabetes were predicted using the QRISK2 and QDiabetes algorithms. Individuals at high risk of either condition were referred to a lifestyle intervention programme. RESULTS: Among over 800 individuals screened a high prevalence of central obesity (75%), systolic hypertension (20%) and diastolic hypertension (23%) were observed in both workforces. In addition, a substantial proportion of the workers were either 'overweight' (42%) or 'obese' (28%). CONCLUSIONS: Introducing CVD and diabetes risk assessments to routine annual medicals in the workplace uncovered significant isolated risk factors for both CVD and diabetes that may otherwise have remained undiagnosed. This approach also gave employers a more detailed awareness of the current health of their employees.

Lessons learnt from the diagnosis and antimicrobial management of necrotising (malignant) otitis externa: our experience in a tertiary referral centre.

Necrotising otitis externa is an uncommon and aggressive infection of the external auditory canal with a tendency to present in the elderly and immunocompromised patient. We report a series of twenty-five patients admitted to our institution over a four-year period with this diagnosis. We review the diagnosis and antimicrobial management of these cases, and propose a treatment algorithm based on our experience.

Epistaxis in people with hereditary haemorrhagic telangiectasia: surgical management and psychological impact.

From the emergency management of acute epistaxis to the surgical procedures for chronic epistaxis, this article covers the options available to control the archetypal symptom of hereditary haemorrhagic telangiectasia while exploring the psychological effect such a disease has on the patient.

Aortopexy for the management of paediatric tracheomalacia - the Alder Hey experience.

BACKGROUND: Whilst aortopexy is an accepted and established procedure, there remains considerable heterogeneity within the literature, with inconsistencies in both the approach taken and the technique employed. Furthermore, limited data exist on both patient selection and long-term outcomes. This study aimed to report the experience of managing severe tracheomalacia by way of aortopexy in a large UK paediatric centre. METHOD: A retrospective case note review was conducted. Mean follow up was five years. RESULTS: Twenty-five patients underwent aortopexy for severe tracheomalacia caused by external vascular compression. Acute life-threatening events precipitated investigation in 72 per cent of cases. Twenty-one patients initially presented to ENT services for investigation, which comprised upper airway endoscopy and imaging with computed tomography angiography. Post-operatively, the majority of patients demonstrated complete resolution of symptoms and were discharged from all associated services. Only four patients required a tracheostomy. CONCLUSION: Aortopexy offers an effective method of treating severe tracheomalacia due to vascular compression.

A multi-centre analysis of a decade of endoscopic pharyngeal pouch surgery in Cheshire and Merseyside.

BACKGROUND: There are sparse data on the outcomes of endoscopic stapling of pharyngeal pouches. The Mersey ENT Trainee Collaborative compared regional practice against published benchmarks. METHODS: A 10-year retrospective analysis of endoscopic pharyngeal pouch surgery was conducted and practice was assessed against eight standards. Comparisons were made between results from the tertiary centre and other sites. RESULTS: A total of 225 procedures were performed (range of 1.2-9.2 cases per centre per year). All centres achieved 90 per cent resumption of oral intake within 2 days. All centres achieved less than 2-day hospital stays. Primary success (84 per cent (i.e. abandonment of endoscopic stapling in 16 per cent)), symptom resolution (83 per cent) and recurrence rates (13 per cent) failed to meet the standard across the non-tertiary centres. CONCLUSION: Endoscopic pharyngeal pouch stapling is a procedure with a low mortality and brief in-patient stay. There was significant variance in outcomes across the region. This raises the question of whether this service should become centralised and the preserve of either tertiary centres or sub-specialist practitioners.

Radial density distribution of chromatin: evidence that chromatin fibers have solid centers.

Fiber diameter, radial distribution of density, and radius of gyration were determined from scanning transmission electron microscopy (STEM) of unstained, frozen-dried chromatin fibers. Chromatin fibers isolated under physiological conditions (ionic strength, 124 mM) from Thyone briareus sperm (DNA linker length, n = 87 bp) and Necturus maculosus erythrocytes (n = 48 bp) were analyzed by objective image-processing techniques. The mean outer diameters were determined to be 38.0 nm (SD = 3.7 nm; SEM = 0.36 nm) and 31.2 nm (SD = 3.6 nm; SEM = 0.32 nm) for Thyone and Necturus, respectively. These data are inconsistent with the twisted-ribbon and solenoid models, which predict constant diameters of approximately 30 nm, independent of DNA linker length. Calculated radial density distributions of chromatin exhibited relatively uniform density with no central hole, although the 4-nm hole in tobacco mosaic virus (TMV) from the same micrographs was visualized clearly. The existence of density at the center of chromatin fibers is in strong disagreement with the hollow-solenoid and hollow-twisted-ribbon models, which predict central holes of 16 and 9 nm for chromatin of 38 and 31 nm diameter, respectively. The cross-sectional radii of gyration were calculated from the radial density distributions and found to be 13.6 nm for Thyone and 11.1 nm for Necturus, in good agreement with x-ray and neutron scattering. The STEM data do not support the solenoid or twisted-ribbon models for chromatin fiber structure. They do, however, support the double-helical crossed-linker models, which exhibit a strong dependence of fiber diameter upon DNA linker length and have linker DNA at the center.

The diameters of frozen-hydrated chromatin fibers increase with DNA linker length: evidence in support of variable diameter models for chromatin.

The diameters of chromatin fibers from Thyone briareus (sea cucumber) sperm (DNA linker length, n = 87 bp) and Necturus maculosus (mudpuppy) erythrocytes (n = 48 bp) were investigated. Soluble fibers were frozen into vitrified aqueous solutions of physiological ionic strength (124 mM), imaged by cryo-EM, and measured interactively using quantitative computer image-processing techniques. Frozen-hydrated Thyone and Necturus fibers had significantly different mean diameters of 43.5 nm (SD = 4.2 nm; SEM = 0.61 nm) and 32.0 nm (SD = 3.0 nm; SEM = 0.36 nm), respectively. Evaluation of previously published EM data shows that the diameters of chromatin from a large number of sources are proportional to linker length. In addition, the inherent variability in fiber diameter suggests a relationship between fiber structure and the heterogeneity of linker length. The cryo-EM data were in quantitative agreement with space-filling double-helical crossed-linker models of Thyone and Necturus chromatin. The data, however, do not support solenoid or twisted-ribbon models for chromatin that specify a constant 30 nm diameter. To reconcile the concept of solenoidal packing with the data, we propose a variable-diameter solid-solenoid model with a fiber diameter that increases with linker length. In principle, each of the variable diameter models for chromatin can be reconciled with local variations in linker length.

The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity.

The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions.

Treatment of sialorrhoea with repeated ultrasound-guided injections of botulinum toxin A into the parotid and submandibular glands.

Botulinum toxin injections are useful in patients with refractory sialorrhoea although the optimum treatment protocol and its efficacy over a long period of follow up are controversial. The aim of our prospective study was to examine the efficacy and complications of a protocol of repeated ultrasound-guided botulinum toxin injections of fixed doses at a tertiary children's hospital. A total of 79 procedures were done in 34 patients who were followed up for two years. The overall complication rate was 3%. The outcome measures considered included the Drooling Frequency Severity Scale (DFSS), visual analogue scale (VAS), and carers' assessments of the reduction in drooling. Our study highlighted two types on non-responders (primary and secondary) of which 3/34 required definitive surgical management. In summary, this study shows that a protocol of repeated injections of fixed doses of botulinum toxin A, while not beneficial in all cases, is a potentially valuable option for the safe and effective treatment of sialorrhoea in children.

VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain.

VEGF is mitogenic, angiogenic, and a potent mediator of vascular permeability. VEGF causes extravasation of plasma protein in skin bioassays and increases hydraulic conductivity in isolated perfused microvessels. Reduced tissue oxygen tension triggers VEGF expression, and increased protein and mRNA levels for VEGF and its receptors (Flt-1, Flk-1/KDR) occur in the ischemic rat brain. Brain edema, provoked in part by enhanced cerebrovascular permeability, is a major complication in central nervous system pathologies, including head trauma and stroke. The role of VEGF in this pathology has remained elusive because of the lack of a suitable experimental antagonist. We used a novel fusion protein, mFlt(1-3)-IgG, which sequesters murine VEGF, to treat mice exposed to transient cortical ischemia followed by reperfusion. Using high-resolution magnetic resonance imaging, we found a significant reduction in volume of the edematous tissue 1 day after onset of ischemia in mice that received mFlt(1-3)-IgG. 8-12 weeks after treatment, measurements of the resultant infarct size revealed a significant sparing of cortical tissue. Regional cerebral blood flow was unaffected by the administration of mFlt(1-3)-IgG. These results demonstrate that antagonism of VEGF reduces ischemia/reperfusion-related brain edema and injury, implicating VEGF in the pathogenesis of stroke and related disorders.

A new member of a family of site-specific retrotransposons is present in the spliced leader RNA genes of Trypanosoma cruzi.

A new member of a family of site-specific retrotransposons is described in the New World trypanosome Trypanosoma cruzi. This element, CZAR (cruzi-associated retrotransposon), resembles two previously described retrotransposons found in the African trypanosome T. brucei gambiense and the mosquito trypanosomatid Crithidia fasciculata in specifically inserting between nucleotides 11 and 12 of the highly conserved 39-mer of the spliced leader RNA (SL-RNA) gene. CZAR is similar in overall organization to the other two SL-RNA-associated elements. It possesses two potential long open reading frames which resemble the gag and pol genes of retroviruses. In the pol open reading frame, all three elements contain similarly arranged endonuclease domains and share extensive amino acid homology in the reverse transcriptase region. All are associated with the SL-RNA gene locus and are present in low copy numbers. They do not appear to have 5' truncated versions. All three retrotransposons are otherwise quite distinct from one another, with no significant overall amino acid homology. The presence of such retroelements inserted into the identical site within SL-RNA gene sequences in at least three evolutionarily distant trypanosomatid species argues for a functional role. Because these elements appear to have a precise target site requirement for integration, we refer to them as SL siteposons.

Effects of early angiotensin-converting enzyme inhibition on cardiac gene expression after acute myocardial infarction.

BACKGROUND: ACE inhibition after myocardial infarction (MI) has been shown to have beneficial effects on cardiac anatomy and function. The purpose of this study was to examine the effects of ACE inhibition on cardiac gene expression after MI. METHODS AND RESULTS: Rats were randomized to receive captopril or no treatment 1 day after MI. Eight weeks later, cardiac function and hemodynamics were measured by use of indwelling catheters and perivascular flow probes. Myocardial gene expression was assessed with DNA microarrays and real-time reverse transcription-polymerase chain reaction. The ratios of heart and left ventricular weights to body weight were significantly increased by MI and normalized by captopril. Cardiac index and stroke volume index were lower in the untreated MI group than in sham controls but were normal in the MI+captopril group. Thirty-seven genes were found to be differentially expressed between the untreated MI group and sham controls; 31 were induced and 6 repressed. Captopril partially or completely inhibited changes in 10 of the genes. The 37 genes clustered into 11 functional groups, and 6 had >/=1 genes whose expression was modified by ACE inhibition. CONCLUSIONS: ACE inhibition after MI inhibits cardiac hypertrophy, preserves cardiac function, and attenuates changes in myocardial gene expression. Gene expression profiling reveals, however, that some elements of the pathophysiology may be unaffected by the treatment and be targets for new therapies.