A survey of occupational skin disease in UK health care workers.

BACKGROUND: Occupational skin disease is a common problem among health care workers (HCWs). The prevalence of occupational skin disease in HCWs has been reported in several international studies, but not in the UK. AIMS: To estimate the prevalence of occupational skin disease in a population of UK HCWs and to explore possible causative factors. METHODS: Clinical and non-clinical HCWs attending for an influenza vaccine during October and November 2013 were invited to complete a brief skin questionnaire. Data from staff who stated their skin had suffered as a result of work were compared with data from staff who did not, to explore differences in potential causative factors. RESULTS: A total of 2762 questionnaires were analysed. The estimated prevalence of occupational skin disease was 20% for clinical and 7% for non-clinical staff. In total, 424 clinical staff stated their skin had been made worse by work. There were statistically significant differences between clinical staff with and without reported skin symptoms regarding a history of eczema, frequent hand washing and moisturizer use but no statistically significant difference in the relative proportions of soap and alcohol hand gel use. Non-clinical staff reported significantly more use of soap relative to alcohol gel than clinical staff. CONCLUSIONS: This study demonstrated the prevalence of occupational skin disease in a population of UK HCWs. More work is indicated to explore if the ratio of soap and alcohol gel reported in this study are typical and whether this has any impact on the development of occupational skin disease.

Healthcare workers' attitude towards influenza vaccination after the 2009 pandemic.

BACKGROUND: Previous studies have demonstrated the variability of healthcare workers' (HCWs) willingness to consider seasonal influenza vaccination, possibly to the detriment of their patients. AIMS: To ascertain HCW uptake of H1N1 and seasonal influenza vaccination and the reasons why one or both might have been declined following the pandemic of 2009. METHODS: An online, anonymous survey of HCWs across five, acute National Health Service trusts was undertaken in 2010. RESULTS: A total of 765 responses were obtained, of which the two main groups of participants were doctors of all grades (42%) and qualified nurses (40%). The willingness to be vaccinated increased with age. Senior doctors were the occupational group most likely to have had both vaccinations, but where they did decline they mainly did so because they perceived influenza to be a minor illness. Females were more likely to decline vaccination due to a fear of side effects, whereas males, particularly younger ones, viewed influenza as a minor illness. Junior doctors cited lack of availability of immunization sessions as one of the main reasons why they may not have had vaccination. CONCLUSIONS: Future influenza vaccination campaigns should consider using different approaches depending on the gender and occupational mix of the target population, rather than adopting a 'one-size' fits all approach.

Slowed Dynamics of Thin Filament Regulatory Units Reduces Ca2+-Sensitivity of Cardiac Biomechanical Function.

Actomyosin kinetics in both skinned skeletal muscle fibers at maximum Ca2+-activation and unregulated in vitro motility assays are modulated by solvent microviscosity in a manner consistent with a diffusion limited process. Viscosity might also influence cardiac thin filament Ca2+-regulatory protein dynamics. In vitro motility assays were conducted using thin filaments reconstituted with recombinant human cardiac troponin and tropomyosin; solvent microviscosity was varied by addition of sucrose or glucose. At saturating Ca2+, filament sliding speed (s) was inversely proportional to viscosity. Ca2+-sensitivity (pCa50 ) of s decreased markedly with elevated viscosity (η/η0 ≥ ~1.3). For comparison with unloaded motility assays, steady-state isometric force (F) and kinetics of isometric tension redevelopment (kTR ) were measured in single, permeabilized porcine cardiomyocytes when viscosity surrounding the myofilaments was altered. Maximum Ca2+-activated F changed little for sucrose ≤ 0.3 M (η/η0 ~1.4) or glucose ≤ 0.875 M (η/η0 ~1.66), but decreased at higher concentrations. Sucrose (0.3 M) or glucose (0.875 M) decreased pCa50 for F. kTR at saturating Ca2+ decreased steeply and monotonically with increased viscosity but there was little effect on kTR at sub-maximum Ca2+. Modeling indicates that increased solutes affect dynamics of cardiac muscle Ca2+-regulatory proteins to a much greater extent than actomyosin cross-bridge cycling.

Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility of human cardiac α-tropomyosin.

α-Tropomyosin (αTm) is central to Ca(2+)-regulation of cardiac muscle contraction. The familial hypertrophic cardiomyopathy mutation αTm E180G enhances Ca(2+)-sensitivity in functional assays. To investigate the molecular basis, we imaged single molecules of human cardiac αTm E180G by direct probe atomic force microscopy. Analyses of tangent angles along molecular contours yielded persistence length corresponding to ~35% increase in flexibility compared to wild-type. Increased flexibility of the mutant was confirmed by fitting end-to-end length distributions to the worm-like chain model. This marked increase in flexibility can significantly impact systolic and possibly diastolic phases of cardiac contraction, ultimately leading to hypertrophy.

Persistence length of human cardiac α-tropomyosin measured by single molecule direct probe microscopy.

α-Tropomyosin (αTm) is the predominant tropomyosin isoform in adult human heart and constitutes a major component in Ca²+-regulated systolic contraction of cardiac muscle. We present here the first direct probe images of WT human cardiac αTm by atomic force microscopy, and quantify its mechanical flexibility with three independent analysis methods. Single molecules of bacterially-expressed human cardiac αTm were imaged on poly-lysine coated mica and their contours were analyzed. Analysis of tangent-angle (θ(s)) correlation along molecular contours, second moment of tangent angles (<θ²(s)>), and end-to-end length (L(e-e)) distributions respectively yielded values of persistence length (L(p)) of 41-46 nm, 40-45 nm, and 42-52 nm, corresponding to 1-1.3 molecular contour lengths (L(c)). We also demonstrate that a sufficiently large population, with at least 100 molecules, is required for a reliable L(p) measurement of αTm in single molecule studies. Our estimate that L(p) for αTm is only slightly longer than L(c) is consistent with a previous study showing there is little spread of cooperative activation into near-neighbor regulatory units of cardiac thin filaments. The L(p) determined here for human cardiac αTm perhaps represents an evolutionarily tuned optimum between Ca²+ sensitivity and cooperativity in cardiac thin filaments and likely constitutes an essential parameter for normal function in the human heart.

Tropomyosin flexural rigidity and single ca(2+) regulatory unit dynamics: implications for cooperative regulation of cardiac muscle contraction and cardiomyocyte hypertrophy.

Striated muscle contraction is regulated by dynamic and cooperative interactions among Ca(2+), troponin, and tropomyosin on the thin filament. While Ca(2+) regulation has been extensively studied, little is known about the dynamics of individual regulatory units and structural changes of individual tropomyosin molecules in relation to their mechanical properties, and how these factors are altered by cardiomyopathy mutations in the Ca(2+) regulatory proteins. In this hypothesis paper, we explore how various experimental and analytical approaches could broaden our understanding of the cooperative regulation of cardiac contraction in health and disease.

Zanamivir for the treatment of influenza A and B infection in high-risk patients: a pooled analysis of randomized controlled trials.

BACKGROUND: Influenza can cause significant morbidity and mortality, particularly in patients considered to be at high risk (such as the elderly and those with chronic disease) of developing influenza-related complications. Data on the efficacy of zanamivir in high-risk patients are lacking because individual studies recruited a limited number of these patients. METHODS: A retrospective pooled analysis of data from high-risk patients in studies completed before or during the 1998-1999 winter season was performed to investigate the efficacy and safety of inhaled zanamivir (10 mg twice daily for 5 days) for the treatment of confirmed influenza. All studies were randomized, double-blind, and placebo-controlled with 21- to 28-day follow-up. A total of 2751 patients was recruited. Of these, 321 (12%) were considered high risk and 154 were randomized to zanamivir. The median time to alleviation of influenza symptoms and time to return to normal activities were the main outcome measures. RESULTS: Zanamivir-treated high-risk patients had a treatment benefit of 2.5 days compared with those given placebo (P = .015). Patients treated with zanamivir returned to normal activities 3.0 days earlier (P = .022) and had an 11% reduction (P = .039) in the median total symptom score over 1 to 5 days relative to those taking placebo. In addition, zanamivir reduced the incidence of complications requiring antibiotic use by 43% relative to placebo users (P = .045). Adverse events reported were of a similar nature and frequency between the two groups. CONCLUSION: This pooled analysis shows that zanamivir is an effective and well-tolerated treatment for influenza in patients considered at high-risk of developing influenza-related complications.

Effectiveness and role of zanamivir in the treatment of influenza infection.

Influenza is a worldwide public health issue. The virus circulates annually in winter and can cause significant morbidity in the general population and increased mortality rates in those who are more susceptible to complications if infected by the virus, especially the elderly. Although antivirals to treat and prevent influenza have been available in several countries for up to 30 years, annual influenza vaccination strategies remain the primary focus in reducing the burden of illness caused by this viral infection. Zanamivir is the first of a new class of compounds to offer significant advantages over existing influenza treatments. It is a potent and specific competitive inhibitor of both influenza A and B virus neuraminidase. The drug is administered topically by inhalation directly to the site of virus replication in a dose of 10 mg twice daily for 5 days. In both experimental and naturally acquired treatment studies, zanamivir has been shown to have efficacy against both influenza A and B virus and to be well tolerated. Significant treatment benefits resulting in reductions in illness of up to 2.5 days have been demonstrated in both the general population and in patients considered at high risk. In addition, patients receiving zanamivir have been able to return to normal activities significantly faster.

The PACE pilot study: 12-month results and implications for future primary prevention trials in the elderly. (Prevention with low-dose Aspirin of Cardiovascular disease in the Elderly)

OBJECTIVE: To document compliance with medication, drop-out and drop-in rates, and baseline cardiovascular event rates during the pilot phase of the PACE (Prevention with low-dose Aspirin of Cardiovascular disease in the Elderly) study. DESIGN: Randomized, double-blind, placebo-controlled trial of low-dose aspirin therapy. SETTING: Community-based, in general practices and residential retirement villages, in Victoria, Australia. SUBJECTS: Four hundred persons aged 70 years and older (53% females), ambulatory and living independently, who volunteered to participate. None had significant vascular disease, peptic ulceration, hemorrhagic symptoms, or were currently taking non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Compliance with medication (assessed by pill count and platelet function tests), self-reported drop-out and drop-in rates, and incidence of cardiovascular events reported by participants and their general practitioners during a 12-month period. RESULTS: Two fatal cardiovascular events, three non-fatal coronary events, and eight non-fatal cerebrovascular events were observed during the 12-month period. These incidence figures were approximately 15%, 15%, and 40%, respectively, of those in the general population of the same age and sex, based on morbidity data available from the Australian Bureau of Statistics. Compliance to medication was excellent (87%), and premature withdrawal (other than for a study end point) was limited to 14.5%. Secondary 'softer' endpoints, such as transient ischaemic attack and unstable angina, necessitated patient withdrawal from randomized therapy and possibly contributed to the small number of primary 'hard' end points observed. The projected power of the main study to detect a 20% treatment effect on overall cardiovascular mortality in 15,000 subjects over a 4-year period may, therefore, be substantially reduced. CONCLUSIONS: These results suggest that any future primary prevention study of cardiovascular disease in the elderly examining the effect of low-dose aspirin on overall cardiovascular mortality will likely need to use much larger numbers of patients or use a combined end point of fatal and non-fatal ischemic events.

Adverse effects of low-dose aspirin in a healthy elderly population.

The adverse effects of low-dose aspirin (100 mg daily) in the elderly were studied over a 12-month period in a double-blind, randomized, placebo-controlled trial of 400 subjects who were 70 years of age or older and had no preexisting major vascular diseases at the time of entry. Subjects were randomized so that 200 subjects received low-dose enteric-coated aspirin (100 mg daily) and 200 subjects received placebo. Compliance with medication, assessed by pill count, was 86%. Gastrointestinal symptoms were reported by 18% (n = 36) of participants receiving aspirin and 13% (n = 26) of those receiving placebo. Clinically evident gastrointestinal bleeding occurred in 3% (n = 6) of subjects receiving aspirin and none receiving placebo. Aspirin-treated subjects had a significant decrease in mean hemoglobin levels of 0.33 gm/dl during the 12-month study period, which was significantly greater than the decrease in the placebo-treated group (0.11 gm/dl; p < 0.05). These rates of unwanted symptoms are comparable with previous studies that used higher doses of aspirin. Until the risk-benefit trade-off from the use of low-dose aspirin in the elderly is established with an appropriate clinical trial, caution should be exercised when this compound is used for primary prevention of cardiovascular disease in this age group.

Haematological profile of healthy elderly Australians.

OBJECTIVE: To determine normal values for haematological parameters in healthy elderly persons, and document any changes in these over a 12 month period. DESIGN: The study was conducted as part of a randomised controlled trial of low-dose aspirin for primary prevention of cardiovascular disease in the elderly. All participants (380) had a full blood examination performed at entry, which was repeated after 12 months. The baseline results for all patients and the 12 month findings in a cohort of 162 persons allocated placebo were used in the present study. SETTING: Community-based (general practices and residential retirement villages). SUBJECTS: Persons aged 70 years and over (53% females) who were ambulatory, living independently, and volunteered to participate. None had significant vascular disease, peptic ulceration, haemorrhagic symptoms or were currently taking non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Full blood examination (excluding white cell differential counts) performed with a Technicon H1 analyser. RESULTS: The mean haemoglobin level +/- standard deviation (SD) was 14.69 +/- 1.10 g/dL (for men) and 13.72 +/- 1.05 g/dL (for women). Significant differences (P less than 0.001) in packed cell volume, red cell and platelet counts were observed between the two sexes. No clinically significant change was observed in any of the parameters over a 12 month period. CONCLUSIONS: Haematological reference values for healthy elderly Australians are consistent with normal values reported in younger populations for both sexes. As a result recommendations are provided for normal reference values among this group in an Australian setting.

Questionnaire development: an examination of the Nordic Musculoskeletal questionnaire.

This paper describes the outcome of user trials of the Nordic Musculoskeletal Questionnaire which encompassed the views of the following groups: data entry clerks, technical staff, administrative clerks and 481 subjects employed in 10 supermarkets. A significant number of improvements was identified, especially concerning its wording, layout and administration. This has led to a standardized version being produced for use in studying the prevalence of reported symptoms in many types of occupational groups.