Highly pathogenic avian influenza virus H5N6 (clade 2.3.4.4b) has a preferable host tropism for waterfowl reflected in its inefficient transmission to terrestrial poultry.

Highly-pathogenic avian influenza virus (HPAIV) H5N6 (clade 2.3.4.4b) incurred into Europe in late 2017 and was predominantly detected in wild birds, with very few terrestrial poultry cases. Pekin ducks directly-infected with a UK virus (H5N6-2017) were donors of infection to investigate contact transmission to three recipient species: Ducks, chickens and turkeys. H5N6-2017 transmission to ducks was 100% efficient, but transmission to in-contact galliforme species was infrequent and unpredictable, thereby reflecting the European 2017-2018 H5N6 epidemiology. Although only two of 28 (7%) infected ducks died, the six turkeys and one chicken which became infected all died and displayed systemic H5N6-2017 dissemination, while pathogenesis in ducks was generally milder. Analysis of H5N6-2017 progeny in the contacts revealed no emergent polymorphisms in an infected duck, but the galliforme species included changes in the polymerase (PB2 A199T, PA D347A), matrix (M1 T218A) and neuraminidase genes (T88I). H5N6-2017 environmental contamination was associated with duck shedding.

Fluopyram Suppresses Population Densities of Heterodera glycines in Field and Greenhouse Studies in Michigan.

The soybean cyst nematode (SCN), Heterodera glycines Ichinohe, causes significant damage to soybean production annually. Fluopyram is a fungicide commonly used in soybean seed treatments intended to control soilborne fungal pathogens; however, recent studies have also suggested inhibitory effects on SCN. We examined the effects of a fluopyram seed treatment, ILeVO, on SCN reproduction, sudden death syndrome (SDS) development, and yield in a 3-year field study. Overall, fluopyram had a significant effect on yield (P = 0.046) and end-of-season SCN eggs and second-stage juveniles (Pf, P = 0.033) but no significant effect on SCN reproduction (Rf) or SDS disease index (P > 0.05). Post hoc tests indicated that fluopyram increased yield and suppressed SCN quantities. However, Rf was consistently greater than 1 whether or not the seed was treated with fluopyram, indicating that SCN populations were still increasing in the presence of fluopyram. A follow-up greenhouse study indicated that fluopyram reduced SCN relative to nontreated controls, as observed in the field, but only reduced SCN DNA within roots of a susceptible cultivar. These results indicate that fluopyram can suppress SCN quantities relative to nontreated seed but may not successfully reduce nematode populations without the use of additional management strategies.

Integrated Effects of Genetic Resistance and Prothioconazole + Tebuconazole Application Timing on Fusarium Head Blight in Wheat.

Integrated Fusarium head blight (FHB) management programs consisting of different combinations of cultivar resistance class and an application of the fungicide prothioconazole + tebuconazole at or after 50% early anthesis were evaluated for efficacy against FHB incidence (INC; percentage of diseased spikes), index (IND; percentage of diseased spikelets per spike), Fusarium damaged kernel (FDK), deoxynivalenol (DON) toxin contamination, grain yield, and test weight (TW) in inoculated field trials conducted in 11 U.S. states in 2014 and 2015. Mean log response ratios and corresponding percent control values for INC, IND, FDK, and DON, and mean differences in yield and TW relative to a nontreated, inoculated susceptible check (S_CK), were estimated through network meta-analyses as measures of efficacy. Results from the analyses were then used to estimate the economic benefit of each management program for a range of grain prices and fungicide applications costs. Management programs consisting of a moderately resistant (MR) cultivar treated with the fungicide were the most efficacious, reducing INC by 60 to 69%, IND by 71 to 76%, FDK by 66 to 72%, and DON by 60 to 64% relative to S_CK, compared with 56 to 62% for INC, 68 to 72% for IND, 66 to 68% for FDK, and 58 to 61% for DON for programs with a moderately susceptible (MS) cultivar. The least efficacious programs were those with a fungicide application to a susceptible (S) cultivar, with less than a 45% reduction of INC, IND, FDK, or DON. All programs were more efficacious under conditions favorable for FHB compared with less favorable conditions, with applications made at 50% early anthesis being of comparable efficacy to those made 2 to 7 days later. Programs with an MS cultivar resulted in the highest mean yield increases relative to S_CK (541 to 753 kg/ha), followed by programs with an S cultivar (386 to 498 kg/ha) and programs with an MR cultivar (250 to 337 kg/ha). Integrated management programs with an MS or MR cultivar treated with the fungicide at or after 50% early anthesis were the most likely to result in a 50 or 75% control of IND, FDK, or DON in a future trial. At a fixed fungicide application cost, these programs were $4 to $319/MT more economically beneficial than corresponding fungicide-only programs, depending on the cultivar and grain price. These findings demonstrate the benefits of combining genetic resistance with a prothioconazole + tebuconazole treatment to manage FHB, even if that treatment is applied a few days after 50% early anthesis.

Publication rates of presentations at the Irish Orthopaedic Association annual meeting.

BACKGROUND: Presentation of scientific research at national and international meetings is an important forum for the dissemination of knowledge. Subsequent publication of a full-text paper in a peer-reviewed journal is the expected outcome of such presentations. The publication rate from these meetings is highly variable. AIMS: To determine the publication rate of abstracts presented at the Irish Orthopaedic Association's Annual Conference and to determine which factors are associated with progression to full-text publication. METHODS: We reviewed the proceedings from the Irish Orthopaedic Association's National Meeting over a 4 year period. We searched the Pubmed database using author names, institution names, and keywords from each abstract's title, to determine how many presented articles progressed to full-text publication. RESULTS: Sixty-six of 203 were published, 97 % within 5 years of presentation. Laboratory based studies presenting novel or innovative findings were more likely to be published than clinical studies. Clinical studies were more likely to be published if they were prospective and had a longer period of follow-up. Retrospective audits were less likely to be published, even with a large cohort size. Changes in authorship of presented papers were related to a longer delay in time to full-text publication. CONCLUSIONS: Thorough planning of research studies is essential to ensure a timely progression to full-text publication in a peer-reviewed journal. Most studies will be published within 5 years of initial presentation.

Induction of GITRL expression in human keratinocytes by Th2 cytokines and TNF-α: implications for atopic dermatitis.

BACKGROUND: Glucocorticoid-induced TNF receptor-related protein ligand (GITRL), a ligand for the T cell co-stimulatory molecule GITR, is expressed by keratinocytes and involved in chemokine production. The expression of GITRL in skin inflammation remains unknown. OBJECTIVES: This study investigated cytokine regulation of keratinocyte GITRL expression. METHODS: Glucocorticoid-induced TNF receptor expression was evaluated in cytokine-treated human epidermal keratinocytes (HEK)s, murine PAM 212 cell line, murine and human skin explants by real time PCR, flow cytometry and immunostaining. Functional responses to GITR fusion protein were examined by real time PCR and ELISA. GITRL expression in AD and psoriasis was studied by immunohistochemistry. RESULTS: Skin biopsies from STAT6VT transgenic mice, which develop spontaneous atopic skin inflammation, were found by immunofluoresence, to have increased keratinocyte GITRL expression. Exposure to Th2 cytokines augmented GITRL mRNA expression in the murine PAM 212 keratinocytic cell line and murine skin explants. In contrast, GITRL mRNA and protein expression was only increased in HEKs and human skin explants in the presence of the combination of TNF-α and Th2 cytokines. A synergistic effect of Th2 cytokines and GITR fusion protein on production of CCL17, the Th2 chemokine, by murine keratinocytes was demonstrated. Immunohistochemical staining showed that acute AD lesions have increased expression of GITRL compared with normal skin, chronic AD lesions and psoriatic plaques. CONCLUSIONS AND CLINICAL RELEVANCE: Our studies demonstrate that GITRL expression is augmented by Th2 cytokines and TNF-α in keratinocytes. Increased GITRL expression in acute AD skin lesions is shown. This observation suggests a link between cytokine-regulated keratinocyte GITRL expression and its role in inflammatory responses in AD.

Research in higher surgical training: which rotation?

BACKGROUND: Orthopaedic higher surgical trainees in Ireland are allocated to one of eight training rotations. Each trainee is expected to publish at least one research paper per year during training. AIM: To assess the research productivity of each training rotation over a 10-year period. METHODS: A PubMed search was performed for each orthopaedic unit affiliated to higher surgical training (HST) in order to identify full-text research papers published between 2001 and 2010. The results were analysed to determine which training rotations are most productive in terms of research. RESULTS: We identified 267 papers published from 16 units over the 10-year period. There were substantial differences in the number of papers published from each unit, and substantial differences between the eight set trainee rotations. CONCLUSIONS: It is essential that each trainee makes an honest assessment of their potential for conducting and producing valuable and relevant research, and chooses an HST rotation that is appropriate to their needs. Publication of research articles is easier to achieve on some HST rotations than on others.

ß-Arrestin 1 inhibits the GTPase-activating protein function of ARHGAP21, promoting activation of RhoA following angiotensin II type 1A receptor stimulation.

Activation of the small GTPase RhoA following angiotensin II stimulation is known to result in actin reorganization and stress fiber formation. Full activation of RhoA, by angiotensin II, depends on the scaffolding protein ß-arrestin 1, although the mechanism behind its involvement remains elusive. Here we uncover a novel partner and function for ß-arrestin 1, namely, in binding to ARHGAP21 (also known as ARHGAP10), a known effector of RhoA activity, whose GTPase-activating protein (GAP) function it inhibits. Using yeast two-hybrid screening, a peptide array, in vitro binding studies, truncation analyses, and coimmunoprecipitation techniques, we show that ß-arrestin 1 binds directly to ARHGAP21 in a region that transects the RhoA effector GAP domain. Moreover, we show that the level of a complex containing ß-arrestin 1 and ARHGAP21 is dynamically increased following angiotensin stimulation and that the kinetics of this interaction modulates the temporal activation of RhoA. Using information gleaned from a peptide array, we developed a cell-permeant peptide that serves to inhibit the interaction of these proteins. Using this peptide, we demonstrate that disruption of the ß-arrestin 1/ARHGAP21 complex results in a more active ARHGAP21, leading to less-efficient signaling via the angiotensin II type 1A receptor and, thereby, attenuation of stimulated stress fiber formation.

How do we know when peanut and tree nut allergy have resolved, and how do we keep it resolved?

Over the last two decades, the prevalence of peanut and tree nut allergy has increased throughout the western world. Adverse reactions to these foods account for over 50% of all deaths resulting from food-related anaphylaxis. Until recently, evidence suggested that all peanut and tree nut allergy were permanent. It is now known that about 20% and 10%, respectively, of young patients outgrow peanut and tree nut allergies. Achieving tolerance is associated with increasing circulating T regulatory cells and reduced production of allergen-specific IgE. Reliable predictors of resolution are not yet available. A direct correlation between skin test weal size and allergen-specific IgE, at the time of diagnosis and likelihood of resolution, has been reported. Resolution of peanut or tree nut allergy cannot be determined conclusively by either allergen-specific IgE analysis or by skin prick testing. Oral food challenge is the gold standard for determining resolution of food allergy. Food challenges should only be undertaken in a clinical setting fully equipped to deal with a potential severe adverse reaction. Approximately 8% of patients who outgrow peanut allergy may suffer a recurrence, but recurrent tree nut allergy has not been reported to date. Infrequent ingestion of peanut may be related to the re-emergence of allergy. Induction of tolerance through oral immunotherapy or sublingual immunotherapy is now being actively studied, but remains experimental. Studies have reported short-term desensitization to peanut, but ongoing follow-up will determine whether tolerance is achieved long term.

"S" Quattro external fixation for complex intra-articular thumb fractures.

PURPOSE: To report outcomes in 10 patients who underwent dynamic "S" Quattro external fixation for complex fractures of the base of the thumb. METHODS: Nine men and one woman aged 18 to 69 (mean, 31) years underwent "S" Quattro external fixation for complex fractures of the base of the thumb. The dominant hand was involved in 8 patients. Three patients had Bennett fractures, 5 had Rolando fractures, one had an open multi-fragmented fracture, and one had a fracture-subluxation. Four of them had had prior (failed) treatment with splints and/or Kirschner wires. The "S" Quattro external fixator was applied for a mean of 4.9 weeks. Patients were followed up in an out-patient setting for a mean of 10.7 months until bone union and removal of the external fixator. Finger flexor function was assessed based on total active movement (TAM). Functional outcomes were assessed using the Disability of Arm, Shoulder and Hand (DASH) questionnaire. RESULTS: No pin-site infection, malunion, or non-union was encountered. Mean loss of TAM was 7.5 degrees. Five patients lost 10 degrees or more, 2 of whom lost 20 degrees (one with an open comminuted fracture and one was elderly). Four patients regained full TAM and 6 attained more than 75% TAM compared to the contralateral thumb. At the 3-year follow-up, the mean DASH score was 3.4. Four patients reported no functional disability. Poorer outcomes were reported in the 2 patients who once had lost 20 degrees of TAM. CONCLUSION: The "S" Quattro external fixator is recommended as a primary and definitive treatment modality for complex intra-articular thumb fractures when conservative and other surgical interventions have failed.

Laboratory diagnosis of Clostridium difficile-associated disease in the Republic of Ireland: a survey of Irish microbiology laboratories.

The Health Protection Surveillance Centre (HPSC) established a group to produce national guidelines for Clostridium difficile in Ireland in 2006. A laboratory questionnaire was distributed to determine current C. difficile diagnostic practices. Twenty-nine out of 44 laboratories providing C. difficile diagnostic services to 34 hospitals responded. Twenty-five out of 29 (86%) laboratories processed specimens for C. difficile and four (13.8%) forwarded specimens to another laboratory. Sixteen laboratories (64%) processed specimens for other healthcare facilities. None routinely examined stool for C. difficile, seven (28%) examined specimens only when requested to do so and 18 (72%) used specific selection criteria, including testing all liquid stools (39%), all nosocomial diarrhoea (44%), specific clinical criteria (28%) and history of antibiotic therapy (22%). All tested stool directly for C. difficile toxin with a variety of enzyme immunoassays, with 24 (96%) detecting both toxin A and B and one detecting toxin A only. Three (12%) laboratories used cytotoxicity assays; none used polymerase chain reaction and six (24%) laboratories performed C. difficile culture but only under specific circumstances. Seven (28%) laboratories had isolates typed during outbreaks, but none had the facilities to do so on-site. The HPSC group will produce national recommendations for laboratory diagnosis, surveillance and management of C. difficile infection. Since there are marked differences in diagnostic practices throughout the country and no national reference laboratory, the implementation of these recommendations will have cost implications that will need to be addressed.

Outcome following deep wound contamination in cemented arthroplasty.

Infection remains a devastating complication of joint replacement surgery causing a significant burden to both patient and surgeon. However, despite exhaustive prophylactic measures, intraoperative contamination still occurs during cemented arthroplasty with current infection rates of 1-2%. A study was undertaken to determine the incidence of perioperative contamination in cemented arthroplasty patients, to identify contaminating organisms, to identify contaminated regions within the operative wound, to identify factors associated with increased contamination, and finally to assess the medium-term clinical outcome in patients with confirmed intraoperative wound contamination. Eighty consecutive patients undergoing hip and knee cemented arthroplasty were prospectively enrolled over a 6-month period. All scrubbed personnel wore total body exhaust isolation suits and procedures were carried out in ultra-clean air theatres. Of 441 samples, contamination was identified at 21 sites (4.8%) representing a cohort of 18 patients (22.5%). Longer duration of surgery predisposed to higher contamination rates while lower contamination rates were significantly related to fewer gowned personnel within the ultra-clean system, and fewer total personnel in theatre during the procedure. None of the patients developed clinical evidence of deep prosthetic infection at follow-up. We noted a high incidence of intraoperative contamination despite standard prophylaxis. However, this was not reflected by a similar rate of postoperative infection. This may be due to a small bacterial inoculum in each case or may be due to the therapeutic effect of perioperative intravenous antibiotic prophylaxis.

Posterior compartment syndrome associated with clopidogrel therapy following trivial trauma.

Haematomata caused by blunt trauma may potentially induce a compartment syndrome by raising intra-compartmental pressure. We report a case of acute posterior compartment syndrome following minimal trauma to the leg of an elderly patient on the antiplatelet agent clopidogrel. This case highlights the high index of clinical suspicion required to detect compartment syndrome in those on long term antiplatelet therapy and prompt surgical decompression is recommended.

A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells.

There is increasing evidence that vascular endothelial growth factor (VEGF) has autocrine as well as paracrine functions in tumour biology. Vascular endothelial growth factor-mediated cell survival signalling occurs via the classical tyrosine kinase receptors Flt-1, KDR/Flk-1 and the more novel neuropilin (NP) receptors, NP-1 and NP-2. A 24-mer peptide, which binds to neuropilin-1, induced apoptosis of murine and human breast carcinoma cells, whereas a peptide directed against KDR had no effect. Both anti-NP1 and anti-KDR peptides induced endothelial cell apoptosis. Confocal microscopy using 5-(6)-carboxyfluorescein-labelled peptides showed that anti-NP1 bound to both tumour and endothelial cells, whereas anti-KDR bound endothelial cells only. This study demonstrates that NP-1 plays an essential role in autocrine antiapoptotic signalling by VEGF in tumour cells and that NP1-blockade induces tumour cell and endothelial cell apoptosis. Specific peptides can therefore be used to target both autocrine (tumour cells) and paracrine (endothelial cells) signalling by VEGF.

Positron emission tomography in the staging and management of breast cancer.

BACKGROUND: Breast cancer is the commonest cause of cancer death in women in the Western world, and imaging is essential in its diagnosis and staging. Metabolic imaging is a novel approach to improving the detection of cancers, as malignant transformation of cells is often associated with increased metabolic activity. This review assesses the possible role of positron emission tomography (PET) as a single non-invasive imaging modality to replace or complement current imaging and surgical practices in the diagnosis and staging of breast cancer. METHODS AND RESULTS: A Medline search was performed and articles were cross-referenced with other relevant material. Evaluation of primary breast cancer with PET has shown a sensitivity of between 64 and 100 per cent and a specificity of 33-100 per cent; diagnostic accuracy appears to be related to tumour size. Difficulties arise in altered fluorodeoxyglucose uptake in lobular carcinoma, carcinoma in situ and benign inflammatory breast disease. In axillary staging, sensitivities of between 25 and 100 per cent have been reported, but with a false-negative of up to 20 per cent. In the assessment of distant metastasis and asymptomatic patients with raised levels of tumour markers, PET was superior to conventional imaging modalities. CONCLUSION: PET is not a single diagnostic and staging tool that can replace current surgical, histological and radiological staging. Its main role in breast cancer lies in the investigation of metastatic disease and the evaluation of pathological response to various chemotherapeutic regimens.

Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease.

We compared the effectiveness of inhaled formoterol with that of ipratropium in the treatment of chronic obstructive pulmonary disease (COPD). After a 2-wk run-in period, 780 patients with COPD were randomized to receive for 12 wk formoterol dry powder 12 or 24 microg twice daily, ipratropium bromide 40 microg four times daily, or placebo in a multicenter, double-blind, parallel-group study. The primary efficacy variable was the area under the curve for forced expiratory volume in 1 s (FEV(1)) measured over 12 h after 12 wk of treatment. Secondary variables included diary symptoms and quality of life. Both doses of formoterol and ipratropium significantly increased the area under the curve for FEV(1) in comparison with placebo (all p < 0.001). Both doses of formoterol were also significantly superior to ipratropium (all p < 0.025). Compared with placebo, both doses of formoterol significantly improved symptoms (all p < or = 0.007) and quality of life (p < 0.01 for total scores) whereas ipratropium did not show significant effects (all p > or = 0.3). All study treatments exhibited a similar safety profile. We conclude that formoterol is more effective than ipratropium bromide in the treatment of COPD, as the efficacy of ipratropium on airflow obstruction does not translate into a clinical benefit that patients can perceive.

Characterization and role of tbuX in utilization of toluene by Ralstonia pickettii PKO1.

The tbu regulon of Ralstonia pickettii PKO1 encodes enzymes involved in the catabolism of toluene, benzene, and related alkylaromatic hydrocarbons. The first operon in this regulon contains genes that encode the tbu pathway's initial catabolic enzyme, toluene-3-monooxygenase, as well as TbuT, the NtrC-like transcriptional activator for the entire regulon. It has been previously shown that the organization of tbuT, which is located immediately downstream of tbuA1UBVA2C, and the associated promoter (PtbuA1) is unique in that it results in a cascade type of up-regulation of tbuT in response to a variety of effector compounds. In our efforts to further characterize this unusual mode of gene regulation, we discovered another open reading frame, encoded on the strand opposite that of tbuT, 63 bp downstream of the tbuT stop codon. The 1,374-bp open reading frame, encoding a 458-amino-acid peptide, was designated tbuX. The predicted amino acid sequence of TbuX exhibited significant similarity to several putative outer membrane proteins from aromatic hydrocarbon-degrading bacteria, as well as to FadL, an outer membrane protein needed for uptake of long-chain fatty acids in Escherichia coli. Based on sequence analysis, transcriptional and expression studies, and deletion analysis, TbuX seems to play an important role in the catabolism of toluene in R. pickettii PKO1. In addition, the expression of tbuX appears to be regulated in a manner such that low levels of TbuX are always present within the cell, whereas upon toluene exposure these levels dramatically increase, even more than those of toluene-3-monooxygenase. This expression pattern may relate to the possible role of TbuX as a facilitator of toluene entry into the cell.

Predictors of non-attendance for second round mammography in an Australian mammographic screening programme.

OBJECTIVE: To determine the socioeconomic, cultural, and clinical predictors of non-attendance for second round mammography. DESIGN/PARTICIPANTS: Retrospective cohort study of 121 889 women aged 50-69 years who attended for first mammography screening in the BreastScreen Victoria programme in 1995/1996 and who were recommended to be invited for routine biennial mammography. Women were considered to be non-attenders if they had not attended for rescreening within 27 months of their initial screening. Relative risk (RR) was used to compare categories for non-attendance for second screening, and a multivariate model was fitted to adjust for possible confounding. SETTING: BreastScreen Victoria, a population based mammographic screening programme, which offers free biennial mammography to all women 40 years and older. The programme specifically targets women aged 50-69 years. RESULTS: In the multivariate analysis, women from non-English speaking backgrounds were more likely not to attend for second round screening (RR ranged from 1.18 to 1.77). Indigenous women (RR 2.02, 95% confidence interval (CI) 1.61 to 2.54) and women who reported either significant symptoms (RR 1.90, 95% CI 1.76 to 2.05) or other breast symptoms (RR 2.25, 95% CI 2.15 to 2.36) at the time of first round screening were also more likely not to attend for second round screening. CONCLUSIONS: Women from non-English speaking backgrounds, indigenous women, and women who report symptoms at the time of first screening are more likely to not attend for second round screening. It is important to investigate why these women do not attend for second round screening so that services can be more appropriately tailored to their needs.

Contribution of increased mitochondrial free Ca2+ to the mitochondrial permeability transition induced by tert-butylhydroperoxide in rat hepatocytes.

Previously, we showed that the oxidant chemical, tert-butylhydroperoxide (t-BuOOH), induces a mitochondrial permeability transition (MPT) in intact hepatocytes, causing lethal cell injury. Here, we investigated the role of mitochondrial free Ca2+ in t-BuOOH cytotoxicity to 1-day-cultured rat hepatocytes using confocal microscopy of autofluorescence and parameter-indicating fluorophores. t-BuOOH (100 micromol/L) caused an early increase of mitochondrial free Ca2+, as assessed by confocal microscopy of Rhod-2 fluorescence. Increased mitochondrial Ca2+ was followed by onset of the MPT, as evidenced by permeation of cytosolic calcein into mitochondria and loss of the mitochondrial membrane potential-indicating dye, tetramethylrhodamine methylester. Preincubation with an intracellular Ca2+ chelator (BAPTA-AM and its derivatives) partially blocked the late phase of mitochondrial NAD(P)H oxidation after t-BuOOH, but failed to prevent the early oxidation of mitochondrial NAD(P)H. Ca2+ chelation also prevented the increase of mitochondrial Ca2+, generation of mitochondrial reactive oxygen species (ROS), onset of the MPT, and subsequent cell death. Confocal images showed that protection occurred when loading of the Ca2+ chelator was predominantly mitochondrial. The antioxidant, desferal, also diminished increased mitochondrial Ca2+ after t-BuOOH and prevented cell death. We conclude that oxidative stress induced by t-BuOOH enhances mitochondrial Ca2+ uptake, leading to increased matrix Ca2+, increased ROS formation, onset of the MPT, and cell death.

Implications of applying widely accepted cholesterol screening and management guidelines to a British adult population: cross sectional study of cardiovascular disease and risk factors.

OBJECTIVE: To compare the implications of four widely used cholesterol screening and treatment guidelines by applying them to a population in the United Kingdom. DESIGN: Guidelines were applied to population based data from a cross sectional study of cardiovascular disease and risk factors. SETTING: Newcastle upon Tyne, United Kingdom. SUBJECTS: General population sample (predominantly of European origin) of 322 men and 319 women aged 25-64 years. MAIN OUTCOME MEASURES: Proportions recommended for screening and treatment. METHODS: Criteria from the British Hyperlipidaemia Association, the British Drugs and Therapeutics Bulletin (which used the Sheffield table), the European Atherosclerosis Society, and the American national cholesterol education programme were applied to the population. RESULTS: Proportions recommended for treatment varied appreciably. Based on the British Drugs and Therapeutics Bulletin guidelines, treatment was recommended for 5.3% (95% confidence interval 2.9% to 7.7%) of men and 3.3% (1.5% to 5.3%) of women, while equivalent respective values were 4.6 (2.3 to 6.9) and 2.8 (1.0 to 4.6) for the British Hyperlipidaemia Association, 23% (18.4% to 27.6%) and 10.6% (7.3% to 14.0%) for the European Atherosclerosis Society, and 37.2% (31.9% to 42.5%) and 22.2% (17.6% to 26.8%) for the national cholesterol education programme. Only the British Hyperlipidaemia Association and Drugs and Therapeutics Bulletin guidelines recommend selective screening. Applying British Hyperlipidaemia Association guidelines, from 7.1% (4.3% to 9.9%) of men in level one to 56.7% (51.3% to 62.1%) of men in level three, and from 4.4% (2.1% to 6.7%) of women in level one to 54.4% (48.9% to 59.9%) of women in level three would have been recommended for cholesterol screening. Had the Drugs and Therapeutics Bulletin guidelines been applied, 22.2% (16.5% to 27.9%) of men and 12.2% (8. 6% to 15.8%) of women would have been screened. CONCLUSIONS: Without evidence based guidelines, there are problems of variation. A consistent approach needs to be developed and agreed across the United Kingdom.