HLA-Cw6-positive patients with psoriasis show improved response to methotrexate treatment.

It is well documented that patients with human leucocyte antigen (HLA)-Cw6+ (type 1) psoriasis have increased severity and reduced age of onset of psoriasis. However, not much is known about any differential response of this genetic subgroup to various treatments. We set out to determine if there was any genetic association of the HLA-Cw6 allele with the first-line systemic treatment commonly used in psoriasis, methotrexate. A cohort of patients from Tayside in Scotland was recruited through a novel generic consenting process (GoShare); they were extensively phenotyped and analysed for an association of their HLA-Cw6 genotype status with treatment outcomes. HLA-Cw6+ patients showed notably improved response to methotrexate (P = 0.05), and further analysis demonstrated an even greater response in a subcohort of the HLA-Cw6+ patients, who did not have concomitant psoriatic arthritis (P = 0.01). HLA-Cw6+ patients also exhibited fewer treatment-limiting adverse events. In addition to these findings, the methodology and primary clinical outcome phenotype, which we validate here, will greatly facilitate replication of the present results in independent cohorts.

Improvement in symptoms of obstructive sleep apnoea in children following tonsillectomy versus tonsillotomy: a systematic review and meta-analysis.

BACKGROUND: Tonsillotomy (or intracapsular tonsillectomy) is a modern technique which is seen by some as potentially superior to traditional (extracapsular) tonsillectomy for the removal of tonsillar tissue to treat obstructive sleep apnoea in children. It has been suggested that peri-operative pain and haemorrhage and postoperative haemorrhage are reduced with the tonsillotomy technique. However, no systematic reviews have been carried out to assess its efficacy in treating obstructive sleep apnoea compared to tonsillectomy. OBJECTIVE OF REVIEW: To assess whether subjective improvement in symptoms of obstructive sleep apnoea following tonsillotomy is comparable to that following tonsillectomy, measured using a standardised questionnaire, the Obstructive sleep apnoea-18 (OSA-18) tool. TYPE OF REVIEW: Systematic review of the literature and meta-analysis. SEARCH STRATEGY: PubMed (MEDLINE), followed by Ovid (MEDLINE), Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, and the British Medical Journal were searched for articles published in English between 1995 and 2015 inclusive. EVALUATION METHOD: Literature search, systematic review and meta-analysis. Studies examining improvement in mean OSA-18 score following tonsillotomy, improvement in mean OSA-18 score following tonsillectomy, and examining both were selected, examined and used for meta-analysis. Studies with and without concurrent adenoidectomy were included. RESULTS: Four studies examining tonsillotomy and 16 studies examining tonsillectomy were included in the analysis. Using a random effects model, the pooled improvement in OSA-18 score for tonsillotomy was 2.46 (95% CI 1.92-2.99), and for tonsillectomy, it was 2.10 (95% CI 1.91-2.30). There was no significant difference between the methods. CONCLUSION: That there is no significant difference in subjective outcome between tonsillotomy and tonsillectomy may support wider use of tonsillotomy over tonsillectomy for the treatment of obstructive sleep apnoea in children.

Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study.

BACKGROUND: Progesterone receptor (PR) expression assessment in early invasive breast cancer remains controversial. This study sought to re-evaluate PR expression as a potential therapeutic guide in early breast cancer; particularly in oestrogen receptor (ER)-positive, lymph node (LN)-negative disease. METHODS: A population cohort of 1074 patients presenting to a single Cancer Centre over 4 years (2000-2004) underwent surgery for primary invasive breast cancer with curative intent. Prospective data collection included patient demographics, pathology, ER and PR expression, HER2 status, adjuvant chemotherapy and endocrine therapy. Progesterone receptor expression was compared with (all causes) overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS). RESULTS: Overall survival was 71.0% and BCSS was 83.0% at median follow-up of 8.34 years. Absent PR expression was significantly associated with poorer prognosis for OS, BCSS and DFS (P<0.0001, log-rank), even within the ER-positive, LN-negative group (hazard ratio for BCSS 3.17, 95% CI 1.43-7.01) and was not influenced by endocrine therapy. Cox's regression analysis demonstrated that PR expression was an independent prognostic variable. CONCLUSION: Absence of PR expression is a powerful, independent prognostic variable in operable, primary breast cancer even in ER-positive, LN-negative patients receiving endocrine therapy. Absence of PR expression should be re-evaluated as a biomarker for poor prognosis in ER-positive breast cancer and such patients considered for additional systemic therapy.

Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial.

INTRODUCTION: Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc. STUDY DESIGN: randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3 months (1 month per drug). Primary endpoints: P1CP, QTc RESULTS: 11 stroke survivors (5 female), aged 71 ± 4, BP 139/81 mmHg ± 20/11 mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone-Placebo = -24 ug/L, 95% CI = -40 to -6.9; Amiloride-Placebo = -28 ug/L, 95% CI = -44 to -11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=-18 ms(1/2), 95% CI = -36 to -0.55; Amiloride vs Placebo = -25 ms(1/2), 95% CI = -42 to -7.5]. CONCLUSIONS: Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.

The open abdomen and temporary abdominal closure systems--historical evolution and systematic review.

AIM: Several techniques for temporary abdominal closure have been developed. We systematically review the literature on temporary abdominal closure to ascertain whether the method can be tailored to the indication. METHOD: Medline, Embase, the Cochrane Central Register of Controlled Trials and relevant meeting abstracts until December 2009 were searched using the following headings: open abdomen, laparostomy, VAC (vacuum assisted closure), TNP (topical negative pressure), fascial closure, temporary abdominal closure, fascial dehiscence and deep wound dehiscence. The data were analysed by closure technique and aetiology. The primary end-points included delayed fascial closure and in-hospital mortality. The secondary end-points were intra-abdominal complications. RESULTS: The search identified 106 papers for inclusion. The techniques described were VAC (38 series), mesh/sheet (30 series), packing (15 series), Wittmann patch (eight series), Bogotá bag (six series), dynamic retention sutures (three series), zipper (15 series), skin only and locking device (one series each). The highest facial closure rates were seen with the Wittmann patch (78%), dynamic retention sutures (71%) and VAC (61%). CONCLUSION: Temporary abdominal closure has evolved from simple packing to VAC based systems. In the absence of sepsis Wittmann patch and VAC offered the best outcome. In its presence VAC had the highest delayed primary closure and the lowest mortality rates. However, due to data heterogeneity only limited conclusions can be drawn from this analysis.

A 12-year follow-up study of all-cause and cardiovascular mortality among 10,532 people newly diagnosed with Type 2 diabetes in Tayside, Scotland.

AIMS: To determine absolute and relative risks of all-cause and cardiovascular mortality among patients newly diagnosed with Type 2 diabetes. METHODS: In an observational cohort study using record-linkage databases, based in Tayside, Scotland, UK, we identified newly diagnosed patients with Type 2 diabetes in 1993-2004. We also identified a set of non-diabetic comparators from lists of patients registered with a general practice, individually matched to the diabetic patients by sex, age and deprivation. We followed up patients for mortality and cardiovascular mortality over a 12-year period and calculated hazard ratios using Cox regression. RESULTS: There were 10,532 patients with Type 2 diabetes and 21,056 non-diabetic comparators. Diabetic patients in every age/sex group had higher absolute mortality rates. Even taking deprivation into account, the hazard ratio for mortality was 1.32 (95% CI 1.25-1.40), decreasing to 1.15 (1.09-1.22) after adjusting for pre-existing cardiovascular disease. The hazard ratios for cardiovascular mortality were higher, decreasing from 1.51 (1.37-1.67) to 1.23 (1.11-1.36) after adjusting for pre-existing cardiovascular disease. The hazard ratios decreased with increasing age at diagnosis, although the difference in absolute rate of mortality increased slightly with age. Increased mortality risks were only evident 2 years after diagnosis and increased thereafter. CONCLUSIONS: Patients with Type 2 diabetes have an increased risk of all-cause and cardiovascular mortality compared with non-diabetic comparators, although this is not observable immediately after diagnosis. Age at diagnosis and duration of the disease independently affect absolute and relative mortality risk.

Index laparoscopic cholecystectomy for acute admissions with cholelithiasis provides excellent training opportunities in emergency general surgery.

BACKGROUND: There is minimal data on the outcome of early laparoscopic cholecystectomy (LC) for acute gallbladder disease when performed by trainees. This study assesses the outcomes of a policy of same admission LC incorporated into a surgical training programme in a major teaching hospital. METHODS: 447 index LCs performed over a 3-year period were reviewed retrospectively. The indications, operating surgeon, operating time, use of IOC, conversion rates, reasons for conversion and post-operative stay were analysed. Multivariate analysis of reasons for conversion was performed. RESULTS: 150 LCs were performed by consultants and 297 by registrars; 67 were performed by year 1-3 specialist registrars (SpR) and 230 by year 4-6 SpRs. The indications were biliary colic (n=7), acute cholecystitis (n=180), chronic cholecystitis (n=260), carcinoma (n=1). No difference was found in demographics, operating time (105 min Vs 115 min), use of IOC (34% Vs 29%; P=0.2) and post-operative stay (2 days Vs 1 day) between consultants and registrars. The conversion rates were higher for consultants compared to registrars (29 (19%) Vs 28 (9%), P=0.004). The overall conversion rate was 11%. There were no bile duct injuries. Predictors for conversion were CRP>50 at admission and acute cholecystitis. CONCLUSION: In a teaching hospital setting most acute admission LCs (66%) were performed by trainees. A step wise training programme with active consultant supervision of all index LCs results in low morbidity, low conversion rates, and a short post-operative stay for acute gallbladder disease. This model of same admission cholecystectomy provides a good training opportunity in emergency general surgery.

Incidence of symptoms in previously symptom-free impacted lower third molars assessed in general dental practice.

AIM: To determine the potential of a pathology-free impacted lower third molar to cause symptoms within a year and whether these symptoms can be linked to clinical characteristics, lifestyle or socio-demographic status. DESIGN: One-year prospective cohort study of patients registered in general dental practice in Scotland with at least one asymptomatic impacted lower third molar. METHODS: All general dental practices with panoramic radiography facilities in Tayside, Fife and Greater Glasgow (Scotland, UK) were invited to participate in the study. Orthopantomographs taken between 1995 and 2002 were reviewed and eligible patients were contacted and invited to participate. Patients were assessed in their own dental surgery by the same research dentist. In this baseline assessment, the presence of impaction was confirmed and all patients with a previous history of symptoms and/or pathology were excluded from further analysis. Clinical characteristics such as the angulation and the degree of impaction were recorded. Patients also completed a socioeconomic questionnaire. Eligible patients were re-assessed by the same research dentist one year later when they were asked about their experience of symptoms within the past year. Information was cross-referenced with patients' dental records. RESULTS: A total of 613 patients attended the baseline appointment. Of those, 30 (4.89%) had a history of symptoms and were excluded from the study, leaving 583 (95.10%) eligible patients. From those, 421 (69%) patients with a total of 676 lower third molars were examined one year later. 22.67% of all vertically impacted teeth examined had developed symptoms, along with 13.15% of all mesially impacted, 30.69% of all distally impacted and 6.45% of all horizontal third molars. This association was statistically significant (p < or =0.001). 23.05% of all partially erupted teeth and a surprising 10.49% of all unerupted teeth were associated with symptoms during the study period. This association was also significant (p < or =0.001). There was also a statistically significant inverse association between the development of symptoms and age (p = 0.0028). CONCLUSIONS: The predictability that an impacted lower third molar will develop symptoms in future remains unclear. However, some clinical characteristics such as the angulation, the degree of impaction and the patient's age could be useful in predicting the likelihood of future symptomatology.

A cohort study of the risk of cancer associated with type 2 diabetes.

BACKGROUND: There is evidence to suggest that diabetes may increase the risk of incidence and mortality from cancer. METHODS: In a cohort study using record-linkage health-care datasets for Tayside, Scotland in 1993-2004, we followed up 9577 newly diagnosed patients with type 2 diabetes, and two matched non-diabetic comparators, in the national cancer register. RESULTS AND CONCLUSIONS: The risk ratio for any cancer, adjusted for deprivation, was 0.99 (95%CI 0.90-1.09). Significantly increased risks were observed for pancreatic, liver and colon cancer.

Meta-analysis of sentinel node biopsy in ductal carcinoma in situ of the breast.

BACKGROUND: The need for sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) is debated. Advocates recommend such biopsy based on a high incidence of SLN involvement in some series. Opponents discourage SLN biopsy based on a perceived low incidence of nodal involvement in this setting. These contradictory arguments are generally based on small studies. The present study is a meta-analysis of the reported data on the incidence of SLN metastasis in patients with DCIS. METHODS: A search of electronic databases identified studies reporting the frequency of SLN metastases in DCIS. The random-effects method was used to combine data. RESULTS: Twenty-two published series were included in the meta-analysis. The estimate for the incidence of SLN metastases in patients with a preoperative diagnosis of DCIS was 7.4 (95 per cent confidence interval (c.i.) 6.2 to 8.9) per cent compared with 3.7 (95 per cent c.i. 2.8 to 4.8) per cent in patients with a definitive (postoperative) diagnosis of DCIS alone. This was a significant difference with an odds ratio of 2.11 (95 per cent c.i. 1.15 to 2.93). CONCLUSION: Patients with a preoperative diagnosis of DCIS should be considered for SLN biopsy.

Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis.

OBJECTIVES: Dose-dependant gastrointestinal and cardiovascular side-effects limit the use of NSAIDs in the management of RA. The n-3 essential fatty acids (EFAs) have previously demonstrated some anti-inflammatory and NSAID-sparing properties. The objective of this study was to determine whether cod liver oil supplementation helps reduce daily NSAID requirement of patients with RA. METHODS: Dual-centre, double-blind placebo-controlled randomized study of 9 months' duration. Ninety-seven patients with RA were randomized to take either 10 g of cod liver oil containing 2.2 g of n-3 EFAs or air-filled identical placebo capsules. Documentation of NSAID daily requirement, clinical and laboratory parameters of RA disease activity and safety checks were done at 0, 4, 12, 24 and 36 weeks. At 12 weeks, patients were instructed to gradually reduce, and if possible, stop their NSAID intake. Relative reduction of daily NSAID requirement by >30% after 9 months was the primary outcome measure. RESULTS: Fifty-eight patients (60%) completed the study. Out of 49 patients 19 (39%) in the cod liver oil group and out of 48 patients 5 (10%) in the placebo group were able to reduce their daily NSAID requirement by >30% (P = 0.002, chi-squared test). No differences between the groups were observed in the clinical parameters of RA disease activity or in the side-effects observed. CONCLUSIONS: This study suggests that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA patients.

Increasing prevalence of type 2 diabetes in a Scottish population: effect of increasing incidence or decreasing mortality?

AIMS/HYPOTHESIS: We examined incidence, prevalence and mortality from type 2 diabetes mellitus in a Scottish population over 12 years, and evaluated the effects on prevalence of increasing incidence and decreasing mortality. MATERIALS AND METHODS: We used a diabetes clinical information system in Tayside (population 387,908), Scotland, to identify new cases of type 2 diabetes between 1993 and 2004 and to calculate incidence rates and mid-year prevalence. We defined mortality rates as the number of deaths of diabetic people divided by mid-year prevalence. We used logistic and Poisson regression to analyse trends. We then modelled the increase in prevalence for each year for three scenarios, based on whether mortality or incidence rates remained unchanged from 1993. RESULTS: There was a doubling in incidence and prevalence of type 2 diabetes in Tayside over the 12 years, with statistically significant increasing trends of 6.3 and 6.7% per year respectively. The mortality rate decreased. If incidence and mortality had remained at 1993 levels, there would have been an increase in prevalence of 855 per 100,000 in 2003, accounting for 60.1% of the actual increase of 1,423 per 100,000. If there had been no mortality decrease, prevalence in 2003 would have been very similar to the actual prevalence observed. CONCLUSIONS/INTERPRETATION: Decreasing mortality rates in Tayside had less effect on the increase in prevalence than did increasing incidence. Even if incidence and mortality remain unchanged, prevalence will increase by over 20% in the next decade.

Effect of social deprivation on mortality and the duration of hospital stay after a stroke.

BACKGROUND: We aim to assess whether social deprivation independently predicts case fatality after a stroke patient has been admitted to hospital, and to assess whether social deprivation affected duration of hospital stay. METHODS: Cohort study in a tertiary teaching hospital included consecutive patients admitted to hospital within 48 h of their stroke between 1988 and 1994. Outcome measures were case fatality at 1 year and length of hospital stay. The socioeconomic category was derived from the postcode sector of residence for the patients (Carstairs index). Cause of death was determined by data linkage to the Registrar General data for Scotland. RESULTS: 2,042 stroke patients were included. A significant age difference existed between the deprivation categories (76.0 +/- 10.9 years in the affluent cohort vs. 71.4 +/- 10.7 years in the deprived cohort). Smoking was more common in the deprived group. ECG findings and neurological score on admission were similar between the groups. No difference existed between groups for length of hospital stay (p = 0.793), and in the proportions remaining alive at 1 year (p = 0.416). When entered into a multivariate Cox regression analysis, the deprivation categories did not predict mortality. Age, sex, Philadelphia Geriatric Center Instrumental Activities of Daily Living (IADL) Scale Score, Orgogozo neurological score on admission, and ECG abnormalities were the significant predictors. CONCLUSIONS: Stroke patients living in more socially deprived areas had their strokes at an earlier age but were not at a greater risk of dying or longer hospital stay once they had been admitted to hospital.

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin. SUBJECTS AND METHODS: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group. RESULTS: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA(1c), smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality. CONCLUSIONS/INTERPRETATION: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

Population-based demographic study of karyotypes in 1709 patients with adult acute myeloid leukemia.

Few large demographic studies of acute myeloid leukemia (AML) are derived from population-based registries. Demographic and karyotypic data were provided for AML cases from two regional leukemia registry databases in Scotland and the Northern Region of England. A population-based dataset was compiled, comprising 1709 patients aged >16 years (1235 North England/474 Scotland patients). The most common cytogenetic abnormalities involved chromosomes 5 and/or 7 (17%). Patients with the following abnormal chromosome 5/7 combinations: -5, del(5q), -5/-7 and del(5q)/-7 represented a significantly older population (P < 0.01, ANOVA). t(8;21) was the only 'favourable' karyotype found in older age. Karyotypic complexity varied within chromosome 5/7 combination groups; those containing -5, -5/-7, -5/del(7q), del(5q)/-7 or del(5q)/del(7q) combinations were significantly more frequently complex than those containing -7 and del(7q) (P < 0.01, chi2 test). Additional recurring cytogenetic abnormalities within complex karyotypes containing chromosome 5/7 combinations included (in order of frequency), abnormalities of chromosomes 17, 12, 3 and 18. Complex karyotypes not involving chromosomes 5 or 7 represented 30% of all complex karyotypes, occurred in younger patients than those involving chromosomes 5 and 7, and frequently included additional trisomy 8 (26%). In conclusion, we describe subgroups within adverse karyotypes, with different demographics, degree of complexity and additional chromosome abnormalities.

Maxillary incisor palatal erosion: no correlation with dietary variables?

The objectives of the study were to examine a relationship between tooth erosion affecting the palatal aspects of permanent maxillary central incisors with dietary, behavioral and medical variables. The methods included, 251 schoolchildren aged 11 to 13 years were recruited to participate. Each subject had dental impressions of the palatal aspects of both upper central incisors recorded at baseline, 9 and 18 months intervals. From these, electroconductive replicas were fabricated, mapped and compared using a surface matching technique. At the end of the study all participants underwent a structured interview that sought to assay the level of potential erosive dietary, behavioral and medical risk factors. Correlation analyses of the responses given in the final structured interview with the degrees of palatal tooth substance loss (both previous and measured) were under taken. The results showed: (1) The degree of previous erosion did not predict the level of measured ongoing erosion. (2) Brushing the teeth more frequently with fluoridated toothpaste correlated significantly with lower levels of ongoing erosion (P = 0 011). It was concluded that: (1) Evidence of previous palatal erosion did not predict future erosion. (2) The application of topical fluoride as a by-product of tooth brushing may provide an element of protection against palatal erosion. (3) In view of the lack of correlation between exposure to potential risk factors and the level of ongoing palatal tooth surface loss in this study, other factors (such as an individual's susceptibility and salivary buffering power) may well be more important predictors. The clinical relevance included: Preventive advice to patients with dental erosion should not only include the use of topical fluoride, in the form of toothpaste, but recognize individual susceptibility to this condition.

QT interval abnormalities are often present at diagnosis in diabetes and are better predictors of cardiac death than ankle brachial pressure index and autonomic function tests.

OBJECTIVES: To study serial measures of maximum QT interval corrected for heart rate (QTc) and QT dispersion (QTD) and their association with cardiac mortality patients with non-insulin dependent diabetes and to compare QT abnormalities with other mortality predictors (ankle brachial pressure index (ABPI) and autonomic function tests) in their ability to predict cardiac death. SETTING: Teaching hospital. METHODS AND PATIENTS: QT interval analysis, heart rate (RR) variation in response to deep breathing and standing, and ABPI were analysed in 192 patients with non-insulin dependent diabetes. Cardiac death was the primary end point. RESULTS: Mean (SD) follow up was 12.7 (3.2) years (range 1.2-17.1 years). There were 48 deaths, of which 26 were cardiac. QTc and QTD were individually significant predictors of cardiac mortality throughout the follow up period (p < 0.001). The predictability of QT parameters was superior to the predictability of ABPI and RR interval analysis. Temporal changes in QT parameters showed that the mean absolute QT parameter was a significant predictor of cardiac death (p < 0.001), whereas an intraindividual change in QT parameter over time was not predictive. CONCLUSION: QT abnormalities seem to exist at the point of diagnosis of diabetes and do not appear to change between then and the subsequent cardiac death. Furthermore, the analysis of QT interval is superior to ABPI and the RR interval in identifying diabetic patients at high risk of cardiac death.

Airway-stabilizing effect of long-acting beta2-agonists as add-on therapy to inhaled corticosteroids.

BACKGROUND: The protection afforded by long-acting beta(2)-agonists against bronchoconstrictor stimuli can be regarded as a surrogate for their stabilizing effects on airway smooth muscle. AIM: To determine the magnitude of residual bronchoprotection after chronic dosing with long-acting beta(2)-agonists. DESIGN: Retrospective meta-analysis. METHODS: Medline, BIDS and Cochrane Library databases were searched from 1990. A meta-analysis was then performed of 13 eligible randomized placebo-controlled trials (596 patients) in which second-line treatment with a long-acting beta(2)-agonist (salmeterol or formoterol) was used for 1 week or more. The residual protection against bronchoconstrictor stimuli as doubling dose/dilution shift was the main outcome measure. RESULTS: Data were assessed according to Quorum criteria. Combining the results of the meta-analysis, the overall estimated protection amounted to a 0.79 (95%CI 0.63-0.96) doubling dose/dilution shift from placebo. Subgroup analysis showed greater protection at peak vs. trough, but no difference between formoterol vs. salmeterol, or between direct vs. indirect challenge. There was no evidence of significant heterogeneity across all the studies, or within any of the subgroups. DISCUSSION: When used as second-line treatment, the overall additive protective effect of long-acting beta(2)-agonists amounts to a 0.8 doubling dose/dilution shift. This stabilizing effect on airway smooth muscle may explain their beneficial effects on exacerbations.

Observer variability in the Goseki grouping of gastric adenocarcinoma in resection and biopsy specimens.

AIMS: The Goseki grouping of gastric adenocarcinoma has been suggested as a possible prognostic factor. In those centres where it is used, it may be valuable to assess the Goseki grouping of a tumour on the initial diagnostic biopsy as well as on the resection specimen since it may in theory influence management. We examined the robustness of Goseki grouping of gastric adenocarcinoma in representative sections from resection and biopsy specimens in order to assess the consistency of agreement among a group of pathologists. METHODS: A single representative block from 100 gastric resection specimens was studied using a haematoxylin and eosin and mucin (alcian blue/periodic acid-Schiff) stain. These were circulated in batches to members of a group of 12 pathologists who each completed a simple proforma confirming the presence of carcinoma and assigning a Goseki group. In a second circulation the diagnostic biopsy specimen taken prior to resection was examined in the same way. This allowed comparison of the Goseki group of the biopsy and resection specimens. RESULTS: In both studies kappa statistics showed good agreement on tubular differentiation of the carcinoma, but only moderate agreement for the intracellular mucin production, resulting in moderate agreement for the final Goseki group. Correlation between the Goseki group assigned on the biopsy and resected specimens was seen in 62% of the cases. However, the reproducibility was low (kappa 0.375). CONCLUSIONS: The Goseki grouping of resected gastric adenocarcinoma is reproducible and can be used in prognostication. Goseki grouping of biopsy specimens is of limited value in predicting the Goseki group assigned to the resected carcinoma.