Association between glycaemic control and common infections in people with Type 2 diabetes: a cohort study.

AIM: To investigate the impact of glycaemic control on infection incidence in people with Type 2 diabetes. METHODS: We compared infection rates during 2014 in people with Type 2 diabetes and people without diabetes in a large primary care cohort in the UK (the Royal College of General Practitioners Research and Surveillance Centre database). We performed multilevel logistic regression to investigate the impact of Type 2 diabetes on presentation with infection, and the effect of glycaemic control on presentation with upper respiratory tract infections, bronchitis, influenza-like illness, pneumonia, intestinal infectious diseases, herpes simplex, skin and soft tissue infections, urinary tract infections, and genital and perineal infections. People with Type 2 diabetes were stratified by good [HbA1c < 53 mmol/mol (< 7%)], moderate [HbA1c 53-69 mmol/mol (7-8.5%)] and poor [HbA1c > 69 mmol/mol (> 8.5%)] glycaemic control using their most recent HbA1c concentration. Infection incidence was adjusted for important sociodemographic factors and patient comorbidities. RESULTS: We identified 34 278 people with Type 2 diabetes and 613 052 people without diabetes for comparison. The incidence of infections was higher in people with Type 2 diabetes for all infections except herpes simplex. Worsening glycaemic control was associated with increased incidence of bronchitis, pneumonia, skin and soft tissue infections, urinary tract infections, and genital and perineal infections, but not with upper respiratory tract infections, influenza-like illness, intestinal infectious diseases or herpes simplex. CONCLUSIONS: Almost all infections analysed were more common in people with Type 2 diabetes. Infections that are most commonly of bacterial, fungal or yeast origin were more frequent in people with worse glycaemic control.

Retrospective cohort study of an enhanced recovery programme in oesophageal and gastric cancer surgery.

Introduction Enhanced recovery programmes have been established in some areas of elective surgery. This study applied enhanced recovery principles to elective oesophageal and gastric cancer surgery. Methods An enhanced recovery programme for patients undergoing open oesophagogastrectomy, total and subtotal gastrectomy for oesophageal and gastric malignancy was designed. A retrospective cohort study compared length of stay on the critical care unit (CCU), total length of inpatient stay, rates of complications and in-hospital mortality prior to (35 patients) and following (27 patients) implementation. Results In the cohort study, the median total length of stay was reduced by 3 days following oesophagogastrectomy and total gastrectomy. The median length of stay on the CCU remained the same for all patients. The rates of complications and mortality were the same. Conclusions The standardised protocol reduced the median overall length of stay but did not reduce CCU stay. Enhanced recovery principles can be applied to patients undergoing major oesophagogastrectomy and total gastrectomy as long as they have minimal or reversible co-morbidity.

Mortality in Barrett's esophagus: three decades of experience at a single center.

BACKGROUND AND STUDY AIMS: There is a view that the majority of deaths in patients with Barrett's esophagus are from causes other than esophageal adenocarcinoma (EAC). The aim of this analysis was to establish the pattern of mortality for a number of causes in patients with Barrett's esophagus. PATIENTS AND METHODS: This was a single-center prospective cohort study of patients from Rotherham District General Hospital, which is a secondary referral center. The cohort consisted of 1239 patients who were diagnosed with Barrett's esophagus between April 1978 and March 2009.  Follow-up for mortality was undertaken by "flagging" the patients with the NHS Information Center. Causes of death were compared with UK Office of National Statistics age- and sex-specific mortality data for 1999, the median year of diagnosis. Analysis was by a "person - years at risk" calculation from date of diagnosis. RESULTS: The ratio of observed deaths from EAC compared with those expected in this cohort was 25.02 - a very large excess. There was no difference in mortality from colorectal cancer or circulatory disease and there were fewer deaths from cancers other than esophageal adenocarcinoma and colon cancer compared with national statistics. There was a small statistically significant difference in mortality from all causes but this disappeared completely when deaths from esophageal adenocarcinoma were excluded. CONCLUSIONS: Overall, mortality in Barrett's esophagus is increased significantly but only as a result of the large excess of deaths from EAC. This strengthens the case for endoscopic surveillance if successful interventions can be undertaken in patients with Barrett's esophagus to prevent development of esophageal adenocarcinoma.

Anti-neutrophil cytoplasmic antibody-associated systemic vasculitis: nature or nurture?

This review examines the environmental and genetic contributions to the anti-neutrophil cytoplasmic antibody-associated systemic vasculitides. The dominant environmental risk factors appear to be silica exposure for all three syndromes, and vitamin D deficiency is strongly suggested by the latitude and ultraviolet radiation gradient observed for Wegener's granulomatosis and Churg-Strauss syndrome. Genetic factors are generally not very strong, consistent with the rarity of these conditions in children. However, multiple genetic factors, each with a relatively small effect, may combine to create a state of susceptibility towards autoimmunity. With infection as a triggering agent, it is possible to synthesise a pathogenetic hypothesis that accounts for both environmental and genetic effects in regard to both necrotising vasculitis and granuloma formation.

Percutaneous transhepatic cholecystoduodenal stent for empyema of the gallbladder.

Acute cholecystitis is treated by antibiotics and cholecystectomy. When the gallbladder neck is obstructed in the presence of infection, preventing pus from draining via the cystic duct, an empyema of the gallbladder develops. Under these circumstances, treatment may be either cholecystectomy or, in the presence of significant comorbidity, by drainage via percutaneous cholecystostomy, followed at a later date by cholecystectomy. We present the case of a patient who presented acutely with an attack of cholecystitis and refused to undergo a cholecystectomy owing to previous respiratory arrest following general anaesthesia. She settled with intravenous antibiotic treatment and was discharged. However, she presented shortly afterwards with a further attack of cholecystitis that was refractory to intravenous antibiotics and so was treated initially with percutaneous drainage. This was subsequently replaced with interno-external drainage of the gallbladder (transpapillary cholecystoduodenal stent) with the use of a J-J ureteric stent, which was then fully internalised. She remained well following this procedure and was discharged home. The long-term patency of the stent is not known and we hope that no further intervention will be required, but if necessary the stent could be exchanged endoscopically, by a percutaneous route, or via a combined approach.

Antireflux surgery.

Gastro-oesophageal reflux disease is extremely common throughout Europe and the United States. This review on antireflux surgery examines the best evidence for surgical treatment of gastro-esophageal reflux disease. Comparison is made with medical antireflux therapy including histamine H2 receptor antagonist and proton pump inhibitor therapy. The randomized trials and systematic reviews available on gastro-esophageal reflux disease are reviewed and where data are scarce, the largest cohort studies available are discussed. Overall, laparoscopic antireflux surgery is safe and has a similar efficacy to open antireflux surgery and best medical therapy with proton pump inhibitors. There is a failure rate, which in some series is greater than 50% at 5 years. Due to the cost of a proportion of patients still taking antireflux medications, it cannot be recommended on cost-effectiveness grounds over best medical therapy. The choice of procedure lies between complete wrap with Nissen's fundoplication and partial fundoplication (most frequently Toupet). Division of the short gastric vessels is not usually necessary and is associated with increased wind-related complications. Total fundoplication tends to produce superior reflux control, but at the cost of increased risk of dysphagia. There is a trend for antireflux surgery to be superior to best medical therapy in cancer prevention in Barrett's oesophagus, but this has not reached statistical significance.

The influence of symptom type and duration on the fate of the metaplastic columnar-lined Barrett's oesophagus.

BACKGROUND: Prolonged gastro-oesophageal reflux resulting in columnar metaplasia of the oesophagus is the main risk factor for oesophageal adenocarcinoma. AIM: To examine the duration of symptoms and associations of different symptoms with the development of columnar-lined oesophagus, dysplasia and adenocarcinoma. METHODS: UK multicentre cohort study of patients with columnar-lined oesophagus whose date of symptom onset (1082 patients) and/or types of symptoms reported (1681 patients) were documented. Follow-up was examined by analysis of histological reports from the registering centers. RESULTS: Symptoms of dysphagia/odynophagia and nausea/vomiting were associated with development of dysplasia. High-grade dysplasia and adenocarcinoma were associated with dysphagia/odynophagia and weight loss. Median duration from symptom onset to detection of columnar-lined oesophagus without intestinal metaplasia: 2.6 years, columnar-lined oesophagus with intestinal metaplasia: 5.0 years, indefinite changes for dysplasia: 19.3 years and low-grade dysplasia: 30.0 years. One tenth of patients had developed high-grade dysplasia at 9.6 years and one tenth had developed adenocarcinoma at 13.8 years from symptom onset. CONCLUSIONS: In patients with columnar-lined oesophagus, symptoms of dysphagia/odynophagia and nausea/vomiting were associated with a higher risk of development of dysplasia and adenocarcinoma. There is a trend for longer duration of symptoms to the detection of dysplasia.

Barrett's columnar-lined oesophagus: demographic and lifestyle associations and adenocarcinoma risk.

OBJECTIVES: Lifestyle and demographic risk factors for the development of oesophageal adenocarcinoma developing from columnar-lined oesophagus are not well defined. METHODS: Demographic and lifestyle factors, endoscopy and histology reports were extracted from 1,761 subjects from seven UK centres. The associations of columnar-lined oesophagus with demographic and lifestyle factors and the development of adenocarcinoma were examined. RESULTS: 5.5% of patients had prevalent adenocarcinoma (more common in males, older patients, patients diagnosed earlier in the cohort and current or recent smokers). Adenocarcinoma incidence was 23 patients in 3,912 years or 0.59% per annum. Only increased age at diagnosis correlated with an increased risk of incident adenocarcinoma. There was no association with obesity or alcohol history. CONCLUSIONS: Oesophageal adenocarcinoma occurs more commonly in older patients and is more frequent in males than females. Once columnar-lined oesophagus had been diagnosed, there were no other demographic or lifestyle factors which were predictive of the development of incident adenocarcinoma in this cohort.

Does the length of the columnar-lined esophagus change with time?

A number of previous studies have reported patients with Barrett's columnar metaplasia who have an increase or decrease in segment length over time. It is not clear whether patients who have an apparent shortening of the metaplastic segment are subsequently at a lower neoplastic risk and those whose segment length appears to increase are at a higher risk of adenocarcinoma development. The aim of this study was to investigate these issues by studying a large cohort of patients from the UK National Barrett's Oesophagus Registry. Medical records of 1533 patients registered with the UK National Barrett's Oesophagus Registry were examined from seven UK centers. Data were extracted on metaplastic segment length at surveillance endoscopies and histological findings on biopsy. Overall changes in segment length, variability in measurement and probability of the development of dysplasia and neoplasia over time were examined. At least two segment lengths were measured in 763 patients. The median change from measured diagnostic length to most outlying measured segment length was 3.0 cm, but overall there was no tendency for segment length to increase or decrease in the majority of patients with a follow up of up to 20 years. Most patients were treated with proton pump inhibitors. One hundred and eighty-six patients had three or more segment lengths over the first 10 years of follow up. No change in risk was demonstrated in these patients where length appeared to consistently increase with time or when it appeared to decrease. Overall, metaplastic columnar-lined esophagus segment length does not change over time, and when an apparent change is observed, this does not influence a risk of dysplasia or adenocarcinoma.

Antiphospholipid antibodies and stroke in Down syndrome.

Two patients with Down syndrome and the primary antiphospholipid antibody are described. One patient had a vasculopathy similar to that previously described as Moyamoya. Down syndrome is characterized by immune defects including a tendency to autoimmune phenomena. This report extends the scope of these observations and particularly draws out the potential role of antiphospholipid antibodies. Indeed antiphospholipid antibodies may well explain the well-known association of Down syndrome and stroke.

The association between synthetic bedding and adverse respiratory outcomes among skin-prick test positive and skin-prick test negative children.

BACKGROUND: Synthetic bedding has been associated with increased child wheeze and also higher allergen levels in several studies. We aimed to examine whether the association between synthetic bedding and adverse respiratory outcomes was more evident among skin-prick test (SPT) positive children. METHODS: A cross-sectional survey involving a population sample of 758 (81% of eligible) school children aged 8-10 years from randomly selected schools in the Australian Capital Territory in 1999. Parental questionnaires for ISAAC respiratory symptoms and child bedding were obtained. SPT results of 10 common allergens were available on 722 of the subjects (77% of those eligible). Synthetic pillow or quilt use was termed synthetic upper bedding. RESULTS: Synthetic quilt use was associated with asthma (Adjusted Odds Ratio 1.67 (1.05, 2.65)), recent wheeze (AOR 1.63 (1.03, 2.59)) and allergic rhinoconjunctivitis (AOR 2.11 (1.33, 3.34)) among SPT-positive children. However, these associations were not apparent for SPT-negative children. Similarly, increasing synthetic upper bedding use was associated with more than 12 episodes of wheeze among SPT-positive children (AOR 1.69 (1.08, 2.64), P=0.02, per category) but not SPT-negative children (AOR 0.77 (0.26, 2.21), P=0.6, per category). CONCLUSION: The apparent association between synthetic upper bedding and adverse respiratory outcomes was evident among SPT-positive but not SPT-negative children. Prospective intervention studies that aim to examine the effect of upper bedding composition on child asthma among SPT-positive children are required.

The relationship between low level nitrogen dioxide exposure and child lung function after cold air challenge.

BACKGROUND: Nitrogen dioxide (NO(2)) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood. OBJECTIVES: (i) To examine the contribution of home gas appliance type and personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status. METHODS: A cross-sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO(2) exposure by passive gas samplers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge. RESULTS: Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO(2) exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO(2) exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There was some evidence that these reductions were greater among the non-mite-sensitized children. CONCLUSIONS: The effect of low-level NO(2) exposure on these respiratory outcomes was not marked. The possible effect of low-level NO(2) exposure on non-specific bronchial reactivity requires confirmation. Future studies on NO(2) and respiratory health should include measures of house dust mite sensitization and bronchial hyper-responsiveness.

Carbon monoxide wash-in method to determine gas transfer in vascular beds: application to rat hindlimb.

The vascular barrier to gas transfer is an important physiological parameter; however, no readily applicable technique exists to quantitate the process. A simple technique to measure the permeability-surface area (PS) product for gas transfer in vascular beds is proposed using wash in of carbon monoxide (CO) and Crone-Renkin analysis. Wash-in experiments were performed on the perfused hindlimbs of male Wistar rats (n = 15) by using CO as a surrogate marker for oxygen and technetium-99m-labeled albumin as the vascular marker. The use of CO and erythrocyte-free perfusate and the collection of outflow samples into tubes preloaded with erythrocytes obviated the need for an anaerobic collection device or consideration of Hb binding in the analysis. The PS product for CO was determined from the early extraction as 0.013 +/- 0.006 ml. s(-1). g(-1). Compartmental analysis revealed that the fractional recovery of CO was 0.45 +/- 0.14 and the volume of distribution was 2.31 +/- 0.76 ml/g. This technique detected a small measurable barrier to the transfer of CO across the hindlimb vasculature and is potentially applicable to other vascular beds in health and disease.

Lepidopterism: two cases of systemic reactions to the cocoon of a common moth, Chelepteryx collesi.

Lepidopterism is a general term for the ill-effects to humans from contact with moths and butterflies. We describe two cases of systemic reactions after contact with the cocoon of the Australian species Chelepteryx collesi, or white-stemmed gum moth--irritant and toxic effects in one and a systemic allergic reaction in the other. Early removal of urticating hairs from the skin in such cases may be advisable.

Family and twin studies in systemic lupus erythematosus.

We have estimated how much of the total genetic predisposition to SLE may be attributable to genes outside the HLA region by comparing figures for concordance of SLE in monozygotic twins with those for concordance in HLA identical siblings in Australia. None of six dizygotic co-twins of white Australian SLE probands was concordant for SLE. One of four (25%) monozygotic co-twins of white Australian SLE probands was concordant for SLE which when added to previously published figures for Caucasoid populations gives an overall concordance rate for SLE in monozygotic twins of 25%. None of 18 HLA identical, same sex siblings of SLE probands, had definite SLE by the study criteria (i.e. less than 6%). The comparison of these figures shows that most of the genetic predisposition to SLE is attributable to genes outside the HLA region.