The dedicated iron deficiency anaemia clinic: a 15-year experience.

OBJECTIVE: To report our cumulative experience from a dedicated iron deficiency anaemia (IDA) clinic over the last 15 years-with particular emphasis on referral rate, uptake of investigation, impact on endoscopy services, diagnostic yield of gastrointestinal (GI) investigation and the issue of recurrent IDA. METHOD: A series of analyses of a register of 2808 referrals to the Poole IDA clinic between 2004 and 2018. RESULTS: The study population of 2808 had a sex ratio of 1.9 (female/male ratio) and a median age of 72 years (IQR: 60-79). A rising referral rate over the study period appears to be plateauing at around 2 cases per 1000 population per annum. On the basis of a snapshot audit, investigation of IDA may now account for over 20% of all diagnostic endoscopies.Overall, 86% of cases underwent examination of the upper and lower GI tract. Significant GI pathology was identified in 27% of the investigated cohort. Adenocarcinoma of the upper or lower GI tract was found in 8.3%, the majority in the right colon. The prevalence of recurrent IDA was estimated at 12.4%, and the results of investigation of this subgroup are reported. CONCLUSION: Unexplained IDA is common, particularly in those over 60 years, and may be the first indication of underlying GI malignancy in over 8% of cases. Unresolved challenges include accommodating the resulting endoscopy workload, establishing a risk/benefit ratio for investigating those with major comorbidities and the management of recurrent IDA.

Broad external validation of a multivariable risk prediction model for gastrointestinal malignancy in iron deficiency anaemia.

BACKGROUND: Using two large datasets from Dorset, we previously reported an internally validated multivariable risk model for predicting the risk of GI malignancy in IDA-the IDIOM score. The aim of this retrospective observational study was to validate the IDIOM model using two independent external datasets. METHODS: The external validation datasets were collected, in a secondary care setting, by different investigators from cohorts in Oxford and Sheffield derived under different circumstances, comprising 1117 and 474 patients with confirmed IDA respectively. The data were anonymised prior to analysis. The predictive performance of the original model was evaluated by estimating measures of calibration, discrimination and clinical utility using the validation datasets. RESULTS: The discrimination of the original model using the external validation data was 70% (95% CI 65, 75) for the Oxford dataset and 70% (95% CI 61, 79) for the Sheffield dataset. The analysis of mean, weak, flexible and across the risk groups' calibration showed no tendency for under or over-estimated risks in the combined validation data. Decision curve analysis demonstrated the clinical value of the IDIOM model with a net benefit that is higher than 'investigate all' and 'investigate no-one' strategies up to a threshold of 18% in the combined validation data, using a risk cut-off of around 1.2% to categorise patients into the very low risk group showed that none of the patients stratified in this risk group proved to have GI cancer on investigation in the validation datasets. CONCLUSION: This external validation exercise has shown promising results for the IDIOM model in predicting the risk of underlying GI malignancy in independent IDA datasets collected in different clinical settings.

Interspecialty referral of oesophagogastric and pharyngolaryngeal cancers delays diagnosis and reduces patient survival: A matched case-control study.

OBJECTIVES: Pharyngolaryngeal and oesophagogastric cancers present with swallowing symptoms and as such, their clinical evaluation traverses boundaries between different specialties. We studied the incidence and significance of interspecialty cancer referrals (ICRs), that is, pharyngolaryngeal cancers first evaluated by gastroenterology and oesophagogastric cancers first evaluated by otolaryngology. DESIGN: A subset analysis of our Integrated Aerodigestive Partnership's audit dataset, of all ICR patients, and an equal number of controls matched for age, sex and cancer subsite. MAIN OUTCOME MEASURES: Information about patient age and presenting symptoms was recorded. The relationship between symptoms and ICR risk was examined with binary logistic regression. Referral-to-diagnosis latency was compared between ICR and control patients with unpaired Student's t test. Cox regression was used to identify independent predictors of overall survival. RESULTS: Of 1130 patients with pharyngolaryngeal and oesophagogastric cancers between 2008 and 2018, 60 diagnoses (5.3%) were preceded by an ICR. Referral-to-diagnosis latency increased from 43 ± 50 days for control patients to 115 ± 140 days for ICR patients (P < .0001). Dysphagia significantly increased the risk of an ICR (odds ratio 3.34; 95% CI 1.30-8.56), and presence of classic gastroesophageal reflux symptoms (heartburn or regurgitation; OR 0.25; 95% CI 0.08-0.83) and "distal" symptoms (nausea/vomiting, abdominal pain or dyspepsia; OR 0.23; 95% CI 0.08-068) significantly reduced the risk. Eleven pharyngolaryngeal cancers (of 26; 42%) were missed by gastroenterology, and eight (of 34; 24%) oesophageal cancers were missed by otolaryngology. An ICR was an independent adverse prognostic risk factor on multivariable analysis (hazard ratio 1.76; 95% CI 1.11-2.73; P < .02; log-rank test). Two systemic root causes were poor visualisation of pharynx and larynx by per-oral oesophago-gastro-duodenoscopy (OGD) for pharyngolaryngeal cancers, and poor sensitivity (62.5%) of barium swallow when it was used to 'evaluate' oesophageal mucosa. CONCLUSIONS: An interspecialty cancer referral occurs in a significant proportion of patients with foregut cancers. It almost triples the time to cancer diagnosis and is associated with a high incidence of missed cancers and diminished patient survival. It is a complex phenomenon, and its reduction requires an integrated approach between primary and secondary care, and within secondary care, to optimise referral pathways and ensure appropriate and expeditious specialist evaluation.

The development of a nurse-led iron deficiency anaemia service in a district general hospital.

OBJECTIVE: To improve the quality of care provided to patients with iron deficiency anaemia (IDA). DESIGN: Service development. SETTING: District General Hospital. PATIENTS: Adults with IDA. MAIN OUTCOME MEASURES: Descriptive report of the practicalities and benefits of establishing an IDA clinic. CONCLUSIONS: The IDA clinic is a novel service development which enhances the management of patients with this common condition, by facilitating prompt confirmation of the diagnosis, replacement therapy and investigation for serious underlying pathology, in particular gastrointestinal malignancy.

Clinical risk factors for underlying gastrointestinal malignancy in iron deficiency anaemia: the IDIOM study.

OBJECTIVE: Ten percent of adults presenting with iron deficiency anaemia (IDA) have underlying cancer. This analysis - the Iron Deficiency as an Indicator Of Malignancy (IDIOM) study - was undertaken to assess whether five simple clinical parameters can usefully predict the likelihood of gastrointestinal (GI) malignancy on subsequent investigation of patients with IDA. DESIGN: Retrospective observational study, with multivariable analysis of the predictive value of sex, age, haemoglobin concentration (Hb), mean red cell volume (MCV) and iron studies for the risk of underlying GI malignancy. SETTING: District General Hospital IDA clinic. PATIENTS: 720 adults with confirmed IDA. RESULTS: Sex, age and Hb were strongly associated with the risk of GI malignancy-the parsimonious model including only these variables yielded ORs of 4.0 (95% CI 2.3 to 7.0) for males compared with females; 3.3 (95% CI 1.7 to 6.4) for age >70 years compared with ≤70 years; and 5.3 (95% CI 2.4 to 11.7) for a Hb of ≤91.4 g/L compared with ≥111.5 g/L. Combining these risk factors identified a subgroup (12% of the study population) at particularly low risk (<2% likelihood), and a second subgroup (16% of the study population) at especially high risk (>20% likelihood) of underlying GI malignancy. CONCLUSIONS: Three simple and objective clinical parameters can be combined to provide a clinically useful cancer risk stratification model for subjects with IDA. This may assist with patient counselling and the prioritisation of investigational resources.

Raised liver enzymes in newly diagnosed Type 2 diabetes are associated with weight and lipids, but not glycaemic control.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is associated with Type 2 diabetes (T2DM) and the metabolic syndrome, and can progress to chronic liver disease. We examined the incidence of elevated (>35 iu/l) alanine transaminase (ALT), as a surrogate marker for NAFLD, in patients with newly diagnosed T2DM. MATERIALS AND METHODS: Retrospective analysis of ALT with metabolic parameters, in 606 consecutive patients presenting to district wide education sessions for newly diagnosed T2DM. RESULTS: ALT was elevated in 155 patients (25.6% (95% CI 22.1, 29.2)), who tended to be older (mean difference 7.3 years (5.2, 9.5), P < 0.001), heavier (body mass index (BMI) mean difference 2.0 kg/m(2) (1.0, 3.0), P < 0.001), and more likely to be male (M:F raised ALT 104:51, normal ALT 219:232, P < 0.001), with higher triglycerides (median difference 0.2 mmol/l, P = 0.001) and lower HDL cholesterol (mean difference 0.09 mmol/l (0.02, 0.15), P = 0.001). There were no statistically significant differences in HBA1C or total cholesterol. CONCLUSIONS: In a well-defined population of newly diagnosed people with T2DM, there is a high incidence of abnormal ALT levels, which is associated with features of the metabolic syndrome (obesity and lipid abnormalities), but not glycemic control.

Do patients really mind mixed sex bays in an emergency assessment unit?

Mixed sex bays are a reality on most Emergency Assessment Units (EAU). However, they are controversial having recently been the focus of political and media attention. We adapted a validated patient satisfaction questionnaire to seek the views of 1000 emergency admissions regarding mixed sex accommodation. Of 1000 respondents, 925 (92%) had been in bays and 665 (66%) shared with the opposite sex. Most 579/665 (87%) were comfortable with this, 97% (966/1000) feeling there was sufficient level of privacy, all (1000/1000) felt they were given privacy when needed. When asked "given the nature and function of EAU would you be willing to share with the opposite sex if it meant a shorter stay?", 857 (86%) said yes. Our study demonstrates that whilst single sex accommodation is ideal it is not the most important factor to most patients admitted to EAU.

Coexpression of neighboring genes in the genome of Arabidopsis thaliana.

Large-scale analyses of expression data of eukaryotic organisms are now becoming increasingly routine. The data sets are revealing interesting and novel patterns of genomic organization, which provide insight both into molecular evolution and how structure and function of a genome interrelate. Our study investigates, for the first time, how genome organization affects expression of a gene in the Arabidopsis genome. The analyses show that neighboring genes are coexpressed. This pattern has been found for all eukaryotic genomes studied so far, but as yet, it remains unclear whether it is due to selective or nonselective influences. We have investigated reasons for coexpression of neighboring genes in Arabidopsis, and our evidence suggests that orientation of gene pairs plays a significant role, with potential sharing of regulatory elements in divergently transcribed genes. Using the data available in the KEGG database, we find evidence that genes in the same pathway are coexpressed, although this is not a major cause for the coexpression of neighboring genes.

Is the risk of adult coeliac disease causally related to cigarette exposure?

OBJECTIVE: Previous studies have shown an association between cigarette smoking and coeliac disease, but it has yet to be established whether this relationship is causal. The aim of this study was to assess causality using the Bradford Hill criteria. METHODS: A matched case-control study using a questionnaire to establish a detailed smoking history for 138 incident cases of adult coeliac disease and 276 age-matched and sex-matched controls. Subjects were categorized according to their active cigarette exposure prior to diagnosis of the matched case, and odds ratios and tests for linear trends were calculated. RESULTS: At the time of diagnosis, 10% of cases and 30% of controls were current smokers (odds ratio, 0.21 and 95% confidence interval, 0.11-0.40 for coeliac disease in current smokers versus never smokers). A biological gradient was demonstrated for total, recent and current cigarette exposure. The greatest risk reduction related to current exposure (odds ratio, 0.15, and 95% confidence interval, 0.06-0.37 for coeliac disease in current heavy smokers versus never smokers). CONCLUSIONS: This study strengthens the case for a causal relationship between smoking and coeliac disease by demonstrating a strong, temporally appropriate and dose-dependent effect, thus meeting the Bradford Hill criteria. This suggests that cigarette smoking truly protects against the development of adult coeliac disease.

Natural selection promotes the conservation of linkage of co-expressed genes.

Although there is increasing evidence that eukaryotic gene order is not always random, there is no evidence that putatively favourable gene arrangements are preserved by selection more than expected by chance. In yeast (Saccharomyces cerevisiae), for example, co-expressed genes tend to be linked, but whether such gene pairs tend to remain linked more often than expected under null neutral expectations is not known. We show using gene pairs in the S. cerevisiae-Candida albicans comparison that highly co-expressed gene pairs are conserved as pairs at about twice the average rate. However, co-expressed genes also tend to be in close physical proximity and, as expected from a null neutral model, genes (be they co-expressed or not) that are physically close together tend to be retained more often. This physical proximity, however, only accounts for a small proportion of the enhanced degree of conservation of co-expressed gene pairs. These results demonstrate that purely neutralist models of gene order evolution are not realistic.

Clustering of tissue-specific genes underlies much of the similarity in rates of protein evolution of linked genes.

Are genes nonrandomly distributed around the genome and might this explain why it was found that, in the mouse genome, proteins of linked genes evolve at similar rates? Anecdotal evidence suggests that the similarity of expression of linked genes might, in part, explain the similarity in their rates of evolution. Immune system genes, for example, are known to evolve at a high rate and sometimes cluster in the genome. Here we develop methods for statistical tests of similarity of expression of linked genes and report that there is a significant tendency for genes of similar expression breadth to be linked. Significantly, when we exclude tissue specific genes from our sample, the similarity in rates of protein evolution of linked genes is greatly diminished, if not abolished. This diminution is not a sampling artifact. In contrast, while half of the immune genes in our sample reside in 1 of 10 immune clusters in the mouse genome, this clustering appears not to affect the extent of local similarity in rates of evolution. The distribution of placentally expressed genes, in contrast, does have an effect.