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To refine and validate a model for predicting the risk of gastrointestinal (GI) cancer in iron deficiency anaemia (IDA) and to develop an app to facilitate use in clinical practice. Three elements: (1) analysis of a dataset of 2390 cases of IDA to validate the predictive value of age, sex, blood haemoglobin concentration (Hb), mean cell volume (MCV) and iron studies on the probability of underlying GI cancer; (2) a pilot study of the benefit of adding faecal immunochemical testing (FIT) into the model; and (3) development of an app based on the model. Age, sex and Hb were all strong, independent predictors of the risk of GI cancer, with ORs (95% CI) of 1.05 per year (1.03 to 1.07, p<0.00001), 2.86 for men (2.03 to 4.06, p<0.00001) and 1.03 for each g/L reduction in Hb (1.01 to 1.04, p<0.0001) respectively. An association with MCV was also revealed, with an OR of 1.03 for each fl reduction (1.01 to 1.05, p<0.02). The model was confirmed to be robust by an internal validation exercise. In the pilot study of high-risk cases, FIT was also predictive of GI cancer (OR 6.6, 95% CI 1.6 to 51.8), but the sensitivity was low at 23.5% (95% CI 6.8% to 49.9%). An app based on the model was developed. This predictive model may help rationalise the use of investigational resources in IDA, by fast-tracking high-risk cases and, with appropriate safeguards, avoiding invasive investigation altogether in those at ultra-low predicted risk. [Abstract copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.]

Objective To refine and validate a model for predicting the risk of gastro-intestinal (GI) cancer in iron deficiency anaemia (IDA), and to develop an App to facilitate use in clinical practice. Design Three elements - (1) Analysis of a dataset of 2390 cases of IDA to validate the predictive value of age, sex, blood haemoglobin concentration (Hb), mean cell volume (MCV) and iron studies on the probability of underlying GI cancer (2) A pilot study of the benefit of adding faecal immunochemical testing (FIT) into the model (3) Development of an App based on the model. Results Age, sex and Hb were all strong, independent predictors of the risk of GI cancer, with ORs (95% CI) of 1.05 per year (1.03 – 1.07, P<0.00001), 2.86 for males (2.03 – 4.06, P<0.00001), and 1.03 for each g/l reduction in Hb (1.01 – 1.04, P<0.0001) respectively. An association with MCV was also revealed, with an OR of 1.03 for each fl reduction (1.01 – 1.05, P<0.02). The model was confirmed to be robust by an internal validation exercise. In the pilot study of high-risk cases, FIT was also predictive of GI cancer (OR = 6.6, 95% CI 1.6 - 51.8), but the sensitivity was low at 23.5% (95% CI 6.8 – 49.9%). An App based on the model was developed. Conclusion This predictive model may help rationalise the use of investigational resources in IDA, by fast-tracking high-risk cases and, with appropriate safeguards, avoiding invasive investigation altogether in those at ultra-low predicted risk.

Colorectal cancer (CRC) is common and carries a relatively poor prognosis. The strong relationship between tumour stage at diagnosis and survival is the basis of the English Bowel Cancer Screening Programme (BCSP) and highlights the importance of early diagnosis. Iron deficiency anaemia (IDA) is also common. About 10% of cases in males and post-menopausal females are due to underlying gastro-intestinal (GI) cancer, most commonly CRC - and IDA is often the first manifestation. This thesis examines the detailed relationship between IDA and CRC. Chapters 4 and 5 describe the analysis of four large IDA datasets, confirming the prevalence of GI cancer, and demonstrating that cancer risk can be predicted from four simple, objective clinical indicators. This IDIOM model proved robust on internal and external validation. This research is valuable for patient counselling, targeting the investigation of high-risk individuals and (perhaps) avoiding invasive investigation in ultra-low risk cases. Chapter 6 outlines the analysis of a subset with recurrent IDA, suggesting that the subsequent risk of GI cancer is higher in those who were incompletely investigated the first time around. Chapter 7 describes the development of the IDIOM App. This is a freely available web-tool which allows cancer risk in IDA to be calculated within seconds, lending itself to clinical usage. Chapters 8 and 9 report the analysis of a large CRC database, demonstrating that diagnosis through the IDA pathway (1) generates as many cases as the BCSP; (2) identifies a distinct sub-population with a predominance of right- sided lesions; and (3) like the BCSP, is associated with a favourable tumour stage profile. The findings suggest that identifying iron deficiency anaemia could play an important role in the early diagnosis of CRC.

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: 1. To assess the clinical outcomes of psychological and educational interventions in children and adults with eczema 2. To summarise the availability and principal findings of relevant economic evaluations

Poor diet quality is a major cause of maternal obesity. We aimed to investigate a priori and a-posteriori derived dietary patterns in childbearing-aged women in UK. An online survey assessed food intake, physical activity (PA), anthropometry and socio-demographics. An a priori defined diet quality was determined via Mediterranean diet (MD) adherence score and Exploratory Factor Analysis (EFA) derived dietary patterns (DPs). Multiple linear regression explored associations between DPs with anthropometric measures, PA and socio-demographics. Participants (n = 123) had low-to-medium MD adherence (average MD-score: 4.0 (2.0)). Age was positively associated with higher MD adherence (X2 (2) = 13.14, p = 0.01). EFA revealed three DPs: 'fruits, nuts, vegetables and legumes' ("Vegetarian-style" DP); 'sweets, cereals, dairy products and potatoes' ("Dairy, sweets and starchy foods" DP); and 'eggs, seafood and meats' ("Protein-rich" DP). "Vegetarian-style" DP was positively associated with higher maternal educational level (p < 0.01) and PA (p = 0.01), but negatively with white ethnicity (p < 0.01). "Dairy, sweets and starchy foods" DP was positively associated with white ethnicity (p = 0.03) and negatively with age (p = 0.03). "Protein-rich" DP was positively associated with age (p < 0.001) and negatively with PA (p = 0.01). A poor diet quality was found among childbearing-aged women; notably in the younger age category, those of white ethnicity, that were more physically inactive and with a lower socioeconomic background.

Background: Obesity is still a major public health concern and a plethora of lifestyle-interventions targeting weight-loss at individual level have shown poor success. Health related behaviours including eating, tend to be concordant in couples which means they might share an obesity risk or support each other’s effort to change these behaviours i.e. weight loss. The aim of this systematic review (SR) and meta-analysis (MA) of randomised controlled trials (RCTs) was to assess the weight change effects of lifestyle interventions targeting couples compared to individuals or no-intervention.

Objective : To report our cumulative experience from a dedicated IDA clinic over the last 15 years – with particular emphasis on referral rate, uptake of investigation, impact on endoscopy services, diagnostic yield of 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 (F/M) 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 sub-group 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 co-morbidities, and the management of recurrent IDA.

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.

Background Faecal occult blood (FOB) positivity and iron deficiency anaemia (IDA) are common manifestations of colorectal cancer (CRC) and both potentially facilitate diagnosis at an earlier, more treatable stage. It has been assumed that both are the consequence of low-grade blood loss from the tumour bed. Method A retrospective analysis of 1121 cases of CRC diagnosed at a single centre between 2010 and 2016, comparing cases presenting via FOB-based Bowel Cancer Screening Programme (BCSP) and IDA pathways for a series of variables including age, sex, tumour location and prevalence of anaemia. Results The BCSP and IDA pathways each accounted for about 15% of the total case load. There were significant differences between the BCSP and IDA sub-groups in median age (68 vs 78 years: p<0.001), median haemoglobin (138 vs 89 g/L: p<0.001) and proportion of lesions in right colon (31.1% vs 82.5%: p<0.001). The major disparity in the prevalence of anaemia (overall 20.0% vs 98.2%: p<0.001) persisted when controlled for tumour location. Conclusion Paradoxically, CRC screening through the detection of FOB positivity and IDA identifies distinctly different sub-populations of cases. The theoretical implication is that an additional mechanism may be required to explain the development of IDA in CRC. The practical implication is that detection of IDA may have a complementary role to the BCSP in population screening for CRC.

Iron deficiency anaemia (IDA) is common in colorectal cancer (CRC), especially, in right-sided CRC which is known to have an overall worse prognosis. The associations between diagnostic pathway (Bowel Cancer Screening Programme (BCSP), IDA, symptomatic) and tumour side/stage was assessed using logistic regression models in 1138 CRC cases presenting during 2010-2016 at a single secondary-care centre in the UK. In the IDA sub-group, the relationship between CRC stage and the event of having a blood count prior to CRC diagnosis was examined using Bayesian parametric survival model. IDA was found as the only significant predictor of right-sided CRC (OR 10.61, 95% CI 7.02-16.52). Early-stage CRC was associated with both the IDA (OR 1.65, 95% CI 1.18-2.29) and BCSP pathway (OR 2.42, 95% CI 1.75-3.37). At any age, the risk of detecting CRC at late-stage was higher in those without a previous blood count check (hazard ratio 1.53, 95% credibility interval 1.08-2.14). The findings of this retrospective observational study suggest a benefit from diagnosing CRC through the detection of IDA, and warrant further research into the prognosis benefit of systematic approach to blood count monitoring of the at-risk population.

To facilitate the clinical use of an algorithm for predicting the risk of gastrointestinal malignancy in iron deficiency anaemia—the IDIOM score, a software application has been developed, with a view to providing free and simple access to healthcare professionals in the UK. A detailed requirements analysis for intended users of the application revealed the need for an automated decision-support tool in which anonymised, individual patient data is entered and gastrointestinal cancer risk is calculated and displayed immediately, which lends itself to use in busy clinical settings. Human-centred design was employed to develop the solution, focusing on the users and their needs, whilst ensuring that they are provided with sufficient details to appropriately interpret the risk score. The IDIOM App has been developed using R Shiny as a web-based application enabling access from different platforms with updates that can be carried out centrally through the host server. The application has been evaluated through literature search, internal/external validation, code testing, risk analysis, and usability assessments. Legal notices, contact system with research and maintenance teams, and all the supportive information for the application such as description of the population and intended users have been embedded within the application interface. With the purpose of providing a guide of developing standalone software medical devices in academic setting, this paper aims to present the theoretical and practical aspects of developing, writing technical documentation, and certifying standalone software medical devices using the case of the IDIOM App as an example.

OBJECTIVE: To determine whether mobilisation timing was associated with the cumulative incidence of hospital discharge by 30 days after hip fracture surgery, accounting for potential confounders and the competing risk of in-hospital death. METHOD: We examined data for 135,105 patients 60 years or older who underwent surgery for nonpathological first hip fracture between 1 January 2014 and 31 December 2016 in any hospital in England or Wales. We tested whether the cumulative incidences of discharge differed between those mobilised early (within 36 h of surgery) and those mobilised late, accounting for potential confounders and the competing risk of in-hospital death. RESULTS: A total of 106,722 (79%) of patients first mobilised early. The average rate of discharge was 39.2 (95% CI 38.9-39.5) per 1,000 patient days, varying from 43.1 (95% CI 42.8-43.5) among those who mobilised early to 27.0 (95% CI 26.6-27.5) among those who mobilised late, accounting for the competing risk of death. By 30-day postoperatively, the crude and adjusted odds ratios of discharge were 2.36 (95% CI 2.29-2.43) and 2.08 (95% CI 2.00-2.16), respectively, among those who first mobilised early compared with those who mobilised late, accounting for the competing risk of death. CONCLUSION: Early mobilisation led to a 2-fold increase in the adjusted odds of discharge by 30-day postoperatively. We recommend inclusion of mobilisation within 36 h of surgery as a new UK Best Practice Tariff to help reduce delays to mobilisation currently experienced by one-fifth of patients surgically treated for hip fracture.

The Diamond Princess cruise ship is a unique COVID-19 transmission case because of the high testing capacity and the confined environment. This exploratory study aims to raise the hypothesis regarding the role of poor ventilation systems in the spread of COVID-19 by analysing count data collected by the onboard clinic during the outbreak, and considering the deck plan and design of the air conditioning system of the ship. Observed symptomatic infection rate after day 5 (incubation period median day) of the quarantine, in cabins without previous confirmed cases are compared to that in cabins with previous confirmed cases. Accordingly, the observed symptomatic infection rate in cabins without a previously confirmed case (1.2%) was higher than for cabins with a previously confirmed case (0.8%); however, the difference was not statistically significant. In addition, age did not appear to be a confounding variable. Airborne transmission of COVID-19 through the ventilation system onboard could explain the higher than expected virus spread into cabins without previously confirmed cases during the quarantine period; thus, this study provides further potential evidence of coronavirus transmission by aerosols. Conflicting results from other studies involving the Diamond Princess outbreak are also discussed in light of our results.

Background: Poor diet quality is associated with obesity-related morbidity and mortality. Psychological stress can increase unhealthy dietary choices, but evidence pertinent to women of reproductive age remains unclear. This paper systematically reviewed the literature to determine the association between psychological stress and diet quality in women of reproductive age. Methods: Medline, CINAHL, Scopus, Cochrane Library, Web of Science, and Sciencedirect were searched. Data extraction was determined by the PEO. Inclusion criteria consisted of: English language, stress (exposure) measured in combination with diet quality (outcome), healthy women of reproductive age (18–49 years old (population)). Observational studies, due to the nature of the PEO, were included. Quality assessment used the Risk of Bias in Non-randomised Studies from the Cochrane Handbook of Systematic Reviews of Interventions. Meta-analysis was conducted using random-effect model to estimate the Fisher’s z transformed correlation between stress and diet quality with 95% confidence interval (CI). Results: From 139,552 hits, 471 papers were screened; 24 studies met the inclusion criteria and were conducted in different countries: 8 studies on diet quality and 16 on food intake and frequency of consumption. Studies of diet quality consisted of six cross-sectional and two longitudinal designs with a total of 3982 participants. Diet quality was measured with diverse indices; Alternate Healthy Eating Index (n = 2), Healthy Eating Index (n = 2), Dietary Approach to Stop Hypertension (DASH) Diet Index (n = 2), Dietary Quality Index- Pregnancy (n = 2), and Dietary Guideline Adherence Index (n = 1). Most studies used Cohen’s perceived stress scale and no study measured biological stress response. After sensitivity analysis, only 5 studies (3471 participants) were included in the meta-analysis. Meta-analysis revealed a significant negative association between stress and diet quality with substantial heteroge

More than half of women in developed countries are overweight or obese. Studies show that 20-25% of women in the UK enter pregnancy as obese. Healthy diet patterns such as the Mediterranean diet (MD) are linked with lower adiposity among women of childbearing age. However there is evidence that maternal diet in the UK is poor and stress increases the consumption of saturated-fat, sweets, and energy-dense foods. There is limited evidence on dietary patterns and stress among women of childbearing age, therefore this study aimed to investigate the association. This was an anonymous online survey of female university students. The survey included: socio-demographic characteristics, physical activity, self-reported BMI and waist circumference. Dietary assessment was done via a validated 100-food item food frequency questionnaire and perceived stress via the Perceived Stress Scale (PSS). The dietary data were compared to the a priori defined Mediterranean Diet Score (MDS) and scored according to eight components (vegetables, legumes, fruit and nuts, cereals, fish, dairy products, meat and meat products, and the ratio of unsaturated to saturated fat). The scores ranged from 0 to 8 with MDS adherence groups being 0-3 low, 4-5 medium, and 6-8 high. Factor analysis was also applied on 11 food components (g/d) (the eight above plus eggs, potatoes, sweets and drinks) to reveal the latent major dietary patterns (DP) in the studied cohort.Negative binomial regression was used to examine the association between stress and the diet patterns, controlling for the socioeconomic factors, physical activity, marital status, BMI, and waist. One hundred twenty-three students (mean age 27.7 (SD 7.3)) participated. Participants had medium (n=49) or low MD adherence (n=48), with fewer participants having high adherence (n=26). Stress was not significantly associated with MD adherence, but was positively associated with sweets intake (p=0.03). The scree plot of Factor analysis showed that the