Role of prescribed medication in the development of iron deficiency anaemia in adults-a case-control study.

OBJECTIVE: To estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA), specifically considering oral anticoagulants (OACs), antidepressants, antiplatelet agents, proton pump inhibitors (PPIs) and non-steroidal anti-inflammatories. DESIGN: A case-control study involving the analysis of community repeat prescriptions among subjects referred with IDA, and unmatched controls referred as gastroenterology fast-tracks for other indications. Multivariable logistic regression modelling was used to calculate ORs for the association between IDA presentation and each medication class, adjusted for age, sex and coprescribing. For those classes showing significance, it was also used to calculate risk differences between those in the IDA group with or without haemorrhagic lesions on investigation. RESULTS: A total of 1210 cases were analysed-409 in the IDA group, and 801 in the control group. Significant associations were identified between presentation with IDA and long-term exposure to PPIs (OR 3.29, 95% CI: 2.47 to 4.41, p<0.001) and to OACs (OR 2.04, 95% CI: 1.29 to 3.24, p=0.002). IDA was not associated with long-term exposure to any of the other three drug classes. In contrast to the relationship with PPIs, the association with OACs was primarily in the IDA sub-group with haemorrhagic lesions. CONCLUSION: Long-term exposure to PPIs and OACs are independently associated with the risk of developing IDA. There are grounds for considering that these associations may be causal, though the underlying mechanisms probably differ.

Frequency, duration, and type of physiotherapy in the week after hip fracture surgery - analysis of implications for discharge home, readmission, survival, and recovery of mobility.

PURPOSE: To examine the association between physiotherapy access after hip fracture and discharge home, readmission, survival, and mobility recovery. METHODS: A 2017 Physiotherapy Hip Fracture Sprint Audit was linked to hospital records for 5383 patients. Logistic regression was used to estimate the association between physiotherapy access in the first postoperative week and discharge home, 30-day readmission post-discharge, 30-day survival and 120-days mobility recovery post-admission adjusted for age, sex, American Society of Anesthesiology grade, Hospital Frailty Risk Score and prefracture mobility/residence. RESULTS: Overall, 73% were female and 40% had high frailty risk. Patients who received ≥2 hours of physiotherapy (versus less) had 3% (95% Confidence Interval: 0-6%), 4% (2-6%), and 6% (1-11%) higher adjusted probabilities of discharge home, survival, and outdoor mobility recovery, and 3% (0-6%) lower adjusted probability of readmission. Recipients of exercise (versus mobilisation alone) had 6% (1-12%), 3% (0-7%), and 11% (3-18%) higher adjusted probabilities of discharge home, survival, and outdoor mobility recovery, and 6% (2-10%) lower adjusted probability of readmission. Recipients of 6-7 days physiotherapy (versus 0-2 days) had 8% (5-11%) higher adjusted probability of survival. For patients with dementia, improved probability of survival, discharge home, readmission and indoor mobility recovery were observed with greater physiotherapy access. CONCLUSION: Greater access to physiotherapy was associated with a higher probability of positive outcomes. For every 100 patients, greater access could equate to an additional eight patients surviving to 30-days and six avoiding 30-day readmission. The findings suggest a potential benefit in terms of home discharge and outdoor mobility recovery. CONTRIBUTION OF THE PAPER.

Colorectal cancer and the blood loss paradox.

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.

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.

Modelling the episodes of care for iron deficiency anemia patients in a secondary-care center using continuous-time multistate Markov chain.

BACKGROUND: Despite the high prevalence of gastro-intestinal (GI) cancer in iron deficiency anemia (IDA), some IDA patients do not complete all the necessary GI investigations at the initial referral. As a result, existing cancers are diagnosed at a later referral with worse prognosis. The potential to detect GI cancer early depends on minimizing the delay time spent between the two consecutive referrals, where a patient did not complete investigations at the first referral, but at the second is diagnosed with positive GI cancer. This retrospective longitudinal study aims to highlight the proper methods to model these referrals. METHODS: Using anonymized data of 168 episodes of care for IDA patients at an IDA clinic in a secondary care setting, continuous-time multi-state Markov chain is employed to determine the transition rates among three observed states for IDA patients at the IDA clinic, "incomplete investigations," "negative GI cancer," and "positive GI cancer" and to estimate the delay time. RESULTS: Once in the state of incomplete investigations, an estimated mean delay time of 3.1 years (95% CI: 1.2, 5) is spent before being diagnosed with positive GI cancer. The probability that a "positive GI diagnosis" is next after the state of "incomplete investigation" is 17%, compared with 11% when it is followed in the state of negative GI cancer. Defining the survival as the event of not being in the state of "positive GI cancer," the survival rate of IDA patients with negative GI cancer is always higher than those with incomplete investigations. Finally, being diagnosed with positive GI cancer is always preceded by the prediction of being considered "very high risk" at the earlier visit. CONCLUSION: A baseline model was proposed to represent episodes of care for IDA patients at a secondary care center. Preliminary results highlight the importance of completing the GI investigations, especially in IDA patients, who are at high risk of GI cancer and fit to go through the investigations.

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.

Evidence for improved prognosis of colorectal cancer diagnosed following the detection of iron deficiency anaemia.

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.

Discharge after hip fracture surgery by mobilisation timing: secondary analysis of the UK National Hip Fracture Database.

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.

A Priori and a Posteriori Dietary Patterns in Women of Childbearing Age in the UK.

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.

Perceived stress and diet quality in women of reproductive age: a systematic review and meta-analysis.

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 heterogeneity between studies (r = - 0.35, 95% CI [- 0.56; - 0.15], p value < 0.001, Cochran Q test P < 0.0001, I2 = 93%). The 16 studies of food intake and frequency of consumption were very heterogeneous in the outcome measure and were not included in the meta-analysis. These studies showed that stress was significantly associated with unhealthy dietary patterns (high in fat, sweets, salt, and fast food and low in fruits, vegetables, fish, and unsaturated fats). CONCLUSION: Future studies that explore diet quality/patterns should include both diet indices and factor analysis and measure biological markers of stress and dietary patterns simultaneously.

Refinement and validation of the IDIOM score for predicting the risk of gastrointestinal cancer in iron deficiency anaemia.

OBJECTIVE: 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. 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; and (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 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. 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.

Evolving patterns in the presentation of coeliac disease over the last 25 years.

OBJECTIVE: To document changes in the clinical features of coeliac disease (CD) at presentation over the last 25 years. DESIGN: Observational study. PATIENTS: 802 subjects diagnosed between 1993 and 2017 at a single general hospital. OUTCOME MEASURES: Date of diagnosis, age, sex, postcode, symptoms, haematinic deficiency, smoking status, serology, family history and autoimmune phenomena. RESULTS: The incidence of diagnosed CD rose threefold during the course of the study, with a rising prevalence of positive coeliac serology and positive family history of CD, and a falling prevalence of symptoms and haematinic deficiencies. There was little change in the female predominance, age at diagnosis or high prevalence of other autoimmune conditions over the 25 years, and a paucity throughout of cigarette smokers, particularly heavy smokers. A cohort of patients with seronegative CD was identified who shared many of the characteristics of seropositive CD, but with a significantly older age at diagnosis and a higher prevalence of cigarette smokers. CONCLUSION: There have been major changes in the epidemiology of CD over the last 25 years, of relevance to both our understanding of the aetiopathogenesis of CD and the requirement for service provision. The implications are discussed.