Concordance with urgent referral guidelines in patients presenting with any of six 'alarm' features of possible cancer: a retrospective cohort study using linked primary care records

BACKGROUND: Clinical guidelines advise GPs in England which patients warrant an urgent referral for suspected cancer. This study assessed how often GPs follow the guidelines, whether certain patients are less likely to be referred, and how many patients were diagnosed with cancer within 1 year of non-referral. METHODS: We used linked primary care (Clinical Practice Research Datalink), secondary care (Hospital Episode Statistics) and cancer registration data. Patients presenting with haematuria, breast lump, dysphagia, iron-deficiency anaemia, post-menopausal or rectal bleeding for the first time during 2014-2015 were included (for ages where guidelines recommend urgent referral). Logistic regression was used to investigate whether receiving a referral was associated with feature type and patient characteristics. Cancer incidence (based on recorded diagnoses in cancer registry data within 1 year of presentation) was compared between those receiving and those not receiving referrals. RESULTS: 48 715 patients were included, of which 40% (n=19 670) received an urgent referral within 14 days of presentation, varying by feature from 17% (dysphagia) to 68% (breast lump). Young patients (18-24 vs 55-64 years; adjusted OR 0.20, 95% CI 0.10 to 0.42, p<0.001) and those with comorbidities (4 vs 0 comorbidities; adjusted OR 0.87, 95% CI 0.80 to 0.94, p<0.001) were less likely to receive a referral. Associations between patient characteristics and referrals differed across features: among patients presenting with anaemia, breast lump or haematuria, those with multi-morbidity, and additionally for breast lump, more deprived patients were less likely to receive a referral. Of 29 045 patients not receiving a referral, 3.6% (1047) were diagnosed with cancer within 1 year, ranging from 2.8% for rectal bleeding to 9.5% for anaemia. CONCLUSIONS: Guideline recommendations for action are not followed for the majority of patients presenting with common possible cancer features. A significant number of these patients developed cancer within 1 year of their consultation, indicating scope for improvement in the diagnostic process

One-vs-One classification for deep neural networks

For performing multi-class classification, deep neural networks almost always employ a One-vs-All (OvA) classification scheme with as many output units as there are classes in a dataset. The problem of this approach is that each output unit requires a complex decision boundary to separate examples from one class from all other examples. In this paper, we propose a novel One-vs-One (OvO) classification scheme for deep neural networks that trains each output unit to distinguish between a specific pair of classes. This method increases the number of output units compared to the One-vs-All classification scheme but makes learning correct decision boundaries much easier. In addition to changing the neural network architecture, we changed the loss function, created a code matrix to transform the one-hot encoding to a new label encoding, and changed the method for classifying examples. To analyze the advantages of the proposed method, we compared the One-vs-One and One-vs-All classification methods on three plant recognition datasets (including a novel dataset that we created) and a dataset with images of different monkey species using two deep architectures. The two deep convolutional neural network (CNN) architectures, Inception-V3 and ResNet-50, are trained from scratch or pre-trained weights. The results show that the One-vs-One classification method outperforms the One-vs-All method on all four datasets when training the CNNs from scratch. However, when using the two classification schemes for fine-tuning pre-trained CNNs, the One-vs-All method leads to the best performances, which is presumably because the CNNs had been pre-trained using the One-vs-All scheme

CentroidNetV2:A hybrid deep neural network for small-object segmentation and counting

This paper presents CentroidNetV2, a novel hybrid Convolutional Neural Network (CNN) that has been specifically designed to segment and count many small and connected object instances. This complete redesign of the original CentroidNet uses a CNN backbone to regress a field of centroid-voting vectors and border-voting vectors. The segmentation masks of the individual object instances are produced by decoding centroid votes and border votes. A loss function that combines cross-entropy loss and Euclidean-distance loss achieves high quality centroids and borders of object instances. Several backbones and loss functions are tested on three different datasets ranging from precision agriculture to microbiology and pathology. CentroidNetV2 is compared to the state-of-the art networks You Only Look Once Version 3 (YOLOv3) and Mask Recurrent Convolutional Neural Network (MRCNN). On two out of three datasets CentroidNetV2 achieves the highest F1 score and on all three datasets CentroidNetV2 achieves the highest recall. CentroidNetV2 demonstrates the best ability to detect small objects although the best segmentation masks for larger objects are produced by MRCNN. (c) 2020 Elsevier B.V. All rights reserved

Recurrent governance challenges in the implementation and alignment of flood risk management strategies: a review

In Europe increasing flood risks challenge societies to diversify their Flood Risk Management Strategies (FRMSs). Such a diversification implies that actors not only focus on flood defence, but also and simultaneously on flood risk prevention, mitigation, preparation and recovery. There is much literature on the implementation of specific strategies and measures as well as on flood risk governance more generally. What is lacking, though, is a clear overview of the complex set of governance challenges which may result from a diversification and alignment of FRM strategies. This paper aims to address this knowledge gap. It elaborates on potential processes and mechanisms for coordinating the activities and capacities of actors that are involved on different levels and in different sectors of flood risk governance, both concerning the implementation of individual strategies and the coordination of the overall set of strategies. It identifies eight overall coordination mechanisms that have proven to be useful in this respect

Examining methodology to identify patterns of consulting in primary care for different groups of patients before a diagnosis of cancer: An exemplar applied to oesophagogastric cancer

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground Current methods for estimating the timeliness of cancer diagnosis are not robust because dates of key defining milestones, for example first presentation, are uncertain. This is exacerbated when patients have other conditions (multimorbidity), particularly those that share symptoms with cancer. Methods independent of this uncertainty are needed for accurate estimates of the timeliness of cancer diagnosis, and to understand how multimorbidity impacts the diagnostic process. Methods Participants were diagnosed with oesophagogastric cancer between 2010 and 2019. Controls were matched on year of birth, sex, general practice and multimorbidity burden calculated using the Cambridge Multimorbidity Score. Primary care data (Clinical Practice Research Datalink) was used to explore population-level consultation rates for up to two years before diagnosis across different multimorbidity burdens. Five approaches were compared on the timing of the consultation frequency increase, the inflection point for different multimorbidity burdens, different aggregated time-periods and sample sizes. Results We included 15,410 participants, of which 13,328 (86.5 %) had a measurable multimorbidity burden. Our new maximum likelihood estimation method found evidence that the inflection point in consultation frequency varied with multimorbidity burden, from 154 days (95 %CI 131.8–176.2) before diagnosis for patients with no multimorbidity, to 126 days (108.5–143.5) for patients with the greatest multimorbidity burden. Inflection points identified using alternative methods were closer to diagnosis for up to three burden groups. Sample size reduction and changing the aggregation period resulted in inflection points closer to diagnosis, with the smallest change for the maximum likelihood method. Discussion Existing methods to identify changes in consultation rates can introduce substantial bias which depends on sample size and aggregation period. The direct maximum likelihood method was less prone to this bias than other methods and offers a robust, population-level alternative for estimating the timeliness of cancer diagnosis.National Institute for Health Research (NIHR)Cancer Research U

Concordance with urgent referral guidelines in patients presenting with any of six ‘alarm’ features of possible cancer: a retrospective cohort study using linked primary care records

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: Data may be obtained from a third party and are not publicly available. Routinely collected patient electronic health data was provided by CPRD. Access to data from CPRD is subject to a licence agreement and protocol approval from the Independent Scientific Advisory Committee (ISAC).Background Clinical guidelines advise GPs in England which patients warrant an urgent referral for suspected cancer. This study assessed how often GPs follow the guidelines, whether certain patients are less likely to be referred, and how many patients were diagnosed with cancer within 1 year of non-referral. Methods We used linked primary care (Clinical Practice Research Datalink), secondary care (Hospital Episode Statistics) and cancer registration data. Patients presenting with haematuria, breast lump, dysphagia, iron-deficiency anaemia, post-menopausal or rectal bleeding for the first time during 2014–2015 were included (for ages where guidelines recommend urgent referral). Logistic regression was used to investigate whether receiving a referral was associated with feature type and patient characteristics. Cancer incidence (based on recorded diagnoses in cancer registry data within 1 year of presentation) was compared between those receiving and those not receiving referrals. Results 48 715 patients were included, of which 40% (n=19 670) received an urgent referral within 14 days of presentation, varying by feature from 17% (dysphagia) to 68% (breast lump). Young patients (18–24 vs 55–64 years; adjusted OR 0.20, 95% CI 0.10 to 0.42, p<0.001) and those with comorbidities (4 vs 0 comorbidities; adjusted OR 0.87, 95% CI 0.80 to 0.94, p<0.001) were less likely to receive a referral. Associations between patient characteristics and referrals differed across features: among patients presenting with anaemia, breast lump or haematuria, those with multi-morbidity, and additionally for breast lump, more deprived patients were less likely to receive a referral. Of 29 045 patients not receiving a referral, 3.6% (1047) were diagnosed with cancer within 1 year, ranging from 2.8% for rectal bleeding to 9.5% for anaemia. Conclusions Guideline recommendations for action are not followed for the majority of patients presenting with common possible cancer features. A significant number of these patients developed cancer within 1 year of their consultation, indicating scope for improvement in the diagnostic process.Cancer Research U

The rural dispensing practice – better medication adherence and clinical outcomes compared to non-dispensing practices? A cross-sectional analysis of routine data

This is the author accepted manuscript. The final version is available on open access from the Royal College of General Practitioners via the DOI in this record.Background Most patients obtain medications from pharmacies by prescription, but rural general practices can dispense medications. Clinical implications of this difference in drug delivery are unknown. We hypothesised that dispensing status may be associated with better medication adherence. This could impact intermediate clinical outcomes dependent on medication adherence in, for example, hypertension or diabetes. Aim We investigated whether dispensing status is associated with differences in achievement of Quality and Outcome Framework (QOF) indicators that rely on medication adherence. Design and Setting Cross-sectional analysis of QOF data for 7,392 general practices in England. Method We analysed QOF data from 2016/17 linked to dispensing status for general practices with list sizes ≥1000 in England. QOF indicators were categorised according to whether their achievement depended on a record of prescribing only, medication adherence, or neither. We estimated differences between dispensing and non-dispensing practices using mixed-effects logistic regression adjusting for practice population age, sex, deprivation, list size, single-handed status and rurality. Results Data existed for 7,392 practices; 1,014 (13.7%) could dispense. Achievement was better in dispensing practices than in non-dispensing practices for seven of nine QOF indicators dependant on adherence, including blood pressure targets. Only one of ten indicators dependent on prescribing but not adherence displayed evidence of a difference; indicators unrelated to prescribing showed a trend towards higher achievement by dispensing practices. Conclusion Dispensing practices may achieve better clinical outcomes than prescribing practices. Further work is required to explore underlying mechanisms for these observations, and to directly study medication adherence rates.South West General Practice Trus

Provenancing Archaeological Wool Textiles from Medieval Northern Europe by Light Stable Isotope Analysis (δ13C, δ15N, δ2H)

We investigate the origin of archaeological wool textiles preserved by anoxic waterlogging from seven medieval archaeological deposits in north-western Europe (c. 700-1600 AD), using geospatial patterning in carbon (δ13C), nitrogen (δ15N) and non-exchangeable hydrogen (δ2H) composition of modern and ancient sheep proteins. δ13C, δ15N and δ2H values from archaeological wool keratin (n = 83) and bone collagen (n = 59) from four sites were interpreted with reference to the composition of modern sheep wool from the same regions. The isotopic composition of wool and bone collagen samples clustered strongly by settlement; inter-regional relationships were largely parallel in modern and ancient samples, though landscape change was also significant. Degradation in archaeological wool samples, examined by elemental and amino acid composition, was greater in samples from Iceland (Reykholt) than in samples from north-east England (York, Newcastle) or northern Germany (Hessens). A nominal assignment approach was used to classify textiles into local/non-local at each site, based on maximal estimates of isotopic variability in modern sheep wool. Light element stable isotope analysis provided new insights into the origins of wool textiles, and demonstrates that isotopic provenancing of keratin preserved in anoxic waterlogged contexts is feasible. We also demonstrate the utility of δ2H analysis to understand the location of origin of archaeological protein samples

Predictors of early recurrence after resection of colorectal liver metastases

BACKGROUND: Early recurrence after resection of colorectal liver metastases (CLM) is common. Patients at risk of early recurrence may be candidates for enhanced preoperative staging and/or earlier postoperative imaging. The aim of this study was to determine if there are any risk factors that specifically predict early liver-only and systemic recurrence. METHODS: Retrospective analysis of prospective database of patients undergoing liver resection (LR) for CLM from 2004 to 2006 was undertaken. Early recurrence was defined as occurring within 18 months of LR. Patients were classified into three groups: early liver-only recurrence, early systemic recurrence and recurrence-free. Preoperative factors were compared between patients with and without early recurrence. RESULTS: Two hundred and forty-three consecutive patients underwent LR for CLM. Twenty-seven patients (11%) developed early liver-only recurrence. Dukes C stage and male sex were significantly associated with early liver-only recurrence (P < 0.05). Sixty-six patients (27%) developed early systemic recurrence. Tumour size ≥3.6 cm and tumour number (>2) were significantly associated with early systemic recurrence (P < 0.001). CONCLUSIONS: It is possible to stratify patients according to the risk of early liver-only or systemic recurrence after resection of CLM. High-risk patients may be candidates for preoperative MRI and/or computed tomography-positron emission tomography (CT-PET) scan and should receive intensive postoperative surveillance

A mixed-methods study to define Textbook Outcome for the treatment of patients with uncomplicated symptomatic gallstone disease with hospital variation analyses in Dutch trial data

Background: International consensus on the ideal outcome for treatment of uncomplicated symptomatic gallstone disease is absent. This mixed-method study defined a Textbook Outcome (TO) for this large group of patients. Methods: First, expert meetings were organised with stakeholders to design the survey and identify possible outcomes. To reach consensus, results from expert meetings were converted in a survey for clinicians and for patients. During the final expert meeting, clinicians and patients discussed survey outcomes and a definitive TO was formulated. Subsequently, TO-rate and hospital variation were analysed in Dutch hospital data from patients with uncomplicated gallstone disease. Results: First expert meetings returned 32 outcomes. Outcomes were distributed in a survey among 830 clinicians from 81 countries and 645 Dutch patients. Consensus-based TO was defined as no more biliary colic, no biliary and surgical complications, and the absence or reduction of abdominal pain. Analysis of individual patient data showed that TO was achieved in 64.2% (1002/1561). Adjusted-TO rates showed modest variation between hospitals (56.6-74.9%). Conclusion: TO for treatment of uncomplicated gallstone disease was defined as no more biliary colic, no biliary and surgical complications, and absence or reduction of abdominal pain.TO may optimise consistent outcome reporting in care and guidelines for treating uncomplicated gallstone disease