Stage-specific risk of colon and rectal cancer in patients presenting with rectal bleeding or change in bowel habit in primary care: A population-based cohort study

INTRODUCTION: Rectal bleeding and change in bowel habit are red-flag symptoms for colon and rectal cancer but how they relate to advanced stage disease is not adequately understood. METHODS: We analysed primary care electronic health records data on patients aged 30-99 years. Using logistic regression, we first examined the risk of colon and rectal cancer within 12 months in patients presenting with change in bowel habit and rectal bleeding, and then the risk of advanced stage at diagnosis within cancer cases. We combined the results to estimate risk of advanced stage colon and rectal cancers at diagnosis. RESULTS: For both symptoms and sexes, risk of cancer (overall and by stage) increased with increasing age. We illustrate the findings for persons at the highest age-specific observed risk (typically aged around 80). In men, change in bowel habit (CIBH) and rectal bleeding were associated with different risk of advanced stage colon and rectal cancers (e.g., for colon, CIBH = 2.7% (95% CI 2.2-3.1) and rectal bleeding = 1.7% (95% CI 1.4-2.0)), but without evidence of risk difference between the two symptoms for non-advanced disease. The opposite pattern was apparent in women, with both symptoms associated with similar risk of advanced disease, but different risk of non-advanced colon and rectal cancers (e.g., for colon, CIBH = 1.0% (95% CI 0.8-1.3) and rectal bleeding = 1.3% (95% CI 1.1-1.6)). DISCUSSION: Change in bowel habit and rectal bleeding have different age-specific associations with advanced stage disease, which vary by sex. A substantial proportion of cases is diagnosed at non-advanced stage, supporting the need for prompt diagnostic assessment of patients who present with those symptoms, taking into account the age-specific nature of risks

Enabling RISC-V support on MaxineVM

In this paper we outline the current state of language Virtual Machines(VMs) running on RISC-V as well as our initiatives in augmentingthe existing ecosystem with Maxine VM, a state-of-theartopen source research Virtual Machine (VM). Maxine VM isa metacircular VM for Java and is currently part of the Beehiveecosystem that provides a unified framework for hardware/softwareco-designed research on managed languages runtimes

Cross-ISA Debugging in Meta-circular VMs

Extending current Virtual Machine implementations to newInstruction Set Architectures entails a significant programmingand debugging effort. Meta-circular VMs add anotherlevel of complexity towards this aim since they have to compilethemselves with the same compiler that is being extended.Therefore, having low-level debugging tools is ofvital importance in decreasing development time and bugsintroduced.In this paper we describe our experiences in extendingMaxine VM to the ARMv7 architecture. During that process,we developed a QEMU-based toolchain which enablesus to debug a wide range of VM features in an automatedway. The presented toolchain has been integrated with theJUNIT testing framework of Maxine VM and is capable ofexecuting from simple assembly instructions to fully JITcompiled code. Furthermore, it is fully open-sourced and can be adapted to any other VMs seamlessly. Finally, we describe a compiler-assisted methodology that helps us identify, at runtime, faulty methods that generate no stack traces, in an automatic and fast manner.<br/

Nominal Contracting Effects on Common Stock Returns: a Multi-Factor Model Approach (Unexpected Inflation).

This study examines the theoretical and empirical impact of nominal contracting effects on common stock real returns. It develops an arbitrage pricing model which has as its primary factors the market portfolio and expected inflation and unexpected inflation rates. It extends the model to test empirically for the impact of different nominal contracting effects. In particular, it examines the short- and long-term net monetary position effects, the depreciation tax effect, the inventory tax effect and the wage contract effect. A common feature among these effects is that they are nominal contracts whose real values are affected by unexpected inflation. The study differs from previous studies by considering the effect of unexpected inflation beyond that already impounded in the market factor. It covers the period from 1964 through 1983 using quarterly data. The sample is selected from all non regulated firms commonly listed on the 1983 versions of the Compustat Annual Industrial tape and the CRSP tape. Equally weighted and sequentially updated portfolios are formed in order to obtain more stable betas. The methodology is based on French, Ruback and Schwert (1983). The preliminary multifactor model analysis shows that the three factors--the market factor, the expected inflation factor and the unexpected inflation factor--are significant in explaining common stock returns. The cross-sectional analysis between unexpected inflation betas and the nominal contracting effects shows that nominal contracting effects are empirically detectable and are consistent with the theory of inflation wealth transfer. The nominal contracting effects appear to have been undetected in previous research. In further support for the nominal contracting hypothesis, the study performed maturity effect tests. According to these tests, the coefficient of a nominal contracting variable with longer term to maturity is larger (in absolute value) than the coefficient of a nominal contracting variable with shorter term to maturity. In general, the results from the maturity effect tests tend also to support the nominal contracting hypothesis

The presenting symptom signatures of incident cancer: evidence from the English 2018 National Cancer Diagnosis Audit

BACKGROUND: Understanding relationships between presenting symptoms and subsequently diagnosed cancers can inform symptom awareness campaigns and investigation strategies. METHODS: We used English National Cancer Diagnosis Audit 2018 data for 55,122 newly diagnosed patients, and examined the relative frequency of presenting symptoms by cancer site, and of cancer sites by presenting symptom. RESULTS: Among 38 cancer sites (16 cancer groups), three classes were apparent: cancers with a dominant single presenting symptom (e.g. melanoma); cancers with diverse presenting symptoms (e.g. pancreatic); and cancers that are often asymptomatically detected (e.g. chronic lymphocytic leukaemia). Among 83 symptoms (13 symptom groups), two classes were apparent: symptoms chiefly relating to cancers of the same body system (e.g. certain respiratory symptoms mostly relating to respiratory cancers); and symptoms with a diverse cancer site case-mix (e.g. fatigue). The cancer site case-mix of certain symptoms varied by sex. CONCLUSION: We detailed associations between presenting symptoms and cancer sites in a large, representative population-based sample of cancer patients. The findings can guide choice of symptoms for inclusion in awareness campaigns, and diagnostic investigation strategies post-presentation when cancer is suspected. They can inform the updating of clinical practice recommendations for specialist referral encompassing a broader range of cancer sites per symptom

Predictive value of abnormal blood tests for detecting cancer in primary care patients with nonspecific abdominal symptoms: A population-based cohort study of 477,870 patients in England

Background: Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms. Methods and findings: Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient’s cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use. Conclusions: In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Further cancer assessment should also be considered in patients aged 30 to 59 with concurrent blood test abnormalities. This approach can detect additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites

Predictive value of abnormal blood tests for detecting cancer in primary care patients with nonspecific abdominal symptoms: A population-based cohort study of 477,870 patients in England

Background: Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms.// Methods and findings: Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations.// A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient’s cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use.// Conclusions: In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Further cancer assessment should also be considered in patients aged 30 to 59 with concurrent blood test abnormalities. This approach can detect additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites