Trends in the full blood count blood test and colorectal cancer detection: a longitudinal, case-control study of UK primary care patient data [version 2; peer review: 2 approved, 1 not approved]

Background: The full blood count (FBC) is a common blood test performed in general practice. It consists of many individual parameters that may change over time due to colorectal cancer. Such changes are likely missed in practice. We identified trends in these FBC parameters to facilitate early detection of colorectal cancer. Methods: We performed a retrospective, case-control, longitudinal analysis of UK primary care patient data. LOWESS smoothing and mixed effects models were derived to compare trends in each FBC parameter between patients diagnosed and not diagnosed over a prior 10-year period. Results: There were 399,405 males (2.3%, n = 9,255 diagnosed) and 540,544 females (1.5%, n = 8,153 diagnosed) in the study. There was no difference between cases and controls in FBC trends between 10 and four years before diagnosis. Within four years of diagnosis, trends in many FBC levels statistically significantly differed between cases and controls, including red blood cell count, haemoglobin, white blood cell count, and platelets (interaction between time and colorectal cancer presence: p <0.05). FBC trends were similar between Duke’s Stage A and D colorectal tumours, but started around one year earlier in Stage D diagnoses. Conclusions: Trends in FBC parameters are different between patients with and without colorectal cancer for up to four years prior to diagnosis. Such trends could help earlier identification

Impact of Treatment Delay on Outcome in the International Subarachnoid Aneurysm Trial

Background and Purpose - ISAT (International Subarachnoid Aneurysm Trial) demonstrated that 1 year after aneurysmal subarachnoid hemorrhage, coiling resulted in a significantly better clinical outcome than clipping. After 5 years, this difference did not reach statistical significance, but mortality was still higher in the clipping group. Here, we present additional analyses, reporting outcome after excluding pretreatment deaths. Methods - Outcome measures were death with or without dependency at 1 and 5 years after treatment, after exclusion of all pretreatment deaths. Treatment differences were assessed using relative risks (RRs). With sensitivity and exploratory analyses, the relation between treatment delay and outcome was analyzed. Results - After exclusion of pretreatment deaths, at 1-year follow-up coiling was favorable over clipping for death or dependency (RR, 0.77 [95% CI, 0.67-0.89]) but not for death alone (RR, 0.88 [95% CI, 0.66-1.19]). After 5 years, no significant differences were observed, neither for death or dependency (RR, 0.88 [95% CI, 0.77-1.02]) nor for death alone (RR, 0.82 [95% CI, 0.64-1.05]). Sensitivity analyses showed a similar picture. In good-grade patients, coiling remained favorable over clipping in the long-term. Time between randomization and treatment was significantly longer in the clipping arm (mean 1.7 versus 1.1 days; P<0.0001), during which 17 patients died because of rebleeding versus 6 pretreatment deaths in the endovascular arm (RR, 2.81 [95% CI, 1.11-7.11]). Conclusions - These additional analyses support the conclusion of ISAT that at 1-year follow-up after aneurysmal subarachnoid hemorrhage coiling has a better outcome than clipping. After 5 years, with pretreatment mortality excluded, the difference between coiling and clipping is not significant. The high number of pretreatment deaths in the clipping group highlights the importance of urgent aneurysm treatment to prevent early rebleeding

Vertical zonation of testate amoebae in the Elatia Mires, northern Greece : palaeoecological evidence for a wetland response to recent climate change or autogenic processes?

The Elatia Mires of northern Greece are unique ecosystems of high conservation value. The mires are climatically marginal and may be sensitive to changing hydroclimate, while northern Greece has experienced a significant increase in aridity since the late twentieth century. To investigate the impact of recent climatic change on the hydrology of the mires, the palaeoecological record was investigated from three near-surface monoliths extracted from two sites. Testate amoebae were analysed as sensitive indicators of hydrology. Results were interpreted using transfer function models to provide quantitative reconstructions of changing water table depth and pH. AMS radiocarbon dates and 210Pb suggest the peats were deposited within the last c. 50 years, but do not allow a secure chronology to be established. Results from all three profiles show a distinct shift towards a more xerophilic community particularly noted by increases in Euglypha species. Transfer function results infer a distinct lowering of water tables in this period. A hydrological response to recent climate change is a tenable hypothesis to explain this change; however other possible explanations include selective test decay, vertical zonation of living amoebae, ombrotrophication and local hydrological change. It is suggested that a peatland response to climatic change is the most probable hypothesis, showing the sensitivity of marginal peatlands to recent climatic change

Incidence and prevalence of dementia in linked administrative health data in Saskatchewan, Canada: a retrospective cohort study.

Determining the epidemiology of dementia among the population as a whole in specific jurisdictions - including the long-term care population-is essential to providing appropriate care. The objectives of this study were to use linked administrative databases in the province of Saskatchewan to determine the 12-month incidence and prevalence of dementia for the 2012/13 period (1) among individuals aged 45 and older in the province of Saskatchewan, (2) according to age group and sex, and (3) according to diagnosis code and other case definition criteria

Patterns in haemoglobin levels over 10 years to predict diagnosis of colorectal cancer by Duke’s staging: preliminary findings using UK primary care routine blood test data

Stage at diagnosis of colorectal cancer influences 5-year survival: 94% at the earliest stage, but 7% at the latest. Tumour growth causes subtle changes in levels of blood components, such as haemoglobin, which may go unnoticed. Such changes have not been explored. We report patterns in haemoglobin levels up to 10 years before a diagnosis of colorectal cancer, by Duke’s tumour staging

Early detection of colorectal cancer using symptoms and the ColonFlag: case-control and cohort studies

Background: Early detection of colorectal cancer confers substantial prognostic benefit. Most symptoms are non-specific and easily missed. The ColonFlag algorithm identifies risk of undiagnosed colorectal cancer using age, sex and changes in full blood count (FBC) indices. The aim of this study was to investigate whether the ColonFlag detects undiagnosed colorectal cancer prior to the recording of symptoms in general practice. Methods: We conducted case-control and cohort studies by linking primary care data from the Clinical Practice Research Datalink with colorectal cancer diagnoses from the National Cancer Registry. A ColonFlag score was derived for each FBC. We assessed the prevalence of symptoms at six-monthly intervals prior to index date (diagnosis date for cases, randomly selected date for controls). We then derived odds ratios (ORs) and area under the receiver operating characteristic (AUROC) curve for the ColonFlag, and for symptoms using logistic regression at each interval (primary outcome 18-24 months). Results: We included 1,893,641 patients, 10,875,556 FBCs and 8,918,037 ColonFlag scores. ColonFlag scores began to increase in cases compared with controls around 3-4 years before diagnosis. The AUROC for a diagnosis 18-24 months following the ColonFlag score was 0.736 (95% CI 0.715-0.759), falling to 0.536 (95% CI 0.523-0.548) with adjustment for age. ORs for individual symptoms became non-significant prior to 12 months before index date, except for abdominal pain (females OR=1.29, p<0.0001 at 12-18 months) and rectal bleeding (females OR=2.09, males OR=1.92, p<0.0001 at 18-24 months). Conclusions: Symptoms appear relatively late in the colorectal cancer process and are limited for supporting early stage detection. The ColonFlag can discriminate usefully at 18-24 months before diagnosis, suggesting a role for this algorithm in primary care, although some of its discriminatory ability comes from the age variable