Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis.

BACKGROUND: People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. METHODS: We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations between genetic liability to VTE and risk of 18 different cancers. RESULTS: We found no conclusive evidence that genetic liability to VTE was causally associated with an increased incidence of cancer, or vice versa. We observed an association between liability to VTE and pancreatic cancer risk [odds ratio for pancreatic cancer: 1.23 (95% confidence interval: 1.08-1.40) per log-odds increase in VTE risk, P = 0.002]. However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence to suggest a causal relationship. CONCLUSIONS: These findings do not support the hypothesis that genetic liability to VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesize evidence for these mechanisms.

Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomisation analysis.

Background: People with cancer experience high rates of venous thromboembolism (VTE). Additionally, risk of subsequent cancer is increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. Methods: We used data from large genome-wide association study meta-analyses to perform bi-directional Mendelian randomisation analyses to estimate causal associations between genetically-proxied lifetime risk of VTE and risk of 18 different cancers. Results: We found no conclusive evidence that genetically-proxied lifetime risk of VTE was causally associated with an increased incidence of cancer, or vice-versa. We observed an association between VTE and pancreatic cancer risk (odds ratio for pancreatic cancer 1.23 (95% confidence interval 1.08 - 1.40) per log-odds increase in risk of VTE, P = 0.002). However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence from Mendelian randomisation to suggest a causal relationship. Conclusions: These findings do not support the hypothesis that genetically-proxied lifetime risk of VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesise evidence for these mechanisms.

Bring on the weekend - Improving the quality of junior doctor weekend handover.

While it is widely recognised that communication and handover are a fundamental component in providing safe clinical care for hospital patients (1,2.3). The Royal College of Physicians found that the majority of hospital doctors are dissatisfied with the standard of their handovers (4). These findings were mirrored by the junior staff at the Royal United Hospital, who felt that the weekend handover was inadequate, and detrimental to patient safety. A group of eight junior doctors at the Royal United Hospital, Bath utilised The Model For Improvement to systematically analyse and improve various aspects of the weekend handover system. Handover sheets from a subset of wards were assessed to observe direct effects of staged interventions over a nine month period, allowing small-scale testing prior to widespread implementation of a standardised intranet-based weekend handover. The effects of interventions were evaluated using a predesigned scoring system and data was collected continuously throughout the project. Over a nine month period the quality of handovers improved significantly from 76% to 93% (p <0.01): a success which was supported by a 100% improvement in formal feedback collected from hospital doctors and highlighted by the desire of senior staff and directors to implement the system throughout the trust. Using The Model For Improvement a group of junior doctors were able to introduce and develop a standardised weekend handover system that met their requirements. A structured, efficient and auditable system has been successfully produced which improves the quality and safety of patient care.