The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

PURPOSE: Pre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality.

METHODS: Using prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality.

RESULTS: Overall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7 %. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95 % CI 0.84-1.26), lung (adjusted HR 1.06, 95 % CI 0.96-1.16), breast (adjusted HR 0.81, 95 % CI 0.62-1.07), or colorectal (adjusted HR 0.88, 95 % CI 0.77-1.01) cancer patients. Dose-response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses.

CONCLUSIONS: There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Factors influencing survival after kidney transplant failure

BACKGROUND: The failure of a kidney transplant is now a common reason for initiation of dialysis therapy. Kidney transplant recipients commencing dialysis have greater morbidity and mortality than transplant-naïve, incident dialysis patients. This study aimed to identify variables associated with survival after graft failure.

METHODS: All recipients of first, deceased donor kidney transplants performed in Northern Ireland between 1986 and 2005 who had a functioning graft at 12 months were included (n = 585). Clinical and blood-derived variables (age, gender, primary renal disease, diabetic status, smoking status, human leukocyte antigen (HLA) mismatch, acute rejection episodes, immunosuppression, cardiovascular disease, graft survival, haemoglobin, albumin, phosphate, C reactive protein, estimated glomerular filtration rate (eGFR), rate of eGFR decline, dialysis modality, and access) were collected prospectively and investigated for association with re-transplantation and survival. The association between re-transplantation and survival was explored by modelling re-transplantation as a time-dependent covariate.

RESULTS: Median follow-up time was 12.1 years. Recipients with a failing graft (158/585) demonstrated rapid loss of eGFR prior to graft failure, reducing the time available to plan for alternative renal replacement therapy. Median survival after graft failure was 3.0 years. In multivariate analysis, age and re-transplantation were associated with survival after graft failure. Re-transplantation was associated with an 88% reduction in mortality.

CONCLUSIONS: Optimal management of kidney transplant recipients with failing grafts requires early recognition of declining function and proactive preparation for re-transplantation given the substantial survival benefit this confers. The survival benefit associated with re-transplantation persists after prolonged exposure to immunosuppressive therapy.

Two-year survival of ART restorations placed in elderly patients: A randomised controlled clinical trial

OBJECTIVES: Older dentate adults are a high caries risk group who could potentially benefit from the use of the atraumatic restorative treatment (ART). This study aimed to compare the survival of ART and a conventional restorative technique (CT) using rotary instruments and a resin-modified glass-ionomer for restoring carious lesions as part of a preventive and restorative programme for older adults after 2 years.

METHODS: In this randomised controlled clinical trial, 99 independently living adults (65-90 years) with carious lesions were randomly allocated to receive either ART or conventional restorations. The survival of restorations was assessed by an independent and blinded examiner 6 months, 1 year and 2 years after restoration placement.

RESULTS: Ninety-six (67.6%) and 121 (76.6%) restorations were assessed in the ART and CT groups, respectively, after 2 years. The cumulative restoration survival percentages after 2 years were 85.4% in the ART and 90.9% in the CT group. No statistically significant between group differences were detected (p=0.2050, logistic regression analysis).

CONCLUSIONS: In terms of restoration survival, ART was as effective as a conventional restorative approach to treat older adults after 2 years. This technique could be a useful tool to provide dental care for older adults particularly in the non-clinical setting. (Trial Registration number: ISRCTN 76299321).

CLINICAL SIGNIFICANCE: The results of this study show that ART presented survival rates similar to conventional restorations in older adults. ART appears to be a cost-effective way to provide dental care to elderly patients, particularly in out of surgery facilities, such as nursing homes.

Degradation, Harm and Survival in a Women’s Prison:Special Issue on Gendered Violence

This article is derived in in-depth qualitative research in the women’s unit of a male prison in Northern Ireland. The researchers had unprecedented observational and interview access and moved freely within the unit including the punishment block. What follows focuses primarily on the experiences of women and girls, recording their accounts of the impact on their lives of a harsh and neglectful regime. It demonstrates how the institutionalisation of violation and neglect within women’s prisons is often gender specific. Finally, it considers the key research recommendations, noting official responses.

Statin Use and Survival from Lung Cancer: A Population-Based Cohort Study

Background: Preclinical evidence from lung cancer cell lines and animal models suggest that statins could have anticancer properties. We investigated whether statin users had reduced risk of cancer-specific mortality in a population based cohort of lung cancer patients.
Methods: Newly diagnosed lung cancer patients, from 1998 to 2009, were identified from English cancer registry data and linked to the UK Clinical Practice Research Datalink, providing prescription records, and to Office of National Statistics mortality data up to 2012. Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by statin use before and after diagnosis and to adjust these HRs for potential confounders.
Results: In 3,638 lung cancer patients, there was some evidence that statin use after diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR=0.89, 95% CI 0.78, 1.02; P=0.09). Associations were more marked after 12 prescriptions (adjusted HR=0.81, 95% CI 0.67, 0.98; P=0.03) and when lipophilic statins were investigated (adjusted HR=0.81, 95% CI 0.70, 0.94; P=0.01) but were attenuated in some sensitivity analyses. Furthermore, in 11,051 lung cancer patients, statin use before diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.83, 0.93; P<0.001).
Conclusions: There was some evidence that lung cancer patients who used statins, and particularly simvastatin, had reduced rates of cancer-specific mortality.
 Impact: These findings should first be confirmed in observational studies, but provide some support for conducting randomized controlled trials of simvastatin as adjuvant cancer therapy in lung cancer patients.

Sphingosine Kinase 1 Promotes Malignant Progression in Colon Cancer and Independently Predicts Survival of Patients With Colon Cancer by Competing Risk Approach in South Asian Population

OBJECTIVES: Sphingosine kinase 1 (SphK1) phosphorylates the membrane sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic mediator, which drives tumor cell growth and survival. Although SphK1 has gained increasing prominence as an oncogenic determinant in several cancers, its potential as a therapeutic target in colon cancer remains uncertain. We investigated the clinical relevance of SphK1 expression in colon cancer as well as its inhibitory effects in vitro.

METHODS: SphK1 expression in human colon tumor tissues was determined by immunohistochemistry and its clinicopathological significance was ascertained in 303 colon cancer cases. The effects of SphK1 inhibition on colon cancer cell viability and the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1 inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also determined.

RESULTS: High SphK1 expression correlated with advanced tumor stages (AJCC classification). Using a competing risk analysis model to take into account disease recurrence, we found that SphK1 is a significant independent predictor for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer cells to 5-FU.

CONCLUSION: Our findings highlight the impact of SphK1 in colon cancer progression and patient survival, and provide evidence supportive of further development in combination strategies that incorporate SphK1 inhibition with current chemotherapeutic agents to improve colon cancer outcomes.

FE Simulation of Viscoplastic Consistency Model

Finite element (FE) simulations provides an inexpensive alternative for material testingof new metal alloys. Carrying out experimental testing is expensive. Nanoindentation is particularly costly due to the equipment needed to work on such a scale. FE simulations provide an inexpensive means of material testing if accurately carried out. This paper will demonstrate the applicability and accuracy of using FE modelling for basic material tests and will propose that the viscoplastic model may be used for nanoindentation testing. The simulations will test the Young’s modulus of materials during analysis when an Abaqus VUMAT is used. The viscoplastic model is incorporated into a subroutine and is tested at the macroscopic scale against previous published results.

Patient survival following arteriovenous fistula formation

PURPOSE: Efforts to promote arteriovenous fistulas (AVFs) have been successful in increasing the prevalence of AVF use as the primary vascular access for haemodialysis (HD). Sustained preference for AVF use may not be the most appropriate vascular access choice for all patient groups. Arteriovenous grafts (AVGs) offer advantages of earlier use and lower primary failure rates compared to AVFs so may be preferable for patients where short-term vascular access is needed. This study was designed to assess comparative mortality in different age groups following AVF formation.

METHODS: A prospective cohort of patients having AVF creation was recruited. Patients were subdivided into three age groups: Group A: lt;50 years; Group B: 50-74 years and Group C: ≥75 years. Survival curves and Cox regression analysis were performed on each of these groups.

RESULTS: One hundred and thirty-four patients (n = 134) were recruited into the study. The prevalence of diabetes increased significantly with age. As expected, mortality was higher in older age groups (log rank (Mantel-Cox) 19.227; p = 0.0001). Mortality rates at 1 year were 0% in group A, 12.5% in group B and 29.1% in group C. Medium-term mortality at 4 years was 7.9% in group A, 39.1% in group B and 54.8% in group C.

CONCLUSIONS: We found a significantly higher mortality rate in patients ≥75 years in comparison to those lt;75 years. The choice of vascular access modality should be tailored to the individual with particular reference to the patient's expected survival.