Digoxin use after diagnosis of breast cancer and survival: a population-based cohort study

Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. These findings, particularly recent observations of increased breast cancer risk, raise questions about the safety of digoxin use in breast cancer patients. Therefore, we investigated whether digoxin use after breast cancer diagnosis increased the risk of breast cancer-specific mortality in breast cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify breast cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and breast cancer-specific and all-cause mortality. In 17,842 breast cancer patients, there were 2219 breast cancer-specific deaths. Digoxin users appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39–2.15) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.91; 95 % CI 0.72–1.14). In this large population-based breast cancer cohort study, there was little evidence of an increase in breast cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in breast cancer patients.

Epidermal Growth Factor Removal or Tyrphostin AG1478 Treatment Reduces Goblet Cells & Mucus Secretion of Epithelial Cells from Asthmatic Children Using the Air-Liquid Interface Model

RATIONALE: Epithelial remodelling in asthma is characterised by goblet cell hyperplasia and mucus hypersecretion for which no therapies exist. Differentiated bronchial air-liquid interface cultures from asthmatic children display high goblet cell numbers. Epidermal growth factor and its receptor have been implicated in goblet cell hyperplasia.

OBJECTIVES: We hypothesised that EGF removal or tyrphostin AG1478 treatment of differentiating air-liquid interface cultures from asthmatic children would result in a reduction of epithelial goblet cells and mucus secretion.

METHODS: In Aim 1 primary bronchial epithelial cells from non-asthmatic (n = 5) and asthmatic (n = 5) children were differentiated under EGF-positive (10ng/ml EGF) and EGF-negative culture conditions for 28 days. In Aim 2, cultures from a further group of asthmatic children (n = 5) were grown under tyrphostin AG1478, a tyrosine kinase inhibitor, conditions. All cultures were analysed for epithelial resistance, markers of differentiation using immunocytochemistry, ELISA for MUC5AC mucin secretion and qPCR for MUC5AC mRNA.

RESULTS: In cultures from asthmatic children the goblet cell number was reduced in the EGF negative group (p = 0.01). Tyrphostin AG1478 treatment of cultures from asthmatic children had significant reductions in goblet cells at 0.2μg/ml (p = 0.03) and 2μg/ml (p = 0.003) as well as mucus secretion at 2μg/ml (p = 0.04).

CONCLUSIONS: We have shown in this preliminary study that through EGF removal and tyrphostin AG1478 treatment the goblet cell number and mucus hypersecretion in differentiating air-liquid interface cultures from asthmatic children is significantly reduced. This further highlights the epidermal growth factor receptor as a potential therapeutic target to inhibit goblet cell hyperplasia and mucus hypersecretion in asthma.

Colorectal cancer risk following adenoma removal: a large prospective population-based cohort study

Background: Randomised controlled trials have demonstrated significant reductions in colorectal cancer (CRC) incidence and mortality associated with polypectomy. However, little is known about whether polypectomy is effective at reducing CRC risk in routine clinical practice. The aim of this investigation was to quantify CRC risk following polypectomy in a large prospective population-based cohort study.

Methods: Patients with incident colorectal polyps between 2000 and 2005 in Northern Ireland (NI) were identified via electronic pathology reports received to the NI Cancer Registry (NICR). Patients were matched to the NICR to detect CRC and deaths up to 31st December 2010. CRC standardised incidence ratios (SIRs) were calculated and Cox proportional hazards modelling applied to determine CRC risk.

Results: During 44,724 person-years of follow-up, 193 CRC cases were diagnosed amongst 6,972 adenoma patients, representing an annual progression rate of 0.43%. CRC risk was significantly elevated in patients who had an adenoma removed (SIR 2.85; 95% CI: 2.61 to 3.25) compared with the general population. Male sex, older age, rectal site and villous architecture were associated with an increased CRC risk in adenoma patients. Further analysis suggested that not having a full colonoscopy performed at, or following, incident polypectomy contributed to the excess CRC risk.

Conclusions: CRC risk was elevated in individuals following polypectomy for adenoma, outside of screening programmes.

Impact: This finding emphasises the need for full colonoscopy and adenoma clearance, and appropriate surveillance, after endoscopic diagnosis of adenoma.

The validity of critical thinking tests for predicting degree performance: A longitudinal study

This study explored the validity of using critical thinking tests to predict final psychology degree marks over and above that already predicted by traditional admission exams (A-levels). Participants were a longitudinal sample of 109 psychology students from a university in the United Kingdom. The outcome measures were: total degree marks; and end of year marks. The predictor measures were: university admission exam results (A-levels); critical thinking test scores (skills & dispositions); and non-verbal intelligence scores. Hierarchical regressions showed A-levels significantly predicted 10% of the final degree score and the 11-item measure of ‘Inference skills’ from the California Critical Thinking Skills Test significantly predicted an additional 6% of degree outcome variance. The findings from this study should inform decisions about the precise measurement constructs included in aptitude tests used in the higher education admission process.

Measuring critical thinking skills and dispositions in undergraduate students

This thesis investigates critical thinking with a particular focus on measurement in undergraduate students. A higher education context was chosen because many regard critical thinking development as a primary goal for third level education. Nine studies, both cross-sectional and longitudinal in design, were conducted with undergraduate psychology students (N=387), using the California Critical Thinking Disposition Inventory (CCTDI) and the California Critical Thinking Skills Test (CCTST). Studies 1-3 revealed psychometric weaknesses in the CCTDI and revised the scale with factor analysis and reliability analysis to form the CCTDI United Kingdom revision (CCTDI-UK). Study 4 investigated convergent validity and showed significant inter-correlation between the sub-scales of the CCTDI-UK, and significant correlations with the Openness scale of the NEO Personality Inventory (NEO PI-R). The study also provided evidence for improvement in scores on three of the six sub-scales in the CCTDI-UK (Truth-Seeking, Inquisitiveness, Open-Mindedness) during the course of an undergraduate degree. Study 5 explored a two factor structure for critical thinking dispositions. Study 6 used reliability analysis to revise the CCTST to produce the CCTST-UK. Study 7 showed that the CCTST-UK had a moderate correlation with degree attainment and a slightly higher correlation with a test of non-verbal intelligence (Raven’s Advanced Progressive Matrices short form); in addition, the study showed that scores on the CCTST-UK improved during the course of the degree. Studies 8 and 9 investigated the potential of critical thinking for predicting degree attainment. A-levels predicted approximately 10% of the variance of degree attainment while entry level scores on the CCTST-UK predicted an additional 5%. Exit level scores on the CCTST-UK and the Inquisitive sub-scale of the CCTDI-UK were found to be predictors of degree attainment The main conclusions of the thesis were that these tests had significant potential for predicting degree attainment and that they measured a substantial proportion of the theoretical constructs identified by the major authors in critical thinking.