Paul M. Walsh

Surgical treatment of early stage breast cancer in elderly: an international comparison

Over 40% of breast cancer patients are diagnosed above the age of 65. Treatment of these elderly patients will probably vary over countries. The aim of this study was to make an international comparison (several European countries and the US) of surgical and radiation treatment for elderly women with early stage breast cancer. Survival comparisons were also made. Data were obtained from national or regional population-based registries in the Netherlands, Switzerland, Ireland, Belgium, Germany, and Portugal. For the US patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Early stage breast cancer patients aged ≥65 diagnosed between 1995 and 2005 were included. An international comparison was made for breast and axillary surgery, radiotherapy after breast conserving surgery (BCS), and relative or cause-specific survival. Overall, 204.885 patients were included. The proportion of patients not receiving any surgery increased with age in many countries; however, differences between countries were large. In most countries more than half of all elderly patients received breast conserving surgery (BCS), with the highest percentage in Switzerland. The proportion of elderly patients that received radiotherapy after BCS decreased with age in all countries. Moreover, in all countries the proportion of patients who do not receive axillary surgery increased with age. No large differences in survival between countries were recorded. International comparisons of surgical treatment for elderly women with early stage breast cancer are scarce. This study showed large international differences in treatment of elderly early stage breast cancer patients, with the most striking result the large proportion of elderly who did not undergo surgery at all. Despite large treatment differences, survival does not seem to be affected in a major way.

Childhood cancer in Ireland: a population-based study

Background: Population-based studies of childhood cancer incidence, survival and mortality make an important contribution to monitoring the successful implementation of new treatment guidelines and to understanding the epidemiology of these diseases. Methods: We analysed incidence and survival data for cancers diagnosed in children under 15 years of age in the Republic of Ireland during 1994–2000 (the first 7 years of National Cancer Registry coverage), and longer term mortality trends. Results: World age-standardised incidence rates in Ireland averaged 142 cases per million children per year, slightly higher than the European average and slightly lower than the US average, although differences varied by diagnostic group. Observed 5-year survival in Ireland (79% overall) was slightly higher than European and US averages, and was significantly higher for acute non-lymphocytic leukaemia (67%) and (compared with the USA) significantly lower for Hodgkin lymphoma (83%). No significant increases in incidence rates were evident from the available 7 years’ data, either overall or for particular diagnostic groups. Rates of childhood cancer mortality have declined markedly since the 1950s. Conclusions: Data presented here are in line with other developed countries and suggest major improvements in treatment and consequent survival.

Childhood cancer survival in Ireland: Temporal, regional and deprivation-related patterns

Survival after childhood cancer varies across Europe, but national or regional studies have so far shown no survival differences related to socio-economic disparity. The relationship of childhood cancer survival to disparity has not been studied in Ireland. We assessed observed survival for Irish children (ages 0-14 years) diagnosed with cancer during the period 1994-2005, overall (for all cancers included in the 3rd edition of the International Classification of Childhood Cancer) and for three main diagnostic groups - leukaemias, lymphomas, and central nervous system tumours. Comparisons were made between two diagnosis periods (1994-1999 and 2000-2005), between four regions of residence, and between five area-based deprivation categories. Regional patterns of treatment were examined to help assess the impact of centralisation of services. There was only limited evidence of improvements in survival over time. No clear evidence was found of deprivation-related influences on childhood cancer survival in Ireland, overall or for the three main diagnostic groups examined, although a weak trend was apparent for lymphoid leukaemias. Regional variation in survival was likewise not clear-cut, with the possible exception of CNS tumours (significantly higher survival amongst patients resident in the Western region). The absence of clear trends or patterns for regional or deprivation-related variation in survival may reflect a high degree of coordination and uniformity of treatment (and perhaps diagnostic) services, and application of standard treatment protocols nationally.

Treatment Strategies and Survival of Older Breast Cancer Patients – An International Comparison between the Netherlands and Ireland

Objectives Forty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland. Material and Methods From the Dutch and Irish national cancer registries, women aged ≥65 years with non-metastatic breast cancer were included (2001-2009). Proportions of patients receiving guideline-adherent locoregional treatment, endocrine therapy, and chemotherapy were calculated and compared between the countries by stage. Secondly, 5-year relative survival was calculated by stage and compared between countries. Results Overall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted p<0.001), stage I (83% vs. 65%, p<0.001), stage II (80% vs. 74%, p<0.001) and stage III (74% vs. 57%, P<0.001) disease. On the other hand, more systemic treatment was provided in Ireland, where endocrine therapy was prescribed to 92% of hormone receptor-positive patients, compared to 59% in The Netherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients. Conclusion Treatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer patients across Europe.

Socioeconomic Disparity in Survival after Breast Cancer in Ireland: Observational Study

We evaluated the relationship between breast cancer survival and deprivation using data from the Irish National Cancer Registry. Cause-specific survival was compared between five area-based socioeconomic deprivation strata using Cox regression. Patient and tumour characteristics and treatment were compared using modified Poisson regression with robust variance estimation. Based on 21356 patients diagnosed 1999–2008, age-standardized five-year survival averaged 80% in the least deprived and 75% in the most deprived stratum. Age-adjusted mortality risk was 33% higher in the most deprived group (hazard ratio 1.33, 95% CI 1.21–1.45, P<0.001). The most deprived groups were more likely to present with advanced stage, high grade or hormone receptor-negative cancer, symptomatically, or with significant comorbidity, and to be smokers or unmarried, and less likely to have breast-conserving surgery. Cox modelling suggested that the available data on patient, tumour and treatment factors could account for only about half of the survival disparity (adjusted hazard ratio 1.18, 95% CI 0.97–1.43, P = 0.093). Survival disparity did not diminish over time, compared with the period 1994–1998. Persistent survival disparities among Irish breast cancer patients suggest unequal use of or access to services and highlight the need for further research to understand and remove the behavioural or other barriers involved.

Cumulative cancer mortality risk and potential years of life lost to 64 years of age in Ireland, 1953-2002.

Premature cancer mortality trends were examined by reviewing cumulative mortality risk (‘cumulative risk’ hereafter) and potential years of life lost (PYLL) up to and including 64 years of age between 1953 and 2002 in Ireland. Trends were assessed quantitatively by Joinpoint analysis of both measures (with PYLL expressed as an age-standardized rate). The age of 64 years was used for these summary measures to reflect the focus of the Irish Governments cancer strategy on cancer in the under-65 population. Some differences emerged when ranking the significant types of cancer using cumulative risk and PYLL values. In general, however, the two methods generated similar overall trends, although PYLL rates tended to show steeper or longer-term declines, presumably reflecting the greater weight given to deaths at younger ages. Most cancers have, in recent years, shown a downward, or levelling-off of, trend for both sexes. The only exceptions were significant increases for oesophageal cancer in men (both measures), and prostate cancer (cumulative risk), cervical cancer (PYLL rate) and lymphoma in both sexes (cumulative risk). Rankings based on both cumulative risk and PYLL showed that male lung cancer is still the leading cause of premature death from cancer in Ireland, despite recent falls in mortality rates. Breast cancer has consistently been the leading cause of premature cancer death in women since the 1950s. Stomach cancer was once the second leading cause of premature cancer death in women, but since the 1960s it has been replaced by lung cancer. Ovarian cancer, having had a middle ranking for many years has, since the early 1990s, become the third leading cause of premature cancer death for women.

A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model

Background Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2) which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase. Hypotheses We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected. Methods We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il)-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed. Results One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (p<0.01) and weight gain (p = 0.08) seemed better in the ibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen. Conclusions Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes. However lung histopathology was not affected and viral shedding was increased.

Survival from twenty adult cancers in the UK and Republic of Ireland in the late twentieth century

AbstractBackground International studies have shown that cancer survival was generally low in the UK and the Republic of Ireland compared to western and northern European countries, but no systematic comparative analysis has been performed between the UK countries and the Republic of Ireland. Methods Population‐based survival for 20 adult malignancies was estimated for the UK and the Republic of Ireland. Data on adults (15–99 years) diagnosed between 1991 and 1999 in England, Scotland, Wales, Northern Ireland (1993–99) and the Republic of Ireland (1994–99) were analysed. All cases were followed up until the end of 2001. Relative survival was estimated by sex, period of diagnosis and country, and for the nine regions of England. Predicted survival was estimated using the hybrid approach. Results Overall, cancer survival in UK and Republic of Ireland improved during the 1990s, but there was geographic variation in survival across the UK and Republic of Ireland. Survival was generally highest in Ireland and Northern Ireland and lowest in England and Wales. Survival tended to be higher in Scotland for cancers for which early detection methods were in place. In England, survival tended to be lower in the north and higher in the south. Conclusions The geographic variations in survival seen across the UK and Republic of Ireland are narrower than between these countries and comparable European countries. Artefact is likely to explain some, but not all of the differences across the UK and Republic of Ireland. Geographic differences in stage at diagnosis, co‐morbidity and other clinical factors may also be relevant. List of Tables, 9

Impact and feasibility of an emergency department–based ventilator-associated pneumonia bundle for patients intubated in an academic emergency department

HighlightsVentilator‐associated pneumonia prevention is standard care in the intensive care unit, but not yet in the emergency department.Ventilator‐associated pneumonia occurs frequently in emergency department intubated patients who may remain in the emergency department for many hours.Starting ventilator‐associated pneumonia prevention in the emergency department results in decreased overall and early ventilator‐associated pneumonia for these patients.High rates of compliance with an emergency department–based ventilator‐associated pneumonia bundle can be achieved.Bundle compliance is improved with a registered nurse (RN) champion. Background: Ventilator‐associated pneumonia (VAP) has been linked to emergency department (ED) intubation and length of stay (LOS). We assessed VAP prevalence in ED intubated patients, feasibility of ED VAP prevention, and effect on VAP rates. Methods: This was a quality improvement initiative using a pre/post design. Phase 1 (PRE1) comprised patients before intensive care unit (ICU) bundle deployment. Phase 2 (PRE2) occurred after ICU but before ED deployment. Phase 3 (POST) included patients received VAP prevention starting at ED intubation. Log‐rank test for equality and Cox regression using a Breslow method for ties were performed. Bundle compliance was reported as percentages. Number needed to treat (NNT) was calculated by ventilator day. Results: PRE1, PRE2, and POST groups were composed of 195, 192, and 153 patients, respectively, with VAP rates of 22 (11.3%), 11 (5.7%), and 6 (3.9%). Log‐rank test showed significant reduction in VAP (χ2 = 9.16, P = .0103). The Cox regression hazard ratio was 1.38 for the Clinical Pulmonary Infection Score (P = .001), and the hazard ratio was 0.26 for the VAP bundle (P = .005). Bundle compliance >50% for head‐of‐bed elevation, oral care, subglottic suctioning, and titrated sedation improved significantly with introduction of a registered nurse champion. NNT varied from 7 to 11. Conclusions: VAP was common for ED intubated patients. ED‐based VAP prevention is feasible. We demonstrate significant reduction in VAP rates, which should be replicated in a multicenter study.

Uveal Melanoma in Ireland

Purpose: To report the clinical features and epidemiology of uveal melanoma in Ireland. Methods: This was an observational study of 253 patients with a new diagnosis of uveal melanoma between June 2010 and December 2015. Main outcome measures included demographics, clinical features, age-adjusted incidence, relative survival, overall survival, and distant metastases-free survival. Results: The mean patient age was 61.7 years. Tumour location was choroidal in 82%, ciliochoroidal in 9%, iridociliary in 2%, and iris in 7%. Treatment modalities included brachytherapy (ruthenium-106 and iodine-125 [64%]), enucleation (27%), and proton beam radiation (8%). The mean age-adjusted incidence of uveal melanoma in Ireland from 2010 to 2015 was 9.5 per million of the population (95% confidence interval [CI]: 8.4–10.7). Four-year relative survival was 81.3% (95% CI: 72.8–87.3). Four-year overall survival was 84% (95% CI: 78–90) and 4-year distant metastases-free survival was 79% (95% CI: 73–86). Conclusion: Based on this data, the incidence of uveal melanoma in Ireland is high when compared with other reported incidence rates in Europe and worldwide. Relative and observed survival were in keeping with other reported European survival rates.