Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups.

Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HRadj:1.62 [95% CI = 1.14-2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95% CI = 1.09-2.66]; HRadj:1.75 [95% CI = 1.08-2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95% CI = 0.78-3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95% CI = 1.62-3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95% CI = 1.95-6.87]; HRadj:1.92 [95% CI = 1.06-3.46]), but less clear in obesity (HRadj:1.40 [95% CI = 0.64-3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.

Estimating population lung cancer risk from radon using a resource efficient stratified population weighted sample survey protocol - Lessons and results from Ireland.

A 2018 estimate indicates that there were 226,057 radon-attributable lung cancer deaths in 66 countries that had representative radon surveys. This is a shocking figure, and as it comes from only 66 countries it underestimates the worldwide death toll. Any research that enables countries to conduct representative radon surveys and to understand better the risk to citizens from radon is surely welcome. We hope this paper provides a useful methodology for estimating population risk. The estimation of population weighted average indoor radon levels requires statistically valid sampling methodologies that use a representative sample of occupied homes throughout the country. A literature review indicates that in many population weighted surveys, the sampling methodology may not have been designed to do this. This paper describes a simple, resource efficient methodology which produces statistically valid and reliable estimates based on a small scale sample that is representative of the population distribution. The resource efficient design of this study enables it to be repeated at frequent intervals providing for a longitudinal analysis of the population risk from indoor radon. This survey was conducted in Ireland using 653 measurements and a representative sampling strategy to provide a baseline population weighted radon exposure for future comparisons. This study estimates the average population weighted indoor radon concentration in Ireland to be 97.83 Bq m-3 (95% Confidence Interval 90.69 Bq m-3 to 105.53 Bq m-3), and that there are an estimated 350 lung cancer cases and 255 deaths per year due to radon exposure. The mortality rate of 5.3 per 100,000 due to indoor radon, demonstrates that radon remains one of the highest preventable causes of death in Ireland.

Global Cropland Connectivity: A Risk Factor for Invasion and Saturation by Emerging Pathogens and Pests.

The geographic pattern of cropland is an important risk factor for invasion and saturation by crop-specific pathogens and arthropods. Understanding cropland networks supports smart pest sampling and mitigation strategies. We evaluate global networks of cropland connectivity for key vegetatively propagated crops (banana and plantain, cassava, potato, sweet potato, and yam) important for food security in the tropics. For each crop, potential movement between geographic location pairs was evaluated using a gravity model, with associated uncertainty quantification. The highly linked hub and bridge locations in cropland connectivity risk maps are likely priorities for surveillance and management, and for tracing intraregion movement of pathogens and pests. Important locations are identified beyond those locations that simply have high crop density. Cropland connectivity risk maps provide a new risk component for integration with other factors-such as climatic suitability, genetic resistance, and global trade routes-to inform pest risk assessment and mitigation.

Treatment of non-small-cell lung cancer after progression on nivolumab or pembrolizumab.

Background: Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated. Methods: All patients with ansclc in British Columbia initiated on nivolumab or pembrolizumab between June 2015 and November 2017, with subsequent progression, were identified. Eligibility criteria for additional st included an Eastern Cooperative Oncology Group (ecog) performance status (ps) of 3 or less and survival for more than 30 days from the last PD1 Ab treatment. Post-progression survival (pps) was assessed by landmark analysis. Baseline characteristics associated with pps were identified by multivariable analysis. Results: Of 94 patients meeting the eligibility criteria, 33 received st after progression. In 75.6%, a PD1 Ab was received as first- or second-line treatment. The most common sts were erlotinib (36.4%) and docetaxel (27.3%). No statistically significant difference in median pps was observed between patients who did and did not receive st within 30 days of their last PD1 Ab treatment (6.9 months vs. 3.6 months, log-rank p = 0.15.) In multivariable analysis, factors associated with increased pps included an ecog ps of 0 or 1 compared with 2 or 3 [hazard ratio (hr): 0.42; 95% confidence interval (ci): 0.24 to 0.73; p = 0.002] and any response compared with no response to PD1 Ab (hr: 0.54; 95% ci: 0.33 to 0.90; p = 0.02). Conclusions: In this cohort, only 35.1% of patients eligible for post-PD1 Ab therapy received st. Post-progression survival was not significantly affected by receipt of post-progression therapy. Prospective trials are needed to clarify the benefit of post-PD1 Ab treatments.

Hospital-diagnosed overweight and obesity related to cancer risk: a 40-year Danish cohort study.

BACKGROUND: Obesity is associated with metabolic abnormalities that predispose patients to increased cancer risk. Contemporary data on the long-term risk of specific cancers are sparse among patients with hospital-diagnosed overweight and obesity. OBJECTIVES: To examine the overall cancer incidence and specific site-related cancer incidences among patients with overweight and obesity, compared to the general Danish population. METHODS: For this 40-year (1977-2016), nationwide, Danish cohort study, we reviewed medical databases to identify individuals with hospital-based overweight and obesity diagnoses. We computed age- and gender-standardized incidence ratios (SIRs) for subsequent cancer compared to the general population. RESULTS: We observed 20 706 cancers among 313 321 patients diagnosed with overweight and obesity (median age 43 years; median follow-up 6.7 years, range 1-40 years) compared to the 18 480 cancers expected; thus, the SIR was 1.12 [95% confidence interval (95% CI): 1.11-1.14]. The SIR associated with overweight and obesity was increased with concomitant comorbidities, like type 2 diabetes (SIR: 1.18; 95% CI: 1.13-1.23) and alcoholism-related diseases (SIR: 1.62; 95% CI: 1.45-1.82). The SIR was 1.31 (95% CI: 1.28-1.34) for cancers previously identified as obesity-related, including pancreatic (SIR: 1.38; 95% CI; 1.27-1.49) and postmenopausal breast cancer (SIR: 1.14; 95% CI: 1.09-1.19). Obesity/overweight status also elevated the SIRs for haematological (SIR: 1.24; 95% CI: 1.18-1.29) and neurological cancers (SIR: 1.19; 95% CI: 1.11-1.27]. In contrast, SIRs were 1.01 (95% CI: 0.97-1.05) for immune-related cancers, 0.88 (95% CI: 0.82-0.95) for malignant melanoma, and 0.88 (95% CI: 0.85-0.92) for hormone-related cancers, other than postmenopausal breast cancer. CONCLUSION: In this large cohort study, overweight and obesity was associated with increased risk of several common cancers.

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence.

Herpes zoster as a marker of occult cancer: A systematic review and meta-analysis.

OBJECTIVES: Researchers have advocated for an increased awareness of occult cancer among herpes zoster patients, but there are no systematic reviews to support these claims. We therefore conducted a systematic review and meta-analysis of evidence on zoster and risk of occult cancer. METHODS: Through February 18, 2016, we searched PubMed, EMBASE and references of relevant papers for studies on zoster and risk of any cancer. One author screened retrieved papers by title and abstract; included papers were reviewed by two authors for eligibility, data extraction, and potential biases. Despite statistical heterogeneity, associations were consistently in the same direction and we therefore computed pooled relative risks using random-effects models. RESULTS: We identified 46 eligible studies, 10 of which considered all cancer types combined. The pooled relative risk for any cancer was 1.42 (95% confidence interval: 1.18, 1.71) overall and 1.83 (95% confidence interval: 1.17, 2.87) at one year after zoster. Considering cancer subtypes, the highest estimates were generally reported for occult hematological cancer. The absolute risk of any cancer at one year after presentation with zoster was 0.7-1.8%. CONCLUSION: This study supports an association between zoster and occult cancer, but the low absolute risk of cancer limits the clinical implications.

Update of Ireland's national average indoor radon concentration - Application of a new survey protocol.

In 2002, a National Radon Survey (NRS) in Ireland established that the geographically weighted national average indoor radon concentration was 89 Bq m-3. Since then a number of developments have taken place which are likely to have impacted on the national average radon level. Key among these was the introduction of amending Building Regulations in 1998 requiring radon preventive measures in new buildings in High Radon Areas (HRAs). In 2014, the Irish Government adopted the National Radon Control Strategy (NRCS) for Ireland. A knowledge gap identified in the NRCS was to update the national average for Ireland given the developments since 2002. The updated national average would also be used as a baseline metric to assess the effectiveness of the NRCS over time. A new national survey protocol was required that would measure radon in a sample of homes representative of radon risk and geographical location. The design of the survey protocol took into account that it is not feasible to repeat the 11,319 measurements carried out for the 2002 NRS due to time and resource constraints. However, the existence of that comprehensive survey allowed for a new protocol to be developed, involving measurements carried out in unbiased randomly selected volunteer homes. This paper sets out the development and application of that survey protocol. The results of the 2015 survey showed that the current national average indoor radon concentration for homes in Ireland is 77 Bq m-3, a decrease from the 89 Bq m-3 reported in the 2002 NRS. Analysis of the results by build date demonstrate that the introduction of the amending Building Regulations in 1998 have led to a reduction in the average indoor radon level in Ireland.

The rate of radon remediation in Ireland 2011-2015: Establishing a base line rate for Ireland's National Radon Control Strategy.

Radon is the greatest source of radiation exposure to the public. In Ireland, it is estimated that approximately 7% of the national housing stock have radon concentrations above the Reference Level of 200 Bq m-3. A radon test can be carried out to identify homes with radon levels above the Reference Level. However there is no health benefit associated with radon testing unless it leads to remediation. Surveys to establish the rate of remediation in Ireland, that is the proportion of householders who having found levels of radon above the Reference Level proceed to carry out remediation work have been carried out in 2011 and 2013. Reasons for not carrying out remediation work were also investigated. In 2015 the survey was repeated to establish the current rate of remediation and reasons for not remediating. This report presents the results of that survey. It also compiles the data from all three surveys to identify any trends over time. The rate of remediation is an important parameter in estimating the effectiveness of programmes aimed at reducing radon levels. Currently the rate of remediation is 22% and the main reasons householders gave for not remediating were not certain there is a serious risk and concern about the cost of the work. In Ireland, this figure of 22% will be now used as a baseline metric against which the effectiveness of its National Radon Control Strategy will be measured over time.

Body mass index, risk of allogeneic red blood cell transfusion, and mortality in elderly patients undergoing hip fracture surgery.

UNLABELLED: Despite improvements in preoperative and postoperative treatment, hip fracture surgery may lead to blood transfusion. Little is known about the impact of body mass index on transfusion risk and subsequent mortality. Opposite overweight and obese patients, underweight patients had increased risk of transfusion and death within 1 year of surgery. INTRODUCTION: Despite improvements in preoperative and postoperative treatment of hip fracture patients, hip fracture surgery may lead to blood loss. We examined the risk of red blood cell transfusion (as an indirect measure of blood loss) and subsequent mortality by body mass index level in patients aged 65 and over undergoing hip fracture surgery. METHODS: This is a population-based cohort study using medical databases. We included all patients who underwent surgery for hip fracture during 2005-2013. We calculated the cumulative risk of red blood cell transfusion within 7 days of surgery treating death as a competing risk and, among transfused patients, short- (8-30 days postsurgery) and long-term mortality (31-365 days postsurgery). RESULTS: Among 56,420 patients, 47.7 % received at least one red blood cell transfusion within 7 days of surgery. In patients with normal weight, the risk was 48.8 % compared with 57.0 % in underweight patients (adjusted RR = 1.11; CI 1.08-1.15), 42.1 % in overweight patients (adjusted RR = 0.89; CI 0.86-0.91), and 42.2 % in obese patients (adjusted RR = 0.87; CI 0.84-0.91). Among transfused patients, adjusted HRs for short-term mortality were 1.52 (CI 1.34-1.71), 0.70 (CI 0.61-0.80), and 0.58 (CI 0.43-0.77) for underweight, overweight, and obese patients, respectively, compared with normal-weight patients. The corresponding adjusted HRs for long-term mortality were 1.45 (CI 1.33-1.57), 0.80 (CI 0.74-0.86), and 0.58 (CI 0.50-0.69). Similar association between BMI and mortality was observed also among non-transfused patients. CONCLUSIONS: Underweight patients had a higher risk of red blood cell transfusion and death in the first year of surgery than normal-weight patients, even when controlling for age and comorbidity. Opposite findings were seen for overweight and obese patients.

Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study.

BACKGROUND: Treatment with synthetic glucocorticoids (GCs) depresses the immune response and may therefore modify cancer outcomes. We investigated the association between GC use and breast cancer recurrence. MATERIALS AND METHODS: We conducted a population-based cohort study to examine the risk of breast cancer recurrence associated with GC use among incident stage I-III female breast cancer patients aged >18 years diagnosed 1996-2003 in Denmark. Data on patients, clinical and treatment factors, recurrence, and comorbidities as well as data on GC prescriptions and potential confounders were obtained from Danish population-based medical registries. GCs were categorized according to administrative route: systemic, inhaled, or intestinal. Women were followed for up to 10 years or until 31 December 2008. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) to evaluate the association between GC use and recurrence. Time-varying drug exposures were lagged by 1 year. RESULTS: We included 18 251 breast cancer patients. Median recurrence follow-up was 6.9 years; 3408 women developed recurrence during follow-up. Four thousand six hundred two women filled at least one GC prescription after diagnosis. In unadjusted models, no association was observed among users of systemic, inhaled, and intestinal GCs (HRsystemic = 1.1, 95% CI 0.9-1.3; HRinhaled = 0.9, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.9-1.2) versus nonusers. In adjusted models, the results were also near null (HRsystemic = 1.1, 95% CI 0.9-1.2; HRinhaled = 0.8, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.8-1.2). CONCLUSION: We found no evidence of an effect of GC use on breast cancer recurrence.

National radon programmes and policies: the RADPAR recommendations.

Results from epidemiological studies on lung cancer and radon exposure in dwellings and mines led to a significant revision of recommendations and regulations of international organisations, such as WHO, IAEA, Nordic Countries, European Commission. Within the European project RADPAR, scientists from 18 institutions of 14 European countries worked together for 3 y (2009-12). Among other reports, a comprehensive booklet of recommendations was produced with the aim that they should be useful both for countries with a well-developed radon programme and for countries with little experience on radon issues. In this paper, the main RADPAR recommendations on radon programmes and policies are described and discussed. These recommendations should be very useful in preparing a national action plan, required by the recent Council Directive 2013/59/Euratom.

Use of health economics in the development of a national radon control strategy in Ireland.

A health economics evaluation of different radon intervention strategies was undertaken including the incorporation of prevention into new buildings, the incorporation of potential remedial measures into new buildings and remediation of existing buildings. The analysis shows that (1) the incorporation of prevention into new houses at the time of construction is generally more cost effective than remediation of existing houses and (2) that the cost effectiveness of programmes aimed at encouraging householders to test and remediate their houses may be poor if they are not undertaken within the context of coherent radon reduction strategy. The results of this evaluation were used to identify the most cost-effective radon interventions in an Irish context in support of the development of a National Radon Control Strategy.

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29.

INTRODUCTION: This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer. METHODS: Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70. RESULTS: The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia. CONCLUSIONS: The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.