Evolution of the consumption trend of proton pump inhibitors in the Lleida Health Region between 2002 and 2015.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most commonly prescribed pharmacological groups. Their high prevalence and duration of use are of important health concern due to the risk they can cause to patients. Despite these risks, their use remains particularly high, especially in the elderly population. We determined the trend in the prevalence of PPI consumption in the population of the Lleida Health Region between 2002 and 2015 to explore patterns of use and associated characteristics. METHODS: An analysis of secular trends between 2002 and 2015 was performed. The database included all individuals who used PPIs in the Lleida Health Region, which had 358.070 inhabitants in 2015. PPI use was evaluated using prescription dispensing data from the public health system. All types of PPIs approved by the pharmaceutical agency were included. Trends were investigated by age and sex. RESULTS: For the whole study period, a total of 215,417 individuals accounted for 292,122 dispensations. Overall, 48% were women, and the mean age was 62 years. The dispensing prevalence of PPI use in 2015 was 18.0% overall-20.4% for women and 15.7% for men-and was 54.6% for those over 65 years. In terms of the subtypes of PPIs, 16.8% of prescriptions were for omeprazole, 0.66% were for pantoprazole, and 0.48% were for lansoprazole. The evolution of the annual PPIs dispensation prevalence showed a progressive increase from 11.3% in 2002 to 18.0% in 2015, which was attributable to an increase in the use of omeprazole (9.0% vs. 16.8%) and, to a lesser extent, esomeprazole (0.02% vs. 0.4%). CONCLUSION: An increase in the prevalence of PPI dispensation was observed over 14 years of follow-up. The prevalence of dispensation was especially high for the population older than 65 years, despite the risk of cognitive decline and falls. Comprehensive actions are required to to increase rational prescribing of PPIs, especially in high-risk populations.

Towards an ecological modelling approach for assessing ionizing radiation impact on wildlife populations.

The emphasis of the international system of radiological protection of the environment is to protect populations of flora and fauna. Throughout the MODARIA programmes, the United Nations' International Atomic Energy Agency (IAEA) has facilitated knowledge sharing, data gathering and model development on the effect of radiation on wildlife. We present a summary of the achievements of MODARIA I and II on wildlife dose effect modelling, extending to a new sensitivity analysis and model development to incorporate other stressors. We reviewed evidence on historical doses and transgenerational effects on wildlife from radioactively contaminated areas. We also evaluated chemical population modelling approaches, discussing similarities and differences between chemical and radiological impact assessment in wildlife. We developed population modelling methodologies by sourcing life history and radiosensitivity data and evaluating the available models, leading to the formulation of an ecosystem-based mathematical approach. This resulted in an ecologically relevant conceptual population model, which we used to produce advice on the evaluation of risk criteria used in the radiological protection of the environment and a proposed modelling extension for chemicals. This work seeks to inform stakeholder dialogue on factors influencing wildlife population responses to radiation, including discussions on the ecological relevance of current environmental protection criteria. The area of assessment of radiation effects in wildlife is still developing with underlying data and models continuing to be improved. IAEA's ongoing support to facilitate the sharing of new knowledge, models and approaches to Member States is highlighted, and we give suggestions for future developments in this regard.

Ensuring robust radiological risk assessment for wildlife: insights from the International Atomic Energy Agency EMRAS and MODARIA programmes.

In response to changing international recommendations and national requirements, a number of assessment approaches, and associated tools and models, have been developed over the last circa 20 years to assess radiological risk to wildlife. In this paper, we summarise international intercomparison exercises and scenario applications of available radiological assessment models for wildlife to aid future model users and those such as regulators who interpret assessments. Through our studies, we have assessed the fitness for purpose of various models and tools, identified the major sources of uncertainty and made recommendations on how the models and tools can best be applied to suit the purposes of an assessment. We conclude that the commonly used tiered or graded assessment tools are generally fit for purpose for conducting screening-level assessments of radiological impacts to wildlife. Radiological protection of the environment (or wildlife) is still a relatively new development within the overall system of radiation protection and environmental assessment approaches are continuing to develop. Given that some new/developing approaches differ considerably from the more established models/tools and there is an increasing international interest in developing approaches that support the effective regulation of multiple stressors (including radiation), we recommend the continuation of coordinated international programmes for model development, intercomparison and scenario testing.

Trends in the consumption rates of benzodiazepines and benzodiazepine-related drugs in the health region of Lleida from 2002 to 2015.

BACKGROUND: The high prevalence and long-term use of benzodiazepines (BZDs) treatment are debated topics because of the risk they can cause to the patients. Despite the current information on the risk-benefit balance of these drugs, their consumption remains particularly high. We determined the trend in the consumption prevalence of benzodiazepines (BZDs) and drugs related to BZDs (Z-drugs) in the population of the Health Region of Lleida to explore patterns of use and the associated characteristics associated between 2002 and 2015. METHODS: An analysis of secular trends was carried out between 2002 and 2015; the databased included all individuals from the Health Region of Lleida, which had 358,157 inhabitants in 2015, that consumed BZDs. The consumption of BZDs was evaluated using prescription billing data from the Public Health System. All types of BZDs and BZD analogues that had been approved by the drug agency were included. Trends by age and sex were investigated. RESULTS: Over the whole study period, a total of 161,125 individuals accounted for 338,148 dispensations. Overall, 59% were women, and the mean age was 56 years. The dispensing prevalence of BZDs use in 2015 was 14.2% overall -18.8% in women and 9.6% in men-and was 36% in those over 65 years. According to the half-life of BZDs, the prevalence of short-intermediate BZD use, intermediate-long BZD use, and Z-drugs use was 9.7, 5.5 and 0.8%, respectively. The evolution of the annual prevalence of BZD dispensing showed a progressive decline, from 15.3% in 2002 to 14.2% in 2015, which was attributed to a decrease in the consumption of intermediate-long half-life BZDs (8.0% vs. 5.5%) and Z-drugs (1.4% vs. 0.8%). CONCLUSION: The dispensing prevalence of BZDs and Z-drugs was high, although a small reduction was observed during this time period. The dispensing prevalence was especially high in the population over 65, despite the risk of cognitive decline and falls. Integral actions are required to lower the BZD prescription rate.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

Diagnosis of inherited von Willebrand disease: comparison of two methodologies and analysis of the discrepancies.

Diagnostics of von Willebrand disease (VWD) includes assessment of factor VIII (FVIII) coagulant activity, von Willebrand factor (VWF) antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo), and more specific tests as multimeric and genetic analyses are necessary for the correct VWD classification. The ACL AcuStar analyzer introduces chemiluminescence (CL) technology in detection of VWD with automated VWF:Ag and VWF:RCo assays. Compare VWF:Ag-ELISA and VWF:RCo by aggregometry conventional assays with new CL VWF:Ag-IL and VWF:RCo-IL assays, investigate the ability to make accurate VWD diagnosis and concordance with multimeric and genetic analyses. 146 patients with congenital VWD (51 Type 1; 34 Type 2A; 16 Type 2B; 31 Type 2M; 5 Type 2N; 9 Type 3) and 30 healthy normal subjects were included. A comparison was made between CL and conventional methods. Diagnostic evaluation included: VWF:RCo/VWF:Ag ratio, multimeric distribution (sodium dodecyl sulfate [SDS]-agarose gel) of VWF and genetic analysis in 110 of 146 patients. CL and conventional methods revealed good correlation. Kappa test agreement diagnosis was >0.8. CL diagnostic sensitivity was 100% and specificity 97%. Multimeric and genetic analysis were of help in clarifying 13 discrepancies of diagnosis between methods, of which six discrepancies were explained by lack of conventional methods' sensibility. CL methodology can detect VWD and discriminate between type 1, 3 and variant forms and offers an automated, faster, sensitive and less cumbersome method when compared to conventional assays, in particular VWF:RCo by aggregometry. In some cases, even with all phenotype and genetic analyses, discrepancies exist in the classification of VWD.

Assessment of radiation dose to people and wildife inhabiting the Grote Nete catchment in Belgium.

We evaluate the impact of the radiological contamination of the Grote Nete catchment in Belgium to people and non-human biota. This region has received effluents from the phosphate and nuclear industries via tributaries of the Grote Nete river in past decades, resulting in the presence of radionuclides such as 241Am, 60Co, 137Cs, 40K, 210Pb, 238Pu, 239,240Pu, 226Ra, 228Ra, 228Th, 232Th, 234U, 235U and 238U. During the period 2016-2021, we measured these radionuclides in the water column, the bed sediment and riverbanks. Additionally, we carried out radon measurements on the riverbanks in 2022. Based on these measurements, the dose rates to people were calculated for different potential exposure scenarios, using the SCK CEN biosphere tool. We also performed an assessment of exposure of ionising radiation to non-human biota (including 222Rn and its daughters) using the ERICA Tool. We observed three types of areas at the Grote Nete riverbank: (a) a lower category exposure with 226Ra concentrations reflecting purely Belgian background values; (b) a middle category with enhanced 226Ra, mainly adsorbed on clay minerals and (c) an upper category extending to maximum values in the order of 103 Bq kg-1. The main component of the dose rate for terrestrial and aquatic organisms is 226Ra followed by 210Pb (terrestrial) or 228Ra, (aquatic). The anthropogenic vector of the contamination (40K, 60Co, 90Sr, 137Cs, 228Th, 232Th, 234,235,238U, 238,239Pu, 241Am) makes a negligible contribution to dose. Overall, the Grote Nete wildlife is not under significant risk from exposure to soil or water-borne radionuclides and radon emanating from the soil, even if the ERICA benchmark of 10 µGy h-1 is occasionally exceeded for 226Ra, 210Pb or 228Ra, because exposures are below the levels at which effects are known to occur. For people, radon inhalation is the main exposure pathway and exposures can reach 1 mSv y-1 for hypothetical residents living at the riverbanks and remaining most of their time in the area, but it can be expected that exposures are much lower at increasing distances from the river. It is concluded that neither people nor the environment are at any significant radiological risk from this situation.

Impact of medical radionuclide discharges on people and the environment.

We present a novel methodology to dynamically calculate dose rates to people and wildlife from hospital-released radionuclides reaching the environment through water treatment plants (WTPs), using the biokinetic model D-DAT for aquatic wildlife, applied to 18F, 123I, 131I, 153Sm, 99mTc and 201Tl. We have also developed a method to calculate doses to WTP workers and to farmers from agricultural practices. This proof-of-concept study simulates a generic source term of radionuclide levels in the Belgian Molse Nete River during the year 2018, chosen because the river flow was very low during that year, which constitutes a very conservative, bounding case. The dose rates to wildlife calculated for this hypothetical scenario under conservative assumptions, are well below the ERICA predicted no effects dose rate to wildlife of 10 µGy h-1. Human exposures are also very low, in most cases not exceeding 10 µSv y-1. This work identifies important data gaps and areas of uncertainty in the assessment of radiopharmaceutical effluents. The study, which is part of the EC project SINFONIA, paves the way for a dynamic screening assessment methodology able to perform consistently assessments of the impact of radiopharmaceuticals on people and wildlife. This is particularly relevant since discharges of radiopharmaceuticals in rivers are on the increase and it is necessary to explicitly demonstrate that people and the environment are adequately protected.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Impact assessment of ionizing radiation on human and non-human biota from the vicinity of a near-surface radioactive waste repository.

This work describes the radiological assessment of the near-surface Maisiagala radioactive waste repository (Lithuania) over the period 2005-2012, with focus on water pathways and special emphasis on tritium. The study includes an assessment of the effect of post-closure upgrading, the durability of which is greater than 30 years. Both human and terrestrial non-human biota are considered, with local low-intensity forestry and small farms being the area of concern. The radiological exposure was evaluated using the RESRAD-OFFSITE, RESRAD-BIOTA and ERICA codes in combination with long-term data from a dedicated environmental monitoring programme. All measurements were performed at the Lithuanian Institute of Physics as part of this project. It is determined that, after repository upgrading, radiological exposure to humans are significantly lower than the human dose constraint of 0.2 mSv/year valid in the Republic of Lithuania. Likewise, for non-human biota, dose rates are below the ERICA/PROTECT screening levels. The potential annual effective inhalation dose that could be incurred by the highest-exposed human individual (which is due to tritiated water vapour airborne release over the most exposed area) does not exceed 0.1 µSv. Tritium-labelled drinking water appears to be the main pathway for human impact, representing about 83 % of the exposure. Annual committed effective dose (CED) values for members of the public consuming birch sap as medical practice are calculated to be several orders of magnitude below the CEDs for the same location associated with drinking of well water. The data presented here indicate that upper soil-layer samples may not provide a good indication of potential exposure to terrestrial deep-rooted trees, as demonstrated by an investigation of stratified (3)H in soil moisture, expressed on a wet soil mass basis, in an area with subsurface contamination.

Estimating the biological half-life for radionuclides in homoeothermic vertebrates: a simplified allometric approach.

The application of allometric, or mass-dependent, relationships within radioecology has increased with the evolution of models to predict the exposure of organisms other than man. Allometry presents a method of addressing the lack of empirical data on radionuclide transfer and metabolism for the many radionuclide-species combinations which may need to be considered. However, sufficient data across a range of species with different masses are required to establish allometric relationships and this is not always available. Here, an alternative allometric approach to predict the biological half-life of radionuclides in homoeothermic vertebrates which does not require such data is derived. Biological half-life values are predicted for four radionuclides and compared to available data for a range of species. All predictions were within a factor of five of the observed values when the model was parameterised appropriate to the feeding strategy of each species. This is an encouraging level of agreement given that the allometric models are intended to provide broad approximations rather than exact values. However, reasons why some radionuclides deviate from what would be anticipated from Kleiber's law need to be determined to allow a more complete exploitation of the potential of allometric extrapolation within radioecological models.

Comparison of methods for the radiological impact assessment of aquatic releases to the waters in the low countries.

Accurate assessment of the radiological impact of liquid discharges on the marine environment is challenging despite all developments in recent years. The lack of consensus on this type of assessment manifests itself even stronger when transborder issues are expected, such as in the Low Countries. Belgium and the Netherlands operate nuclear power plants with discharges in the shared estuary of the Western Scheldt, therefore if there are safety concerns, information on both sides of the border must be coherent. This work provides a comparison of two computational methods used for assessment of aquatic releases in the Western Scheldt estuary and the adjacent North Sea.The work demonstrates a fair degree of consistency in modelling the uptake and fate of key anthropogenic radionuclides. Nevertheless, there are also considerable differences found in sediment and sea species with concentrations ranging by over two orders of magnitude in some cases. These explainable differences are methodological in nature, occurring in codes that underwent extensive validation during development. Therefore, the outcomes of this work clearly demonstrate the need to produce explicit guidance that is specifically tailored to the (inter)national water system of concern. This should not be limited to releases from nuclear power plants, but also include other nuclear applications. For all these reasons, more intensive collaboration and model harmonisation across borders is essential, signalling the direction for future investigations.

Dual-age-class population model to assess radiation dose effects on non-human biota populations.

In the present paper, a two-age-class group, logistic growth model for generic populations of non-human biota is described in order to assess non-stochastic effects of low linear energy-transfer radiation using three endpoints: repairable radiation damage, impairment of reproductive ability and, at higher radiation dose rates, mortality. This model represents mathematically the exchange between two life stages considering fecundity, growth and mortality. Radiation effects are modeled with a built-in self-recovery pool whereupon individuals can repair themselves. In acute effects mode, the repairing pool becomes depleted due to radiation and the model tends to lethality mode. A base calibration of the model's two free parameters is possible assuming that in acute mode 50% of the individuals die on 30 days when a radiation dose equal to the LD(50/30) is applied during that period. The model, which requires 10 species-dependent life-history parameters, was applied to fish and mammals. Its use in the derivation of dose-rate screening values for the protection of non-human biota from the effects of ionizing radiation is demonstrated through several applications. First, results of model testing with radiation effects data for fish populations from the EPIC project show the predictive capability of the model in a practical case. Secondly, the model was further verified with FREDERICA radiation effects data for mice and voles. Then, consolidated predictions for mouse, rabbit, dog and deer were generated for use in a population model comparison made within the IAEA EMRAS II project. Taken together, model predictions suggest that radiation effects are more harmful for larger organisms that generate lower numbers of offspring. For small mammal and fish populations, dose rates that are below 0.02 Gy day(-1) are not fatal; in contrast, for large mammals, chronic exposure at this level is predicted to be harmful. At low exposure rates similar to the ERICA screening dose rate of 2.4 × 10(-4) Gy day(-1), long-term effects on the survivability of populations are negligible, supporting the appropriateness of this value for radiological assessments to wildlife.

[Implementation of simplified diagnostic method Apnealink™Air® to diagnose sleep apnea by general practioners of primary care]. / Implementación del método simplificado Apnealink™Air® por médicos de atención primaria para el diagnóstico del síndrome de apnea-hipopnea durante el sueño.

OBJECTIVES: To assess diagnosis and therapeutic decisions-making by General Practitioners (GP) using ApnealinkTM® (AL) in patients with high suspicion of obstructive sleep apnea (OSA), in comparison with conclusions of Hospital Sleep Unit (HSU) specialists based on home respiratory polygraphy (PGR) results. METHODS: This study involved patients previously selected by HSU for sleep testing by PGR. After it, patients were offered to complete AL test. PGR was checked at HSU; AL was checked by hemoglobin desaturation index of 4% (4% ODI), (4% AL) and 3% (3% ODI) patients with positive test to proceed with CPAP; and those with negative test for further testing. Automatically adjusted 4% AL, was considered valid as it was demonstrated to be equivalent to manual AL. Results were compared by automatically adjusted 3%AL against PGR results. RESULTS: 48 patients were collected. 43 had AL valid test, 45 had PGR valid study, and 41 had both valid test. 27 patients (62,8%) had positive 4% AL (OR 5,51, p < 0,05), that showed AHI ≥ 15/h at 3% AL test; and 19 patients (42,2%) had a positive PGR test. 31 (72%) patients had a positive 3% AL. AL had shown to be a good screening method of SAHS. CONCLUSIONS: There is equivalence between the decisions of GP and HSU. AL is a good diagnostic tool and screening method for OSA in primary care when it is used in patients with high suspicion of moderate-severe OSA.

Prophylaxis therapy in haemophilia A: current situation in Spain.

The Spanish Epidemiological Study in Haemophilia carried out in 2006 enrolled 2400 patients [2081-86.7% with haemophilia A (HA) and 319-13.3% with haemophilia B]; 465 of them (19.4%) were on prophylaxis. These rates were higher in patients with severe haemophilia (45.4%) and severe paediatric cases (72.5%). On the basis of information recorded in this study, we analysed the current situation of prophylaxis therapy administered to patients with HA in Spain, as well as their orthopaedic status. Prophylaxis was used in 399 (19.2%) patients with HA; such prophylaxis was primary (PP) in 20.3% and secondary (SP) in 75.9% of cases. Among severe HA patients, 313 (45.9%) were on prophylaxis (22.3% on PP and 74.7% on SP). Taking into account the patients' age, 34.7% of severe HA adults were on prophylaxis (6% PP and 92.1% SP), whereas 71.5% of severe HA paediatric patients (40.5% PP and 55.4% SP) received this kind of treatment. Established haemophilic arthropathy (EHA) was detected in 142 from 313 severe HA patients (45.3%) on prophylaxis, but only in 2.9% of patients under PP vs. 59% of patients receiving SP. There was no EHA in adult severe HA patient on PP, whereas 70.4% on SP had joint damage (P < 0.00001). Among paediatric severe HA patients, EHA was detected in 3.3% under PP and 37.8% under SP (P < 0.00001). In conclusion, our data suggest that an early initiation of prophylaxis avoids EHA in the long-term in patients with severe HA. We should emphasize the early onset of prophylaxis regimens.

Immunohistochemical analysis of tumour regression grade for rectal cancer after neoadjuvant chemoradiotherapy.

AIM: Tumour regression grade (TRG) as defined by Rödel et al. has been used as an independent prognostic factor for rectal carcinoma after preoperative treatment by chemoradiotherapy (CRT). Determination of TRG 2 and 3, semiquantitatively defined as more or less than 50% tumour regression, respectively, does not appear to correlate with prognosis. The purpose of this study was to find an immunohistochemical pattern to permit improved stratification of intermediate responders defined by disease free (DFS) and overall survival (OS). METHOD: Immunohistochemistry of EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), CD133 antibody, p53 antibody and Ki67 antibody was evaluated using tissue microarrays (TMA) on post-treatment surgical specimens from 88 patients. CD133 expression was confirmed in the whole section when available. RESULTS: At a median follow-up of 40 months, TRG was found to be an independent predictor of DFS (P = 0.05) and OS (P = 0.001) but no differences were found between TRG 2 and 3 in terms of DFS (P = 0.74) or OS (P = 0.41). The results of TMA showed an immunohistochemically poor prognostic profile for intermediate responders configured by negativity of CD133 expression. However, when examining CD133 expression in the whole section, there was an intermediate correlation with TMA and the prognostic significance was lost. CONCLUSION: The results did not confirm the value of immunohistochemistry in predicting the prognosis of patients with rectal cancer following neoadjuvant chemoradiotherapy. This questions the accuracy of TMA in detecting CD133 expression in this setting.

Irinotecan-cetuximab-bevacizumab as a salvage treatment in heavily pretreated metastatic colorectal cancer patients: a retrospective observational study.

BACKGROUND: The objective was to evaluate the efficacy of irinotecan-cetuximab-bevacizumab in combination as a salvage treatment for heavily pretreated metastatic colorectal cancer patients. METHODS: A total of 39 patients resistant to both oxaliplatin and irinotecan were included in this retrospective study. Treatment consisted of irinotecan 180/m(2) every 14 days, weekly cetuximab standard dose and bevacizumab 5 mg/kg every 14 days. RESULTS: Partial response was observed in 8 patients (20%), stable disease in 24 (61%) and progressive disease in 7 (18%). Overall response rate in KRAS wild type was 6/22 (27%) and in mutated KRAS it was 2/15 (13%). Median time to progression was 8 months (6.4-9.4) and median overall survival 12 months (10.1-13.8). Overall, grade 3-4 adverse events were observed in 24 patients (62%). CONCLUSIONS: This regimen is active and moderately well tolerated in heavily pretreated advanced colorectal patients. However, caution is advisable when interpreting these results, because they run against the findings of two large phase III trials.

Model-derived dose rates per unit concentration of radon in air in a generic plant geometry.

A model for the derivation of dose rates per unit radon concentration in plants was developed in line with the activities of a Task Group of the International Commission on Radiological Protection (ICRP), aimed at developing more realistic dosimetry for non-human biota. The model considers interception of the unattached and attached fractions of the airborne radon daughters by plant stomata, diffusion of radon gas through stomata, permeation through the plant's epidermis and translocation of deposited activity to plant interior. The endpoint of the model is the derivation of dose conversion coefficients relative to radon gas concentration at ground level. The model predicts that the main contributor to dose is deposition of (214)Po α-activity on the plant surface and that diffusion of radon daughters through the stomata is of relatively minor importance; hence, daily variations have a small effect on total dose.