Uncertainties in the adaptation of alpine pastures to climate change based on remote sensing products and modelling.

Over the last century, the management of pastoral systems has undergone major changes to meet the livelihood needs of alpine communities. Faced with the changes induced by recent global warming, the ecological status of many pastoral systems has seriously deteriorated in the western alpine region. We assessed changes in pasture dynamics by integrating information from remote-sensing products and two process-based models, i.e. the grassland-specific, biogeochemical growth model PaSim and the generic crop-growth model DayCent. Meteorological observations and satellite-derived Normalised Difference Vegetation Index (NDVI) trajectories of three pasture macro-types (high, medium and low productivity classes) in two study areas - Parc National des Écrins (PNE) in France and Parco Nazionale Gran Paradiso (PNGP) in Italy - were used as a basis for the model calibration work. The performance of the models was satisfactory in reproducing pasture production dynamics (R2 = 0.52 to 0.83). Projected changes in alpine pastures due to climate-change impacts and adaptation strategies indicate that: i) the length of the growing season is expected to increase between 15 and 40 days, resulting in changes in the timing and amount of biomass production, ii) summer water stress could limit pasture productivity; iii) earlier onset of grazing could enhance pasture productivity; iv) higher livestock densities could increase the rate of biomass regrowth, but major uncertainties in modelling processes need to be considered; and v) the carbon sequestration potential of pastures could decrease under limited water availability and warming.

Population-based cancer registries in Spain and their role in cancer control.

Population-based cancer registries (PBCRs) are a key element for cancer control. They measure cancer incidence and trends, provide indicators for planning and evaluating cancer control activities, and undertake research. The first two PBCRs in Spain were established in Zaragoza in 1960 and Navarre in 1970, but it was from 1980 to 1995 when most of the existing registries went into operation. Today, 26.5% of the Spanish population is served by a cancer registry. All registries' quality-control indicators meet the inclusion criteria for comparability and quality of data required by the International Agency for Research on Cancer, and indeed some fulfil most of the excellence criteria for gold standard certification. After their initiation into recording accurate and complete information targeted at ascertaining cancer incidence in their catchment areas, PBCRs are progressively broadening their scope and becoming increasingly involved in collecting and analysing additional data on patient care, diagnosis, disease stage, treatment and follow-up. Spanish registries have become actively engaged in research projects, domestic and international, at a rate that has risen remarkably in the past decade. The creation of a network of Spanish cancer registries is being considered, with the aim of its becoming a key player in developing standards for cancer registration, providing training and technical assistance, undertaking quality audits and promoting the use of cancer surveillance data to reduce the burden of cancer in Spain.

Childhood cancer incidence and survival in Spain.

BACKGROUND: This article affords an overview of the patterns and time trends of childhood cancer incidence (1983-2002) and survival (1991-2002) in Spain. PATIENTS AND METHODS: A population-based study was conducted, including 5936 cases for incidence and 3257 for survival analyses. Differences in incidence were tested with the standardised incidence ratio. Trends were analysed for all tumours, and for all malignant, haematological, central nervous system (CNS) (all and only malignant) and other solid tumours. Incidence trends were analysed using Poisson and Bayesian joinpoint models. Observed, relative and age-adjusted survival rates were calculated, and trends were tested using the log-rank test. RESULTS: The incidence pattern in Spain was similar to that in Europe. Rates, both overall and for leukaemias, lymphomas, CNS, soft tissue and, remarkably, for sympathetic nervous system and bone tumours, were high. Upward incidence trends were present for all tumour groups. All groups, except solid tumours (excluding CNS), displayed a change-point centred around 1990-95, after which the trend stopped rising. Five-year survival increased significantly across the period for all groups, except for CNS tumours. Recent survival results were in line with Italy, the UK and the European average. CONCLUSIONS: To confirm these results, ongoing surveillance of incidence and survival trends, and studies targeting specific tumours are called for.

The effects of liposuction removal of subcutaneous abdominal fat on lipid metabolism are independent of insulin sensitivity in normal-overweight individuals.

BACKGROUND: Abdominal fat (both visceral and subcutaneous) accumulation is associated with an increased risk of developing insulin resistance. The latter stands as the basis upon which diabetes, hypertension, and atherogenic dyslipidemia tend to build up. Hence, abdominal liposuction (AL) could theoretically hold metabolic benefits. We undertook the present study to assess the effects of AL on carbohydrate and lipid metabolism. METHODS: This is a prospective study including 20 healthy volunteers (M2/F18) aged 39.6 +/- 7.7 years old (24-52), body mass index (BMI) = 25.3 +/- 4.7 kg/m(2) (19.8-36) who underwent AL. Before and 4 months after AL, we measured glucose and insulin concentrations, HOMA index [glucose (mM) x IRI (microUI/l)/22.5], free fatty acids (FFA), glycerol, total cholesterol and triglycerides, high-density lipoprotein (HDL)-cholesterol (HDL-c), low-density lipoprotein (LDL)-cholesterol (LDL-c), very low-density lipoprotein (VLDL)-cholesterol (VLDL-c) and apolipoproteins (apo) B, AI and AII, adiponectin (Adp), and ultra-sensitive C-reactive protein (CRP). RESULTS: Lipo-aspirate averaged 5.494 +/- 5.297 cc (600-19.000). Weight, BMI, and waist circumference decreased significantly 4 months after surgery by 4.6, 4.6 and 5.9%, respectively. There were significant decrements in FFA (-35%, p < 0.0001), glycerol (-63%, p < 0.0005), VLDL-c (-15.2%; p < 0.001), and triglycerides (-21.3%, p < 0.002), an increase in HDL-c (+10%, p < 0.03), Apo AI (+10.1%, p < 0.02), and Apo AII (+11.8%, p < 0.001). Total cholesterol, LDL-c, ApoB, and the LDL-c/ApoB ratio raised by +15% (p < 0.0005), +27.3% (p < 0.000), +15.1% (p < 0.008) and +2.76% (p < 0.008), respectively. Glucose, insulin, the HOMA index, Adp, and CRP were not significantly altered after AL. CONCLUSION: AL in healthy normal weight or slightly overweight subjects improves the major lipoprotein components of obesity-associated dyslipidemia. This improvement occurs independent of insulin sensitivity.

The role of tocilizumab in the treatment of inflammatory diseases of the eye and orbit: A useful alternative.

PURPOSE: With uveitis being one of the leading causes of blindness worldwide, biological therapies have arisen as an option for the treatment of refractory cases based on good results shown in clinical practice. The goal of this study is to provide a systematic review of current knowledge of the role and possible uses of tocilizumab in the field of ophthalmology. MATERIALS AND METHODS: We performed a search for records reporting the use of tocilizumab for various diseases in MEDLINE (PubMed and OVID). We conducted an analysis of several individual studies and their reported individual patient data (82 eyes of 45 patients) published from 2011 to 2017. CONCLUSIONS: Tocilizumab may prove to be an effective choice for the treatment of a variety of ocular conditions such as refractory uveitis, inflammatory macular edema, vitreo-retinal tumors and thyroid orbitopathy, leading to control of the inflammation in these patients. Further studies need to be conducted to establish its safety and efficacy.

Childhood and adolescent lymphoma in Spain: incidence and survival trends over 20 years.

BACKGROUND: Lymphoma is the third most common malignancy in children (0-14 years) and the first in adolescents (15-19 years). This population-based study-the largest ever done in Spain-analyses incidence and survival of lymphomas among Spanish children and adolescents. PATIENTS AND METHODS: 1664 lymphoma cases (1983-2007) for incidence and 1030 for survival (1991-2005) followed until 31/12/2010, were provided by 11 cancer registries. Age-adjusted incidence rates (ASRw) to the world standard population were obtained; incidence trends were modelled using the Joinpoint programme, observed survival (OS) was estimated with Kaplan-Meier and trends tested with a log-rank test. Results are presented according to the International Classification of Childhood Cancer-3. RESULTS: In Spain, the ASRw0-14 for lymphomas was 17.5 per 1.000.000 child-years and 50.0 the specific rate for adolescents. Overall incidence increased significantly during 1983-1997 with no increases thereafter. Patients over 9 years old showed significant rising trends for all subtypes, except for Burkitt lymphoma (BL) in adolescents. During 2001-2005 (age 0-19 years), 5-year OS was 94 (90-98), 73 (64-83) and 86 (78-94) for Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and BL, respectively. No improvement in survival was found. The incidence in Spain was higher than overall European rates, but within the range of that in Southern Europe. Comparing OS in Spain 1991-1995 and 2001-2005 with results for Europe of the Automated Childhood Cancer Information System (ACCIS) (1988-1997) and the European cancer registry-based study on survival and care of cancer patients (EUROCARE) (2000-2007), it was similar for HL and lower for NHL and BL. CONCLUSIONS: Systematic monitoring and analysis of lymphoma paediatric data would provide clinical and epidemiological information to improve the health care of these patients and the outcomes for these malignancies in Spain.

Up-to-date monitoring of childhood cancer long-term survival in Europe: central nervous system tumours.

BACKGROUND: Tumours of the central nervous system (CNS) account for 15-20% of all malignant childhood tumours in developed countries. Steady improvement of survival of children with CNS tumours has been reported for the past decades. However, these results, obtained by cohort analysis of survival, do not reflect the full extent of recent improvement. METHODS: Using selected registries from the database of the Automated Childhood Cancer Information System (ACCIS), we calculated period survival estimates for the years 1995-99 for children diagnosed with a malignant CNS tumour. RESULTS: The overall 10-year period survival estimate for the years 1995-99 was 59% for children with all CNS tumours combined, 73% for children with astrocytoma, 53% for children with ependymoma and 45% for children with primitive neuroectodermal tumours. On average, estimates derived by cohort analysis (pertaining to children diagnosed in 1985-89) were around 4% units lower. Region-specific analysis revealed that recent progress was largest in Eastern Europe, where prognosis nevertheless remained lower than in other European regions. In Northern and Southern Europe, 10-year survival remained essentially unchanged. CONCLUSION: Although period survival of children with CNS tumours is higher than previously reported cohort survival, their long-term prognosis remains modest compared to other childhood malignancies.

Update of choroidal imaging techniques: Past, present and future. / Actualización en técnicas de imagen coroidea: pasado, presente y futuro.

The choroid is the middle layer of the eye, a very vascular and pigmented tissue, with its role in several ophthalmological pathologies already having been clearly established. But it was not until the last few years that we have been able to reliably and precisely measure and quantify its shape and thickness. Ultrasound technology and indocyanine green angiography were the first techniques used for the study of the choroid, and they still maintain their use and clinical indications for the diagnosis and management of several pathologies. But it was the advent of optical coherence tomography that was the greatest breakthrough in choroidal imaging. In this chapter, the past, current and future image modalities for the study of the choroid will be discussed, with special focus on optical coherence tomography and its latest developments.

Cancer incidence in Spain, 2015.

PURPOSE: Periodic cancer incidence estimates of Spain from all existing population-based cancer registries at any given time are required. The objective of this study was to present the current situation of cancer incidence in Spain. METHODS: The Spanish Network of Cancer Registries (REDECAN) estimated the numbers of new cancer cases occurred in Spain in 2015 by applying the incidence-mortality ratios method. In the calculus, incidence data from population-based cancer registries and mortality data of all Spain were used. RESULTS: In 2015, nearly a quarter of a million new invasive cancer cases were diagnosed in Spain, almost 149,000 in men (60.0%) and 99,000 in women. Globally, the five most common cancers were those of colon-rectum, prostate, lung, breast and urinary bladder. By gender, the four most common cancers in men were those of prostate (22.4%), colon-rectum (16.6%), lung (15.1%) and urinary bladder (11.7%). In women, the most common ones were those of breast (28.0%), colon-rectum (16.9%), corpus uteri (6.2%) and lung (6.0%). In recent years, cancer incidence in men seems to have stabilized due to the fact that the decrease in tobacco-related cancers compensates for the increase in other types of cancer like those of colon and prostate. In women, despite the stabilization of breast cancer incidence, increased incidence is due, above all, to the rise of colorectal and tobacco-related cancers. CONCLUSION: To reduce these incident cancer cases, improvement of smoking control policies and extension of colorectal cancer screening should be the two priorities in cancer prevention for the next years.

Geographical variability in survival of European children with central nervous system tumours.

Survival for childhood central nervous system (CNS) tumours varies across Europe, partly because of the difficulty of distinguishing malignant from non-malignant disease. This study examines bias in CNS tumours survival analysis to obtain the reliable and comparable survival figures. We analysed survival data for about 15,000 children (age <15) diagnosed with CNS between 2000 and 2007, from 71 population-based cancer registries in 27 countries. We selected high-quality data based on registry-specific data quality indicators and recorded observed 1-year and 5-year survival by countries and CNS entity. We provided age-adjusted survival and used a Cox model to calculate the hazard ratios (HRs) of death, adjusting by age, site and grading by country. Recording of non-malignant lesions, use of appropriate morphology codes and completeness of life status follow-up differed among registries. Five-year survival by countries varied less when non-malignant tumours were included, with rates between 79.5% and 42.8%. The HRs of dying, for registries with good data, adjusting by age and grading, were between 0.7 and 1.2; differences were similar when site (supra- and infra-tentorial) was included. Several sources of bias affect the correct definition of CNS tumours, the completeness of incidence series and the goodness of follow-up. The European Network of Cancer Registries needs to improve childhood cancer registration and stress the need to update the International Classification for Cancer. Since survival differences persisted even when restricting the analysis to registries with satisfactory data, and since diagnosis of CNS tumours is difficult and treatment complex, national plans must aim for the revision of the diagnosis and the coordination of care, with adequate national and international networks.

Incidence and survival time trends for Spanish children and adolescents with leukaemia from 1983 to 2007.

OBJECTIVE: We have analysed incidence and survival trends of children and adolescents with leukaemia registered in Spanish population-based cancer registries during the period 1983-2007. METHODS: Childhood and adolescent leukaemia cases were drawn from the 11 Spanish population-based cancer registries. For survival, registries with data for the period 1991-2005 and follow-up until 31-12-2010 were included. Overall incidence trends were evaluated using joinpoint analysis. Observed survival rates were estimated using Kaplan-Meier, and trends were tested using the log-rank test. RESULTS: Based on 2606 cases (2274 children and 332 adolescents), the overall age-adjusted incidence rate (ASRw) of leukaemia was 47.9 cases per million child-years in children and 23.8 in adolescents. The ASRw of leukaemia increased with an annual percentage change of 9.6 % (95 % CI: 2.2-17.6) until 1990 followed by a stabilisation of rates. In adolescents, incidence did not increase. Five-year survival increased from 66 % in 1991-1995 to 76 % in 2001-2005. By age, survival was dramatically lower in infants (0) and adolescents (15-19) than in the other age groups and no improvement was observed. In both children and adolescents, differences in 5-year survival rates among major subgroups of leukaemias were significant. CONCLUSIONS: The increasing incidence trends observed in childhood leukaemias during the study period were confined to the beginning of the period. Remarkable improvements in survival have been observed in Spanish children with leukaemias. However, this improvement was not observed in infants and adolescents.

Quantitative effect of glycaemic improvement on the components of diabetic dyslipidaemia: a longitudinal study.

In order to assess the effect of glycaemic improvement on lipoprotein concentrations, we studied 73 type 2 diabetic subjects before (HbA1c 10.1 (6.2-16)%) and after (HbA1c 6.6 (3.8-8.0)%) glycaemic improvement. Total triglyceride and cholesterol (c), LDLc, HDLc, non-HDLc and apolipoproteins AI (apoAI) and B (apoB) were measured. Bivariate correlations and step-wise, multivariate analysis were performed to find predictors of change in the different components of diabetic dyslipidaemia. Changes in HDLc (r = -0.358, P = 0.001), apoAI (r = -0.355, P = 0.003), apoAI/apoB ratio (r = -0.333, P = 0.005), weight (r = -0.245, P = 0.046) and BMI (r = -0.253, P = 0.039) correlated with that of HbA1c, but, in multivariate analysis, only changes in HDLc, apoAI and apoAI/apoB ratio were predicted by the decrease in HbA1c. For the median observed change in HbA1c (-3.3 percentage-points), the estimated changes were +0.14 mmol/l, +0.12 g/l and +0.20 for HDLc, apoAI and apoAI/apoB ratio, respectively, accounting for 81, 92 and 80% of the observed changes. In conclusion, for the component of diabetic dyslipidaemia for which less therapeutic tools are available, glycaemic improvement is most effective.

Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients.

OBJECTIVE: Apolipoprotein(B) [apo(B)] reflects the total mass of atherogenic particles (VLDL, IDL, and LDL), and its increase is associated with cardiovascular disease independently of LDL cholesterol (LDLc) levels. Apo(B) determination has been recently standardized, but attention to regional reference limits is advisable. Our aim was to analyze the frequency of dyslipidemic phenotypes, including those dependent on increased apo(B) in normocholesterolemic type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 100 consecutively seen type 2 diabetic patients (63 men, 37 women; aged 59 +/- 11 years) were included, after excluding those on lipid-lowering therapy. Apo(B) cutoff (1.1 g/l) was obtained from a group of normolipidemic (47 men, 21 women) control subjects, and LDLc, triglycerides, and HDL cholesterol (HDLc) cutoff points were those from the National Cholesterol Education Program guidelines. LDLc levels were obtained by ultracentrifugation if triglyceride levels were > 3.45 mmol/l; otherwise, they were calculated (Friedwald). Apo(B) levels were measured by immunoturbidimetry. RESULTS: Normocholesterolemia (LDLc < 4.13 mmol/l) appeared in 75 of the 100 patients, of whom 55 were normo- and 20 hypertriglyceridemic. Hyperapolipoprotein(B) [hyperapo(B)] was the most frequent lipid disorder, present in 34 (45%) of the normocholesterolemic patients (22 normo- and 12 hypertriglyceridemic). Low HDLc levels were more prevalent (53%) in patients with hyperapo(B) than in the rest (24%). CONCLUSIONS: Hyperapo(B) was found in almost half of the normocholesterolemic type 2 diabetic patients and was frequently associated with low HDLc levels and hypertriglyceridemia. Thus, given its independent association with cardiovascular disease and that it identifies high-risk phenotypes in normocholesterolemic diabetic patients apo(B) should be used to evaluate the lipidic pattern of these patients.

Plasma lipoprotein(a) levels are not influenced by glycemic control in type 1 diabetes.

OBJECTIVE: To determine the influence of glycemic control improvement with intensive therapy on lipoprotein(a) [Lp(a)] concentrations in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 105 poorly controlled type 1 diabetic patients (60 men, 45 women) without diabetic complications participated in a longitudinal study performed in a tertiary referral center, to compare lipid, lipoprotein, and Lp(a) levels before and after 3 months of intensive therapy with multiple insulin doses. Lp(a) levels were measured by the Terumo method. Differences between the two periods were assessed by the paired t test and Wilcoxon's test. RESULTS: After 3 months of intensive therapy, all patients exhibited improved glycemic control. HbA1c decreased from 8.9 +/- 2.4 to 6.5 +/- 1.6% (P < 0.0001), being < or =6% in 47% of patients. However, although a more favorable lipoprotein profile was obtained, no changes in Lp(a) concentrations were observed in the whole group of patients (16.7 +/- 17.3 vs. 17.2 +/- 17.7 mg/dl) or in patients with baseline Lp(a) levels above 30 mg/dl (47.1 +/- 14.8 vs. 47.4 +/- 18.9 mg/dl) or below 30 mg/dl (9.6 +/- 7.3 vs. 10.2 +/- 6.7 mg/dl). In addition, patients reaching HbA1c < or =6 or >6% presented similar Lp(a) levels (19.7 +/- 18.0 vs. 15.0 +/- 17.4 mg/dl), and changes in Lp(a) did not correlate with those observed in HbA1c. CONCLUSIONS: These data demonstrate that the improvement of glycemic control does not influence plasma Lp(a) concentrations in type 1 diabetic patients independently of baseline Lp(a) levels and the degree of glycemic control.

Lack of change of lipoprotein(a) levels by the optimization of glycemic control with insulin therapy in NIDDM patients.

OBJECTIVE: To evaluate the effect of glycemic control improvement with insulin therapy on lipoprotein(a) [Lp(a)] levels in patients with NIDDM. RESEARCH DESIGN AND METHODS: We performed a longitudinal study in a tertiary referral center to compare lipid and Lp(a) levels before and after 3 months of insulin therapy in 60 poorly controlled NIDDM patients (32 men, 28 women). Patients previously treated with oral hypoglycemic agents (n = 50) received one to two insulin doses, and those previously treated with insulin (n = 10) received multiple insulin doses. Lp(a) levels were measured by the Terumo method. Differences between the two periods were assessed by the paired t test and Wilcoxon's test. RESULTS: After 3 months of insulin therapy, HbA1c decreased from 9.6 +/- 1.9 to 6.0 +/- 1.4% (P < 0.0005) in all patients and from 9.1 +/- 2.1 to 6.1 +/- 2.9% (P < 0.05) in patients under multiple insulin doses, being < or = 6.0% in 59% of patients. Total triglyceride and VLDL cholesterol levels decreased (P < 0.01) and HDL cholesterol increased significantly (P < 0.0005). However, no changes in Lp(a) levels were observed in all patients (25.3 +/- 25.0 vs 25.7 +/- 27.2% mg/dl) and in patients with baseline Lp(a) levels above (63.5 +/- 15.5 vs. 65.1 +/- 23.1 mg/dl) or below 30 mg/dl (11.5 +/- 7.5 vs. 11.5 +/- 7.3 mg/dl). In addition, patients reaching HbA1c levels < or = 6.0% or > 6.0% presented similar Lp(a) levels (26.0 +/- 29.1 vs 25.3 +/- 25.0 mg/dl). Moreover, no correlations were observed between changes in Lp(a) levels and in the glycemic control parameters. CONCLUSIONS: This study shows that the improvement of glycemic control by insulin therapy does not influence plasma Lp(a) levels, measured by the Terumo method, in NIDDM patients, independently of baseline values and the degree of glycemic control reached.

Cost-Effectiveness of Highly Sensitive Cardiac Troponin T to Rule Out Acute Rejection After Heart Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) remains the gold standard for detecting acute rejection (AR) after heart transplantation (HTx). Non-invasive detection of AR thus far remains a challenge. Several studies have demonstrated that highly sensitive cardiac troponin T (hs-cTnT) concentrations have a low positive predictive value for diagnosing AR. Nevertheless, hs-cTnT proved to be useful for ruling out AR after HTx. An hs-cTnT concentration <17 ng/L, a value close to that used for rule-in or rule-out myocardial infarction, was associated with a 100% negative predictive value of AR. However, the cost-effectiveness of a strategy with the use of hs-cTnT for ruling out AR in HTx patients remains to be proven. METHODS: The cost-effectiveness of hs-cTnT determination for ruling out AR was assessed, comparing the costs of hs-cTnT measurements in 305 blood samples obtained at the time of EMB. Eighteen samples were excluded because the EMB was not assessable. RESULTS: Hs-cTnT determination cost 16.00€ per sample, whereas EMB cost 1752.00€ per biopsy; cost estimations included direct and indirect (30%) charges. Thirty-nine (13.6%) of the 287 blood samples presented hs-cTnT concentrations <17 ng/L; in none of them was an AR >2R degree found in the EMB. The cost of the assessment in the 287 blood samples and biopsies was of 4592.00€ for hs-cTnT and 502,824.00€ for EMB. Hs-cTnT systematic measurement would have avoided 39 EMB, with a saving of 68,328.00€, which represents the 13.5% of the total budget expended in these cases. CONCLUSIONS: The use of hs-cTnT values to rule out the need of EMB for AR diagnosis after HTx appears to be a cost-effective procedure.

Isolation of cDNA clones encoding proteins of complex structures: analysis of the Trypanosoma brucei cytoskeleton.

We have adapted a group of well-known procedures in order to devise a simple method that allows the isolation of specific cDNAs encoding proteins located in different regions of the Trypanosoma brucei cytoskeleton. cDNA clones were isolated by screening a lambda gt11 expression library with a polyspecific, polyclonal antiserum against a complex immunogen, in this case the complete cytoskeleton. The fusion proteins produced by the clones were then used as an affinity immunoadsorbant to select monospecific polyclonals. The monospecific antisera isolated were used as probes to identify and localize different cytoskeleton proteins by Western blotting and immunofluorescence. This method proved particularly useful for the molecular identification of minor components in a complex structure. It should prove applicable to the molecular analysis of other organelles or protein complexes.

Population density and childhood leukaemia: results of the EUROCLUS Study.

The EUROCLUS study assembled incidence data for 13,551 cases of childhood leukaemia (CL) diagnosed between 1980 and 1989 in 17 countries (or regions of countries). These were referenced by location at diagnosis to small census areas of which there were 25,723 in the study area. Population counts, surface area and, hence, population density were available for all these small areas. Previous analyses have shown limited extra-Poisson variation (EPV) of case counts within small areas; this is most pronounced in areas of intermediate population density (150-499 persons/km2). In this study, the data set was examined in more detail for evidence that variations in incidence and EPV of CL are associated with population density. Incidence showed a curvilinear association with population density and was highest in areas which were somewhat more densely populated (500-750 persons/km2), where the incidence rate ratio relative to areas having > or = 1000 persons/km2 was 1.16 (95% confidence interval 1.07-1.26) and the P value for quadratic trend across eight strata of population density was 0.02. Incidence in these areas is uniformly elevated and showed no evidence of heterogeneity (i.e. EPV). Statistically significant evidence of EPV was evident amongst some of the areas previously classified as intermediate density areas (specifically, those with a density of 250-499 persons/km2, P < 0.001 for CL). These results were interpreted in terms of the current aetiological hypotheses for CL which propose that exposure to localised epidemics of one or more common infectious agent may contribute to the development of leukaemia. They suggest that such epidemics arise regularly in moderately densely populated areas and also sporadically in areas which are somewhat less densely populated. Although other interpretations are possible, these results may assist in the identification of characteristics which infectious agents must possess if direct or indirect causes of CL.

Results from an international case-control study of childhood brain tumors: the role of prenatal vitamin supplementation.

An international case-control study of primary pediatric brain tumors included interviews with mothers of cases diagnosed from 1976 to 1994 and mothers of population controls. Data are available on maternal vitamin use during pregnancy for 1051 cases and 1919 controls from eight geographic areas in North America, Europe, and Israel. Although risk estimates varied by study center, combined results suggest that maternal supplementation for two trimesters may decrease risk of brain tumor (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5-0.9), with a trend of less risk with longer duration of use (p trend = 0.0007). The greatest risk reduction was among children diagnosed under 5 years of age whose mothers used supplements during all three trimesters (OR 0.5, CI 0.3-0.8). This effect did not vary by histology and was seen for supplementation during pregnancy rather than during the month before pregnancy or while breast feeding. These findings are largely driven by data from the United States, where most mothers took vitamins. The proportion of control mothers who took vitamins during pregnancy varied tremendously: from 3% in Israel and France, 21% in Italy, 33% in Canada, 52% in Spain and 86 to 92% at the three U.S. centers. The composition of the various multivitamin compounds taken also varied: the daily dose of vitamin C ranged from 0 to 600 mg, vitamin E ranged from 0 to 70 mg, vitamin A ranged from 0 to 30,000 IU, and folate ranged from 0 to 2000 micrograms. Mothers also took individual micronutrient supplements (e.g., vitamin C tablets), but most mothers who took these also took multivitamins, making it impossible to determine potential independent effects of these micronutrients.