Evaluating sampling strategies and logistic regression methods for modelling complex land cover changes

The role of land cover change as a significant component of global change has become increasingly recognized in recent decades. Large databases measuring land cover change, and the data which can potentially be used to explain the observed changes, are also becoming more commonly available. When developing statistical models to investigate observed changes, it is important to be aware that the chosen sampling strategy and modelling techniques can influence results. We present a comparison of three sampling strategies and two forms of grouped logistic regression models (multinomial and ordinal) in the investigation of patterns of successional change after agricultural land abandonment in Switzerland. Results indicated that both ordinal and nominal transitional change occurs in the landscape and that the use of different sampling regimes and modelling techniques as investigative tools yield different results. Synthesis and applications. Our multimodel inference identified successfully a set of consistently selected indicators of land cover change, which can be used to predict further change, including annual average temperature, the number of already overgrown neighbouring areas of land and distance to historically destructive avalanche sites. This allows for more reliable decision making and planning with respect to landscape management. Although both model approaches gave similar results, ordinal regression yielded more parsimonious models that identified the important predictors of land cover change more efficiently. Thus, this approach is favourable where land cover change pattern can be interpreted as an ordinal process. Otherwise, multinomial logistic regression is a viable alternative.

Validation of Logistic Regression Models for Landslide Susceptibility Maps

A wide range of numerical models and tools have been developed over the last decades to support the decision making process in environmental applications, ranging from physical models to a variety of statistically-based methods. In this study, a landslide susceptibility map of a part of Three Gorges Reservoir region of China was produced, employing binary logistic regression analyses. The available information includes the digital elevation model of the region, geological map and different GIS layers including land cover data obtained from satellite imagery. The landslides were observed and documented during the field studies. The validation analysis is exploited to investigate the quality of mapping.

Daily physical activities and sports in adult survivors of childhood cancer and healthy controls: a population-based questionnaire survey.

BACKGROUND: Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. METHODOLOGY/PRINCIPAL FINDINGS: The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976-2003 at age 0-15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5 years and reached adulthood (≥20 years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35 years: 1.5, 95CI 1.2-2.0), female gender (OR 1.6, 95CI 1.3-1.9), French/Italian Speaking (OR 1.4, 95CI 1.1-1.7), and higher education (OR for university education: 2.0, 95CI 1.5-2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1-1.6), older age (OR for ≥35 years: 1.4, 95CI 1.1-1.8), migration background (OR 1.5, 95CI 1.3-1.8), French/Italian speaking (OR 1.4, 95CI 1.2-1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2-2.2), being married (OR 1.7, 95CI 1.5-2.0), having children (OR 1.3, 95CI 1.4-1.9), obesity (OR 2.4, 95CI 1.7-3.3), and smoking (OR 1.7, 95CI 1.5-2.1). Type of diagnosis was only associated with sports. CONCLUSIONS/SIGNIFICANCE: Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population.

Trends in overweight and obesity levels in Geneva: time for optimism?

Background/Introduction: ln Switzerland, most trends in overweight and obesity levels have been assessed using reported data, a methodology which is prone to reporting bias. ln this study, we aimed at assessing trends in overweight and obesity levels using objectively measured data. Methods: We used independent cross-sectional data collected between 2005 and 2011 by the Bus Santé study on representative samples of the Geneva population. Trends were assessed overall and according to different characteristics of the participants. Overweight and obesity were defined as a body mass index (BMI) between 25 and 29.9 kg/m2 and >=30 kg/m2, respectively. Results: Data from 4093 participants (2012 men) was assessed. Mean BMI was 25.2 ± 4.3 kg/m2 (mean ±standard deviation) in 2005 and 25.4 ± 4.3 in 2011 (p for trend using linear regression=0.98). For men, mean BMI was 26.3 ± 3.8 kg/m2 in 2005 and 26.1 ± 3.7 in 2011 (p for trend=0.37); for women, the corresponding values were 24.3 ± 4.6 and 24.7 ± 4.7 kg/m2 (p for trend=0.42). Overall prevalence of overweight and obesity was 32.2% and 13.3%, respectively, in 2005 and 33.6% and 13.7% in 2011 (p for trend using polytomous logistic regression adjusting for gender, age and smoking=0.49 and 0.94 for overweight and obesity, respectively). For men, prevalence of overweight and obesity was 45.9% and 12.2% in 2005 and 42.1 % and 14.6% in 2011 (P for trend=0.03 for overweight and 0.81 for obesity); for women, the corresponding values were 20.4% and 14.2% in 2005 and 25.4% and 12.9% in 2011 (p for trend=0.13 for overweight and 0.99 for obesity). Conclusion: Overweight and obesity levels appear to have levelled in Geneva, with a possible decrease in overweight levels in men. These favorable findings should be replicated in other geographical locations.

Prediction of 18-month survival in patients with primary myelodysplastic syndrome. A regression model and scoring system based on the combination of chromosome findings and the Bournemouth score.

The predictive potential of six selected factors was assessed in 72 patients with primary myelodysplastic syndrome using univariate and multivariate logistic regression analysis of survival at 18 months. Factors were age (above median of 69 years), dysplastic features in the three myeloid bone marrow cell lineages, presence of chromosome defects, all metaphases abnormal, double or complex chromosome defects (C23), and a Bournemouth score of 2, 3, or 4 (B234). In the multivariate approach, B234 and C23 proved to be significantly associated with a reduction in the survival probability. The similarity of the regression coefficients associated with these two factors means that they have about the same weight. Consequently, the model was simplified by counting the number of factors (0, 1, or 2) present in each patient, thus generating a scoring system called the Lausanne-Bournemouth score (LB score). The LB score combines the well-recognized and easy-to-use Bournemouth score (B score) with the chromosome defect complexity, C23 constituting an additional indicator of patient outcome. The predicted risk of death within 18 months calculated from the model is as follows: 7.1% (confidence interval: 1.7-24.8) for patients with an LB score of 0, 60.1% (44.7-73.8) for an LB score of 1, and 96.8% (84.5-99.4) for an LB score of 2. The scoring system presented here has several interesting features. The LB score may improve the predictive value of the B score, as it is able to recognize two prognostic groups in the intermediate risk category of patients with B scores of 2 or 3. It has also the ability to identify two distinct prognostic subclasses among RAEB and possibly CMML patients. In addition to its above-described usefulness in the prognostic evaluation, the LB score may bring new insights into the understanding of evolution patterns in MDS. We used the combination of the B score and chromosome complexity to define four classes which may be considered four possible states of myelodysplasia and which describe two distinct evolutional pathways.

Drinking Patterns and Their Predictive Factors in CONTROL: a 12-Month Prospective Study in a Sample of Alcohol-Dependent Patients Initiating Treatment.

Aims: To describe the drinking patterns and their baseline predictive factors during a 12-month period after an initial evaluation for alcohol treatment. Methods CONTROL is a single-center, prospective, observational study evaluating consecutive alcohol-dependent patients. Using a curve clustering methodology based on a polynomial regression mixture model, we identified three clusters of patients with dominant alcohol use patterns described as mostly abstainers, mostly moderate drinkers and mostly heavy drinkers. Multinomial logistic regression analysis was used to identify baseline factors (socio-demographic, alcohol dependence consequences and related factors) predictive of belonging to each drinking cluster. ResultsThe sample included 143 alcohol-dependent adults (63.6% males), mean age 44.6 ± 11.8 years. The clustering method identified 47 (32.9%) mostly abstainers, 56 (39.2%) mostly moderate drinkers and 40 (28.0%) mostly heavy drinkers. Multivariate analyses indicated that mild or severe depression at baseline predicted belonging to the mostly moderate drinkers cluster during follow-up (relative risk ratio (RRR) 2.42, CI [1.02-5.73, P = 0.045] P = 0.045), while living alone (RRR 2.78, CI [1.03-7.50], P = 0.044) and reporting more alcohol-related consequences (RRR 1.03, CI [1.01-1.05], P = 0.004) predicted belonging to the mostly heavy drinkers cluster during follow-up. Conclusion In this sample, the drinking patterns of alcohol-dependent patients were predicted by baseline factors, i.e. depression, living alone or alcohol-related consequences and findings that may inform clinicians about the likely drinking patterns of their alcohol-dependent patient over the year following the initial evaluation for alcohol treatment.

Effects of particulate matters on inflammatory markers in the general adult population

Summary: Particulate air pollution is associated with increased cardiovascular risk. The induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway. The purpose of this study was to assess the associations of short-term exposure to ambient particulate matters of aerodynamic diameter less than 10 μm (PM10) with circulating inflammatory markers in 6183 adults in Lausanne, Switzerland. The results show that short-term exposure to PM10 was associated with higher levels of circulating IL-6 and TNF-α. The positive association of PM10 with markers of systemic inflammation materializes the link between air pollution and cardiovascular risk. Background: Variations in short-term exposure to particulate matters (PM) have been repeatedly associated with daily all-cause mortality. Particle-induced inflammation has been postulated to be one of the important mechanisms for increased cardiovascular risk. Experimental in-vitro, in-vivo and controlled human studies suggest that interleukin 6 (IL-6) and tumor-necrosis-factor alpha (TNF-α) could represent key mediators of the inflammatory response to PM. The associations of short-term exposure to ambient PM with circulating inflammatory markers have been inconsistent in studies including specific subgroups so far. The epidemiological evidence linking short-term exposure to ambient PM and systemic inflammation in the general population is scarce. So far, large-scale population-based studies have not explored important inflammatory markers such as IL-6, IL-1β or TNF-α. We therefore analyzed the associations between short-term exposure to ambient PM10 and circulating levels of high-sensitive CRP (hs-CRP), IL-6, IL-1β and TNF-α in the population-based CoLaus study. Objectives: To assess the associations of short-term exposure to ambient particulate matters of aerodynamic diameter less than 10 μm (PM10) with circulating inflammatory markers, including hs-CRP, IL-6, IL-1β and TNF-α, in adults aged 35 to 75 years from the general population. Methodology: All study subjects were participants to the CoLaus study (www.colaus.ch) and the baseline examination was carried out from 2003 to 2006. Overall, 6184 participants were included. For the present analysis, 6183 participants had data on at least one of the four measured circulating inflammatory markers. The monitoring data was obtained from the website of Swiss National Air Pollution Monitoring Network (NABEL). We analyzed data on PM10 as well as outside air temperature, pressure and humidity. Hourly concentrations of PM10 were collected from 1 January 2003 to 31 December 2006. Robust linear regression (PROC ROBUSTREG) was used to evaluate the relationship between cytokine inflammatory and PM10. We adjusted all analyses for age, sex, body mass index, smoking status, alcohol consumption, diabetes status, hypertension status, education levels, zip code, and statin intake. All data were adjusted for the effects of weather by including temperature, barometric pressure, and season as covariates in the adjusted models. We performed simple and multiple logistic regression analyses. Descriptive statistical analysis used the Wilcoxon rank sum test (for medians). All data analyses were performed using SAS software (version 9.2; SAS Institute Inc., Cary, NC, USA), and a two-sided significance level of 5% was used. Results: PM10 levels averaged over 24 hours were significantly and positively associated with continuous IL-6 and TNF-α levels, in the whole study population both in unadjusted and adjusted analyses. For each cytokine, there was a similar seasonal pattern, with wider confidence intervals in summer than during the other seasons, which might partly be due to the smaller number of participants examined in summer. The associations of PM10 with IL-6 and TNF-α were also found after having dichotomized these cytokines into high versus low levels, which suggests that the associations of PM10 with the continuous cytokine levels are very robust to any distributional assumption and to potential outlier values. In contrast with what we observed for continuous IL-1β levels, high PM10 levels were significantly associated with high IL-1β. PM10 was significantly associated with IL-6 and TNF-α in men, but with TNF-α only in women. However, there was no significant statistical interaction between PM10 and sex. For IL-6 and TNF-α, the associations tended to be stronger in younger people, with a significant interaction between PM10 and age groups for IL-6. PM10 was significantly associated with IL-6 and TNF-α in the healthy group and also in the "non-healthy" group, although the statistical interaction between healthy status and PM10 was not significant. Conclusion: In summary, we found significant independent positive associations of short-term exposure to PM10 with circulating levels of IL-6 and TNF-α in the adult population of Lausanne. Our findings strongly support the idea that short-term exposure to PM10 is sufficient to induce systemic inflammation on a broad scale in the general population. From a public health perspective, the reported association of elevated inflammatory cytokines with short-term exposure to PM10 in a city with relatively clean air such as Lausanne supports the importance of limiting urban air pollution levels.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

BACKGROUND: Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. AIM: To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. METHODS: Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. RESULTS: A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. CONCLUSIONS: Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Scenario-based assessment of future land use change on butterfly species distributions

Species distribution models (SDMs) are increasingly used to predict environmentally induced range shifts of habitats of plant and animal species. Consequently SDMs are valuable tools for scientifically based conservation decisions. The aims of this paper are (1) to identify important drivers of butterfly species persistence or extinction, and (2) to analyse the responses of endangered butterfly species of dry grasslands and wetlands to likely future landscape changes in Switzerland. Future land use was represented by four scenarios describing: (1) ongoing land use changes as observed at the end of the last century; (2) a liberalisation of the agricultural markets; (3) a slightly lowered agricultural production; and (4) a strongly lowered agricultural production. Two model approaches have been applied. The first (logistic regression with principal components) explains what environmental variables have significant impact on species presence (and absence). The second (predictive SDM) is used to project species distribution under current and likely future land uses. The results of the explanatory analyses reveal that four principal components related to urbanisation, abandonment of open land and intensive agricultural practices as well as two climate parameters are primary drivers of species occurrence (decline). The scenario analyses show that lowered agricultural production is likely to favour dry grassland species due to an increase of non-intensively used land, open canopy forests, and overgrown areas. In the liberalisation scenario dry grassland species show a decrease in abundance due to a strong increase of forested patches. Wetland butterfly species would decrease under all four scenarios as their habitats become overgrown

The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.

BACKGROUND: Hypotension, a common intra-operative incident, bears an important potential for morbidity. It is most often manageable and sometimes preventable, which renders its study important. Therefore, we aimed at examining hospital variations in the occurrence of intra-operative hypotension and its predictors. As secondary endpoints, we determined to what extent hypotension relates to the risk of post-operative incidents and death. METHODS: We used the Anaesthesia Databank Switzerland, built on routinely and prospectively collected data on all anaesthesias in 21 hospitals. The three outcomes were assessed using multi-level logistic regression models. RESULTS: Among 147,573 anaesthesias, hypotension ranged from 0.6% to 5.2% in participating hospitals, and from 0.3% up to 12% in different surgical specialties. Most (73.4%) were minor single events. Age, ASA status, combined general and regional anaesthesia techniques, duration of surgery and hospitalization were significantly associated with hypotension. Although significantly associated, the emergency status of the surgery had a weaker effect. Hospitals' odds ratios for hypotension varied between 0.12 and 2.50 (P < or = 0.001), even after adjusting for patient and anaesthesia factors, and for type of surgery. At least one post-operative incident occurred in 9.7% of the procedures, including 0.03% deaths. Intra-operative hypotension was associated with a higher risk of post-operative incidents and death. CONCLUSION: Wide variations remain in the occurrence of hypotension among hospitals after adjustment for risk factors. Although differential reporting from hospitals may exist, variations in anaesthesia techniques and blood pressure maintenance may also have contributed. Intra-operative hypotension is associated with morbidities and sometimes death, and constant vigilance must thus be advocated.

A novel gene expression signature in peripheral blood mononuclear cells for early detection of colorectal cancer.

BACKGROUND: Early detection and treatment of colorectal adenomatous polyps (AP) and colorectal cancer (CRC) is associated with decreased mortality for CRC. However, accurate, non-invasive and compliant tests to screen for AP and early stages of CRC are not yet available. A blood-based screening test is highly attractive due to limited invasiveness and high acceptance rate among patients. AIM: To demonstrate whether gene expression signatures in the peripheral blood mononuclear cells (PBMC) were able to detect the presence of AP and early stages CRC. METHODS: A total of 85 PBMC samples derived from colonoscopy-verified subjects without lesion (controls) (n = 41), with AP (n = 21) or with CRC (n = 23) were used as training sets. A 42-gene panel for CRC and AP discrimination, including genes identified by Digital Gene Expression-tag profiling of PBMC, and genes previously characterised and reported in the literature, was validated on the training set by qPCR. Logistic regression analysis followed by bootstrap validation determined CRC- and AP-specific classifiers, which discriminate patients with CRC and AP from controls. RESULTS: The CRC and AP classifiers were able to detect CRC with a sensitivity of 78% and AP with a sensitivity of 46% respectively. Both classifiers had a specificity of 92% with very low false-positive detection when applied on subjects with inflammatory bowel disease (n = 23) or tumours other than CRC (n = 14). CONCLUSION: This pilot study demonstrates the potential of developing a minimally invasive, accurate test to screen patients at average risk for colorectal cancer, based on gene expression analysis of peripheral blood mononuclear cells obtained from a simple blood sample.

Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study.

BACKGROUND & AIMS: Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy. METHODS: The analysis included 1362 individuals: 1015 with chronic hepatitis C and 347 who spontaneously cleared the virus (448 were coinfected with human immunodeficiency virus [HIV]). Responses to pegylated interferon alfa and ribavirin were assessed in 465 individuals. Associations between more than 500,000 single nucleotide polymorphisms (SNPs) and outcomes were assessed by multivariate logistic regression. RESULTS: Chronic hepatitis C was associated with SNPs in the IL28B locus, which encodes the antiviral cytokine interferon lambda. The rs8099917 minor allele was associated with progression to chronic HCV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.74-3.06; P = 6.07 x 10(-9)). The association was observed in HCV mono-infected (OR, 2.49; 95% CI, 1.64-3.79; P = 1.96 x 10(-5)) and HCV/HIV coinfected individuals (OR, 2.16; 95% CI, 1.47-3.18; P = 8.24 x 10(-5)). rs8099917 was also associated with failure to respond to therapy (OR, 5.19; 95% CI, 2.90-9.30; P = 3.11 x 10(-8)), with the strongest effects in patients with HCV genotype 1 or 4. This risk allele was identified in 24% of individuals with spontaneous HCV clearance, 32% of chronically infected patients who responded to therapy, and 58% who did not respond (P = 3.2 x 10(-10)). Resequencing of IL28B identified distinct haplotypes that were associated with the clinical phenotype. CONCLUSIONS: The association of the IL28B locus with natural and treatment-associated control of HCV indicates the importance of innate immunity and interferon lambda in the pathogenesis of HCV infection.

Coffee and tea intake and risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: Only a few studies have explored the relation between coffee and tea intake and head and neck cancers, with inconsistent results. METHODS: We pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for potential confounders. RESULTS: Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94-0.98) for an increment of 1 cup per day and 0.61 (95% CI, 0.47-0.80) in drinkers of >4 cups per day versus nondrinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46; 95% CI, 0.30-0.71 for oral cavity; OR, 0.58; 95% CI, 0.41-0.82 for oropharynx/hypopharynx; and OR, 0.61; 95% CI, 0.37-1.01 for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; 95% CI, 0.64-1.45 in drinkers of >4 cups per day versus nondrinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk (OR, 0.99; 95% CI, 0.89-1.11 for drinkers versus nondrinkers). CONCLUSIONS: This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx. IMPACT: Given widespread use of coffee and the relatively high incidence and low survival of head and neck cancers, the observed inverse association may have appreciable public health relevance.

Relationships between imatinib plasma levels and efficacy

Purpose: While imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumors (GIST), its pharmacokinetic-pharmacodynamic relationships have been poorly studied. This study aimed to explore the issue in oncologic patients, and to evaluate the specific influence of the target genotype in a GIST subpopulation. Patients and methods: Data from 59 patients (321 plasma samples) were collected during a previous pharmacokinetic study. Based on a population model purposely developed, individual post-hoc Bayesian estimates of pharmacokinetic parameters were derived, and used to estimate drug exposure (AUC; area under curve). Free fraction parameters were deduced from a model incorporating plasma alpha1-acid glycoprotein levels. Associations between AUC (or clearance) and therapeutic response (coded on a 3-point scale), or tolerability (4-point scale), were explored by ordered logistic regression. Influence of KIT genotype on response was also assessed in GIST patients. Results: Total and free drug exposure correlated with the number of side effects (p < 0.005). A relationship with response was not evident in the whole patient set (with good-responders tending to receive lower doses and bad-responders higher doses). In GIST patients however, higher free drug exposure predicted better responses. A strong association was notably observed in patients harboring an exon 9 mutation or a wild type KIT, known to decrease tumor sensitivity towards imatinib (p < 0.005). Conclusions: Our results are arguments to further evaluate the potential benefit of a therapeutic monitoring program for imatinib. Our data also suggest that stratification by genotype will be important in future trials.