Elderly age is not a negative predictive factor for virological response to therapy with pegylated interferon-α and ribavirin in chronic hepatitis C virus patients.

BACKGROUND & AIMS: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral therapy of chronic hepatitis C. However, elderly patients often show advanced fibrosis/cirrhosis as known negative predictive factor. The aim of this study was to assess age as an independent predictive factor during antiviral therapy. METHODS: Overall, 516 hepatitis C patients were treated with pegylated interferon-α and ribavirin, thereof 66 patients ≥60 years. We analysed the impact of host factors (age, gender, fibrosis, haemoglobin, previous hepatitis C treatment) and viral factors (genotype, viral load) on SVR per therapy course by performing a generalized estimating equations (GEE) regression modelling, a matched pair analysis and a classification tree analysis. RESULTS: Overall, SVR per therapy course was 42.9 and 26.1%, respectively, in young and elderly patients with hepatitis C virus (HCV) genotypes 1/4/6. The corresponding figures for HCV genotypes 2/3 were 74.4 and 84%. In the GEE model, age had no significant influence on achieving SVR. In matched pair analysis, SVR was not different in young and elderly patients (54.2 and 55.9% respectively; P = 0.795 in binominal test). In classification tree analysis, age was not a relevant splitting variable. CONCLUSIONS: Age is not a significant predictive factor for achieving SVR, when relevant confounders are taken into account. As life expectancy in Western Europe at age 60 is more than 20 years, it is reasonable to treat chronic hepatitis C in selected elderly patients with relevant fibrosis or cirrhosis but without major concomitant diseases, as SVR improves survival and reduces carcinogenesis.

Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03.

BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.

Risk of a Down syndrome live birth in women 45 years of age and older.

OBJECTIVES: To determine the risk of a Down syndrome (DS) live birth for women 45 years of age and over. METHODS: A meta-analysis of data from five published articles, 13 EUROCAT congenital anomaly population registers and two unpublished sources. RESULTS: Information was available on the number of DS live births occurring amongst 13,745 live births to women 45 years of age and over. Information was also available on DS pregnancies diagnosed prenatally that were subsequently terminated. These pregnancies were adjusted for expected fetal loss to estimate the number of live births that would have occurred in the absence of prenatal diagnoses, when a total of 471 DS live births were estimated to have occurred. The risk of a DS birth did not increase for women 45 years of age and over. The average risk was 34 per 1000 births (95% CI: 31-37). CONCLUSION: The risk of a DS live birth for women 45 years of age and over is considerably lower than has often been previously assumed. The most likely explanation is that women of this age are more likely to miscarry DS pregnancies than younger mothers.

Prevalence of overweight and obesity in the Swiss population

Introduction: The latest data on prevalence of overweight (OW) and obesity (OB) in the general Swiss resident population rely on the Swiss Health Survey (SHS), a telephonic interview performed in 2007. However, body mass index (BMI) is underestimated when self-reported, leading to a misclassification of up to 60% of obese subjects. The last survey with measured BMI performed in the 3 linguistic regions of Switzerland dates back to 1977. We explored the regional prevalences of OW and OB by measured BMI in the general Swiss resident population. Methods: Cross-sectional population-based survey in the 3 linguistic regions of Switzerland in 2010-2011. Data on 1471 participants aged 15-95 years (712 men, 759 women) were available for the analysis. BMI was calculated from measured height and weight and categorized into 3 groups according to WHO classification: lean (<25 kg/m2), overweight (25-30 kg/m2) and obese (>= 30 kg/m2). Data on medication, smoking, education, physical activity and dietary habitudes were collected using a questionnaire. Results: The overall prevalence of OW and OB was 32.1% and 13.9%, respectively. OB prevalence was similar across the 3 linguistic regions (13.5% in German-, 15.6% in French- and 12.0% in Italian-speaking Switzerland, p = 0.40), unlike OW prevalence, which significantly differed in unadjusted analyses (35.4%, 29.1% and 25.4%, respectively, p = 0.005). In analyses including age, sex, smoking, physical activity and education as covariates, living in the Italian-speaking region was associated neither with BMI (linear regression) nor with OW or OB (logistic regressions) . Age (beta coefficient [SE]: 0.064[0.006] kg/m2 per year, p <0.001) and sex (-1.76 [0.23] kg/m2 in women, p <0.001) were significantly associated with BMI. Conclusions: Overweight and obesity affect nearly half of the Swiss population aged >15 years. We observed no significant differences across regions once we accounted for age, sex, education and lifestyle. Public health interventions addressing modifiable behavioral factors to reduce overweight and obesity in Switzerland can be expected to have substantial benefits.

A systematic review of longitudinal population-based studies on the predictors of smoking cessation in adolescent and young adult smokers.

OBJECTIVE: To describe the determinants of self-initiated smoking cessation of duration of at least 6 months as identified in longitudinal population-based studies of adolescent and young adult smokers. METHODS: A systematic search of the PubMed and EMBASE databases using smoking, tobacco, cessation, quit and stop as keywords was performed. Limits included articles related to humans, in English, published between January 1984 and August 2010, and study population aged 10-29 years. A total of 4502 titles and 871 abstracts were reviewed independently by 2 and 3 reviewers, respectively. Nine articles were retained for data abstraction. Data on study location, timeframe, duration of follow-up, number of data collection points, sample size, age/grade of participants, number of quitters, smoking status at baseline, definition of cessation, covariates and analytic method were abstracted from each article. The number of studies that reported a statistically significant association between each determinant investigated and cessation were tabulated, from among all studies that assessed the determinant. RESULTS: Despite heterogeneity in methods across studies, five factors robustly predicted quitting across studies in which the factor was investigated: not having friends who smoke, not having intentions to smoke in the future, resisting peer pressure to smoke, being older at first use of cigarette and having negative beliefs about smoking. CONCLUSIONS: The literature on longitudinal predictors of cessation in adolescent and young adult smokers is not well developed. Cessation interventions for this population will remain less than optimally effective until there is a solid evidence base on which to develop interventions.

Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with leukemia following matched-sibling myeloablative allogeneic hematopoietic cell transplantation.

BACKGROUND AND OBJECTIVES: Donor cytomegalovirus seropositivity was reported to improve leukemia outcomes in HLA-A2 identical hematopoietic cell transplant (HCT) recipients, due to a possible cross-reactivity of donor HLA-A2-restricted CMV-specific T cells with minor histocompatibility (H) antigen of recipient cells. This study analyzed the role of donor CMV serostatus and HLA-A2 status on leukemia outcomes in a large population of HLA-identical HCT recipients. DESIGN AND METHODS: Leukemia patients transplanted between 1992 and 2003 at the Fred Hutchinson Cancer Research Center were categorized as standard risk [leukemia first remission, chronic myeloid leukemia in chronic phase (CML-CP)] and high risk (advanced disease) patients. Time-to-event analysis was used to evaluate the risk of relapse and death associated with HLA-A2 status and donor CMV serostatus. RESULTS: In standard risk patients, acute leukemia (p<0.001) and sex mismatch (female to male, p=0.004)) independently increased the risk of death, while acute leukemia increased the risk of relapse (p<0.001). In high risk patients acute leukemia (p=0.01), recipient age > or = 40 (p=0.005) and herpes simplex virus (HSV) seropositivity (p<0.001) significantly increased the risk death; HSV seropositivity (p=0.006) increased the risk of relapse. Donor CMV serostatus had no significant effect on mortality or relapse in any HLA group. INTERPRETATION AND CONCLUSION: This epidemiological study did not confirm the previously reported effect of donor CMV serostatus on the outcomes of leukemia in HLA-A2-identical HCT recipients. Addressing the question of cross-reactivity of HLA-A2-restricted CMV-specific T cells with minor H antigens in a clinical study would require knowledge of the patient's minor H antigen genotype. However, because of the unbalanced distribution of HLA-A2-restricted minor H antigens in the population and their incomplete identification, this question might be more appropriately evaluated in in vitro experiments than in a clinical study.

Objective Sleep Structure and Cardiovascular Risk Factors in the General Population: The HypnoLaus Study.

STUDY OBJECTIVES: To evaluate the association between objective sleep measures and metabolic syndrome (MS), hypertension, diabetes, and obesity. DESIGN: Cross-sectional study. SETTING: General population sample. PARTICIPANTS: There were 2,162 patients (51.2% women, mean age 58.4 ± 11.1). INTERVENTIONS: Patients were evaluated for hypertension, diabetes, overweight/obesity, and MS, and underwent a full polysomnography (PSG). MEASUREMENTS AND RESULTS: PSG measured variables included: total sleep time (TST), percentage and time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep, sleep efficiency and arousal index (ArI). In univariate analyses, MS was associated with decreased TST, SWS, REM sleep, and sleep efficiency, and increased ArI. After adjustment for age, sex, smoking, alcohol, physical activity, drugs that affect sleep and depression, the ArI remained significantly higher, but the difference disappeared in patients without significant sleep disordered breathing (SDB). Differences in sleep structure were also found according to the presence or absence of hypertension, diabetes, and overweight/obesity in univariate analysis. However, these differences were attenuated after multivariate adjustment and after excluding subjects with significant SDB. CONCLUSIONS: In this population-based sample we found significant associations between sleep structure and MS, hypertension, diabetes, and obesity. However, these associations were cancelled after multivariate adjustment. We conclude that normal variations in sleep contribute little if any to MS and associated disorders.

Population demography of an endangered lizard, the Blue Mountains Water Skink.

BACKGROUND: Information on the age structure within populations of an endangered species can facilitate effective management. The Blue Mountains Water Skink (Eulamprus leuraensis) is a viviparous scincid lizard that is restricted to < 40 isolated montane swamps in south-eastern Australia. We used skeletochronology of phalanges (corroborated by mark-recapture data) to estimate ages of 222 individuals from 13 populations. RESULTS: These lizards grow rapidly, from neonatal size (30 mm snout-vent length) to adult size (about 70 mm SVL) within two to three years. Fecundity is low (mean 2.9 offspring per litter) and is affected by maternal body length and age. Offspring quality may decline with maternal age, based upon captive-born neonates (older females gave birth to slower offspring). In contrast to its broadly sympatric (and abundant) congener E. tympanum, E. leuraensis is short-lived (maximum 6 years, vs 15 years for E. tympanum). Litter size and offspring size are similar in the two species, but female E. leuraensis reproduce annually whereas many E. tympanum produce litters biennially. Thus, a low survival rate (rather than delayed maturation or low annual fecundity) is the key reason why E. leuraensis is endangered. Our 13 populations exhibited similar growth rates and population age structures despite substantial variation in elevation, geographic location and swamp size. However, larger populations (based on a genetic estimate of effective population size) contained older lizards, and thus a wider variance in ages. CONCLUSION: Our study suggests that low adult survival rates, as well as specialisation on a rare and fragmented habitat type (montane swamps) contribute to the endangered status of the Blue Mountains Water Skink.

A genome-wide association study of neuroticism in a population-based sample.

Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p < 10(-6)) and GPC6 showed suggestive evidence for interaction with age (p approximately = 10(-7)). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.

CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II.

Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m(-2)) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN+). Median age was 60 years (range 43-75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2-15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48-0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population.

Phase II study of imatinib in advanced chordoma.

PURPOSE: To explore the antitumor activity of imatinib in patients with advanced platelet-derived growth factor β (PDGFB)/PDGF receptor β (PDGFRB)-positive chordomas.¦PATIENTS AND METHODS: In a collaborative Italian-Swiss, prospective, phase II clinical study conducted from November 2004 through April 2006, 56 patients with advanced PDGFB and/or PDGFRB chordoma received 800 mg/d of imatinib until progression. The primary end point was the overall tumor response rate (ORR), defined by RECIST. Secondary, exploratory end points included tissue response (ie, changes in tumor density or signal intensity/contrast enhancement, and/or [18F]-fluorodeoxyglucose positron emission tomography [PET] uptake), overall survival, progression-free survival (PFS), and pain score.¦RESULTS: Among 50 patients evaluable by RECIST, the best response was one partial response (PR) obtained at 6 months (ORR, 2%). There were 35 patients with stable disease (SD, 70%) and a 64% clinical benefit rate (ie, RECIST complete response + PR + SD ≥ 6 months). A minor dimensional response (< 20%) was detected in nine patients. A maximum standard uptake value decrease ≥ 25% was observed in 10 (39%) of 26 patients evaluable for PET response at 3 months. Changes in the Brief Pain Inventory score were consistent with the response assessment. Median PFS (intention-to-treat population, 56 patients) was 9 months. No unexpected toxicities were observed.¦CONCLUSION: This is the largest phase II study in chordoma to date. It confirms anecdotal evidence that imatinib has antitumor activity in this orphan disease, and therefore, it is worth further investigation.

Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib.

Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24-80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2-18) responded to nilotinib and 19 patients (37%; 95% CI 24-50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9-15; range 0-104) and median overall survival was 34 weeks (95% CI 3-65; range 2-135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. These results warrant further investigation of nilotinib in GIST.

Who eats healthily? A population-based study among young Swiss residents.

OBJECTIVE: To assess whether Swiss residents aged 15-24 years follow current nutritional guidelines and whether differences exist according to gender and weight status. DESIGN: Cross-sectional national survey. SETTING: Switzerland. SUBJECTS: The 1786 participants (48·4 % women) were divided into overweight, normal weight and underweight. We used traditional BMI cut-offs for people ≥18 years of age (underweight = BMI < 18·5 kg/m2, normal weight = BMI ≥ 18·5 kg/m2 and <25 kg/m2, overweight = BMI ≥ 25 kg/m2) and age- and gender-appropriate tables for people aged <18 years, with BMI calculated from self-reported weight and height. We performed bivariate analyses by gender, and then bivariate and multivariate analyses comparing overweight to normal weight people (excluding underweight, n 129, 71·6 % women) regarding adherence to recommendations for fruit, vegetables, meat, fish and dairy products; physical activity; attitude towards body weight; depression, smoking and alcohol consumption. RESULTS: Overall, adherence to nutritional guidelines was low, particularly for vegetables and dairy products. Women had a higher adherence than men except for fish and dairy products. In the multivariate analyses, overweight women had a lower vegetable intake, were less satisfied with body weight and had more often been on a diet, whereas overweight men were less satisfied with body weight and wanted to lose weight more often than their normal weight peers. There were no significant differences for physical activity. CONCLUSIONS: Overweight prevention programmes should target youth specifically by gender and promote an appropriate self-perception. Overweight women should be encouraged to eat more vegetables and men to be more sensitised on healthy food. Further research is needed to assess how to make nutritional guidelines more adaptable to young people's daily life.

Assessment of the COOP charts with and without pictures in a Swiss population.

OBJECTIVES: This study aimed to assess the validity of COOP charts in a general population sample, to examine whether illustrations contribute to instrument validity, and to establish general population norms. METHODS: A general population mail survey was conducted among 20-79 years old residents of the Swiss canton of Vaud. Participants were invited to complete COOP charts, the SF-36 Health Survey; they also provided data on health service use in the previous month. Two thirds of the respondents received standard COOP charts, the rest received charts without illustrations. RESULTS: Overall 1250 persons responded (54%). The presence of illustrations did not affect score distributions, except that the illustrated 'physical fitness' chart drew greater non-response (10 vs. 3%, p < 0.001). Validity tests were similar for illustrated and picture-less charts. Factor analysis yielded two principal components, corresponding to physical and mental health. Six COOP charts showed strong and nearly linear relationships with corresponding SF36 scores (all p < 0.001), demonstrating concurrent validity. Similarly, most COOP charts were associated with the use of medical services in the past month. Only the chart on 'social support' partly deviated from construct validity hypotheses. Population norms revealed a generally lower health status in women and an age-related decline in physical health. CONCLUSIONS: COOP charts can be used to assess the health status of a general population. Their validity is good, with the possible exception of the 'social support' chart. The illustrations do not affect the properties of this instrument.