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New articles - Uudet artikkelit 25.8.2008 - ISI Web of Knowledge & PubMed Search Alert
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Family history of prostate cancer and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
Ahn, J., Moslehi, R., Weinstein, S. J., Snyder, K., Virtamo, J. and Albanes, D. International Journal of Cancer. 2008; 123(5): 1154-1159. Article. IF 4.555 Prostate cancer family history has been associated with increased risk of the malignancy. Most prior studies have been retrospective and subject to recall bias, however, and data evaluating interactions with other important risk factors are limited. We examined the relationship between a family history of prostate cancer and prostate cancer risk in relation to body size, micronutrients and other exposures in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of Finnish male smokers. Family history of cancer information was self-reported once during the study in 1991, and anthropometry was measured by trained personnel. Among 19,652 men with complete data, 1,111 incident cases were identified during up to 12.3 years of follow-up. A first-degree family history of prostate cancer was associated with an overall relative risk (RR) of 1.91 (95% CI = 1.49-2.47) and a RR of 4.16 (95% CI = 2.67-6.49) for advanced disease (stage : 3), adjusted for age and trial intervention. Our data also suggest that to some degree, height, body mass index, and serum a-tocopherol and P-carotene modify the family history and prostate cancer association, although the interactions were not statistically significant. Supplementation with vitamin E or beta-carotene did not modify the family history-prostate cancer association. This study provides additional evidence that family history is a significant risk factor for prostate cancer. Published 2008 Wiley-Liss, Inc. Cardiovascular health of Finnish war evacuees 60 years later Alastalo, H., Raikkonen, K., Pesonen, A. K., Osmond, C., Barker, D. J., Kajantie, E., Heinonen, K., Forsen, T. J. and Eriksson, J. G. Ann Med. 2008: 1-7. IF 5.779 Background. Early life experiences might have long-term effects on health. Aim. To assess prevalence of cardiovascular disease and diabetes in later life among individuals exposed to traumatic separation in early childhood due to World War II. Methods. Of the participants of the Helsinki Birth Cohort 1934-44 Study (n=2003), 320 had been evacuated abroad to temporary foster care in childhood. The remaining participants served as controls. The mean age at evacuation was 4.8 (SD =2.4) years and the mean duration of the evacuation was 1.7 (SD =1.0) years. Results. Cardiovascular morbidity was higher among the former war evacuees (14.7% versus 7.9%; odds ratio (OR) =2.0, 95% confidence interval (95% CI) 1.4-2.9; P<0.001). A similar difference in prevalence of type 2 diabetes was observed (19.7% versus 14.8%; OR =1.4, 95% CI 1.1-1.9, P=0.025). The former war evacuees were also more likely to be hypertensive (P<0.05). The effects on morbidity were not explained by age at testing or socio-economic circumstances in childhood or adulthood. Conclusion. Early life traumatic events may extend lifelong effects on health. This study is among the first to show that early life trauma predicts higher prevalence of cardiovascular disease and type 2 diabetes in late adulthood, in a longitudinal clinical study setting. The diabetes-cardiovascular risk paradox: results from a Finnish population-based prospective study Barengo, N. C., Katoh, S., Moltchanov, V., Tajima, N. and Tuomilehto, J. European Heart Journal. 2008; 29(15): 1889-1895. Article. IF 7.924 Aims To assess changes in coronary heart disease (CHD) event rates and CHD mortality rates among diabetic and non-diabetic individuals between two large study cohorts with baseline assessments 10 years apart and followed up for 10 years. Methods and results Four population surveys were carried out in 1972, 1977, 1982, and 1987 in a randomly selected independent population in Finland. For the analyses, we combined the 1972 and 1977 cohorts (cohort 1) and similarly also the 1982 and 1987 cohorts (cohort 2). A total of 16 779 men and 18 235 women were followed up for 10 years. Whereas the risk of first cardiovascular disease event in women did not change between the two cohorts, the risk in diabetic men aged 25-49 years and men of all age groups with incidence diabetes during the follow-up decreased compared with the earlier cohort. The relative risk of CHD mortality in men with baseline diabetes or incident diabetes compared with non-diabetic individuals increased (from 1.67 to 1.75 and 1.00 to 1.92, respectively). CHD event rates and CHD mortality rates decreased among non-diabetic individuals between the two study cohorts. Conclusion Special attention should be given to prevent the onset of diabetes in the population and to intensify the management of patients with diabetes. Eight years of experience with molecular identification of human enteroviruses Blomqvist, S., Paananen, A., Savolainen-Kopra, C., Hovi, T. and Roivainen, M. J Clin Microbiol. 2008; 46(7): 2410-3. IF 3.708 We have successfully typed 1,121 human enterovirus (HEV) isolates during the last 8 years by adapting partial VP1 sequencing to routine identification of HEV isolated from diverse clinical and environmental specimens. The isolates include 48 of the 59 traditional nonpoliovirus HEV serotypes and members of 8 newly discovered types, which would have remained untypeable by neutralization using the conventional cross-sectional pools of antisera. Boyko, E. J., Shaw, J. E., Zimmet, P. Z., Chitson, P., Tuomilehto, J. and Alberti, K. G. J Hypertens. 2008; 26(9): 1742-1749. IF 4.364 OBJECTIVE: To estimate the associations between new-onset hypertension and glycemia, insulin resistance, and overall and regional adiposity in a prospective study conducted in Mauritius. RESEARCH DESIGN AND METHODS: Three thousand five hundred and eighty-one adults without hypertension, pregnancy, or known diabetes at baseline (1987) were followed for incident hypertension in 1992 and 1998, (systolic blood pressure >/=140 mmHg or diastolic blood pressure >/=90 mmHg or antihypertensive medication treatment). Other measurements included fasting plasma glucose and 2-h plasma glucose after a 75-g oral glucose load, fasting insulin, BMI, waist circumference, smoking, alcohol use, exercise, and demographic information. Insulin sensitivity was estimated by the computerized homeostasis model assessment (HOMA2) program. RESULTS: In multivariable logistic models that included age, gender, ethnicity, alcohol use, exercise, education, systolic blood pressure, diastolic blood pressure, homeostasis model assessment, fasting plasma glucose, 2-h plasma glucose, BMI, and waist circumference, the independent predictors of incident hypertension by time of follow-up were (odds ratio for a 1 SD increase; 95% confidence interval): 1992 - age (1.73; 1.47-2.03), Creole ethnicity (1.42; 1.04-1.94), 2-h plasma glucose (1.26; 1.04-1.51); 1998 - age (1.60; 1.40-1.83) and BMI (1.33; 1.05-1.69). Also, systolic blood pressure and diastolic blood pressure significantly predicted hypertension at both time points. CONCLUSION: Risk factor patterns depended on duration of follow-up. Over 5 years, hypertension was related to 2-h plasma glucose but not to measures of body size or homeostasis model assessment, while over 11 years, incident hypertension was related to BMI but not waist circumference, 2-h plasma glucose, or homeostasis model assessment. These findings support a more important role for 2-h plasma glucose and overall adiposity than waist circumference, fasting plasma glucose, or insulin resistance in the development of hypertension in Mauritius. Hallast, P., Saarela, J., Palotie, A. and Laan, M. BMC Evolutionary Biology. 2008; 8. Article. IF 4.091 Background: Low nucleotide divergence between human and chimpanzee does not sufficiently explain the species-specific morphological, physiological and behavioral traits. As gene duplication is a major prerequisite for the emergence of new genes and novel biological processes, comparative studies of human and chimpanzee duplicated genes may assist in understanding the mechanisms behind primate evolution. We addressed the divergence between human and chimpanzee duplicated genomic regions by using Luteinizing Hormone Beta (LHB)/Chorionic Gonadotropin Beta (CGB) gene cluster as a model. The placental CGB genes that are essential for implantation have evolved from an ancestral pituitary LHB gene by duplications in the primate lineage. Results: We shotgun sequenced and compared the human (45,165 bp) and chimpanzee (39,876 bp) LHB/CGB regions and hereby present evidence for structural variation resulting in discordant number of CGB genes (6 in human, 5 in chimpanzee). The scenario of species-specific parallel duplications was supported (i) as the most parsimonious solution requiring the least rearrangement events to explain the interspecies structural differences; (ii) by the phylogenetic trees constructed with fragments of intergenic regions; (iii) by the sequence similarity calculations. Across the orthologous regions of LHB/CGB cluster, substitutions and indels contributed approximately equally to the interspecies divergence and the distribution of nucleotide identity was correlated with the regional repeat content. Intraspecies gene conversion may have shaped the LHB/CGB gene cluster. The substitution divergence ( 1.8-2.59%) exceeded two-three fold the estimates for single-copy loci and the fraction of transversional mutations was increased compared to the unique sequences (43% versus similar to 30%). Despite the high sequence identity among LHB/CGB genes, there are signs of functional differentiation among the gene copies. Estimates for d(n)/d(s) rate ratio suggested a purifying selection on LHB and CGB8, and a positive evolution of CGB1. Conclusion: If generalized, our data suggests that in addition to species-specific deletions and duplications, parallel duplication events may have contributed to genetic differences separating humans from their closest relatives. Compared to unique genomic segments, duplicated regions are characterized by high divergence promoted by intraspecies gene conversion and species-specific chromosomal rearrangements, including the alterations in gene copy number. Haukka, J., Tiihonen, J., Härkänen, T. and Lönnqvist, J. Pharmacoepidemiol Drug Saf. 2008; 17(7): 686-96. IF 2.475 PURPOSE: Mortality among schizophrenia patients is substantially higher than in the general population. The aim of this study was to investigate, in a nationwide cohort of suicidal schizophrenic individuals, how the risks of suicide, severe suicide attempts and death are associated with usage of antidepressant or antipsychotic treatment. METHODS: The study population included all individuals in Finland who were hospitalised with a diagnosis of attempted suicide between 1 January 1997 and 31 December 2003, who also had at least one hospitalisation due to schizophrenia diagnosis (ICD-10 F20), and were at least 16 years old when the index hospitalisation began. Cox's proportional hazards modelling and Bayesian intensity estimation were used in the analysis. RESULTS: There were 1611 patients with a mean follow-up time of 4.3 years. Current use of antipsychotics was associated with decreased mortality due to suicide (HR 0.52, 95% CI 0.34-0.81, p = 0.004), but no significant decrease in mortality was observed during current use of antidepressants (0.66, 0.41-1.08, p = 0.099), when compared to past use. In more detailed analysis when current users were compared to non-users, olanzapine, and mixed use of antipsychotics, were associated with reduced all-cause mortality, and mixed use also with reduced risk of suicide mortality. Current use of citalopram was associated with decreased all-cause and suicide mortality. CONCLUSIONS: In a population of suicidal schizophrenic individuals antipsychotic medication, treatment was associated with lower mortality from suicide and all-causes. Antidepressive medication was associated with lower all-cause mortality when used in combination with antipsychotics. Geographical variation of medicated parkinsonism in Finland during 1995 to 2000 Havulinna, A. S., Tienari, P. J., Marttila, R. J., Martikainen, K. K., Eriksson, J. G., Taskinen, O., Moltchanova, E. and Karvonen, M. Mov Disord. 2008; 23(7): 1024-31. IF 3.207 We performed a nation-wide study on geographical variation in the incidence and prevalence of medicated parkinsonism among the Finns aged > or =30 years using Bayesian spatial conditional autoregressive models. Registry of reimbursed medication for parkinsonism and a prescription database of purchase of these drugs were used to identify the study subjects. They were located by the map coordinates of the place of residence and aggregated into regular 100 km(2) grid cells. A total of 7,190 incident and 10,616 prevalent cases were found. The age-adjusted annual incidence was 32.6/100,000 (95% HDR 31.8-33.4) during the years 1995 to 2000 and prevalence was 268/100,000 (95% HDR 263-274) in 2000. The male to female ratio was 1.45 (95% HDR 1.39-1.51) in incidence and 1.54 (95% HDR 1.47-1.61) in prevalence. There was strong evidence for geographic variation in incidence and prevalence. A zone with high incidence and prevalence was identified in the eastern and central part of Finland. There was no evidence for difference in incidence and prevalence between urban and rural areas. The marked (more than two-fold) geographic variation can hardly be caused solely by practices of the registration and collection of data on diagnosis or by methodological issues, but rather suggests to geographic variation in protective and predisposing factors of Parkinsonism in Finland. Gastrointestinal complaints among subjects with depressive symptoms in the general population Hillila, M. T., Hämäläinen, J., Heikkinen, M. E. and Farkkila, M. A. Alimentary Pharmacology & Therapeutics. 2008; 28(5): 648-654. Article. IF 3.201 Background Patients with depression have irritable bowel syndrome (IBS) more often than do nondepressed patients, but the comorbidity of depression and gastrointestinal (GI) symptoms in the general population has received little study. Aim To study the co-occurrence of depressive and GI symptoms in a general population sample and to assess the rate of health-care utilization particularly for GI reasons among subjects with depressive symptoms. Methods A questionnaire containing the Finnish version of the Beck Depression Inventory Short Form and questions covering GI symptoms according to Rome II criteria was mailed to 5000 randomly selected adults. Results Response rate was 73%. Prevalence of depressive symptoms was 17% (95% CI: 15.7-18.2). Frequent abdominal pain, diarrhoea, constipation, dyspepsia or IBS were present in 54% of those with depressive symptoms and in 29% of nondepressed controls (P < 0.0001). Of those with depressive symptoms, 24% had visited a physician at least once because of abdominal symptoms during the previous year, compared to 13% of controls (P < 0.0001). Conclusions Depressive symptoms are prevalent in the general population. They are associated with a high rate of GI symptoms, leading to increased use of health-care services and work absenteeism because of abdominal complaints. Holma, K. M., Melartin, T. K., Holma, I. A. and Isometsa, E. T. J Clin Psychiatry. 2008: e1-e9. IF 5.060 OBJECTIVE: In this naturalistic study, we investigated the rate, time course, and predictors of a diagnostic switch from unipolar major depressive disorder (MDD) to bipolar disorder type I or II during a 5-year follow-up. METHOD: The Vantaa Depression Study included at baseline 269 psychiatric outpatients (82.9%) and inpatients (17.1%) with DSM-IV MDD, diagnosed using structured and semi-structured interviews and followed up at 6 months, 18 months, and 5 years between February 1, 1997 and April 30, 2004. Information on 248 MDD patients (92.2%) was available for analyses of the risk of diagnostic switch. Cox proportional hazards models were used. RESULTS: Twenty-two subjects (8.9%) with previous unipolar MDD switched to bipolar disorder type II and 7 (2.8%) to type I. Median time for switch to bipolar type I was significantly shorter than to type II. In Cox proportional hazards analyses, severity of MDD (hazard ratio [HR] = 1.08, 95% CI = 1.00 to 1.15, p = .036), obsessive-compulsive disorder (OCD) (HR = 5.00, 95% CI = 2.04 to 12.5, p < .001), social phobia (HR = 2.33, 95% CI = 1.00 to 5.26, p = .050), and large number of cluster B personality disorder symptoms (HR = 1.10, 95% CI = 1.02 to 1.20, p = .022) predicted switch. CONCLUSION: Among outpatients with MDD in secondary level psychiatric settings, diagnostic switch to bipolar disorder usually refers to type II rather than type I. The few switching to bipolar type I do so relatively early. Predictors for diagnostic switch include not only features of mood disorder, such as severity, but may also include some features of psychiatric comorbidity, such as concurrent social phobia, OCD, and symptoms of cluster B personality disorders. Jalava, P. I., Salonen, R. O., Pennanen, A. S., Happo, M. S., Penttinen, P., Halinen, A. I., Sillanpaa, M., Hillamo, R. and Hirvonen, M. R. Toxicol Appl Pharmacol. 2008; 229(2): 146-60. IF 3.846 We investigated the inflammatory and cytotoxic activities of the water-soluble and -insoluble as well as organic-solvent-soluble and -insoluble fractions of urban air fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples. The samples were collected with a high volume cascade impactor (HVCI) in 7-week sampling campaigns of selected seasons in six European cities. Mouse macrophage cells (RAW 264.7) were exposed to the samples for 24 h. The production of nitric oxide (NO) and proinflammatory cytokines (TNFalpha, IL-6), and cytotoxicity (MTT-test, apoptosis, cell cycle) were measured. The inflammatory and cytotoxic responses in both size ranges were mostly associated with the insoluble particulate fractions. However, both the water- and organic-solvent-soluble particulate fractions induced TNFalpha production and apoptosis and had some other cytotoxic effects. Soil-derived water-soluble and -insoluble components of the chemical PM(2.5-0.2) mass closure had consistent positive correlations with the responses, while the correlations were negative with the secondary inorganic anions (NO(3)(-), NH(4)(+), non-sea-salt SO(4)(2-)) and particulate organic matter (POM). With the PM(10-2.5) samples, sea salt and soluble soil components correlated positively with the induced toxic responses. In this size range, a possible underestimation of the insoluble, soil-related compounds containing Si and Ca, and biological components of POM, increased uncertainties in the evaluation of associations of the mass closure components with the responses. It is concluded that insoluble components of the complex urban air particulate mixture exert the highest inflammatory and cytotoxic activities in the macrophage cell line but, at the same time, they may operate as carriers for active water- and lipid-soluble components. Jylhä, P., Melartin, T. and Isometsä, E. J Affect Disord. 2008. IF 3.144 BACKGROUND: High comorbidity with axis I and II disorders among major depressive disorder (MDD) patients may in part be due to the predisposing personality dimensions of neuroticism and extraversion. However, a comprehensive view of this relationship is lacking. METHODS: MDD patients (n=193) in the Vantaa Depression Study were interviewed at baseline and at 6 and 18 months with the SCAN and SCID-II, and a general population comparison group (n=388) surveyed by mail. Neuroticism and extraversion were measured with the Eysenck Personality Inventory. A dose-exposure relationship between standardized levels of neuroticism and extraversion and type and number of comorbid axis I and II disorders among patients with MDD was hypothesized. RESULTS: Prevalence and number of comorbid axis I and II disorders increased significantly with increasing level of neuroticism. In contrast, as the level of extraversion increased, the prevalences of social phobia and cluster C personality disorders decreased. Patients with pure MDD or with any comorbid axis I or II disorder had z-scores of neuroticism of +0.46, +0.90 and +1.30 and of extraversion of -0.34, -0.47 and -0.84, respectively. LIMITATIONS: Patients' personality scores were not pre-morbid. CONCLUSION: Among MDD patients, a positive dose-exposure relationship appears to exist between neuroticism and prevalence and number of comorbid axis I and II disorders. A negative relationship exists between level of extraversion and prevalence of social phobia and cluster C personality disorders. These findings are consistent with the hypothesis that high neuroticism and low extraversion predispose to comorbid axis I and II disorders among patients with MDD. Kemppainen, T., Ruoppi, P., Seppä, J., Sahlman, J., Peltonen, M., Tukiainen, H., Gylling, H., Vanninen, E. and Tuomilehto, H. American Journal of Rhinology. 2008; 22(4): 410-415. Article. IF 1.363 Background: Elevated nasal resistance and obesity predispose to obstructive sleep apnea (OSA). Weight loss has been shown to result in an alleviation of OSA, but its effect on nasal air flow has not been studied. Methods: This study was a prospective, randomized, controlled study with two parallel groups. A total of 52 adult overweight patients (body mass index [BMI] 28-40 kg/m(2)) with mild obstructive sleep apnea (apnea-hypopnea index [AHI], 5-15) were randomized into two study groups. The intervention group (n = 26)followed a very low calorie diet with a supervised lifestyle intervention while the control group (n = 26) received routine lifestyle counseling. The changes in BMI, total nasal resistance, total nasal volume, and quality of life scores (Mini Rhinoconjunctivitis Quality of Life Questionnaire, MiniRQLQ) were assessed at baseline and after the intervention at 3 months. Results: The reduction in BMI in the intervention group was significantly greater than that achieved by patients in the control group (5.4 kg /m(2) versus 0.5 kg/m(2)). Accordingly, AHI was reduced by 3.2 events/hour in the intervention group and by 1.3 in the control group. However, there were no significant changes in rhinometric measurements despite significant weight loss. There was no correlation between the reduction of BMI and the change in nasal resistance or MiniRQLQ scores. Conclusion: Weight reduction does not seem to have any effect on nasal resistance or volume in overweight patients with mild OSA. Patients with OSA and impaired nasal breathing need specific medical or surgical treatment to restore nasal airflow. Keskitalo, K., Tuorila, H., Spector, T. D., Cherkas, L. F., Knaapila, A., Kaprio, J., Silventoinen, K. and Perola, M. Am J Clin Nutr. 2008; 88(2): 263-71. IF 6.603 BACKGROUND: The relation between body weight and energy-dense foods remains unclear. OBJECTIVE: We estimated the effects of genetic and environmental factors on cognitive and emotional aspects of dieting behavior, body mass index (BMI), and responses to fatty foods and on their relations. DESIGN: A total of 1326 adult twin persons (aged 17-82 y; 17% M and 83% F) from the United Kingdom and Finland completed the revised version of the Three-Factor Eating Questionnaire (TFEQ-R18) and reported the liking and use-frequency of 4 sweet-and-fatty and salty-and-fatty food items (6 items in the United Kingdom and 5 items in Finland). Genetic modeling was done by using linear structural equations. RESULTS: Heritability estimates were calculated separately for the countries and sexes; they were 26-63% for cognitive restraint, 45-69% for uncontrolled eating, and 9-45% for emotional eating, respectively. Of the variation in liking and use-frequency of fatty foods, 24-54% was attributed to interindividual genetic differences. No significant correlations were observed between BMI and fatty food use or liking. However, BMI was positively (mostly genetically) correlated (genetic r = 0.16-0.51) with all of the dieting behaviors, and they correlated with fatty food use and liking ratings. Uncontrolled eating was both genetically and environmentally associated with liking for salty-and-fatty foods (genetic and environmental r = 0.16), and emotional eating was genetically associated with liking for sweet-and-fatty foods (genetic r = 0.31). CONCLUSIONS: The relation between BMI and diet appears to be mediated through dieting behaviors. Dietary counseling should focus on unhealthy dieting behaviors rather than only on direct advice on food use. Childhood and current determinants of heavy drinking in early adulthood Kestila, L., Martelin, T., Rahkonen, O., Joutsenniemi, K., Pirkola, S., Poikolainen, K. and Koskinen, S. Alcohol Alcohol. 2008; 43(4): 460-9. IF 2.092 AIMS: To explore the association of parental education, childhood living conditions and several adversities with heavy drinking in early adulthood, and to analyze the effect of the respondent's current circumstances on these associations. METHOD: The analyses were conducted in a sample of 1234 adults aged 18-29 years participating in the Finnish Health 2000 Survey (65% of the original representative two-stage cluster sample, N = 1894). The outcome measure was heavy drinking measured by g/week for pure alcohol (for men >or=280 g/week and for women >or=140 g/week). RESULTS: 8% of young adult men and 5% of women were heavy drinkers. In both genders, parental alcohol problems and other childhood adversities, poor own education, and unemployment status increased the risk of heavy drinking. The impact of childhood on heavy drinking was partly independent and partly mediated by adult characteristics, in particular, for both genders, low level of education. CONCLUSIONS: Childhood adversities are associated with heavy drinking in early adulthood among both genders. Childhood social circumstances as well as low educational level and unemployment should be taken into account in planning preventive policies to tackle the harms caused by excessive alcohol use at the individual and population level. Antibiotic use predicts an increased risk of cancer Kilkkinen, A., Rissanen, H., Klaukka, T., Pukkala, E., Heliövaara, M., Huovinen, P., Männistö, S., Aromaa, A. and Knekt, P. Int J Cancer. 2008. IF 4.555 Antibiotic use has been hypothesized to be associated with the risk of cancer but the evidence is sparse and inconsistent. The aim of the present study was to determine whether antibiotic use predicts the development of various cancers. This nationwide cohort study included 3,112,624 individuals, aged 30-79 years, with no history of cancer. Information on their antibiotic use between 1995 and 1997 was obtained from the Drug Prescription Registry. During the period 1998-2004, 134,070 cancer cases were ascertained from the Finnish Cancer Registry. Cox proportional hazards regression was used to estimate the relative risks (RRs) with 95% confidence intervals (95% CIs). Antibiotic use was associated with an increased risk of cancer: for categories of increasing antibiotic use (0-1, 2-5 and >/=6 prescriptions), RRs (95% CIs) for cancer were 1.0 (reference), 1.27 (1.26-1.29) and 1.37 (1.34-1.40). RRs (for comparison of lowest and highest exposure group) for the most common primary sites i.e. prostate, breast, lung and colon were 1.39 (1.31-1.48), 1.14 (1.09-1.20), 1.79 (1.67-1.92), and 1.15 (1.04-1.26), respectively. RRs for other primary sites varied between 0.90 (0.76-1.05) for ovary to 2.60 (1.60-4.20) for endocrine gland (excluding thyroid). In conclusion, antibiotic use predicts an increased risk of cancer. Because of the design of our study the possibility of residual confounding cannot be excluded and further studies are required to confirm the results. (c) 2008 Wiley-Liss, Inc. Kilpi, T. M., Silfverdal, S. A., Nilsson, L., Syrjanen, R., Belloni, C., Desole, M., Triban, C., Storsaeter, J., Soila, M. and Jacquet, J. M. Hum Vaccin. 2008; 5(1). IF The use of combination vaccines in the routine childhood program reduces distress to the recipients and is likely to improve uptake rates and timeliness of vaccination but requires careful evaluation and surveillance. The aim of this study was to evaluate the immunogenicity and reactogenicity of two commercial diphtheria-tetanus- acellular pertussis-hepatitis b-inactivated polio virus-Haemophilus influenzae type b (DTaP-HBV-IPV/Hib) combination vaccines when administered to infants at 3, 5 and 11-12 months of age. A total of 494 infants were randomized to receive three doses of either Infanrix hexa(trade mark) (GlaxoSmithKline Biologicals; N = 246) or Hexavac(trade mark) (Sanofi Pasteur MSD; N = 248) in 10 centers in Italy, Finland and Sweden. After the third dose, antibodies to diphtheria, tetanus, polio and Hib were at the protective level in nearly all infants in both groups whereas the proportion of subjects who had achieved the protective concentration of >/=10 mIU/ml to hepatitis B surface antigen was 99.1% (95% CI 96.7-99.9) in the Infanrix hexa(trade mark) group as compared to 94.4% (95% CI 90.4-97.1) in the Hexavac(trade mark) group. Antibody titers to all three polio antigens were highest in Italy and lowest in Finland. Clinically relevant general reactions (such as fever of >39.5 degrees C) were mostly reported in less than 5% of the vaccinees. Three doses of DTaP-HBV-IPV/Hib combination vaccines produced sufficient immune responses in nearly all vaccinees. Night-time work predisposes to non-Hodgkin lymphoma Lahti, T. A., Partonen, T., Kyyrönen, P., Kauppinen, T. and Pukkala, E. Int J Cancer. 2008. IF 4.555 Our aim was to find out whether non-Hodgkin lymphoma (NHL) was more common than expected among night-time shift workers. The Finnish job-exposure matrix (FINJEM) provided estimates of the proportion of exposed persons and the mean level of exposure among the exposed in each occupation. The probability of night-time work in each occupation was assessed, the observed and expected numbers of cancer cases in a cohort of persons born in 1906-1945 during the years of 1971-1995 were calculated, and the cumulative index of night-time work was scored. The cohort compromised of 1,669,272 persons of whom 6,307 (3,813 men and 2,494 women) had NHL during the follow-up. Night-time work increased significantly (p = 0.01) the risk of NHL in men, the overall relative risk being 1.10 (95% confidence interval of 1.03-1.19). Using the lag period of 10 years, the risk ratio was 1.28 (1.03-1.59) for men who worked in night-time shifts to a high degree as compared with those who had not been exposed to night-time work. Night-time workers are cancer prone and have a greater risk of NHL than population on average. (c) 2008 Wiley-Liss, Inc. Use of eye care services and need for assistance in the visually impaired Laitinen, A., Koskinen, S., Rudanko, S. L., Martelin, T., Laatikainen, L. and Aromaa, A. Optom Vis Sci. 2008; 85(5): 341-9. IF 1.638 PURPOSE: To assess the use of eye care services and unmet need for assistance in visually impaired people. METHODS: Cross-sectional population-based survey on a sample representing the Finnish population aged 30 years and older. Of the 7979 eligible people, 6645 (83.3%) were both interviewed and had their distance visual acuity (VA) assessed. One hundred forty-seven people were classified as visually impaired (VA < or = 0.25). A home interview included an assessment of the use of eye care services, need for assistance, sociodemographic variables, cognitive functioning, and mobility. Binocular VA for distance was measured with the participants' current spectacles, if any, as a part of a comprehensive health examination. RESULTS: One-half (58%) of visually impaired people had had a recent vision examination and 79% had received some vision rehabilitation services, mainly in form of spectacles (70%). Only one third (31%) had received formal low vision rehabilitation. People with moderate visual impairment (VA 0.1 to 0.25) were less likely to have received low vision rehabilitation, magnifying glasses, or other low vision aids compared with people with severe low vision (VA < 0.1). Furthermore, low cognitive capacity and living in an institution were associated with limited use of vision rehabilitation services. Of the visually impaired people living in the community, 71% reported need for assistance and 24% of them had unmet need for assistance in everyday activities. Although need for assistance was more common in people with severe low vision (83% vs. 67%, p = 0.09), unmet need for assistance seemed to be more common in people with moderate low vision (20% vs. 9%, p = 0.23). CONCLUSIONS: Many visually impaired people, older persons in particular, have not had a recent vision examination and lack adequate low vision rehabilitation. This highlights the need for regular evaluation of vision function in elderly people and for actively supplying information about rehabilitation services. Drug testing in oral fluid - Evaluation of sample collection devices Langel, K., Engblom, C., Pehrsson, A., Gunnar, T., Ariniemi, K. and Lillsunde, P. Journal of Analytical Toxicology. 2008; 32(6): 393-401. Article. IF 2.068 Comparative risk analysis of dioxins in fish and fine particles from heavy-duty vehicles Leino, O., Tainio, M. and Tuomisto, J. T. Risk Anal. 2008; 28(1): 127-40. IF 1.784 Dioxins and airborne fine particles are both environmental health problems that have been the subject of active public debate. Knowledge on fine particles has increased substantially during the last 10 years, and even the current, lowered levels in the Europe and in the United States appear to be a major public health problem. On the other hand, dioxins are ubiquitous persistent contaminants, some being carcinogens at high doses, and therefore of great concern. Our aim was to (a) quantitatively analyze the two pollutant health risks and (b) study the changes in risk in view of the current and forthcoming EU legislations on pollutants. We performed a comparative risk assessment for both pollutants in the Helsinki metropolitan area (Finland) and estimated the health effects with several scenarios. For primary fine particles: a comparison between the present emission situation for heavy-duty vehicles and the new fine particle emission standards set by the EU. For dioxins: an EU directive that regulates commercial fishing of Baltic salmon and herring that exceed the dioxin concentration limit set for fish meat, and a derogation (= exemption) from the directive for these two species. Both of these two decisions are very topical issues and this study estimates the expected changes in health effects due to these regulations. It was found that the estimated fine particle risk clearly outweighed the estimated dioxin risk. A substantial improvement to public health could be achieved by initiating reductions in emission standards; about 30 avoided premature deaths annually in the study area. In addition, the benefits of fish consumption due to omega-3 exposure were notably higher than the potential dioxin cancer risk. Both regulations were instigated as ways of promoting public health. Lindström, J., Peltonen, M., Eriksson, J. G., Aunola, S., Hämäläinen, H., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Uusitupa, M. and Tuomilehto, J. Diabetes Care. 2008; 31(5): 857-62. IF 7.851 OBJECTIVE: Intensive lifestyle intervention significantly reduced diabetes incidence among the participants in the Finnish Diabetes Prevention Study. We investigated whether and to what extent risk factors for type 2 diabetes and other baseline characteristics of the study participants modified the effectiveness of the lifestyle intervention. RESEARCH DESIGN AND METHODS: Overweight, middle-aged volunteers with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention (n = 265) or to a control group (n = 257) for a median of 4 years. Diabetes status was ascertained annually with repeated oral glucose tolerance testing. Incidence rates of diabetes and hazard ratios (HRs) comparing the intervention group with the control group were calculated by sex and baseline tertiles of age, BMI, waist circumference, plasma glucose concentration at fasting and 2 h after a glucose load, fasting serum insulin and insulin resistance index, and categories of composite baseline Finnish Diabetes Risk Score (FINDRISC). Interactions between the intervention assignment and baseline risk factors on diabetes risk were analyzed. RESULTS: The intervention was most effective among the oldest individuals (HRs 0.77, 0.49, and 0.36 by increasing age tertiles, respectively; P(interaction) = 0.0130) and those with a high baseline FINDRISC (HRs 1.09, 0.84, 0.34, and 0.22 by increasing risk score category, respectively; P(interaction) = 0.0400). The effect of the intervention on diabetes risk was not modified by other baseline characteristics or risk factors. CONCLUSIONS: The FINDRISC may be useful in identifying high-risk groups most likely to benefit from intensive lifestyle intervention to prevent type 2 diabetes. Madhi, S. A., Whitney, C. G. and Nohynek, H. Vaccine. 2008; 26: B9-B15. Article. IF 3.377 This article discusses lessons learned from clinical trials with pneumococcal conjugate vaccines (PCVs). A review of major clinical trials investigating PCV efficacy, this article provides the context to explore challenges associated with studying pneumococcal pneumonia and vaccine efficacy, particularly related to non-bacteremic disease, serotypes, and radiograph interpretation. Throughout these clinical trials, improving the pneumonia diagnosis specificity increased vaccine efficacy estimates. Additional analysis suggests this improvement may come at a cost of detecting much less of the disease burden. The article concludes with a discussion of the potential value of C-reactive protein as an adjunctive marker in measuring PCV efficacy against non-bacteremic pneumococcal pneumonia. (c) 2008 Elsevier Ltd. All rights reserved. Differences in outcome of DSM-IV bipolar I and II disorders Mantere, O., Suominen, K., Valtonen, H. M., Arvilommi, P., Leppamaki, S., Melartin, T. and Isometsa, E. Bipolar Disord. 2008; 10(3): 413-25. IF 4.442 OBJECTIVES: To investigate whether the course of bipolar disorder (BD) type II is more depressive than that of BD I, and, if so, to explore the underlying factors that cause this difference. METHODS: In a prospective, naturalistic study of 191 secondary care psychiatric in- and outpatients diagnosed in an acute phase of BD I or II, 160 patients (85.1%) were followed for 18 months. Using a life chart, the exact timing of symptom states in follow-up was examined. Differences between BD I (n = 75) and II (n = 85) in duration of index phase and episode, time to full remission and recurrence, and time in any mood episode were investigated. RESULTS: Patients with BD II spent a higher proportion of time ill (47.5% versus 37.7%; p = 0.02) and in depressive symptom states (58.0% versus 41.7%; p = 0.003) than BD I patients. This was a result of the higher proportion (61.7% versus 48.6%; p = 0.03) and mean number (1.69 versus 1.11; p = 0.006) of depressive illness phases in BD II, rather than of differences in the duration of depressive phases. Type of index phase strongly predicted the outcome. In linear regression models, both BD II and type of index phase predicted more time spent in depressive symptom states. CONCLUSIONS: In medium-term follow-up, BD II patients spend about 40% more time in depressive symptom states than BD I patients because a higher proportion of BD II patients have depressive phases and the frequency of these is higher. Differences in type of index phase may markedly confound differences in outcome between BD I and II. Marttila, H. J., Makinen, J., Marjamaki, M. and Soini, H. Eur J Clin Microbiol Infect Dis. 2008. IF 2.309 A pyrosequencing-based method for the rapid detection of isoniazid (INH) and rifampin (RIF) resistance in Mycobacterium tuberculosis was evaluated in clinical practice. The method can detect the INH resistance-causing katG315 mutation, and all mutations in the RIF resistance-determining rpoB core region, in less than 6 h from cultured isolates. The method was first validated with 42 isolates, and was subsequently prospectively evaluated with 91 isolates, including clinical isolates and external quality control assessment strains, over a period of 2.5 years. The pyrosequencing results of clinical isolates were available, on average, 19 days earlier (median 19 days; range 3-43 days) than conventional susceptibility testing results. The composite data showed that the sensitivity of pyrosequencing for detecting resistance correctly was 66.7% for INH and 97.4% for RIF. The specificity of pyrosequencing was 100% for both drugs. Acceptable sensitivity for detecting resistance and the rapidness of pyrosequencing make it a valuable tool in the clinical setting. Mustelin, L., Pietilainen, K. H., Rissanen, A., Sovijarvi, A. R., Piirila, P., Naukkarinen, J., Peltonen, L., Kaprio, J. and Yki-Jarvinen, H. American Journal of Physiology-Endocrinology and Metabolism. 2008; 295(1): E148-E154. Article. IF 4.138 Defects in expression of genes of oxidative phosphorylation in mitochondria have been suggested to be a key pathophysiological feature in familial insulin resistance. We examined whether such defects can arise from lifestyle-related factors alone. Fourteen obesity-discordant (BMI difference 5.2 +/- 1.8 kg/m(2)) and 10 concordant (1.0 +/- 0.7 kg/m(2)) monozygotic (MZ) twin pairs aged 24-27 yr were identified among 658 MZ pairs in the population-based FinnTwin16 study. Whole body insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique. Transcript profiles of mitochondrial genes were compared using microarray data of fat biopsies from discordant twins. Body composition of twins was determined using DEXA and maximal oxygen uptake ((V) over dot O-2max) and working capacity (W-max) using a bicycle ergometer exercise test with gas exchange analysis. The obese cotwins had lower insulin sensitivity than their nonobese counterparts (M value 6.1 +/- 2.0 vs. 9.2 +/- 3.2 mg . kg LBM-1 . min(-1), P < 0.01). Transcript levels of genes involved in the oxidative phosphorylation pathway (GO: 0006119) in adipose tissue were lower (P < 0.05) in the obese compared with the nonobese cotwins. The obese cotwins were also less fit, as measured by (V) over dot O-2max (50.6 +/- 6.5 vs. 54.2 +/- 6.4 ml . kg LBM-1 . min(-1), for obese vs. nonobese, P < 0.05), Wmax (3.9 +/- 0.5 vs. 4.4 +/- 0.7 W/kg LBM, P < 0.01) and also less active, by the Baecke leisure time physical activity index (2.8 +/- 0.5 vs. 3.3 +/- 0.6, P < 0.01). This implies that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria. Serum uric acid and incident diabetes in Mauritian Indian and Creole populations Nan, H., Qiao, Q., Soderberg, S., Pitkaniemi, J., Zimmet, P., Shaw, J., Alberti, G., Uusitalo, U., Pauvaday, V., Chitson, P. and Tuomilehto, J. Diabetes Res Clin Pract. 2008; 80(2): 321-7. IF 1.823 OBJECTIVE: To investigate the predictive value of serum uric acid (UA) for the development of diabetes in Asian Indians and Creoles living in Mauritius. METHODS: A total of 1941 men (1409 Indians, 532 Creoles) and 2318 non-pregnant women (1645 Indians, 673 Creoles), aged 25-74 years and free of diabetes, cardiovascular disease and gout at baseline examinations in 1987 or 1992, were re-examined in 1992 and/or 1998. Diabetes was determined according to WHO/IDF 2006 criteria. The relationship between baseline UA and the development of diabetes during the follow-up was estimated using interval censored survival analysis. RESULTS: In this cohort 337 (17.4%) men and 379 (16.4%) women developed diabetes during the follow-up. Individuals who developed diabetes during the follow-up had a lower serum UA levels at follow-up compared with their baseline UA levels, but this is not observed for post-menopausal women. Multivariate adjusted hazard ratios (HRs) (95% CIs) for the development of diabetes corresponding to one S.D. increase in UA concentration at baseline were 1.14 (1.01, 1.30) in Indian men and 1.37 (1.11, 1.68) in Creole men. They were 1.07 (0.95, 1.22) and 1.01 (0.84, 1.22), respectively, in Indians and Creole women. CONCLUSION: Elevated serum UA is an independent risk marker for future diabetes in Mauritian men, whereas the prediction is weak in women. Hydrolethalus syndrome: Neuropathology of 21 cases confirmed by HYLS1 gene mutation analysis Paetau, A., Honkala, H., Salonen, R., Ignatius, J., Kestilia, M. and Herva, R. Journal of Neuropathology and Experimental Neurology. 2008; 67(8): 750-762. Article. IF 4.718 Hydrolethalus syndrome is a lethal malformation syndrome with a severe brain malformation, most often hydrocephaly and absent midline structures. Other frequent findings are micrognathia, polydactyly, and defective lobation of the lungs. Hydrolethalus syndrome is inherited in an autosomal recessive manner and is caused by a missense mutation in the HYLS1 gene. Here, we report the neuropathologic features of 21 genetically confirmed cases. Typically, 2 separated cerebral hemispheres could be identified, but they lacked midline and olfactory structures and were situated basally with a massive accumulation of cerebrospinal fluid. Temporal and occipital lobes were hypoplastic, and normally developed hippocampi were not found. Primitive thalami and basal ganglia were fused in the midline. A hypothalamic hamartoma was a frequent finding, and brainstem and cerebellum were hypoplastic. Three cases were bydranencephalic, and I was anencephalic. A midline "keyhole" defect in the skull base was a constant finding. Histologically, the cortex was dysplastic. This pattern of brain pathology, clearly belonging to the midline patterning defects, seems to be unique for the hydrolethalus syndrome and combines features of disturbed neurulation, prosencephalization, and migration. Despite variation in the clinicopathologic phenotype, all cases in the series carried the same homozygous missense mutation in HYLS1. Paiva, H., Kahonen, M., Lehtimaki, T., Raitakari, O. T., Jula, A., Viikari, J., Alfthan, G., Juonala, M., Laaksonen, R. and Hutri-Kahonen, N. American Journal of Hypertension. 2008; 21(8): 873-878. Article. IF 3.102 BACKGROUND This study was designed to evaluate whether plasma asymmetric dimethylarginine (ADMA) has any role in predicting hemodynamic responses in clinically healthy young subjects. ADMA, as an endogenous nitric oxide (NO) synthase inhibitor, has been demonstrated to associate with hypertension and vascular reactivity in experimental but not undoubtedly in physiological settings. METHODS A total of 199 subjects aged 31.4 years (range 24-39 years) were studied. Plasma ADMA and symmetric dimethylarginine (SDMA) were assessed by isocratic high-pressure liquid chromatography using precolumn derivatization with o-phtaldialdehyde at baseline. Blood pressure (BP) was measured by casual measurements in the beginning of the study and after a follow-up period of 2.45 +/- 0.42 years (range, 1.86-3.19 years). Hemodynamic regulation was assessed by noninvasive methods after a follow-up. RESULTS Plasma ADMA had a negative association with resting systemic vascular resistance index (SVRI) (r=-0.23, P < 0.01) and pulse wave velocity (PWV) (r=-0.17, P < 0.05) and positive association with wcardiac index (0) (r=0.21, P < 0.01) after the follow-up. Plasma ADMA had also negative association with responses of SVRI (r=-0.19, P < 0.01) and positive association with Cl (r=0.25, P < 0.001) in a hemodynamic reactivity test. In a multivariate linear model (R-2 = 0.20, P < 0.00001), diastolic BP (R = 0.37, P < 0.00001) and ADMA (R=-0.20, P < 0.01) were significant predictors of SVRI. CONCLUSIONS These results suggest that plasma ADMA seems to play a role in the regulation of vascular tone in young healthy subjects. Patja, K., Vainiotalo, S., Laatikainen, T., Kuusimäki, L., Peltonen, K. and Vartiainen, E. Nicotine Tob Res. 2008; 10(8): 1327-33. IF 2.129 Environmental tobacco smoke (ETS) is among the most common environmental health risks, with a striking and immediate biological response and increased disease risk. Exposure studies have looked mostly at worksite or home exposures, whereas total exposure levels at the population level are rarely reported. This study examined ETS exposure at work, at home, and during leisure time in a cross-sectional population sample of working-age adults. Our aim was to monitor changes in ETS exposure from 1992 to 2002. More detailed information on duration of exposure, distribution of exposure sites, and patterns of exposure was obtained in 2002. Data were based on Finland's national population chronic disease risk-factor surveys (conducted every 5 years). Total sample size varied from 8,000 to 13,500. The survey includes a self-administered questionnaire about ETS exposure at different sites. The proportion of nonsmoking persons exposed to ETS declined throughout the study period among both men and women. In 2002, 5.9% of male and 3.6% of female nonsmokers were exposed to ETS 1 hour or more per day, whereas 5.8% of men and 1.7% women were exposed less than 1 hour daily. Worksite exposure was more common among younger age groups of both sexes, but nonsmoking women in older age groups received more exposure at home than at worksites. Policy developments on ETS should aim to protect the whole population from ETS in all environments given that health risks from ETS often persist at home and in leisure environments. Total exposure levels should be studied to assess the health impacts of ETS. Problems in using incidence to analyze risk factors in follow-up studies Pekkanen, J. and Sunyer, J. Eur J Epidemiol. 2008. IF 1.727 The most common practice to analyze epidemiological follow-up studies is to analyze risk factors of new, i.e. incident, cases of disease. However, analysis of incidence assumes that diseases exist in true dichotomies, which is unlikely to be true. It has also recently been shown that in many typical situations it is very difficult to separate the association between risk factors of disease at baseline and during follow-up using analyses of incidence. Situation is especially problematic for diseases that have large misclassification and low incidence, like asthma. We suggest that reliance on analysis of incidence may be a major obstacle into discovering causes of such disease. Only with greater attention into how to define and how to analyze prospective studies are we likely to learn sufficiently of risk factors of such disease to finally arrive at means for their prevention. Peters, R., Beckett, N., Forette, F., Tuomilehto, J., Clarke, R., Ritchie, C., Waldman, A., Walton, I., Poulter, R., Ma, S., Comsa, M., Burch, L., Fletcher, A. and Bulpitt, C. Lancet Neurology. 2008; 7(8): 683-689. Article. IF 10.169 Background Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia; however, the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting, and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence. The Hypertension in the Very Elderly trial (HYVET) was designed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function. Methods Patients with hypertension (systolic pressure 160-200 mm. Hg; diastolic pressure < 110 mm Hg) who were aged 80 years or older were enrolled in this double-blind, placebo-controlled trial. Participants were randomly assigned to receive 1.5 mg slow release indapamide, with the option of 2-4 mg perindopril, or placebo. The target systolic blood pressure was 150 mm Hg; the target diastolic blood pressure was 80 mm Hg. Participants had no clinical diagnosis of dementia at baseline, and cognitive function was assessed at baseline and annually with the mini-mental state examination (MMSE). Possible cases of incident dementia (a fall in the MMSE score to < 24 points or a drop of three points in 1 year) were assessed by standard diagnostic criteria and expert review. The trial was stopped in 2007 at the second interim analysis after treatment resulted in a reduction in stroke and total mortality. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00122811. Findings 3336 HYVET participants had at least one follow-up assessment (mean 2.2 years) and were included: 1687 participants were randomly assigned to the treatment group and 1649 to the placebo group. Only five reports of adverse effects were attributed to the medication: three in the placebo group and two in the treatment group. The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg, p < 0.0001; and diastolic -5.9 mm Hg, p < 0.0001. There were 263 incident cases of dementia. The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group. There was no significant difference between treatment and placebo groups (hazard ratio [HR] 0.86, 95% CI 0.67-1.09); however, when these data were combined in a meta-analysis with other placebo-controlled trials of antihypertensive treatment, the combined risk ratio favoured treatment (HR 0.87, 0.76-1.00, p=0.045). Interpretation Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia. This negative finding might have been due to the short follow-up, owing to the early termination of the trial, or the modest effect of treatment. Nevertheless, the HYVET findings, when included in a meta-analysis, might support antihypertensive treatment to reduce incident dementia. Pointon, J. J., Chapman, K., Harvey, D., Sims, A. M., Bradbury, L., Laiho, K., Kauppi, M., Kaarela, K., Tuomilehto, J., Brown, M. A. and Wordsworth, B. P. Journal of Rheumatology. 2008; 35(8): 1609-1612. Article. IF 3.151 Objective. To investigate the association of CD14 and Toll-like receptor (TLR4) with ankylosing spondylitis (AS). Methods. A promoter variant in CD14 and 2 coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies was performed. Results. In the Finnish study the CD14-260bp T variant showed an association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak association (global p = 0.03), with AS. No associations were seen in the UK based studies or in the metaanalyses. Conclusion. CD14 and TLR4 showed an association with AS in the Firms only. Puumalainen, T., Quiambao, B., Abucejo-Ladesma, E., Lupisan, S., Heiskanen-Kosma, T., Ruutu, P., Lucero, M. G., Nohynek, H., Simoes, E. A. F. and Riley, I. Bmc Infectious Diseases. 2008; 8. Review. IF 2.021 Background: The World Health Organization's (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies. Methods: A group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population. Results: Among the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO-defined severe pneumonia (with chest indrawing) had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation. Conclusion: The WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings. Seasonal changes in mood and behavior are linked to metabolic syndrome Rintamaki, R., Grimaldi, S., Englund, A., Haukka, J., Partonen, T., Reunanen, A., Aromaa, A. and Lonnqvist, J. PLoS ONE. 2008; 3(1): e1482. IF BACKGROUND: Obesity is a major public health problem worldwide. Metabolic syndrome is a risk factor to the cardiovascular diseases. It has been reported that disruptions of the circadian clockwork are associated with and may predispose to metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: 8028 individuals attended a nationwide health examination survey in Finland. Data were collected with a face-to-face interview at home and during an individual health status examination. The waist circumference, height, weight and blood pressure were measured and samples were taken for laboratory tests. Participants were assessed using the ATP-III criteria for metabolic syndrome and with the Seasonal Pattern Assessment Questionnaire for their seasonal changes in mood and behavior. Seasonal changes in weight in particular were a risk factor of metabolic syndrome, after controlling for a number of known risk and potential confounding factors. CONCLUSIONS AND SIGNIFICANCE: Metabolic syndrome is associated with high global scores on the seasonal changes in mood and behavior, and with those in weight in particular. Assessment of these changes may serve as a useful indicator of metabolic syndrome, because of easy assessment. Abnormalities in the circadian clockwork which links seasonal fluctuations to metabolic cycles may predispose to seasonal changes in weight and to metabolic syndrome. Body composition in psychotic disorders: a general population survey Saarni, S. E., Saarni, S. I., Fogelholm, M., Heliovaara, M., Perala, J., Suvisaari, J. and Lonnqvist, J. Psychol Med. 2008: 1-10. IF 4.212 BACKGROUND: The literature suggests an association between obesity and schizophrenia but fat mass and fat-free mass, which have been shown to be more predictive of all-cause mortality than only waist circumference and obesity [body mass index (BMI) 30 kg/m2], have not been reported in psychotic disorders. We examined the detailed body composition of people with different psychotic disorders in a large population-based sample.MethodWe used a nationally representative sample of 8082 adult Finns aged 30 years with measured anthropometrics (height, weight, waist circumference, fat percentage, fat-free mass and segmental muscle mass). Psychiatric diagnoses were based on a consensus procedure utilizing the Structured Clinical Interview for DSM-IV (SCID)-interview, case-notes and comprehensive register data. RESULTS: Schizophrenia (including schizo-affective disorder) was associated with obesity [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.5-3.6], abdominal obesity (waist circumference 88 cm for women, 102 cm for men) (OR 2.2, 95% CI 1.3-3.6) and with higher fat percentage (mean difference 3.8%, 95% CI 2.0-5.7%), adjusted for age and gender, than in the remaining sample. The associations between schizophrenia and low fat-free mass and decreased muscle mass on trunk and upper limbs became statistically significant after adjusting for BMI. After further adjusting for current antipsychotic medication, education, diet and smoking, schizophrenia remained associated with obesity (OR 1.9, 95% CI 1.1-3.6) and abdominal obesity (OR 3.8, 95% CI 1.5-9.4). Participants with affective psychoses did not differ from the general population. CONCLUSIONS: Individuals with schizophrenia have metabolically unfavorable body composition, comprising abdominal obesity, high fat percentage and low muscle mass. This leads to increased risk of metabolic and cardiovascular diseases. Gender and injury in Finnish comprehensive schools Salminen, S., Lounamaa, A. and Kurenniemi, M. Accident Analysis and Prevention. 2008; 40(4): 1267-1272. Article. IF 1.586 The aim of this study is to analyze the gender differences in injuries at Finnish comprehensive schools. Nine schools reported a total of 1135 injuries to the injury register over two school years. Boys (56%) were injured more often than girls, their injuries happened more often during breaks at school yard, whereas girls hurt themselves during sport lectures in the gymnastic halls. The proportion of boys' injuries also increased with age. More often, boys' injuries were caused by intentional actions by other pupils. Girls injured their lower extremities more often, whereas boys injured their faces and head. Boys also suffered concussion more often than girls, and were also referred for further care to health care centres or hospitals more often than girls. The higher injury frequency among boys at school corresponds to the higher injury rate of males in general, which is true for work, traffic, and leisure-time injuries. Increased adult supervisor control especially during breaks can prevent most of school injuries. (c) 2008 Elsevier Ltd. All rights reserved. The mutation spectrum in RECQL4 diseases Siitonen, H. A., Sotkasiira, J., Biervliet, M., Benmansour, A., Capri, Y., Cormier-Daire, V., Crandall, B., Hannula-Jouppi, K., Hennekam, R., Herzog, D., Keymolen, K., Lipsanen-Nyman, M., Miny, P., Plon, S. E., Riedl, S., Sarkar, A., Vargas, F. R., Verloes, A., Wang, L. L., Kaariainen, H. and Kestila, M. Eur J Hum Genet. 2008. IF 4.003 Mutations in the RECQL4 gene can lead to three clinical phenotypes with overlapping features. All these syndromes, Rothmund-Thomson (RTS), RAPADILINO and Baller-Gerold (BGS), are characterized by growth retardation and radial defects, but RAPADILINO syndrome lacks the main dermal manifestation, poikiloderma that is a hallmark feature in both RTS and BGS. It has been previously shown that RTS patients with RECQL4 mutations are at increased risk of osteosarcoma, but the precise incidence of cancer in RAPADILINO and BGS has not been determined. Here, we report that RAPADILINO patients identified as carriers of the c.1390+2delT mutation (p.Ala420_Ala463del) are at increased risk to develop lymphoma or osteosarcoma (6 out of 15 patients). We also summarize all the published RECQL4 mutations and their associated cancer cases and provide an update of 14 novel RECQL4 mutations with accompanying clinical data.European Journal of Human Genetics advance online publication, 20 August 2008; doi:10.1038/ejhg.2008.154. Suvilehto, J., Jarva, H., Seppanen, M., Siljander, T., Vuopio-Varkila, J. and Meri, S. Microbes and Infection. 2008; 10(7): 757-763. Article. IF 2.523 Group A streptococcus (GAS) is the most common pathogen causing bacterial pharyngitis. We isolated streptococcal strains from tonsils removed from patients with tonsillar disease (n = 202) and studied their ability to bind the complement regulators factor H (FH) and C4b binding protein (C4BP) using I-125-labeled proteins. Blood isolates of GAS (n = 10) were obtained from patients with bacteraemia. Streptococci were isolated from 21% of the tonsillitis patients. The emm and T types of the GAS strains were determined. Of the 26 GAS strains studied, only six could bind FH and/or C4BP above the threshold levels. The fraction of the offered radioactive protein bound ranged between 6-12% for FH and 19-56% for C4BP. The clinical course of the tonsillar disease was not related to the binding of FH or C4BP by GAS. The binding strains were mostly of the T4M4 or T28M28 type. From the invasive strains (n = 10), three bound FH (binding level: 8-11 %) and two C413P (36-39%). The binding correlated only partially to M-protein (emm) type suggesting that the binding was not exclusively due to M-protein. The results indicate that complement regulator binding by GAS is only partially related to pathogenicity and not a universal property of all group A streptococci. (C) 2008 Elsevier Masson SAS. All rights reserved. Mortality in offspring of mothers with psychotic disorder Suvisaari, J., Häkkinen, L., Haukka, J. and Lönnqvist, J. Psychological Medicine. 2008; 38(8): 1203-1210. Article. IF 4.212 Background. Previous studies suggest that offspring of mothers with psychotic disorders have an almost two-fold higher mortality risk from birth until early adulthood. We investigated predictors of mortality from late adolescence until middle age in offspring of mothers with psychotic disorders. Method. The Helsinki High-Risk Study follows up offspring (n = 337) of women treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975. Factors related to mortality up to 2005 among offspring of these mothers was investigated with a survival model. Hazard rate ratios (HRR) were calculated using sex, diagnosis of psychotic disorder, childhood socio-economic status, maternal diagnosis, and maternal suicide attempts and aggressive symptoms as explanatory variables. The effect of family was investigated by including a frailty term in the model. We also compared mortality between the high-risk group and the Finnish general population. Results. Within the high-risk group, females had lower all-cause mortality (HRR 0.43, p=0.05) and mortality from unnatural causes (HRR 0.24,p-0.03) than males. Having themselves been diagnosed with a psychotic disorder was associated with higher mortality from unnatural causes (HRR 4.76, p=0.01), while maternal suicide attempts were associated with higher suicide mortality (HRR 8.64,p=0.03). Mortality in the high-risk group was over two-fold higher (HRR 2.44, p < 0.0001) than in the general population, and remained significantly higher when high-risk offspring who later developed psychotic disorders were excluded from the study sample (HRR 2.30, p < 0.0001). Conclusions. Offspring of mothers with psychotic disorder are at increased risk of several adverse outcomes, including premature death. Trend in sports injuries among young people in Finland Tiirikainen, K., Lounamaa, A., Paavola, M., Kumpula, H. and Parkkari, J. Int J Sports Med. 2008; 29(6): 529-36. IF 1.524 The main purpose of this study was to explore how the number of home, sports, and other leisure time injuries among young people aged 15 - 25 years has developed in Finland in 1988 - 2003. In 1988, 2559 people aged 15 - 25 years were interviewed by Statistics Finland. In 1993, 1997 and 2003 those amounts were 751, 1638 and 1382. The subjects were asked in a telephone interview to report the injuries in which they had been involved during the previous 12 months. The crude injury incidence in 2003 was 364 per 1000 person years in men and 246 in women. The total number of injuries increased 49 % between the years 1988 and 2003. The number of sports injuries increased the most. The increase was greater among men than women, and the injury rate was higher among both men and women aged 15 - 19 years than those aged 20 - 25 years. More research is needed on whether and how exercise and time at home have changed and become riskier among young people. It is also essential to find out which prevention methods are the most effective among young people and implement these measures in a well-planned and targeted manner. Hopelessness across phases of bipolar I or II disorder: A prospective study Valtonen, H. M., Suominen, K., Haukka, J., Mantere, O., Arvilommi, P., Leppamaki, S. and Isometsa, E. T. J Affect Disord. 2008. IF 3.144 BACKGROUND: Hopelessness, a key risk factor for suicidal behaviour overall, has been studied little among bipolar disorder (BD) patients. For purposes of prevention, it is important to know whether it is predominantly a patient's permanent trait or merely reflects the highly variable illness states. We investigated the degree to which hopelessness is trait- or state-related during the course of BD. METHODS: The Jorvi Bipolar Study (JoBS) is a naturalistic prospective study representing psychiatric in- and outpatients with DSM-IV BD I and II. Repeated measurements with the Beck Hopelessness Scale of 188 patients at baseline, 6 months and 18 months were analysed using a linear regression model with general estimation equations. Factors covarying with hopelessness during follow-up were investigated. RESULTS: Levels of hopelessness varied markedly between illness phases, being highest in depressive and mixed phases, and lowest in euthymia, hypomania or mania. Hopelessness was independently associated with concurrent severity of depression (estimate 0.231, p<0.001), anxiety (0.105, p<0.001), fewer manic symptoms (-0.096, p=0.001) and comorbid personality disorder (1.741, p=0.001). However, the strongest predictor of degree of hopelessness during follow-up was previous hopelessness (0.403, p<0.001). LIMITATIONS: After baseline, relatively few patients had manic, hypomanic, mixed or depressive mixed phases. Hopelessness was measured at only three time-points. CONCLUSIONS: Level of hopelessness varies markedly between patients in different phases of BD, but is also, to a degree, a permanent feature. Among BD patients, hopelessness appears to be both a trait- and state-related characteristic. Wedenoja, J., Loukola, A., Tuulio-Henriksson, A., Paunio, T., Ekelund, J., Silander, K., Varilo, T., Heikkilä, K., Suvisaari, J., Partonen, T., Lönnqvist, J. and Peltonen, L. Mol Psychiatry. 2008; 13(7): 673-84. IF 10.900 Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n=1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n=1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n=861) of the sample showed significant association to RELN variants for traits related to verbal (P=0.000003) and visual working memory (P=0.002), memory (P=0.002) and executive functioning (P=0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P=0.0004-0.0000000004), memory (P=0.02-0.0001) and executive functioning (P=0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia. |