Evaluation of voice commands for mode change in virtual reality implant planning procedure.

PURPOSE: In dental implantology, the optimal placement of dental implants is important to meet functional and aesthetic requirements. Planning dental implants in virtual three-dimensional (3D) environment is possible using virtual reality (VR) technologies. The three-dimensional stereoscopic virtual reality environment offers advantages over three-dimensional projection on a two-dimensional display. The use of voice commands in virtual reality environment to replace button presses and other simple actions frees the user's hands and eyes for other tasks. METHODS: Six dentomaxillofacial radiologists experimented using a prototype version of a three-dimensional virtual reality implant planning tool, and used two different tool selection methods, using either only button presses or also voice commands. We collected objective measurements of the results and subjective data of the participant experience to compare the two conditions. RESULTS: The tool was approved by the experts and they were able to do the multiple-implant planning satisfactorily. The radiologists liked the possibility to use the voice commands. Most of the radiologists were willing to use the tool as part of their daily work routines. CONCLUSION: The voice commands were useful, natural, and accurate for mode change, and they could be expanded to other tasks. Button presses and the voice commands should be both available and used in parallel. The input methods can be further improved based on the expert comments.

Evaluation of virtual handles for dental implant manipulation in virtual reality implant planning procedure.

PURPOSE: Many surgical complications can be prevented by careful operation planning and preoperative evaluation of the anatomical features. Virtual dental implant planning in three-dimensional stereoscopic virtual reality environment has advantages over three-dimensional projections on two-dimensional screens. In the virtual environment, the anatomical areas of the body can be assessed and interacted with in six degrees-of-freedom. Our aim was to make a preliminary evaluation of how professional users perceive the use of the virtual environment on their field. METHODS: We prepared a novel implementation of a virtual dental implant planning system and conducted a small-scale user study with four dentomaxillofacial radiologists to evaluate the usability of direct and indirect interaction in a planning task. RESULTS: We found that all four participants ranked direct interaction, planning the implant placement without handles, to be better than the indirect condition where the implant model had handles. CONCLUSION: The radiologists valued the three-dimensional environment for three-dimensional object manipulation even if usability issues of the handles affected the feel of use and the evaluation results. Direct interaction was seen as easy, accurate, and natural.

Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

[This corrects the article DOI: 10.1371/journal.pone.0191172.].

Evolutionary methods for variable selection in the epidemiological modeling of cardiovascular diseases.

BACKGROUND: The redundancy of information is becoming a critical issue for epidemiologists. High-dimensional datasets require new effective variable selection methods to be developed. This study implements an advanced evolutionary variable selection method which is applied for cardiovascular predictive modeling. The epidemiological follow-up study KIHD (Kuopio Ischemic Heart Disease Risk Factor Study) was used to compare the designed variable selection method based on an evolutionary search with conventional stepwise selection. The sample contains in total 433 predictor variables and a response variable indicating incidents of cardiovascular diseases for 1465 study subjects. RESULTS: The effectiveness of variable selection methods was investigated in combination with two models: Generalized Linear Logistic Regression and Support Vector Machine. We managed to decrease the number of variables from 433 to 38 and save the predictive ability of the models used. Their performance was evaluated with an F-score metric. At most, we gained 65.6% and 67.4% of the F-score before and after variable selection respectively. All the results were averaged over 5-folds of a cross-validation procedure. CONCLUSIONS: The presented evolutionary variable selection method allows a reduced set of variables to be chosen which are relevant to predicting cardiovascular diseases. A reference list of the most meaningful variables is introduced to be used as a basis for new epidemiological studies. In general, the multicollinearity of variables enables different combinations of predictors to be used and the same performance of models to be attained.

Determinants of hospitalizations for pneumonia among Finnish drug users.

OBJECTIVE: The study examined the determinants of being hospitalized for pneumonia in a large cohort of drug users. METHODS: Information of 4817 clients seeking treatment for illicit drug use was linked with the Finnish hospital discharge register to identify those who were hospitalized with main/primary diagnoses of pneumonia during 1997-2013. Cox regression models were used to examine the association between age, gender, homelessness, and route of drug administration of the primary drug at initial clinical consultation and pneumonia hospitalization. Findings were presented as adjusted hazard ratios and 95% confidence intervals. RESULTS: There were 354 persons diagnosed with pneumonia, with a total of 522 hospitalizations at the end of 2013. The univariate Cox models revealed that being over 44 years of age, male gender, homelessness, and intravenous drug use at initial clinical consultation increased the risk of being hospitalized for pneumonia. In the fully adjusted multivariate model, being over 44 years was the strongest factor independently associated with pneumonia hospitalization (adjusted hazard ratio: 2.67, 95% confidence interval: 1.56-4.57, p < 0.001), followed by homelessness (adjusted hazard ratio: 1.75, 95% confidence interval: 1.38-2.22, p < 0.001) and intravenous drug use (adjusted hazard ratio: 1.27, 95% confidence interval: 1.01-1.59, p = 0.041). Of the 354 clients hospitalized for pneumonia, 31.9% (n = 113) were rehospitalized within 30 days of being discharged. One-third of the reasons for the 30-day rehospitalization were pneumonia-related. CONCLUSION: Vaccination, measures addressing housing instability, safe injecting and good hygienic practices, and treating underlying drug use problems could help to reduce morbidity for pneumonia in this cohort.

Diabetes hospitalizations and deaths in a cohort of treatment-seeking illicit drug users.

BACKGROUND: Studies on diabetes among illicit drug users are scarce in Finland. This study aimed to describe hospitalization and death due to diabetes among treatment-seeking illicit drug users. METHODS: Information of 4817 treatment-seeking drug users (3365 men and 1452 women) aged 11-65 years (mean 24.5 years) was linked to the Finnish national hospital discharge register and the national death registry to identify those clients who were hospitalized or died from diabetes mellitus during 1997-2013. RESULTS: Fifty-three persons (42 men and 11 women) had primary diagnoses of diabetes, with a total of 146 hospitalizations (121 among men and 25 among women). The total length of stay among men (1183 days) far exceeded those of women (138 days). Overall, type 1 diabetes was the main contributor to hospitalizations (67%, n = 98/146). The proportion of Type 1 diabetes with complications was 31% in men (n = 37/121) and 44% in women (n = 11/25). All cases of deaths due to diabetes (n = 7) occurred in men. CONCLUSION: Diabetes hospitalizations were mainly due to Type 1 diabetes. Longer length of hospital stay was observed in men, and all diabetes deaths occurred among men. Male drug users and drug users in general would require more support to reduce morbidity and mortality due to diabetes.

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Follicle-Stimulating Hormone Levels and Subclinical Atherosclerosis in Older Postmenopausal Women.

Recent studies of perimenopausal women suggest that follicle-stimulating hormone (FSH) levels may be associated with atherosclerosis, independent of estradiol. Whether FSH is related to atherosclerosis in older postmenopausal women, who have completed the menopausal transition, remains unknown. We assessed the relationship of serum FSH and estradiol levels with carotid artery intima-media thickness (IMT) among 587 postmenopausal participants in the Kuopio Ischemic Heart Disease Risk Factor Study (Kuopio, Finland). Participants were aged 53-73 years and not using hormone therapy at baseline (1998-2001). Mean IMT was measured via high-resolution ultrasonography. We observed a significant inverse association between FSH levels and IMT. Mean IMTs among women in quartiles 1-4 of FSH were 0.94 mm, 0.91 mm, 0.87 mm, and 0.85 mm, respectively (P-trend < 0.001). After adjustment for age, estradiol, testosterone, body mass index (weight (kg)/height (m)2), lipids, and other factors, FSH levels remained significantly associated with IMT (regression coefficients for quartiles 2-4 vs. quartile 1 were -0.038, -0.045, and -0.062, respectively; P-trend = 0.01). Findings were strongest in women aged 64-73 years (P-trend = 0.006) and did not vary by body mass index. In contrast, estradiol levels were not related to IMT. In summary, high postmenopausal FSH levels were associated with a lower atherosclerotic burden, independent of estradiol, adiposity, and other factors. Our findings warrant replication and the further exploration of potential underlying mechanisms.

Association between route of illicit drug administration and hospitalizations for infective endocarditis.

OBJECTIVE: This study examined the association between the route of drug administration and being hospitalized for infective endocarditis among 4817 treatment-seeking illicit drug users in Finland. METHODS: Cox regression models were used to examine the association between the route of drug administration and infective endocarditis hospitalization, adjusted for age, gender, and homelessness. Cases of infective endocarditis as a primary/main diagnosis were tracked using the 10th version of the International Classification of Disease code I33. RESULTS: In all, 47 persons had a primary diagnosis of infective endocarditis. These 47 persons contributed a total of 95 hospitalizations and their total length of hospital stay was 1393 days. There was a statistically significant difference in hospitalizations between injectors and non-injectors (Log-Rank test p = 0.018). Univariate Cox model showed that injectors had higher hazard or risk for infective endocarditis hospitalization compared to non-injectors (hazard ratio: 2.04, 95% confidence interval: 1.12-3.73, p = 0.020). After adjusting for age, gender, and homelessness in the multivariate model, the elevated hazard among injectors compared to non-injectors remained statistically significant with adjusted hazard ratio of 2.12 (95% confidence interval: 1.11-4.07, p = 0.024). CONCLUSION: The study findings suggested a need to boost harm reduction measures targeting high-risk injecting and other health behaviors among injecting drug users in order to reduce their hospitalizations for infective endocarditis.

Association of follicle-stimulating hormone levels and risk of type 2 diabetes in older postmenopausal women.

OBJECTIVE: Recent studies of perimenopausal women have observed associations of follicle-stimulating hormone (FSH) levels with markers of insulin resistance, independent of estradiol. Whether FSH is related to type 2 diabetes (T2D) in older women who have completed the menopause transition remains unknown. We assessed the association of FSH levels with diabetes and measures of insulin resistance among 588 postmenopausal Finnish women. METHODS: Study participants were aged 53 to 73 years and not using hormone therapy at baseline (1998-2001) when FSH was measured. Prevalence of T2D was assessed at baseline, along with fasting insulin and glucose levels. Incident T2D, and insulin and glucose levels were assessed 7 to 9 years later at follow-up examination. RESULTS: After adjustment for age, estradiol, body mass index, smoking, lipids levels, and other factors, women with higher FSH (>50 IU/L) had a lower prevalence of T2D (odds ratio 0.49, 95% confidence interval [CI] 0.28-0.86) than women with lower FSH. Each 1 unit increase in FSH level was associated with a significant 1.9% lower risk of T2D (95% CI 0.966-0.997, P = 0.02). Higher FSH was associated with marginally significant lower incidence of T2D at follow-up (hazard ratio 0.53, 95% CI 0.27-1.02). Baseline FSH levels were inversely correlated with fasting insulin and glucose levels at both baseline and follow-up visits (all P < 0.05). After adjustment, FSH was modestly associated with fasting insulin at baseline (P = 0.01) and at follow-up (P = 0.11). CONCLUSIONS: Higher postmenopausal FSH levels were associated with lower prevalent and incident T2D and fasting insulin levels. These findings warrant replication in larger prospective studies.

Exercise cardiac power and the risk of coronary heart disease and cardiovascular mortality in men.

PURPOSE: The aim of this study was to examine the relationship of exercise cardiac power (ECP), defined as a ratio of directly measured maximal oxygen uptake with peak systolic blood pressure during exercise, with the risk of mortality from coronary heart diseases (CHD) and cardiovascular diseases (CVD). DESIGN: Population-based cohort study with an average follow-up of 25 years from eastern Finland. About 2358 men at baseline participated in exercise stress test and 182 CHD and 302 CVD deaths occurred. RESULTS: Men with low ECP (< 8.7 mL/mmHg, lowest quartile) had a 3.5-fold (95% CI 2.1-5.8, p < 0.0001) risk of CHD mortality as compared with men with high ECP (>16.4 mL/mmHg, highest quartile) after adjusting for age and examination year. Low ECP was associated with a 2.8-fold risk of CHD and 2.4-fold for CVD mortality after additional adjustment for conventional risk factors. After further adjustment for leisure time physical activity, the results hardly changed (HR 2.5, 95% CI 1.71-3.67, p < 0.001). CONCLUSION: ECP provides non-invasive and easily available measure for the prediction of CHD and CVD mortality. One of the most potential explanation for the association between ECP and the risk of CHD and CVD mortality is an elevated afterload and peripheral resistance indicated by hypertension. Key messages Index of exercise cardiac power defined as the ratio of directly measured maximal oxygen uptake (VO2max) with peak systolic blood pressure gives prognostic information in coronary heart disease (CHD) and CVD mortality risk stratification. ECP provides non-invasive and easily available measure for the prediction of CHD and CVD mortality. One of the most potential explanation for the association between ECP and the risk of CHD and CVD mortality is an elevated afterload and peripheral resistance indicated by hypertension.

Inflammatory biomarker score and cancer: A population-based prospective cohort study.

BACKGROUND: Inflammation is associated with cancer but there are conflicting reports on associations of biomarkers of inflammation with cancer risk and mortality. We investigated the associations of C-reactive protein (CRP) and leukocyte count with cancer risk and mortality using individual biomarkers, and an inflammatory score derived from both biomarkers. METHODS: We conducted this analysis among 2,570 men enrolled in the population-based, prospective Kuopio Ischemic Heart Disease Risk Factor Study in Finland. During an average follow-up period of 26 years, 653 cancer cases and 287 cancer deaths occurred. We computed a z-score for each participant, with the combined z-score being the sum of each individual's CRP and leukocyte z-scores. Multivariable-adjusted Cox proportional hazard model was used to evaluate associations with cancer risk and mortality. RESULTS: Using individual biomarkers, elevated leukocyte count was associated with an increased risk of cancer (RR = 1.31, 95% CI 1.04-1.66), and cancer mortality (RR=, 95% CI 1.39, 0.98-1.97). The corresponding results for CRP were (RR = 1.23, 95% CI 0.97-1.55) for risk and (RR = 1.15, 95% CI 0.81-1.64) for cancer mortality. Associations of the biomarkers with cancer appeared to be more robust using the combined z-score. HRs comparing men within the highest z-score quartile to those within the lowest z-score quartiles were 1.47 (95% CI 1.16-1.88, p-trend < 0.01) for cancer risk, and 1.48 (95% CI 1.03-2.14, p-trend = 0.09) for cancer mortality. CONCLUSION: Our study suggests that inflammation is associated with cancer risk and mortality, and combining inflammatory biomarkers into a score is a robust method of elucidating this association.

Reduced kidney function is a risk factor for atrial fibrillation.

There is limited knowledge on the relationship between kidney function and incidence of atrial fibrillation. Thus, this prospective study was designed to evaluate whether various biomarkers of kidney function are associated to the risk of atrial fibrillation. The study population consisted of 1840 subjects (615 women and 1225 men) aged 61-82 years. Cystatin C- and creatinine-based estimation of glomerular filtration rate (eGFRcys and eGRFcreat , respectively) and urinary albumin/creatinine ratio (ACR) were assessed to investigate their relationship with the risk of atrial fibrillation. During a median follow-up of 3.7 years, a total of 159 incident atrial fibrillation cases occurred. After adjustment for potential confounders, the risk of atrial fibrillation was increased (hazard ratio 2.74, 95% confidence interval (CI) 1.56-4.81, P < 0.001) in subjects with reduced kidney function (eGFRcys , 15-59 mL/min per 1.73 m(2) ) compared to subjects with normal kidney function (≥90 mL/min per 1.73 m(2) ). Similar results were also found when comparing the respective groups of subjects defined by their eGRFcreat levels (hazard ratio 2.41, CI 1.09-5.30, P = 0.029). Consistently, subjects with ACR ≥300 mg/g had an increased risk of incident atrial fibrillation (hazard ratio 2.16, CI 1.35-2.82, P < 0.001) compared to those with ACR <30 mg/g. Reduced eGFR and albuminuria were associated with an increased risk of atrial fibrillation.

Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?

BACKGROUND: The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. DESIGN: Meta-analysis of individual participant data. METHOD: From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. RESULTS: Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. CONCLUSIONS: The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

Metabolic syndrome and the risk of sudden cardiac death in middle-aged men.

BACKGROUND: Little is known about the relationship between metabolic syndrome and sudden cardiac death (SCD). We examined the association of metabolic syndrome, as defined by World Health Organization (WHO), International Diabetes Federation (IDF), National Cholesterol Education Program (NCEP) and American Heart Association (AHA)--IDF interim criteria, with incident SCD. We also assessed the association of a continuous metabolic risk score with SCD. METHODS: A total of 1466 middle-aged men participating in a prospective population-based cohort study from eastern Finland with no history of coronary heart disease or diabetes at baseline were included. RESULTS: During the average follow-up of 21 years 85 SCDs occurred. Men with the metabolic syndrome as defined by the WHO, NCEP, IDF and interim criteria had a 2.2-2.6 fold, increased risk for SCD, after adjusting for lifestyle and traditional cardiovascular risk factors not included in the metabolic syndrome definition (P<0.001-0.011). A one-standard deviation increase in the metabolic risk score (composed of the sum of Z-scores for waist circumference, insulin, glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and blood pressure) was associated with a 1.68-fold higher (95% CI 1.33-2.11) risk of SCD. Even when adjusting further for systolic blood pressure, HDL cholesterol and body mass index, the association remained significant for the interim criteria and the metabolic risk score, but not for WHO, NCEP, or IDF definitions. CONCLUSIONS: Men with metabolic syndrome are at increased risk for SCD. Incident SCD associated with the IDF/AHA interim criteria and metabolic risk clustering estimated by a score is not explained by obesity or traditional cardiovascular risk factors. KEY MESSAGES: Men with metabolic syndrome are at increased risk for sudden cardiac death. Incident sudden cardiac death associated with metabolic risk clustering estimated by a score in not explained by obesity or traditional cardiovascular risk factors. Prevention of the metabolic syndrome may help reduce the health burden of SCD.

Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration.

BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. METHODS: Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. RESULTS: Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015). CONCLUSION: Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.

Cardiorespiratory fitness and lung cancer risk: A prospective population-based cohort study.

OBJECTIVES: Little is known about the role of cardiorespiratory fitness (CRF) and leisure-time physical activity (LTPA) with the risk of lung cancer. Previous research shows that maintaining a sufficient amount of physical activity may have a protective effect against cancer. The aim of this study is to examine the associations of CRF, LTPA and lung cancer among middle-aged Finnish men. DESIGN: Prospective cohort study. METHODS: In a population-based cohort study of 2305 men from Eastern Finland with no history of cancer at baseline. CRF and LTPA data was collected at baseline, 73 cases of lung cancer occurred during an average follow-up of 20-years. RESULTS: In a multivariate adjusted model, every 3.8mL/kg/min (1 SD) increase of CRF was related to a 31% decrease in lung cancer risk across all VO2max quartiles. Furthermore, a 2.8-fold (95% CI 1.14-7.22, p=0.024) increased risk of lung cancer among men in the lowest quartile (≤20.3mL/kg/min) of CRF as compared those in the highest quartile (>35.1mL/kg/min). In a multivariate adjusted model LTPA was not associated to lung cancer. CONCLUSIONS: In middle-aged men with no history of lung cancer, increasing levels of CRF serves as a protective factor against lung cancer. Increasing CRF may reduce the risk of lung cancer. Furthermore, CRF is a better predictor of lung cancer than LTPA.

Independent and combined effects of physical activity and body mass index on the development of Type 2 Diabetes - a meta-analysis of 9 prospective cohort studies.

BACKGROUND: The aim of this harmonized meta-analysis was to examine the independent and combined effects of physical activity and BMI on the incidence of type 2 diabetes. METHODS: Our systematic literature review in 2011 identified 127 potentially relevant prospective studies of which 9 fulfilled the inclusion criteria (total N = 117,878, 56.2 % female, mean age = 50.0 years, range = 25-65 years). Measures of baseline physical activity (low, intermediate, high), BMI-category [BMI < 18.4 (underweight), 18.5-24.9 (normal weight), 25.0-29.9 (overweight), 30+ (obese)] and incident type 2 diabetes were harmonized across studies. The associations between physical activity, BMI and incident type 2 diabetes were analyzed using Cox regression with a standardized analysis protocol including adjustments for age, gender, educational level, and smoking. Hazard ratios from individual studies were combined in a random-effects meta-analysis. RESULTS: Mean follow-up time was 9.1 years. A total of 11,237 incident type 2 diabetes cases were recorded. In mutually adjusted models, being overweight or obese (compared with normal weight) and having low physical activity (compared with high physical activity) were associated with an increased risk of incident type 2 diabetes (hazard ratios 2.33, 95 % CI 1.95-2.78; 6.10, 95 % CI: 4.63-8.04, and 1.23, 95 % CI: 1.09-1.39, respectively). Individuals who were both obese and had low physical activity had 7.4-fold (95 % CI 3.47-15.89) increased risk of type 2 diabetes compared with normal weight, high physically active participants. CONCLUSIONS: This harmonized meta-analysis shows the importance of maintaining a healthy weight and being physically active in diabetes prevention.

Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.

OBJECTIVE: Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS: In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS: Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08). CONCLUSIONS: Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

Impaired pulmonary function is a risk predictor for sudden cardiac death in men.

OBJECTIVES: Little is known about the association of reduced pulmonary function and the risk of sudden cardiac death (SCD). Our aim was to examine the relation of forced expiratory volume (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC with SCD in a population-based sample of men. METHODS: This study was based on 1250 men 42-60 years of age without chronic obstructive pulmonary disease, asthma, and lung cancer. During the 20-year follow-up, 95 SCDs occurred. FEV1, FVC, and ratio of FEV1 to FVC were used as lung function tests. RESULTS: As a continuous variable, each 10% increase in the percentage predicted FEV1 was associated with 18% (adjusted risk 0.82, 95% CI 0.73-0.93, P < 0.002) reduced risk for SCD. Subjects with most reduced (lowest quintile) FEV1 had a 3.5-fold increased risk for SCD (95% CI 1.42-8.41, P = 0.006), after adjustment for conventional risk factors. Similar results were observed with FVC. The results remained statistically significant among non-smokers and smokers respectively. CONCLUSION: Our study shows that reduced lung function is a robust predictor of SCD in middle-aged men. Lung function test may be useful in risk stratification for SCD in general population.