Background: Chronic obstructive pulmonary disease (COPD) is associated with increased mortality and poor health-related quality of life (HRQoL) compared with the general population. The objective of this study was to identify clinical characteristics which predict mortality and very poor HRQoL among the COPD population and to develop a Bayesian prediction model. Methods: The data consisted of 738 patients with COPD who had visited the Pulmonary Clinic of the Helsinki and Turku University Hospitals during 1995-2006. The data set contained 49 potential predictor variables and two outcome variables: survival (dead/alive) and HRQoL measured with a 15D instrument (very poor HRQoL <0.70 vs. typical HRQoL >= 0.70). In the first phase of model validation we randomly divided the material into a training set (n = 538), and a test set (n = 200). This procedure was repeated ten times in random fashion to obtain independently created training sets and corresponding test sets. Modeling was performed by using the training set, and each model was tested by using the corresponding test set, repeated in each training set. In the second phase the final model was created by using the total material and eighteen most predictive variables. The performance of six logistic regressions approaches were shown for comparison purposes. Results: In the final model, the following variables were associated with mortality or very poor HRQoL: age at onset, cerebrovascular disease, diabetes, alcohol abuse, cancer, psychiatric disease, body mass index, Forced Expiratory Volume (FEV1) % of predicted, atrial fibrillation, and prolonged QT time in ECG. The prediction accuracy of the model was 77%, sensitivity 0.30, specificity 0.95, positive predictive value 0.68, negative predictive value 0.78, and area under the ROC curve 0.69. While the sensitivity of the model reminded limited, good specificity, moderate accuracy, comparable or better performance in classification and better performance in variable selection and data usage in comparison to the logistic regression approaches, and positive and negative predictive values indicate that the model has potential in predicting mortality and very poor HRQoL in COPD patients. Conclusion: We developed a Bayesian prediction model which is potentially useful in predicting mortality and very poor HRQoL in patients with COPD.

There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13,P = 0.95). Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.

Objectives Present study examines the relationship between the estimated risk of developing type 2 diabetes (T2D) and health-related quality of life (HRQoL). We quantify the association between Finnish Diabetes Risk Score (FINDRISC) and HRQoL, and examine the potential use of FINDRISC as tool to evaluate HRQoL indirectly. Methods We conducted a cross-sectional study comprising 707 Finnish people without a diagnosis of T2D between the ages of 51 and 75 years. The risk of developing T2D was assessed using the validated and widely used FINDRISC (range 0-26 points), and quality of life was measured using two preference-based HRQoL instruments (15D and SF-6D) and one health profile instrument (SF-36). Effects of the individual FINDRISC items and demographic and clinical characteristics, such as co-morbidities, on HRQoL were studied using multivariable Tobit regression models. Results Low HRQoL was significantly and directly associated with the estimated risk of developing T2D. An approximate 4-5 point change in FINDRISC score was observed to be associated with clinically noticeable changes in the preference-based instrument HRQoL index scores. The association between HRQoL and the risk of developing T2D was also observed for most dimensions of HRQoL in all applied HRQoL instruments. Overall, old age, lack of physical activity, obesity, and history of high blood glucose were the FINDRISC factors most prominently associated with lower HRQoL. Conclusions The findings may help the health care professionals to substantiate the possible improvement in glucose metabolism and HRQoL potentially achieved by lifestyle changes, and better convince people at high risk of T2D to take action towards healthier lifestyle habits. FINDRISC may also provide an accurate proxy for HRQoL, and thus by estimating the risk of T2D with the FINDRISC, information about patients' HRQoL may also be obtained indirectly, when it is not feasible to use HRQoL instruments.

Background: Web-based interventions are promising tools for increasing the understanding of illness and treatment among patients with serious mental disorders. Objective: This study aimed to test the feasibility and acceptability of a Web-based patient education intervention using a quasi-experimental cluster design to report feedback on patient education sessions and the website used and to report preliminary evidence of the intervention's impact on patients with schizophrenia spectrum disorder. Methods: A single-blind, parallel, quasi-experimental cluster study over a 6-month period comparing Web-based education (n=33) with a nonequivalent control group (treatment as usual, n=24) for people with schizophrenia spectrum disorder was conducted. Participants (N=57) were recruited from one psychiatric hospital (6 wards). Feasibility was assessed by participants' commitment (refusal rate, dropout rate) to the study. Acceptability was assessed as participants' commitment to the intervention. Patient education sessions and website feedback were assessed by the patients and health care professionals. The preliminary impact of the sessions on patients' self-efficacy, self-esteem, illness cognition, and knowledge level was measured at baseline and follow-ups (8 weeks, 6 months) with self-rated questionnaires. Results: The refusal rate among patients was high with no statistically significant difference (69% [74/107] in the intervention group, 76% [76/100] in the control group; P =.21). The same result was found for the dropout rates (48% [16/33] vs 58% [14/24]; P=. 46). The acceptability of the intervention was good; 31 participants out of 33 (94%) completed all five sessions. Feedback on the intervention was mainly positive; three out of four subscales of session were rated above the midpoint of 4.0. Feedback on the website was also positive, with a grade of good for content (69%, 20/29 patients; 75%, 21/28 professionals), layout (62%, 18/29 patients; 61%, 17/28 professionals), and usability (62%, 18/29 patients; and 68%, 19/28 professionals). The patients using the intervention had significantly higher scores 6 months after the sessions in self-efficacy (baseline mean 26.12, SD 5.64 vs 6-month mean 29.24, SD 6.05; P=.003) and regarding knowledge level about schizophrenia (mean 11.39, SD 4.65 vs 6-month mean 15.06, SD 5.26; P=. 002), and lower scores in the subscale of helplessness in illness cognition (mean 2.26, SD 0.96 vs 6-month mean 1.85, SD 0.59; P=.03). Differences from the control group were not significant. No differences were found in patients' self-esteem or other subscales in illness cognition. Conclusions: The patients were reluctant to participate in the study and tended to drop out before the follow-ups. Once they had participated, their acceptance of the intervention was high. A more effective recruitment strategy and monitoring method will be needed in future studies. To assess the impact of the intervention, a more rigorous study design with an adequately powered sample size will be used in cooperation with outpatient mental health services.

Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid-to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (beta = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; beta = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (P-heterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P >= 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analysed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomisation, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. The systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R-2 = 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate [beta (standard deviation difference vs. placebo): 0.69; 95% CI = 0.24, 1.15; p = 0.003], valine (beta: -0.62; -1.03, -0.02; p = 0.004), pyruvate (beta: -0.56; -0.95, -0.16; p = 0.006) and docosahexaenoic acid (beta: -0.50; -085, -0.14; p = 0.006). Valine and diacylglycerol were lower in the lycopene dietary advice group (beta: -0.65; -1.04, -0.26; p = 0.001 and beta: -0.59; -1.01, -0.18; p = 0.006). A genetically instrumented SD increase in pyruvate increased the odds of prostate cancer by 1.29 (1.03, 1.62; p = 0.027). An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomisation analysis suggests may be causally related to reduced prostate cancer risk.

The lower extremity functional scale (LEFS) is a patient-reported outcome measure for lower extremity disorders. Aim of this study was to assess the longitudinal validity including responsiveness and test-retest reliability of the revised 15-item version, and to define the minimal important change (MIC) of the modified LEFS in a generic sample of orthopedic foot and ankle patients who underwent surgery. Responsiveness, effect size, and standardized response mean were measured by determining the score change between the baseline and 6 months administration of the LEFS from 156 patients. There was no significant difference between preoperative (median 78, interquartile range [IQR] 64.2-90.3) and postoperative (median 75.0, IQR 61.7-95.0) scores. Both effect size and standardized response mean were low (0.06 and 0.06, respectively). Test-retest reliability of the LEFS was satisfactory. Intraclass correlation coefficient was 0.85 (95% confidence interval 0.81-0.88). MIC value could not be estimated due to the lack of significant score change. The modified LEFS presented with relatively low longitudinal validity in a cohort of generic orthopedic foot and ankle patients. The findings of this study indicate that the modified LEFS might not be the optimal instrument in assessing the clinical change over time for these patients. (c) 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Background Epidemiological studies have linked lifestyle, cardiometabolic, reproductive, developmental, and inflammatory factors to the risk of colorectal cancer. However, which specific factors affect risk and the strength of these effects are unknown. We aimed to examine the relationship between potentially modifiable risk factors and colorectal cancer. Methods We used a random-effects model to examine the relationship between 39 potentially modifiable risk factors and colorectal cancer in 26 397 patients with colorectal cancer and 41 481 controls (ie, people without colorectal cancer). These population data came from a genome-wide association study of people of European ancestry, which was amended to exclude UK BioBank data. In the model, we used genetic variants as instruments via two-sample mendelian randomisation to limit bias from confounding and reverse causation. We calculated odds ratios per genetically predicted SD unit increase in each putative risk factor (OR SD) for colorectal cancer risk. We did mendelian randomisation Egger regressions to identify evidence of potential violations of mendelian randomisation assumptions. A Bonferroni-corrected threshold of p=1.3 x 10(-3) was considered significant, and p values less than 0.05 were considered to be suggestive of an association. Findings No putative risk factors were significantly associated with colorectal cancer risk after correction for multiple testing. However, suggestive associations with increased risk were noted for genetically predicted body fat percentage (OR SD 1.14 [95% CI 1.03-1.25]; p=0.0086), body-mass index (1.09 [1.01-1.17]; p=0.023), waist circumference (1.13 [1.02-1.26]; p=0.018), basal metabolic rate (1.10 [1.03-1.18]; p=0.0079), and concentrations of LDL cholesterol (1.14 [1.04-1.25]; p=0.0056), total cholesterol (1.09 [1.01-1.18]; p=0.025), circulating serum iron (1.17 [1.00-1.36]; p=0.049), and serum vitamin B12 (1.21 [1.04-1.42]; p=0.016), although potential pleiotropy among genetic variants used as instruments for vitamin B12 constrains the finding. A suggestive association was also noted between adult height and increased risk of colorectal cancer (OR SD 1.04 [95% CI 1.00-1.08]; p=0.032). Low blood selenium concentration had a suggestive association with decreased risk of colorectal cancer (OR SD 0.85 [95% CI 0.75-0.96]; p=0.0078) based on a single variant, as did plasma concentrations of interleukin-6 receptor subunit a (also based on a single variant; 0.98 [0.96-1.00]; p=0.035). Risk of colorectal cancer was not associated with any sex hormone or reproductive factor, serum calcium, or circulating 25-hydroxyvitamin D concentrations. Interpretation This analysis identified several modifiable targets for primary prevention of colorectal cancer, including lifestyle, obesity, and cardiometabolic factors, that should inform public health policy. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background: There have previously been no validated foot and ankle-specific patient-reported outcome measures in Finnish. Methods: The Visual Analogue Scale Foot and Ankle (VAS-FA) was translated and adapted into Finnish. Thereafter, 165 patients who had undergone foot and ankle surgery completed a questionnaire set on two separate occasions. Analyses included testing of floor-ceiling effect, internal consistency, reproducibility, and validity. Results: Minor linguistic differences emerged during the translation. Some structural adjustments were made. The mean (SD) total VAS-FA score was 74 (23). In the three subscales, maximum scores were noted in 2-5% of the responses, and internal consistency ranged from 0.81 to 0.94. Reproducibility was excellent (ICC, 0.97). The total VAS-FA score correlated significantly with the Lower Extremity Functional Scale (r = 0.84) and the 15D Mobility dimension (r = 0.79). The VAS-FA loaded on two factors (pain/movement and problems/limitations). Conclusions: The Finnish version of the VAS-FA has high reliability and strong validity. (C) 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Objectives: Psychosocial difficulties (PSDs) are common in people with substance use disorders (SUDs). The PARADISE24 has been shown to be an adequate tool for measuring PSDs in inpatients with SUDs. The aim of this study is to evaluate the psychometric properties of the PARADISE24 in a sample of patients with SUDs. Methods: 2637 participants with SUDs completed the PARADISE24 questionnaire during their treatment. The latent structure of the PARADISE24 questionnaire was analyzed in the outpatient sample by means of exploratory and confirmatory factor analysis (EFA and CFA). Metric invariance was then assessed in relation to the inpatient sample using multiple group CFA. Finally, evidences of known-groups validity were checked to test the ability of the questionnaire to differentiate between socio-demographic and clinical groups. Results: The one-factor model presented an adequate fit in both the EFA (CFI = 0.98; TLI = 0.98; RMSEA = 0.07) and the CFA (CFI = 0.98; TLI = 0.98; RMSEA = 0.07) solutions. The reliability of the scale was found to be high (alpha = 0.93). Strict metric invariance between inpatients and outpatients was achieved (RMSEA = 0.063; TLI = 0.983; CFI = 0.981). The PARADISE24 was able to discriminate between the inpatients and outpatients at both latent (d = 0.98) and observed levels (d = 0.86). Conclusions: The PARADISE24 is a unidimensional tool that is reliable for assessing and comparing PSDs in both outpatients and inpatients with SUDs. Further research is required for evaluating the ability of the PARADISE24 to quantify longitudinal changes in PSDs.