A Deep Neural Network-Based Decision Support Tool for the Detection of Lymph Node Metastases in Colorectal Cancer Specimens.

The identification of lymph node metastases in colorectal cancer (CRC) specimens is crucial for the planning of postoperative treatment and can be a time-consuming task for pathologists. In this study, we developed a deep neural network (DNN) algorithm for the detection of metastatic CRC in digitized histologic sections of lymph nodes and evaluated its performance as a diagnostic support tool. First, the DNN algorithm was trained using pixel-level annotations of cancerous areas on 758 whole slide images (360 with cancerous areas). The algorithm's performance was evaluated on 74 whole slide images (43 with cancerous areas). Second, the algorithm was evaluated as a decision support tool on 288 whole slide images covering 1517 lymph node sections, randomized in 16 batches. Two senior pathologists (C.K. and C.O.) assessed each batch with and without the help of the algorithm in a 2 × 2 crossover design, with a washout period of 1 month in between. The time needed for the evaluation of each node section was recorded. The DNN algorithm achieved a median pixel-level accuracy of 0.952 on slides with cancerous areas and 0.996 on slides with benign samples. N+ disease (metastases, micrometastases, or tumor deposits) was present in 103 of the 1517 sections. The algorithm highlighted cancerous areas in 102 of these sections, with a sensitivity of 0.990. Assisted by the algorithm, the median time needed for evaluation was significantly shortened for both pathologists (median time for pathologist 1, 26 vs 14 seconds; P < .001; 95% CI, 11.0-12.0; median time for pathologist 2, 25 vs 23 seconds; P < .001; 95% CI, 2.0-4.0). Our DNN showed high accuracy for detecting metastatic CRC in digitized histologic sections of lymph nodes. This decision support tool has the potential to improve the diagnostic workflow by shortening the time needed for the evaluation of lymph nodes in CRC specimens without impairing diagnostic accuracy.

Enigma of the cholesterol paradox in acute myocardial infarction: lessons from an 8-year follow-up of all-cause mortality in an age-matched and sex-matched case-control study with controls from the patients' recruitment area.

OBJECTIVE: To assess the impact of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) on long-term all-cause mortality (ACM) in patients with acute myocardial infarction (AMI) and controls. DESIGN: Matched case-control study with 8-year follow-up. SETTING: Vastmanland County Hospital, Vasteras, Sweden. PARTICIPANTS: Consecutive patients with AMI admitted to the coronary care unit from March 2005 to May 2010 and age-matched and sex-matched controls from the general population. OUTCOME MEASURES: ACM. RESULTS: Person-year at risk among patients with AMI and controls was 11 667 (cases: 5780 and controls: 5887). During follow-up, 199 patients and 84 controls died, implying 3.4 deaths among patients and 1.4 among controls per 100 person-years at risk. Unadjusted Cox analyses showed significantly increasing mortality by decreasing TC and LDL-C levels in both patients (HR=0.70, 95% CI 0.62 to 0.79, p<0.001, and HR=0.64, 95% CI 0.56 to 0.74, p<0.001) and controls (HR=0.73, 95% CI 0.60 to 0.89, p=0.002, and HR=0.74, 95% CI 0.59 to 0.93, p=0.010). After adjusting for clinical variables, the results for the patients remained significant. Cox analyses of the relations between mortality and TC and LDL-C below and above their respective medians revealed the following pattern. PATIENTS: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians there were no relations with mortality. CONTROLS: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians were LDL-C levels significantly positively related to mortality. Mean LDL-C level in patients with blood sampled >12 hours after symptom onset was 0.41 mmol/L lower than that in patients with blood sampled ≤12 hours (p=0.030). This LDL-C decrease was reasonably caused by ongoing AMI and reflects the difference in LDL-C levels between patients and controls. CONCLUSIONS: In patients with AMI, lower TC and LDL-C levels independently predict higher ACM. In their controls, LDL-C levels above the median independently predict higher ACM. This study adds to the body of evidence supporting the existence of a cholesterol paradox.

Higher age and obesity limit atelectasis formation during anaesthesia: an analysis of computed tomography data in 243 subjects.

BACKGROUND: General anaesthesia is increasingly common in elderly and obese patients. Greater age and body mass index (BMI) worsen gas exchange. We assessed whether this is related to increasing atelectasis during general anaesthesia. METHODS: This primary analysis included pooled data from previously published studies of 243 subjects aged 18-78 yr, with BMI of 18-52 kg m-2. The subjects had no clinical signs of cardiopulmonary disease, and they underwent computed tomography (CT) awake and during anaesthesia before surgery after preoxygenation with an inspired oxygen fraction (FIO2) of >0.8, followed by mechanical ventilation with FIO2 of 0.3 or higher with no PEEP. Atelectasis was assessed by CT. RESULTS: Atelectasis area of up to 39 cm2 in a transverse scan near the diaphragm was seen in 90% of the subjects during anaesthesia. The log of atelectasis area was related to a quadratic function of (age+age2) with the most atelectasis at ∼50 yr (r2=0.08; P<0.001). Log atelectasis area was also related to a broken-line function of the BMI with the knee at 30 kg m-2 (r2=0.06; P<0.001). Greater atelectasis was seen in the subjects receiving FIO2 of 1.0 than FIO2 of 0.3-0.5 (12.8 vs 8.1 cm2; P<0.001). A multiple regression analysis, including a quadratic function of age, a broken-line function of the BMI, and dichotomised FIO2 (0.3-0.5/1.0) adjusting for ventilatory frequency, strengthened the association (r2=0.23; P<0.001). PaO2 decreased with both age and BMI. CONCLUSIONS: Atelectasis during general anaesthesia increased with age up to 50 yr and decreased beyond that. Atelectasis increased with BMI in normal and overweight patients, but showed no further increase in obese subjects (BMI ≥30 kg m-2). Therefore, greater age and obesity appear to limit atelectasis formation during general anaesthesia.

Oxygenation Impairment during Anesthesia: Influence of Age and Body Weight.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: During anesthesia oxygenation is impaired, especially in the elderly or obese, but the mechanisms are uncertain. WHAT THIS ARTICLE TELLS US THAT IS NEW: Pooled data were examined from 80 patients studied with multiple inert gas elimination technique and computed tomography. Oxygenation was impaired by anesthesia, more so with greater age or body mass index. The key contributors were low ventilation/perfusion ratio (likely airway closure) in the elderly and shunt (atelectasis) in the obese. BACKGROUND: Anesthesia is increasingly common in elderly and overweight patients and prompted the current study to explore mechanisms of age- and weight-dependent worsening of arterial oxygen tension (PaO2). METHODS: This is a primary analysis of pooled data in patients with (1) American Society of Anesthesiologists (ASA) classification of 1; (2) normal forced vital capacity; (3) preoxygenation with an inspired oxygen fraction (FIO2) more than 0.8 and ventilated with FIO2 0.3 to 0.4; (4) measurements done during anesthesia before surgery. Eighty patients (21 women and 59 men, aged 19 to 69 yr, body mass index up to 30 kg/m2) were studied with multiple inert gas elimination technique to assess shunt and perfusion of poorly ventilated regions (low ventilation/perfusion ratio [(Equation is included in full-text article.)]) and computed tomography to assess atelectasis. RESULTS: PaO2/FIO2 was lower during anesthesia than awake (368; 291 to 470 [median; quartiles] vs. 441; 397 to 462 mm Hg; P = 0.003) and fell with increasing age and body mass index. Log shunt was best related to a quadratic function of age with largest shunt at 45 yr (r2 =0.17, P = 0.001). Log shunt was linearly related to body mass index (r2 = 0.15, P < 0.001). A multiple regression analysis including age, age2, and body mass index strengthened the association further (r2 = 0.27). Shunt was highly associated to atelectasis (r2 = 0.58, P < 0.001). Log low (Equation is included in full-text article.)showed a linear relation to age (r2 = 0.14, P = 0.001). CONCLUSIONS: PaO2/FIO2 ratio was impaired during anesthesia, and the impairment increased with age and body mass index. Shunt was related to atelectasis and was a more important cause of oxygenation impairment in middle-aged patients, whereas low(Equation is included in full-text article.), likely caused by airway closure, was more important in elderly patients. Shunt but not low(Equation is included in full-text article.)increased with increasing body mass index. Thus, increasing age and body mass index impaired gas exchange by different mechanisms during anesthesia.

Psychometric evaluation of the Scandinavian version of the caregiver priorities and child health index of life with disabilities.

PURPOSE: To examine test-retest reliability and construct validity of the Scandinavian version of the caregiver priorities and child health index of life with disabilities (CPCHILD) questionnaire for children with cerebral palsy (CP). METHODS: Families were recruited in Sweden and Norway and stratified according to the gross motor function classification system levels I-V for children born 2000-2011, mean age 7.9 (SD 3.2). Construct validity based on the first questionnaire (n = 106) was evaluated for known groups, using linear regression analysis. Intraclass correlation coefficient was used to estimate test-retest reliability (n = 64), and Cronbach's alpha was calculated as an indicator of internal consistency. RESULTS: The questionnaire showed construct validity and the ability to discriminate between levels of gross motor function for the total score and all domain scores (p < 0.05). Test-retest reliability was high with intraclass correlation coefficient of 0.92 for the total score and of 0.72-0.92 for the domain scores. Cronbach's alpha was 0.96 for the total score and 0.83-0.96 for the domain scores. CONCLUSIONS: The Scandinavian version of the CPCHILD for children with CP seems to be a valid and reliable proxy measure for health related quality of life. Implications for rehabilitation Valid and reliable outcome measures are needed to evaluate whether follow-up programs enhance health related quality of life in different countries. The Scandinavian version of the caregiver priorities and child health index of life with disabilities (CPCHILD) was evaluated for known-groups validity and test-retest reliability. The Scandinavian version of the CPCHILD is a sound and valid measurement for evaluation and comparison of health related quality of life of children with cerebral palsy in different countries.

Basic Anthropometric Measures in Acute Myocardial Infarction Patients and Individually Sex- and Age-Matched Controls from the General Population.

We compared weight, height, waist and hip circumferences (hip), body mass index (BMI), and waist-to-hip ratio in acute myocardial infarction (MI) patients and individually sex- and age-matched control subjects from the general population in the catchment area of the patients and predicted the risk of MI status by these basic anthropometric measures. The study cohort comprised 748 patients ≤80 years of age with acute MI from a major Swedish cardiac center and their individually sex- and age-matched controls. The analyses were stratified for sex and age (≤65/≥66 years). Risk of MI was assessed by conditional logistic regression. A narrow hip in men ≥66 years was the single strongest risk factor of MI among the anthropometric measures. The combination of hip and weight was particularly efficient in discriminating men ≥66 years with MI from their controls (area under the receiver operating characteristic (AUROC) curve = 0.82). In men ≤65 years, the best combination was hip, BMI, and height (AUROC = 0.79). In women ≥66 years, the best discriminatory model contained only waist-to-hip ratio (AUROC = 0.67), whereas in women ≤65 years, the best combination was hip and BMI (AUROC = 0.68). A narrow hip reasonably reflects small gluteal muscles. This finding might suggest an association between MI and sarcopenia, possibly related to deficiencies in physical activity and nutrition.

Self-perceived ability to cope with stress and depressive mood without smoking predicts successful smoking cessation 12 months later in a quitline setting: a secondary analysis of a randomized trial.

BACKGROUND: Telephone-based smoking cessation services ('quitlines') are both effective and cost-effective. Knowledge of modifiable baseline factors in real-life settings with heterogeneous participants is essential for the development and improvement of treatment protocols to assist in telephone-based smoking cessation. The aim was to assess if self-perceived abilities to cope measured at baseline, would predict abstinence at the 12-month follow-up at the Swedish National Tobacco Quitline (SNTQ). METHODS: The data were retrieved from a previous randomized controlled trial comparing the effectiveness of proactive and reactive service at the SNTQ. Included were 612 clients calling the SNTQ between February 2009 and September 2010. Outcome measures were self-reported point prevalence and 6-month continuous abstinence at the 12-month follow-up. Plausible predictors of smoking cessation were assessed at the first call and in a baseline questionnaire. Self-perceived abilities at baseline were measured by two questions: (1) How likely is it that you will be smoke-free in one year? and (2) How likely are you to be able to handle stress and depressive mood without smoking? The associations between potential predictors and outcome (smoke-free at 12-month follow-up) were assessed by logistic regression analysis. RESULTS: Of the two potential predictors for abstinence at 12-month follow-up, only the perceived ability to handle stress and depressive mood without smoking remained significant in the adjusted analyses (Odds Ratio, OR 1.13, 95% CI 1.00-1.27 for point prevalence and OR 1.16, 95% CI 1.01-1.33 for 6-month continuous abstinence according to intention-to-treat). The overall strongest predictor in the adjusted analyses was smoking status in the week before baseline (OR 3.30, 95% CI 1.79-6.09 for point prevalence and OR 3.97, 95% CI 2.01-7.83 for 6-month continuous abstinence). CONCLUSIONS: The perceived ability to handle stress and depressive mood without smoking at baseline predicted the subjects' abstinence at the 12-month follow-up. An assessment of/adjustment for stress and depressive mood coping skills may be appropriate in future smoking cessation treatment and research. The treatment protocol can be tailored to individual differences and needs for optimal support. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02085616 . Registered March 10, 2014, 'retrospectively registered'.

Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact.

BACKGROUND: Despite the growing body of evidence on growth differentiation factor 15 (GDF-15) reference values for patients with existing cardiovascular disease, limited investigation has been dedicated to characterizing the distribution and prognostic impact of GDF-15 in predominantly healthy populations. Furthermore, current cutoff values for GDF-15 fail to account for the well-documented age-dependence of circulating GDF-15. METHODS: From 810 community-dwelling older adults, we selected a group of apparently healthy participants (n = 268). From this sample, circulating GDF-15 was modeled using the generalized additive models for location scale and shape (GAMLSS) to develop age-dependent centile values. Unadjusted and adjusted Cox proportional hazards models were used to assess the association between the derived GDF-15 reference values (expressed as centiles) and all-cause mortality. RESULTS: Smoothed centile curves showed increasing GDF-15 with age in the apparently healthy participants. An approximately three-fold difference was observed between the 95th and 5th GDF-15 centiles across ages. In a median 8.0 years of follow-up, 97 all-cause deaths were observed in 806 participants with eligible values. In unadjusted Cox regression analyses, the hazard ratio (95% CI) for all-cause mortality per 25-unit increase in GDF-15 centile was 1.80 (1.48-2.20) and dichotomized at the 95th centile, ≥95th versus <95th, was 3.04 (1.99-4.65). Age-dependent GDF-15 centiles remained a significant predictor of all-cause mortality in all subsequent adjusted models. CONCLUSIONS: Age-dependent GDF-15 centile values developed from a population of apparently healthy older adults are independently predictive of all-cause mortality. Therefore, GDF-15 reference values could be a useful tool for risk-stratification in a clinical setting. ClinicalTrials.gov Identifier: NCT01452178.

Corrigendum to "Basic Anthropometric Measures in Acute Myocardial Infarction Patients and Individually Sex- and Age-Matched Controls from the General Population".

[This corrects the article DOI: 10.1155/2018/3839482.].

Excess atherosclerosis in systemic lupus erythematosus,-A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls.

BACKGROUND: Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups. METHODS: 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls. RESULTS: Median age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035). CONCLUSIONS: In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.

Association between depressive symptoms and parental stress among mothers and fathers in early parenthood: A Swedish cohort study.

Aim To determine whether there is an association between depressive symptoms and parental stress among mothers and fathers during early parenthood in Sweden. Methods In this study, 401 mothers and 396 fathers (393 couples) were included; the Edinburgh Postnatal Depression Scale and the Sense of Coherence Scale were measured 3 months after childbirth, and the Swedish Parenthood Stress Questionnaire and the Sense of Coherence Scale after 18 months. Complete data for multivariable analysis were available for 264 mothers and 252 fathers. Results The mothers estimated greater total depressive symptoms and parental stress than the fathers did. Both the mothers and the fathers had the greatest level of stress in the sub-area 'Role restriction'. The mothers had the lowest level of stress in the sub-area 'Social isolation' and the fathers in the sub-area 'Incompetence'. The mothers perceived greater levels of stress than the fathers did in all sub-areas except for 'Social isolation', where the fathers perceived higher stress. There was an association between the parents' depressive symptoms and parental stress. The parents' own depressive symptoms at 3 months and sense of coherence and the partners' parental stress at 18 months were positively associated with the parental stress at 18 months in univariable and multivariable analyses. Conclusions Understanding the relationship between depressive symptoms and parental stress is important for health professionals so they can offer parents adequate support in early parenthood to optimize the conditions for raising a child. This knowledge should also be communicated to the parents.

Non-responders in a quitline evaluation are more likely to be smokers - a drop-out and long-term follow-up study of the Swedish National Tobacco Quitline.

BACKGROUND: A previous randomized controlled trial (RCT) of the Swedish National Tobacco Quitline detected no significant differences in smoking cessation outcomes between proactive and reactive services at 12-month follow-up. However, the response rate was only 59 % and non-responders were over-represented in the proactive service. We performed a drop-out analysis to assess the smoking status of initial responders and non-responders. METHODS: At 29-48 months after the first call, a postal questionnaire with six questions was sent to 150 random clients from the RCT database, with equal numbers from the proactive and reactive services as well as responders and non-responders at 12-month follow-up. Clients who did not return the questionnaire were contacted by telephone. The outcome measures were point prevalence (PP) and 6-month continuous abstinence (CA), and their associations with response status at 12 months were assessed by logistic regression. RESULTS: The response rate was 74 % (111/150). Abstinence was significantly higher among initial responders than non-responders (PP 54 % vs. 32 %, p = .023 and CA 49 % vs. 21 %, p = .003). The odds ratios for initial responders vs. initial non-responders were, for PP = 2.5 (95 % CI 1.1-5.6, p = .024), and for CA = 3.7 (95 % CI 1.5-8.9, p = .004), after adjusting for proactive/reactive service. CONCLUSIONS: Non-responders to a 12-month follow-up smoking cessation questionnaire in a quitline setting were more likely to be smokers 1.5-3 years later. We propose a conservative correction factor of 0.8 for self-reported abstinence in telephone-based cessation studies if the response rate is approximately 55-65 %.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors.

BACKGROUND: The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease (CVD). The relationship between circulating PCSK9 and incident CVD in the general population is unknown. We investigated whether serum PCSK9 concentration is associated with incident CVD in a prospective cohort study of 4232 men and women 60 years of age at the time of recruitment. METHODS AND RESULTS: Incident CVD was recorded by matching to national registries. After 15 years of follow-up, a total of 491 incident events (fatal and nonfatal myocardial infarctions, unstable angina, deaths from coronary heart disease, fatal and nonfatal ischemic strokes) were recorded. Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. Baseline serum PCSK9 concentration predicted incident CVD; concentration in quartile 4 compared with quartile 1 was associated with a hazard ratio of 1.69 (95% confidence interval, 1.30-2.19) after adjustment for sex. Further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), triglycerides, hypertension, diabetes mellitus, smoking, overweight, obesity, physical inactivity, and statin use resulted in a decrease in the hazard ratio to 1.48 (95% confidence interval, 1.12-1.95). CONCLUSIONS: Serum PCSK9 concentration is associated with future risk of CVD even after adjustments for established CVD risk factors. Further studies are needed to confirm this observation.

Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease.

IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA=0.11, P=6.73E(-5) and chromosome 14, rs4902762, BETA=0.12, P=5.76E(-6)) and one for eosinophil count (rs72797327, BETA=-0.10, P=1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA=0.04, P=0.2763, I(2)=24, I(2)-P=0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2=0.93 with rs56183820) BETA=-0.10, P=8.64E(-6) and rs11739623 (r2=0.96 with rs72797327) BETA=-0.23, P=1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.

Associations among pain, disability and psychosocial factors and the predictive value of expectations on returning to work in patients who undergo lumbar disc surgery.

PURPOSE: The aim of this study was to describe the associations among pain, disability and psychosocial factors preoperatively as well as 3 and 24 months later for patients who undergo first time discectomy and to analyse the predictive value of psychosocial factors on the outcome 24 months after surgery. METHODS: Fifty-nine patients, 41 % women, with a mean age of 40 years and without comorbidities were included, of whom 56 responded to the 24-month follow-up; at that point, they were divided into patients with complaints (C, n = 36) and patients without complaints (NC, n = 20). Correlations among the pain intensity, disability and psychosocial factors were analysed preoperatively, 3 and 24 months after discectomy, and regression analyses of psychosocial factors on the outcome at 24 months were performed. RESULTS: Psychosocial variables were weakly correlated with the pain intensity and disability preoperatively. High expectations on the return to work were predictive of both pain intensity (ß = 8.0, p = 0.03) and disability (ß = 9.1, p < 0.001) at 24 months. Associations between psychosocial variables and outcome variables were strengthened at the 3-month follow-up in the C group, and this association remained 24 months after surgery. Fear of movement was most strongly correlated with leg pain intensity (r (s) 0.64, p < 0.001) and the ability to decrease pain was the most correlated with disability (r (s) 0.78, p < 0.001). CONCLUSION: Having high expectations on the return to work after surgery was the strongest predictor for a favourable outcome. Therefore, low preoperative expectations on return to work convey an important prognostic signal.

Association between parental depressive symptoms and impaired bonding with the infant.

Impaired bonding with the infant is associated with maternal postpartum depression but has not been investigated extensively in fathers. The primary study aim was to evaluate associations between maternal and paternal depressive symptoms and impaired bonding with their infant. A secondary aim was to determine the associations between parents' marital problems and impaired bonding with the infant. The study is part of a population-based cohort project (UPPSAT) in Uppsala, Sweden. The Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks and 6 months postpartum and the Postpartum Bonding Questionnaire at 6 months postpartum were completed by 727 couples. The prevalence of impaired bonding was highest among couples in which both spouses had depressive symptoms. Impaired bonding was associated with higher EPDS scores in both mothers and fathers, as well as with experiencing a deteriorated marital relationship. The association between maternal and paternal impaired bonding and the mothers' and fathers' EPDS scores remained significant even after adjustment for relevant confounding factors. Depressive symptoms at 6 weeks postpartum are associated with impaired bonding with the infant at 6 months postpartum for both mothers and fathers. It is critical to screen for and prevent depressive symptoms in both parents during early parenthood.

Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease.

BACKGROUND: Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. METHODS AND RESULTS: Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (ß=-0.018, P<0.001) in men but not in women (ß=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (ß=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (ß=-0.0008, P=0.004) but not in women (ß=-0.0003, P=0.522; P for interaction=0.007). CONCLUSIONS: This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.

Plasma IL-5 concentration and subclinical carotid atherosclerosis.

OBJECTIVE: Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT). METHODS: We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline. RESULTS: IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women. CONCLUSIONS: Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease.

Effectiveness of proactive and reactive services at the Swedish National Tobacco Quitline in a randomized trial.

BACKGROUND: The Swedish National Tobacco Quitline (SNTQ), which has both a proactive and a reactive service, has successfully provided tobacco cessation support since 1998. As there is a demand for an increase in national cessation support, and because the quitline works under funding constraints, it is crucial to identify the most clinically effective and cost-effective service. A randomized controlled trial was performed to compare the effectiveness of the high-intensity proactive service with the low-intensity reactive service at the SNTQ. METHODS: Those who called the SNTQ for smoking or tobacco cessation from February 2009 to September 2010 were randomized to proactive service (even dates) and reactive service (odd dates). Data were collected through postal questionnaires at baseline and after 12 months. Those who replied to the baseline questionnaire constituted the study base. Outcome measures were self-reported point prevalence and 6-month continuous abstinence at the 12-month follow-up. Intention-to-treat (ITT) and responder-only analyses were performed. RESULTS: The study base consisted of 586 persons, and 59% completed the 12-month follow-up. Neither ITT- nor responder-only analyses showed any differences in outcome between proactive and reactive service. Point prevalence was 27% and continuous abstinence was 21% in analyses treating non-responders as smokers, and 47% and 35%, respectively, in responder-only analyses. CONCLUSION: Reactive service may be used as the standard procedure to optimize resource utilization at the SNTQ. However, further research is needed to assess effectiveness in different subgroups of clients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02085616.

Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism.

INTRODUCTION: We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n=2753) from Sweden. MATERIALS AND METHODS: 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. RESULTS: Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n=7181). CONCLUSIONS: It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.