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Introduction: This study aimed to describe exclusive breastfeeding (EBF, Step 6 of the Baby-Friendly Hospital Initiative) in Finnish maternity hospitals and identify factors that promote or limit EBF. Methods: A cross-sectional study design was used, and data were collected from eight maternity hospitals in Finland during a 10-day period in May 2014. The staff completed questionnaires (n=1554) from separate work shifts. The data were analyzed using descriptive statistics, and chi-squared and Fisher’s tests. Responses to open-ended questions were analyzed using content analysis. Results: Maternity ward staff reported that 72% (n=1105) of the infants were exclusively breastfed during their work shift. The strongest promoting factors of exclusive breastfeeding were: maternity ward staffs’ profession and education in breastfeeding counselling; multiparity; vaginal delivery; early skin-to-skin contact between mother and infant; initial breastfeeding after birth; rooming-in; and initial success of breastfeeding. The use of a nipple shield, the need for additional breastfeeding counselling, and infants’ blood tests were limiting factors to exclusive breastfeeding. Open-ended answers revealed that exclusive breastfeeding was mainly delayed because of medical issues for the mother or infant. Conclusions: Finnish maternity hospitals could improve exclusive breastfeeding rates by focusing attention and resources on breastfeeding counselling and evidence-based maternity care practices related to immediate care after birth, promoting vaginal delivery, rooming-in and availability of skilled counselling.

We aimed to compare the feasibility of automatically and manually scored cardiorespiratory polygraphy results for sleep apnea screening in the acute phase of ischemic stroke.Prospective study included 204 ischemic stroke patients, who underwent nocturnal unattended portable monitoring with three-channel device during 48 h after onset of stroke symptoms. Sleep apnea diagnosis was determined as a respiratory event index (REI) ≥5/hour.The mean age of the patients was 67.7 years and 62.7% were males. Automatic scoring identified sleep apnea in 148/72.5% and manual scoring in 186/91.2% of patients, showing moderate agreement (Kappa value 0.407). Of the cohort, 39 (19.1%) patients fulfilled the criteria for diagnosis of central sleep apnea (CSA) (50% of events central) and 165 (80.9%) had obstructive sleep apnea (OSA). Automatic scoring identified poorly the type of events, and missed 18.6% of recordings. Oxygen desaturation 4% index (ODI4), interclass correlation coefficient (ICC) value 0.993, (95% CI 0.990-0.994), lowest saturation (ICC value 0.989, 95% CI 0.985-0.991) and percent of time spent90% (ICC value 0.987, 95% CI 0.982-0.990) showed excellent agreement. Interclass correlation value for REI was 0.869 (95% CI 0.828 to 0.901) and ICC value 0.848 (95% CI 0.800 to 0.885) for obstructive apnea index, both indicating good agreement. Automatic scoring underestimated the severity of sleep apnea.Both automatically and manually scored results recognized sleep apnea, albeit manual scoring identified more sleep apnea. Sleep apnea diagnosis agreement was moderate. Underestimation of the severity of sleep apnea by automatic scoring may result in undertreatment of sleep apnea.URL:http://www.clinicaltrials.cov. Unique identifier: NCT01861275.

The Goal: The aim of the study was to investigate whether stroke volume or the presence of ischemic stroke lesion on follow-up computed tomography 1 day after admission had association with sleep apnea among ischemic stroke patients undergoing thrombolysis. Materials and Methods: We prospectively recruited 110 consecutive ischemic stroke patients and performed computed tomography on admission and after 24 hours after intravenous thrombolysis. Stroke volume was measured from post-thrombolysis computed tomography scans. Unattended cardiorespiratory polygraphy with a 3-channel device was performed during 48 hours after admission. Findings: Of 110 ischemic stroke patients treated with thrombolysis 65.5% were men. Mean age was 65.8 years and body mass index 27.5 kg/m 2 . The mean Epworth sleepiness scale score was 4.7. Eight patients (12.7%) with visible acute stroke after thrombolysis and none in the other group had hemorrhage as complication ( P ˂ .001). Sleep apnea, determined as a respiratory event index greater than or equal to 5/hour, was diagnosed in 96.4% patients. Respiratory event index greater than 15/h was found in 72.8% of patients. Both mean baseline oxygen desaturation index (23.9 versus 16.5, P = .028) and obstructive apneas/hour (6.2 versus 2.7, P = .007) were higher in visible stroke group. Stroke volume (mean 15.9 mL) correlated with proportion of time spent below saturation less than 90%, P = .025. Conclusions: Acute ischemic stroke patients treated with thrombolysis with visible stroke were more likely to have nocturnal hypoxemia than patients with not visible strokes. Stroke volume correlated with time spent below saturation of 90%.

Background: While alcohol use is linked with a wide variety of health problems, the question of whether differences in drinking patterns could yield different outcomes has remained unclear. Patients and methods: We measured liver enzymes (ALT, GGT) from alcohol consumers with or without binge drinking from a population-based sample in Finland, where binge-type drinking is common. Data on alcohol use, diet, body weight, lifestyle (smoking, coffee consumption, physical activity), and health status were collected from 19225 subjects (9492 men, 9733 women), aged 25–74 years. The participants were subsequently classified to subgroups, both according to the frequencies of binge drinking and the amounts of regular alcohol intake (low-, medium-, and high-risk drinking). Results: The quantity of regular alcohol use was roughly linearly related with GGT and ALT activities. ANOVA analyses of the trends according to the frequency of binge drinking showed a significant GGT increase in both men (p < 0.0005) and women (p < 0.0005), and a significant increase of ALT in men (p < 0.0005). In those with low-risk overall consumption, markedly higher GGT (p < 0.0005) and ALT (p < 0.0005) occurred in those with binge drinking more than once a month, compared with those with no such occasions. Binge drinking occurring ≤1/month also resulted in higher GGT (p < 0.0005) and ALT (p < 0.05) activities. Conclusions: These results emphasize possible adverse consequences of binge drinking on hepatic function even in those with low-risk overall consumption. The pattern of drinking should be more systematically implicated in clinical recommendations for drinking reduction.

ObjectivesTo determine cell differential counts and the number of asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid obtained from patients with asbestosis, and to correlate the results with their survival.MethodsThe BAL cell differential counts and ABs from 91 patients with asbestosis were determined. The BAL cell differential counts were analysed in relation to smoking status. BAL cell differential counts and the number of ABs were correlated with the patients’ survivals.ResultsA neutrophilic cell pattern was observed independently of smoking habits with both Papanicolau (8.4%) and May-Grunwald-Giemsa (6.5%) staining. Smoking and a high number of ABs (>2 AB/mL) were associated with high total cell counts and high macrophage and low lymphocyte differential counts. The median survival of the patients was 131.8 months. Shortened survival was associated with high numbers of ABs (78 vs 165 months; p=0.042) and low lymphocyte (77 vs 179 months; p=0.005), high neutrophil (102 vs 180 months; p=0.016) and high eosinophil (104 vs170 months; p=0.007) differential counts.ConclusionA neutrophilic cell pattern was evident in BAL from patients with asbestosis. Smoking and ABs both affected the total cell count and the macrophage and lymphocyte differential counts. Several BAL parameters associated with patient survival, suggesting that BAL cell count analyses could be used in the estimation of the prognosis of patients with asbestosis.

AIMS Alcohol consumption has been suggested a major role in the pathogenesis and prognosis of depression. However, reliable identification of hazardous drinking continues to be problematic. We compared the accuracy of different biomarkers and self-reports of alcohol consumption in the follow-up study of depression. METHODS Data from 202 patients with major depressive disorder were obtained through self-reports, AUDIT and AUDIT-C questionnaires and biomarker analyses. The clinical assessments and measurements of biomarkers (GT, CDT, GT-CDT-combination, MCV, ALT, AST, hs-CRP, IL-6) were performed at baseline and after six months of treatment. Based on self-reported alcohol intake at baseline the patients were classified to three subgroups. RESULTS About 27.2% of patients were categorized to high-risk drinkers, 26.3% low-risk drinkers and 46.5% abstainers. High-risk drinkers showed significantly higher mean values of GT, CDT, GT-CDT-combination and IL-6 than abstainers, diagnostic accuracy being highest with the combined marker of GT-CDT. The accuracy of AUDIT and AUDIT-C to detect high-risk drinking was also significant. During follow-up, the differences observed in the biomarkers at baseline disappeared together with recovery from depression. CONCLUSIONS Our data suggest the combined use of GT-CDT and AUDIT questionnaires to improve the identification of drinking of patients with depression. This approach could be useful for improving treatment adherence and outcome in depressed patients.

Aims: Previous studies have indicated that heavy alcohol intake stimulates inflammation and impairs the body's ability to regulate inflammation. The aim of this study was to compare changes in neutrophil calprotectin and a wide spectrum of other inflammatory mediators in response to heavy alcohol drinking. Methods: Serum calprotectin (a marker of neutrophil activation), suPAR, CD163, and pro- (IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10, TGF-β) cytokines were measured from 61 alcohol-dependent subjects (46 men, 15 women, mean age 43.6 ± 11.0 years) at the time of admission for detoxification and after 8 ± 2 days of abstinence. These biomarkers were also measured from age- and sex-matched healthy controls representing abstainers or light drinkers. The clinical assessments included detailed clinical interviews on the amounts and patterns of alcohol consumption and assays for biomarkers of alcohol consumption (GGT, CDT, MCV, GGT-CDT) and liver function (AST, ALT). Results: The subjects with alcohol use disorder showed significantly higher concentrations of serum calprotectin (p < 0.0005), suPAR (p < 0.01), CD163 (p < 0.01), IL-6 (p < 0.0005), IL-8 (p < 0.0005), TNF-α (p < 0.001), and IL-10 (p < 0.0005) than healthy controls. These inflammatory mediators, except for CD163, remained elevated after the 8 ± 2-day period of supervised abstinence, which resulted in significant decreases in the biomarkers of alcohol consumption and indices of liver status. The AUC (0.855) for serum calprotectin in differentiating between the heavy drinkers and healthy controls was equal or equivalent with those of the conventional biomarkers of alcohol consumption (GGT:0.835 or CDT:0.803). Conclusions: The data indicate that neutrophil calprotectin is released in response to heavy alcohol intake in a sensitive manner and may be associated with perpetuation of inflammation in patients with alcohol use disorder. Serum calprotectin may also prove to be a useful biomarker for inflammatory activity in alcohol-consuming patients.

Background Frequent attendance is largely a temporary phenomenon, but only few previous studies have made a distinction between long-term frequent attenders (FAs) and short-term FAs. Aims The aim of this study is to compare the characteristics of middle-aged long-term FAs and short-term FAs. Methods Data from a large Northern Finland Birth Cohort 1966 study's (NFBC1966) 46-year follow-up study (performed in 2012, N = 10 321) were used. The participants (n = 4390) had used public primary healthcare (PPHC) services at least once during 2013-2016 according to Finnish national register data on outpatient visits. A FA was considered a patient who had used PPHC services ≥8 times during 1 year. A long-term FA: a patient who was a FA in at least 3 years during 2013-2016. A short-term FA: a patient who was a FA in 1 or 2 years in 2013-2016. Cross-tabulation, Pearson's chi-squared test, Mann-Whitney U test, and univariate and multivariate binary logistic regression analyses were used. Results Of the 4390 participants, 132 (3.0%) were long-term FAs, 645 (14.7%) were short-term FAs, and 3613 (82.3%) were non-FAs. During 2013-2016, long-term FAs accounted for 34.8% of PPHC visits, while short-term FAs accounted 15.4%. Compared to short-term FAs, depression and high income (preventive attribute) were associated with long-term FAs. Female gender and managing usual activities were associated with short-term FAs. Poor self-reported health was associated with both long-term FAs and short-term FAs but increased the risk of being a long-term FA over three times compared to short-term FAs. Conclusions Middle-aged long-term FAs and short-term FAs have distinct characteristics; namely, depression and high income differentiate long-term FAs from short-term FAs. Poor self-reported health was associated with long-term FAs in particular. In order to identify FAs with prolonged service needs and to develop far-reaching interventions, the focus of research should be on long-term FAs.

Markus Niemelä,1,2 Onni Niemelä,2 Risto Bloigu,3 Aini Bloigu,4 Päivikki Kangastupa,2 Tatu Juvonen1,5 1Department of Surgery, Oulu University Hospital, Oulu 90029, Finland; 2Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and Tampere University, Seinäjoki 60220, Finland; 3Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu 90014, Finland; 4Center for Life Course Health Research, University of Oulu, Oulu 90014, Finland; 5Department of Cardiac Surgery, Helsinki University Hospital, Helsinki 00029, FinlandCorrespondence: Onni Niemelä Tel +358 50 474 4719Email onni.niemela@epshp.fiPurpose: While extreme physical exertion is known to induce changes in the status of inflammation comparisons of the responses for various mediators of inflammation after acute bouts of high-intensity exercise have been limited.Subjects and Methods: We examined the responses in serum levels of novel inflammatory proteins, calprotectin, suPAR, CD163, and pro- and anti-inflammatory cytokines in 12 physically active volunteers (10 men, 2 women, mean age 37± 14 years) before and after completing various types of extreme physical exertion (marathon run, half-marathon run or 24-h cross-country skiing). For comparisons, the levels of the biomarkers were also measured at rest in 30 healthy controls (25 men, 5 women, mean age 42 ± 12 years) with low or sedentary activity.Results: Extreme physical exertion induced significant increases in serum calprotectin (p < 0.0005), suPAR (p < 0.01), CD163 (p < 0.05), IL-6 (p < 0.0005), IL-8 (p < 0.01) and IL-10 (p < 0.0005) (pre- vs 3h-post-exercise). These responses were found to normalize within 48 hours. While the increases in blood leukocytes were of similar magnitude following the different types of exercise, markedly more pronounced responses occurred in serum TNF-α (p < 0.01), IL-8 (p < 0.01) and CD163 (p < 0.05) in those with more intense activity. In 3-h post-exercise samples significant correlations were observed between serum calprotectin and IL-6 (rs = 0.720, p < 0.01), IL-10 (rs = 0.615, p < 0.05), TNF-α (rs = 0.594, p < 0.05), suPAR (rs = 0.587, p < 0.05) and blood leukocytes (rs = 0.762, p < 0.01).Conclusion: The present results suggest distinct exercise-intensity dependent changes in mediators of inflammation (including calprotectin, suPAR and CD163) following extreme physical exertion. Our findings indicate that there is a major reversible impact of high-intensity physical exertion on the status of inflammation.Keywords: acute exercise, cytokine, immune status, leukocyte, oxidative stress &nbsp

BackgroundThe aim of this study was to compare the clinical characteristics, causes of death and factors impacting on the prognosis of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung disease (FILD) with a history of acute exacerbation (AE) of IPF or FILD.MethodsRetrospective data of hospital treatment periods caused by AE-IPF and AE-FILD were collected from medical records. Clinical features and survival data of IPF and non-IPF cases were evaluated and compared. The underlying and immediate causes of death were gathered from death certificates.ResultsA total of 128 patients fulfilled the criteria for inclusion. IPF (n=79/62%), rheumatoid arthritis-associated interstitial lung disease (RA-ILD; n=17/14%) and asbestosis (n=11/8.6%) were the most common FILD subgroups in the study. The median survival after hospitalisation in AE-IPF was 2.6 months compared with 21 months in other AE-FILDs (pConclusionsWe detected a significantly longer survival in AE of patients with non-IPF compared with that of AE-IPFs. The prognosis of patients was affected by the underlying lung disease since pulmonary fibrosis was the underlying cause of death in the majority of all patients with FILD having experienced an AE.

A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde–modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD ( n = 133), stable CAD ( n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL ( P = 0.016, P = 0.043), Rgp44 ( P = 0.012, P = 0.004), Aa-HSP60 ( P = 0.032, P = 0.030), Tannerella forsythia ( P = 0.002, P = 0.004), Porphyromonas endodontalis ( P = 0.016, P = 0.020), Prevotella intermedia ( P = 0.038, P = 0.005), and with total IgA antibody concentration ( P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.

Study Objectives:Our goal was to investigate the evolution of prevalence, severity, and type of sleep apnea among patients who had an ischemic stroke, with or without treatment with thrombolysis af...

Hypertension is a global health threat and major cardiovascular risk. Various risk-prediction models for incident hypertension have been developed but not many of them have studied the risk-predictive value of life style factors in combination with cardiovascular biomarkers during long-term period of over 10 years.We examined differences in several classical variables for 299 subjects in OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort in subjects with no or new hypertension during a follow-up period of 21 years. Effect of both various life style habits and biomarkers were investigated.Baseline blood pressure, being overweight and smoking actively were independent predictors of new hypertension in majority of multivariate models during long-term follow-up of 21 years in subjects without previous hypertension. Increased high-sensitive C-reactive protein (hsCRP) level (3 mg/L) was the strongest predictor of incident hypertension in univariate model. Subjects with two or all three of main risk factors (being overweight, smoking actively and having high hsCRP) had 4-fold risk for incident hypertension.Smoking, overweight and increased hsCRP level had risk-predictive value in incident hypertension prediction during long-term follow-up of 21 years. Assessment and measurement of these parameters could be used in help of detecting high risk subjects and primary prevention of hypertension very early on. In addition, the study shows that blood pressure at the middle-age should be followed and treated intensively to prevent hypertension in the older age.Baseline blood pressure, being overweight and smoking actively are independent predictors of new hypertension during a long-term follow-up of 21 years. Having two or all three risk factors (smoking actively, body mass index over 25 kg/m

The association between dietary salt intake and hypertension has been well documented. We evaluated the association between dietary sodium intake and the incidence of new-onset atrial fibrillation (AF) during a mean follow-up of 19 years among 716 subjects from the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) cohort.Dietary sodium intake was evaluated from a seven-day food record. The diagnosis of AF (atrial flutter included) was made if ICD-10 code I48 was listed in the hospital discharge records during follow-up.In the Kaplan-Meier curves, when quartiles of sodium consumption were considered, the cumulative proportional probabilities for AF events were higher in the highest (4th) quartile (16.8%) than in the lower quartiles (1st 6.7%, 2nd 7.3% and 3rd 10.6%) (p = .003). In the Cox regression analysis, sodium consumption (g/1000 kcal) as a continuous variable was independently associated with AF events (Hazard Ratio = 2.1 (95% CI, 1.2 to 3.7) p =.015) when age, body mass index, smoking (pack-years), office systolic blood pressure, left atrium diameter, left ventricular mass index and the use of any antihypertensive therapy were added as covariates.These findings indicate that sodium intake is associated with the long-term risk of new-onset AF. Further confirmatory studies are needed. Key messages Sodium consumption correlated positively with CV risk factors: age, smoking, SBP, BMI and LDL-cholesterol. When quartiles of sodium consumption were considered, the AF incidence was higher in the highest quartile compared to lower quartiles. Sodium consumption as a continuous variable was independently associated with AF events when age, BMI, smoking, SBP, LAD, LVMI and the use of any antihypertensive therapy were considered.

Recent studies suggest that the ubiquitin-specific protease USP28 plays an important role in cellular repair and tissue remodeling, which implies that it has a direct role in carcinogenesis. The carcinogenic potential of USP28 was investigated in a comprehensive manner using patients, animal models, and cell culture. The findings demonstrate that overexpression of USP28 correlates with a better survival in patients with invasive ductal breast carcinoma. Mouse xenograft experiments with USP28-deficient breast cancer cells also support this view. Furthermore, lack of USP28 promotes a more malignant state of breast cancer cells, indicated by an epithelial-to-mesenchymal (EMT) transition, elevated proliferation, migration, and angiogenesis as well as a decreased adhesion. In addition to breast cancer, lack of USP28 in mice promoted an earlier onset and a more severe tumor formation in a chemical-induced liver cancer model. Mechanistically, the angio- and carcinogenic processes driven by the lack of USP28 appeared to be independent of HIF-1α, p53, and 53BP1. Implications: The findings of this study are not limited to one particular type of cancer but are rather applicable for carcinogenesis in a more general manner. The obtained data support the view that USP28 is involved in tumor suppression and has the potential to be a prognostic marker. Mol Cancer Res; 16(6); 1000–12. ©2018 AACR.

The histologic manifestation of idiopathic pulmonary fibrosis (IPF) is usual interstitial pneumonia (UIP), which is a good prognostic determinant of survival compared with other histologic interstitial lung disease patterns. According to the current international guidelines, the histologic features of suspected IPF/UIP are divided into 4 categories: UIP, probable UIP, possible UIP, and not UIP pattern. Four pulmonary pathologists who were blinded to clinicoradiologic information reevaluated 50 surgical lung biopsies (83.3%), 6 lung explant (10.0%), and 4 autopsy samples (6.7%) from the FinnishIPF registry (N=60) using the current diagnostic guidelines. Additional histologic features atypical for UIP were also evaluated and compared with clinicora-diologic information. The interobserver agreement of pathologists was examined by Cohen kappa (κ) coefficient; the survival of the patients was estimated with Kaplan-Meier curves. The histologic reevaluation indicated that 38 of 60 patients (63.3%) had definite UIP. Inflammation was the most common additional histologic finding (15/60, 25.0%). The interobserver agreement on histologic diagnosis ranged from slight (κ=0.044) to substantial (κ=0.779). The interobserver agreement varied extensively with regard to the presence of giant cells. The observed histologic features displayed no association with radiologic patterns or survival. Definite UIP and honeycombing findings in high-resolution computed tomography correlated with poor prognosis. A high level of interobserver variability was observed between pathologists, even in this well-defined cohort of IPF patients, which highlights the importance of multidisciplinary decision making in IPF diagnostics and stresses the need for a reassessment of the histologic criteria.

Antibodies to phosphocholine and oxidized LDL (oxLDL) are proposed to modify progression of atherosclerosis. We investigated the prognostic value of antibodies to phosphocholine (PCho), Streptococcus pneumoniae cell wall polysaccharide (CWPS) and oxLDL in defining long-term CVD survival.CVD incidence was followed for 18 years and analyzed with baseline plasma IgM, IgG and IgA antibody levels to PCho, CWPS and oxLDL in 1044 subjects of Oulu Project Elucidating Risk of Atherosclerosis study (OPERA).During the follow-up period, 195 subjects (18.7%) had a CVD event. Cox model with ACC/AHA CVD adjustments (ASCVD) showed that IgA levels to PCho and IgA to CWPS were statistically significant factors predicting CVD risk. IgM and IgG antibodies to PCho, CWPS and oxLDL had no effect on CVD risk after adjusting for other risk factors. Net reclassification improvement (categories: 17-year risk15%, 15-30%,30%), was 0.06 (-0.001-0.12, p 0.054), and IDI was 0.0124 (0.0036-0.0211, p 0.006) with IgA-PCho added to the ASCVD risk model. Seventeen (9.4%) study subjects with CVD events were correctly reclassified into higher risk category while 9 (5.0%) subjects were classified into lower risk category. Among the non-cases, 58 (8.7%) subjects were correctly reclassified into lower risk, and 46 (5.9%) were reclassified into higher risk category.Plasma IgA antibodies to PCho and Streptococcus pneumoniae CWPS are significant predictors of long-term CVD risk. Additional studies on the role of IgA antibodies in atherogenesis and CVD are warranted.

The aim of the study was to compare the prevalence, type, and severity of sleep apnea during the acute phase of ischemic stroke among patients either receiving or not receiving thrombolysis.We recruited 246 consecutive adult ischemic stroke patients. Patients underwent cardiorespiratory sleep study with portable three-channel device during the first 48 h after the symptom onset of ischemic stroke.We enrolled 110 (65.5% male) stroke patients in the thrombolysis group and 94 (59.6% male) in the nonthrombolysis group. In the thrombolysis group, the median National Institutes of Health Stroke Scale (NIHSS) score was higher (5.5) compared to the nonthrombolysis group (2.0) (p 0.001). There was a lower incidence of lacunar (17.3% vs 36.2%, p = 0.002) and cerebellar (2.7% vs 16.0%, p 0.001) strokes and a higher frequency of middle cerebral artery syndrome (60.9% vs 33.0%, p 0.001) in the thrombolysis group compared to the nonthrombolysis group. Sleep apnea defined as an apnea-hypopnea index (AHI) ≥ 5/h was diagnosed in 186 (91.2%) patients, its prevalence being higher in the thrombolysis (96.4%) compared to the nonthrombolysis (85.1%) group (p = 0.007). The mean baseline AHI was 33.7/h in the thrombolysis group compared to 26.8/h in the nonthrombolysis group (p = 0.017).Sleep apnea was present in the vast majority of ischemic stroke patients. The stroke patients treated with thrombolysis were more likely to have sleep apnea, to have elevated NIHSS score at admission, and to be younger. Sleep apnea was more severe among those receiving thrombolysis as compared to those who were not.URL: http://www.clinicaltrials.cov. Unique identifier: NCT01861275.

OBJECTIVE In diffuse large B-cell lymphoma (DLBCL), there is an unmet medical need to select patients who would benefit from intensified frontline treatments such as adding etoposide to an R-CHOP regimen. METHODS The present work included a retrospective clinical analysis of two patient cohorts and an in vitro study. Primary biopsy samples from DLBCL patients treated with an etoposide-containing high-dose regimen (n = 37) and etoposide-containing frontline treatment (n = 69, R-CHOEP) were studied using immunohistochemical thioredoxin-1 (Trx1) staining. Two DLBCL cell lines expressing Trx1 were cultured, and their expression was silenced using the small interfering RNA knockdown technique. Chemoresistance was tested with doxorubicin, etoposide, vincristine, prednisolone and carboplatin. RESULTS Thioredoxin-1 knockdown sensitised DLBCL cells to doxorubicin (P

Purpose: Non-dipping blood pressure (BP) pattern has been associated with metabolic changes and cardiovascular events. With regard of diabetes, studies are scarce. Our aim was to investigate if the...

BackgroundAdopting a healthy lifestyle is associated with prolonged life expectancy. The main modifiable lifestyle-related risk factors are hazardous alcohol drinking, smoking, excess body weight and lack of physical activity. Our aim was to estimate the impact of unfavourable lifestyle factors on abnormalities in laboratory tests reflecting liver status, inflammation and lipid metabolism in a population-based cross-sectional study.MethodsThe study included 22,273 participants (10,561 men, 11,712 women) aged 25-74 years from the National FINRISK Study. Data on alcohol use, smoking, body weight, and physical activity were recorded from structured interviews. The risk scores for the various life style factors were established on a 0-8 scale and used to stratify the population in classes to allow estimates of their joint effects. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques.ResultsConsistent dose-response relationships were observed between the number of unfavourable risk factors and serum levels of GGT, ALT, CRP, cholesterol, HDL, LDL and triglycerides (p < 0.0005 for linear trend in all comparisons). When compared with those with zero risk factors, the multivariable-adjusted odds ratios (ORs) for abnormalities in all biomarkers were significantly higher in those with a sum of risk score two or more. The most striking increases in ORs in the group with the highest numbers of risk factors were observed among men in serum GGT: 26.6 (12.4-57.0), ALT: 40.3 (5.3-307.8), CRP: 16.2 (7.8-33.7) and serum triglycerides: 14.4 (8.6-24.0).ConclusionsThe data support the view that the presence of unfavourable life style risk factors is associated with distinct abnormalities in laboratory tests for liver function, inflammation and lipid status. Such biomarkers may prove to be of value in the assessment of interventions aimed at reducing unfavourable risk factors and in helping individuals in long-term maintenance of lifestyle modifications.

Low-risk thresholds for alcohol use differ across various national guidelines. To assess the novel WHO risk drinking levels in light of alcohol-sensitive common laboratory tests, we analysed biomarkers of liver status, inflammation and lipid profiles from a population-based survey of individuals classified to abstainers and different WHO risk drinking levels defined in terms of mean alcohol consumption per day. The study included 22,327 participants aged 25-74 years from the National FINRISK Study. Data on alcohol use, health status, diet, body weight and lifestyle (smoking, coffee consumption and physical activity) were recorded from structured interviews. Alcohol data from self-reports covering the past 12 months were used to categorize the participants into subgroups of abstainers and WHO risk drinking categories representing low, moderate, high and very high risk drinkers. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Alcohol risk category was roughly linearly related with the occurrence of elevated values for GGT, ALT and CRP. Alcohol drinking also significantly influenced the incidence of abnormalities in serum lipids. Significantly higher odds for abnormal GGT, ALT and altered lipid profiles remained in alcohol drinkers even after adjustment for age, waist circumference, physical inactivity, smoking and coffee consumption. A more systematic use of laboratory tests during treatment of individuals classified to WHO risk drinking categories may improve the assessment of alcohol-related health risks. Follow-ups of biomarker responses may also prove to be useful in health interventions aimed at reducing alcohol consumption.

Background:Oral tongue squamous cell carcinoma (OTSCC) metastasises early, especially to regional lymph nodes. There is an ongoing debate on which early stage (T1-T2N0) patients should be treated with elective neck dissection. We need prognosticators for early stage tongue cancer. Methods: Mice immunisation with human mesenchymal stromal cells resulted in production of antibodies against tenascin-C (TNC) and fibronectin (FN), which were used to stain 178 (98 early stage), oral tongue squamous cell carcinoma samples. TenascinC and FN expression in the stroma (negative, moderate or abundant) and tumour cells (negative or positive) were assessed. Similar staining was obtained using corresponding commercial antibodies. Results: Expression of TNC and FN in the stroma, but not in the tumour cells, proved to be excellent prognosticators both in all stages and in early stage cases. Among early stages, when stromal TNC was negative, the 5-year survival rate was 88%. Correspondingly, when FN was negative, no cancer deaths were observed. Five-year survival rates for abundant expression of TNC and FN were 43% and 25%, respectively. Conclusions: Stromal TNC and, especially, FN expressions differentiate patients into low-and high-risk groups. Surgery alone of early stage primary tumours might be adequate when stromal FN is negative. Aggressive treatments should be considered when both TNC and FN are abundant.

Background/Aims: To report objective and subjective outcomes and adverse events after placement of Elevate® Posterior transvaginal mesh without concurrent surgery. Changes in non-affected anterior compartment were under special interest. Methods: A prospective study of Elevate® Posterior procedure in patients with symptomatic posterior compartment prolapse. Pelvic organ prolapse (POP) quantification (POP-Q) measurements and Pelvic Floor Dysfunction Inventory-20 (PFDI-20) and POP/urinary Incontinence Sexual Questionnaire (PISQ-12) questionnaires were used. Primary outcome was the incidence of de novo anterior prolapse. Secondary outcomes were complication rate and posterior compartment objective and subjective cure. Results: A total of 111 women underwent an Elevate® Posterior mesh procedure and 109 attended a control visit at 3 months. De novo anterior prolapse emerged in 3.2-15% of the women, depending on the definition. Posterior POP-Q stage ≤I was obtained in 92 (84%) women and leading edge at or above the hymen in 107 (98%) women. Bulge symptoms disappeared in 86% of the cases. One (0.9%) mesh exposure was detected. Reoperation rate was 2.8, and 3.7% patients experienced postoperative pain. PFDI-20 and PISQ-12 scores improved significantly. Conclusions: A trend of de novo prolapse formation in the non-affected vaginal compartment is observed. The Elevate® Posterior method is effective in terms of both objective and subjective outcomes. According to our results, the mesh exposure rate is low.

Purpose – The purpose of this study is to evaluate how LEAN thinking is used as a management and development tool in the Finnish public healthcare system and what kind of outcomes have been achieved or expected by using it. The main focus is in managing and developing patient and treatment processes. Design/methodology/approach – A mixed-method approach incorporating the Webropol survey was used. Findings – LEAN is quite a new concept in Finnish public healthcare. It is mainly used as a development tool to seek financial savings and to improve the efficiency of patient processes, but has not yet been deeply implemented. However, the experiences from LEAN initiatives have been positive, and the methodology is already quite well-known. It can be concluded that, because of positive experiences from LEAN, the environment in Finnish healthcare is ready for the deeper implementation of LEAN. Originality/value – This paper evaluates the usage of LEAN thinking for the first time in the public healthcare system of Finland as a development tool and a management system. It highlights the implementation and achieved results of LEAN thinking when used in the healthcare environment. It also highlights the expectations for LEAN thinking in Finnish public healthcare.

Background: The optic disc examination is critical for the diagnostics of several acute neurological disorders. However, dilation of the pupil is not recommended for neurological patients, which complicates ophthalmoscopy. Aims of the study: Present pilot study compared a portable fundus camera to an ophthalmoscope in fundus examinations of neurological emergency patients. To our knowledge, this is the first comparative study of the subject. The fundus photographs were later reviewed with an ophthalmologist. Methods: The study included 60 adults, volunteer neurological emergency patients with either headache, cerebrovascular disorder, or acute confusional state (delirium). Patients’ non‐mydriatic fundus examination was conducted with an ophthalmoscope and a Smartscope Pro fundus camera. Results: Fundus photography succeeded in 56 (93%), partially succeeded in 2 (3%), and failed in 2 (3%) cases compared with ophthalmoscopy that succeeded in 35 (58%), partially succeeded in 14 (23%), and failed in 11 (18%) cases (P < 0.0005). The researcher and the ophthalmologist agreed in the findings in 54 out of 58 cases (93%). In six cases (7%), the researcher had failed to detect a non‐critical ophthalmic finding. Conclusions: The neurological fundus examination by fundus camera seems to be superior to regular ophthalmoscopy in defining the critical optic disc findings in emergency patients.

Objective was to evaluate serum anti-Mullerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and in its different phenotypes in relation to clinical, endocrine and metabolic parameters using a new automated VIDAS((R)) method and to compare it with the Gen II method. Study design was multi-center study including 319 PCOS women and 109 healthy controls. Serum AMH levels measured using VIDAS((R)) were significantly higher in PCOS women than controls (p

Introduction Rooming-in is an evidence-based practice during which postpartum mothers and infants stay together. Rooming-in benefits both the mother and infant, and is especially important for breastfeeding. This study aims to describe rooming-in (Step 7 of the BFHI), according to mothers and maternity-ward staff in Finnish maternity hospitals, as well as the factors associated with its implementation. Methods The presented research adopted a cross-sectional study approach. Questionnaires were used to collect data from mothers (n=111) who had given birth and the attending maternity-ward staff (f=1554 reported events) at 8 Finnish maternity hospitals. The data were analysed using descriptive statistics, as well as chi-squared, t-test, and Fisher, Mann-Whitney, Kruskal-Wallis tests. Answers to the open-ended questions were analysed using content specifications. Results Rooming-in was utilised to a satisfactory extent, especially after vaginal birth. Most of the mothers regarded it as a very positive experience. Rooming-in was delayed mainly because of a mother's tiredness and the infant's condition. Factors such as a staff member's age, work experience, and completion of breastfeeding counselling training (WHO 20-h), a mother's parity, need for supplementation, and mode of childbirth, were found to be associated with the decision to implement rooming-in. Conclusions Rooming-in should be used more with infants born by caesarean section and primiparous mothers. The need for supplementation clearly increased when roomingin was not employed. The presented information could be crucial for effectively allocating maternity ward resources and demonstrating the importance of rooming-in to a diverse audience of health care professionals.

Background: Frontotemporal lobar degeneration (FTLD) is responsible for as many as every fifth case of early-onset dementia. Very few epidemiological studies of FTLD have been conducted; there are no published epidemiological data of FTLD from Finland or the other Nordic countries. The C9ORF72 expansion-associated FTLD is common in Finland; thus, the prevalence of FTLD is expected to be high in this population. Methods: We retrospectively evaluated the incidence and prevalence of FTLD in university hospital settings in Northern Finland. Results: The mean 1-year incidence of FTLD was 5.54/100,000 (range 1.9-11.3/100,000) in the population aged 45-65 years. The prevalence of FTLD in the same age group was 20.5/100,000. Conclusion: The incidence and prevalence of FTLD in Finland seem to be the highest in Europe. However, studies from different countries may not be directly mutually comparable due to methodological issues.

Aims Diffuse large B-cell lymphoma (DLBCL) is an aggressive and potentially fatal disease. Prediction of risk of relapse is based on clinical markers. There is a need for more accurate biomarkers to select patients for more aggressive first-line treatments. Peroxiredoxins (Prxs) are a family of potent antioxidant proteins. Their prognostic role in DLBCL is unknown. Methods Altogether, 103 diagnostic biopsy samples from patients with DLBCL were immunohistochemically stained for Prxs I, II, III, V and VI. Results Strong Prx VI expression was associated with the presence of B-symptoms. There were no other significant associations with traditional risk factors. Five-year disease-specific survival was 68.6% in patients with high cytoplasmic Prx VI intensity vs 97.0% in those with low intensity. In multivariate analysis, high Prx VI expression (HR 12.846, 95% CI 1.722 to 95.807, p=0.013) was an independent risk factor of lymphoma-associated death not related to International Prognostic Index score (HR 2.514, 95% CI 1.040 to 6.073, p=0.041). Conclusions High intensity of cytoplasmic Prx VI expression in pretreatment DLBCL samples predicts worse outcome in patients with DLBCL. Whether Prx VI is associated with chemoresistance, and therefore a poorer outcome, needs to be evaluated. If Prx VI is a predictive marker and it proves causality, it would be crucial to study Prx VI ability to become a target enzyme for treatment.

The association of dietary sodium and cardiovascular disease (CVD), as well as the reduction of sodium intake in the prevention of CVD, has been under debate. To study whether sodium consumption has a role as a risk factor for fatal and non-fatal CVD. A well-defined population-based cohort of 1045 subjects collected between 1991 and 1993 (mean age 51.4 years) was used with approximately 19 years’ follow-up. At the baseline, 716 subjects filled in a 1-week food follow-up diary, which was used to calculate the daily sodium intake (mg/1000 kcal). The baseline sodium intake correlated significantly with age (rs=0.117, P=0.002), BMI (rs=0.216, P=0.000), waist circumference (rs=0.268, P=0.000), smoking (rs=0.144, P=0.000), alcohol consumption (rs=0.111, P=0.003), systolic blood pressure (rs=0.106, P=0.005) and low-density lipoprotein (LDL) cholesterol (rs=0.081, P=0.033). Those who had cardiovascular events in the follow-up consumed more sodium at the baseline (mean 2010.4 mg/1000 kcal/day, s.d. 435.2, n=101) compared with the subjects without events (mean 1849.9 mg/1000 kcal/day, s.d. 361.2, n=589; t-test; P=0.001). The incidence of cardiovascular events was greater in the highest quartile (22.1%) than in the lower quartiles (first 11.0%, second 9.9% and third 15.6%; X2; P=0.005). Cox regression analysis showed that sodium intake as a continuous variable predicts CVD events (P=0.031) independently when age, sex, smoking, alcohol consumption, systolic blood pressure, LDL cholesterol and waist circumference were added as covariates. This predictive role is seen especially in the group of subjects on hypertensive medication (P=0.001). Dietary sodium intake is a significant independent predictor of cardiovascular events in the study population.

Objective The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. Methods HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. Results While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p, published version, peerReviewed

Objective Hyperandrogenism, hyperinsulinemia and obesity, known characteristics of polycystic ovary syndrome (PCOS), may influence bone mineral density and biochemical markers of bone turnover (BTMs) can provide a non-invasive assessment of bone turnover. To this end, the serum concentrations of BTMs and 25-hydroxyvitamin D (25OHD) were analysed in women with PCOS and their possible associations with metabolic parameters of PCOS were determined. Subjects and methods Bone formation markers procollagen type I amino-terminal propeptide (PINP) and osteocalcin (OC), and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX), along with 25OHD, were measured in 298 women with PCOS and 194 healthy controls. Results Serum levels of PINP (47.0 ± 20.2 vs. 58.1 ± 28.6 μg/L, p < 0.001) and OC (18.2 ± 7.5 vs. 20.6 ± 9.8 μg/L, p < 0.001) were decreased in women with PCOS compared with controls, whereas no significant differences were found in CTX and 25OHD levels. Age-stratified analyses suggested that PINP (50.5 ± 21.7 vs. 68.2 ± 26.6 μg/L, p < 0.001) and OC levels (20.4 ± 7.6 vs. 25.5 ± 9.6 μg/L, p < 0.001) were decreased only in the younger age group (≤ 30 years) women with PCOS compared with controls. The formation markers and resorption marker decreased with age in both study groups. Conclusions Bone formation markers were decreased in younger women with PCOS when compared with healthy women, which may affect bone mass in these women. This article is protected by copyright. All rights reserved.

Objectives The purpose of this study was to determine the prevalence and etiology of hearing impairment (HI) in Finnish children and to evaluate the frequency and type of additional disabilities among children with HI. Methods Subjects consisted of 214 children with mild to profound HI ascertained until the age of 10 years. They belonged to the birth cohort spanning the years 1993–2002 in northern Finland. The clinical data were collected from the electronic patient records of the Oulu University Hospital. Age at ascertainment, degree and type of HI and audiogram configuration were determined. Risk factors and etiology of HI and co-existing disabilities were recorded. Results The prevalence of childhood HI was 2.3/1000 live births (95% CI; 2.0, 2.7). The etiology of HI was genetic in 47.2%, acquired in 16.4% and unknown in 36.4% children. Among the 214 children with HI, 101 (47.2%) had other minor or major disabilities. The frequency of additional disabilities did not differ between children with mild HI and those with moderate or severe HI (p = 0.78). Additional disabilities were more common (65.7%) in children with acquired HI than in children with genetic or unknown HI (43.6%) (p = 0.035). Conclusion The prevalence of childhood HI has remained unchanged in northern Finland as compared to previous studies. Genetic causes were the most common (47%) etiology of childhood HI. Among acquired causes of HI, perinatal risk factors were more common than previously. The frequency of additional disabilities was similar among children with different degrees of HI. Because almost 40% of children had one or more additional disabilities affecting development or learning, it is important to take them into consideration in rehabilitation.

ObjectiveTo evaluate the occurrence of vitreous haemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR) and the efficacy of intravitreal bevacizumab (IVB) for VH in 5-year real-life data.Methods and analysis850 adult patients with type 1 (T1D) or type 2 diabetes (T2D) with PDR were screened for VH. The effect of IVB was evaluated by the clearage of VH and the change in best corrected visual acuity (BCVA). The rates of VHs, reinjections, macular oedema, complications, additional treatments and outcomes of spontaneous resorption, panretinal photocoagulation or pars plana vitrectomy (PPV) for VH were also investigated.ResultsVH occurred in 16% of patients with T1D and 9% of patients with T2D with PDR. 336 VHs in 140 eyes of 103 patients were documented. VH was cleared in 92% of cases in less than 3 months by the initial IVB. IVB was superior to other treatment methods in shortening the time for clearance of VH (Kaplan-Meier, pConclusionVH occurs mostly in patients with T1D. The therapeutic effect of IVB for VH was significant and led to improved clearance of VH and visual outcome. Moreover, IVB prevented persistent and recurrent VHs and decreased the need for costly PPV.

Objective There is increasing interest in the survival of multiple sclerosis (MS). MS itself may decrease life expectancy; however, several other comorbid diseases may also influence survival. We aimed to evaluate frequency of other neurological conditions and survival in the population-based Finnish Northern Ostrobothnia MS cohort. Methods The frequencies of neurological comorbid diseases and their associations with gender, clinical course, disability level (EDSS) and duration of MS were evaluated in population based cohort of 491 patients with clinically definite MS that was diagnosed between 1990 and 2010. The survival rate of the patients was also analysed. Results One or more neurological comorbid disease was present in 17.1% of patients ( n =84). The prevalence of epilepsy in MS patients was 4.7%, which is greater than that in the general population. Migraine was significantly more common in women with a benign MS course when compared to other types of MS ( p =0.046). A significant association between peripheral nervous system disorders and primary progressive MS was found ( p =0.027). The 21-year survival rate from time of diagnosis was 90.5%. Stroke decreased the 21-year survival rate of the patients ( p =0.003). An association between stroke prevalence and the duration of MS disease was also detected ( p =0.023). Conclusions This is the first report of multifaceted neurological comorbidities in MS patients. Neurological comorbidity is rather common in MS. However, only the prevalence of epilepsy was increased in MS patients compared to the general population. An association between peripheral nervous system disorders and primary progressive MS was also found. The 21-year survival rate was greater in the present population based cohort compared in other studies, but stroke seems to decrease the survival rate in MS patients.

Purpose Diabetic retinopathy (DR) is the most common complication of diabetes and needs to be diagnosed early to prevent severe sight-threatening retinopathy. Digital photography with telemedicine connections is a novel way to deliver cost-effective, accessible screening to remote areas. Screening for DR in a mobile eye examination unit (EyeMo) is compared to traditional service models (i.e. local municipal services or a commercial service provider). The quality of images, delays from screening to treatment, the stage of DR, coverage of screening and the rate of visual impairment due to DR are evaluated. Methods EyeMo utilizes telemedicine technology. The electronic databases of the hospital and information from the Finnish Register of Visual Impairment were used to determine delays and the rate of visual impairment. Results Fourteen thousand eight hundred and sixty-six fundus photographs were taken in EyeMo in 2007–2011. Coverage reached 78% of potential clients. No DR was detected in 43%, mild background retinopathy in 23%, moderate or severe background retinopathy in 31% and proliferative retinopathy in 3% of the evaluations. The quality of images was higher (p

Objectives To estimate the prevalence and risk factors for abnormal liver enzymes in a large age- and gender stratified population-based sample of apparently healthy individuals with or without alcohol consumption and other health-related risk factors (adiposity, physical inactivity, smoking). Methods Data on alcohol use, smoking, diet and physical activity were recorded using structured questionnaires from 13,976 subjects (6513 men, 7463 women, aged 25–74 years) in the national FINRISK studies. Alcohol data was used to categorize the participants into abstainers, light drinkers, moderate drinkers and heavy drinkers. Serum gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) activities were measured using standard kinetic methods. Results Male light drinkers, moderate drinkers and heavy drinkers showed significantly higher relative risks of abnormal GGT than abstainers: 1.37 (95% confidence interval 1.11 to 1.71, p < 0.01), 2.72 (2.08 to 3.56, p < 0.0005), and 6.10 (4.55 to 7.17, p < 0.0005), respectively. Corresponding values for women were 1.22 (0.99 to 1.51, p = 0.065), 1.90 (1.44 to 2.51, p < 0.0005), and 5.91 (3.80 to 9.17, p < 0.0005). Estimated threshold doses for a significant GGT elevation was 14 standard weekly alcohol doses for men and 7 for women. Excess body weight and age over 40 years modulated the thresholds towards smaller quantities of alcohol. The risk of abnormal GGT was also significantly influenced by physical inactivity and smoking. The relative risks of abnormal ALT activities were increased in male heavy drinkers, especially in those presenting with adiposity and sedentary lifestyle. Conclusions Alcohol use markedly increases the risk for abnormal liver enzyme activities in those presenting with age over 40 years, obesity, smoking or sedentary lifestyle. The data should be considered in public health recommendations and in the definitions of safe limits of alcohol use., published version, peerReviewed

Adverse drug events (ADEs) are more likely to affect geriatric patients due to physiological changes occurring with aging. Even though this is an internationally recognized problem, similar research data in Finland is still lacking. The aim of this study was to determine the number of geriatric medication-related hospitalizations in the Finnish patient population and to discover the potential means of recognizing patients particularly at risk of ADEs. The study was conducted retrospectively from the 2014 emergency department patient records in Oulu University Hospital. A total number of 290 admissions were screened for ADEs, adverse drug reactions (ADRs) and drug-drug interactions (DDIs) by a multi-disciplinary research team. Customized Naranjo scale was used as a control method. All admissions were categorized into ‘probable’, ‘possible’, or ‘doubtful’ by both assessment methods. In total, 23.1% of admissions were categorized as ‘probably’ or ‘possibly’ medication-related. Vertigo, falling, and fractures formed the largest group of ADEs. The most common ADEs were related to medicines from N class of the ATC-code system. Age, sex, residence, or specialty did not increase the risk for medication-related admission significantly (min p= 0.077). Polypharmacy was, however, found to increase the risk (OR 3,3; 95% CI, 1.5-6.9 p = 0.01). In conclusion, screening patients for specific demographics or symptoms would not significantly improve the recognition of ADEs. In addition, as ADE detection today is largely based on voluntary reporting systems and retrospective manual tracking of errors, it is evident that more effective methods for ADE detection are needed in the future.

Although strenuous physical activity is known to cause notable perturbations in blood chemistries, only few studies exist observing exercise-induced simultaneous changes in biomarkers of health status. We compared markers of muscle, cardiovascular, renal, hepatic and inflammatory status at baseline and at 3-h and at 48-h postrace in recreational runners who successfully completed either a marathon (mean age 27 ± 13 years, finishing time 199 ± 8 min, n = 4) or half-marathon (mean age 38 ± 13 years, finishing time 131 ± 6 min, n = 6) race. Significant postrace changes occurred in myoglobin (p .001), creatinine kinase (p .01), CK-MB-mass (p .01), high sensitivity troponin I (p .05), high sensitivity troponin T (p .05), brain natriuretic peptide (p .001), creatinine (p .01), aminotransferase enzymes (p .001 for AST and p .01 for ALT), uric acid (p .001) cortisol (p .01), C-reactive protein (p .05), leukocytes (p .001), haematocrit (p .05) and mean corpuscular volume (p .01). In comparison between the two types of exercise, marathon running lead to more pronounced responses in myoglobin, CK-MB-mass, ALT, AST, lactate and phosphate. Notable elevations in troponin levels were observed only in young participants (30 years), most strikingly in those ≤20 years of age. The data indicates that prolonged running leads to distinct biomarker alterations, which should be considered in the assessment of health status after recent acute bouts of strenuous exercise. The observations suggesting more pronounced cardiac troponin responses in young individuals warrant further studies in larger populations.

Background Breastfeeding and skin-to-skin contact are the best start for infant life. Breastfeeding ensures the best trajectory for development and growth while preventing many diseases later in life. It is recommended that initial breastfeeding occur during the first hour and that generally exclusive breastfeeding is adopted during the first six months. Objective The aim of this study is to describe how initial breastfeeding and skin-to-skin contact (Step 4 of the BFHI) is implemented in Finnish maternity hospitals as well as to explain the factors connected to it. The information can be used to develop maternity care during the immediate postpartum period. Design Cross‐sectional study. Methods The data were collected from mothers who had given birth as well as their midwives via questionnaire during the spring of 2014 during one week at eight maternity hospitals in Finland. The response rate was 59% for the new mothers ( n =111), while it was 57% for the midwives ( n =272). The data were analysed statistically and the open-ended questions in the questionnaire using content specifications. Findings On the basis of the results, initial breastfeeding succeeded well after vaginal birth. Initial breastfeeding began, on average, at 41minutes of age and lasted for 51minutes. Of mothers, 87% regarded it a very positive experience. Initial breastfeeding was delayed mainly because of caesarean section and for reasons related to an infant's condition. Many background factors such as midwives' age, mothers' parity and the mode of childbirth were statistically significant in respect to the success of initial breastfeeding. Conclusions More attention should be placed on the initial breastfeeding of infants born by caesarean section and primiparous mothers.

Growing evidence supports the existence of clinically significant social-emotional/behavioral (SEB) problems among as young as 1-year-old infants. However, a substantial proportion of early SEB problems remain unidentified during contacts with child healthcare professionals. In this study, child healthcare nurse (CHCN; N = 1008) and parental (N = 518) reports about SEB worries were gathered, along with the maternal and paternal Brief Infant-Toddler Social and Emotional Assessment (BITSEA) ratings, for 12-month-old infants randomly recruited through Finnish child health centers. Only 1.4-1.8 % of CHCNs, 3.9 % of mothers, and 3.2 % of fathers reported of being worried about the assessed child's SEB development. When the CHCNs' and parental reports were combined, 7.7 % (33/428) of the infants assessed each by all three adults had one (7.0 %), two (0.7 %) or three (0 %) worry reports. Even the combination of the CHCN's and parental worry reports identified only 7.0-13.8 % of the infants with the maternal and/or paternal BITSEA Problem or Competence rating in the of-concern range. Identified associations across the three informants' worry reports, parental BITSEA ratings and sociodemographic factors are discussed in the paper. Routine and frequent use of developmentally appropriate screening measures, such as the BITSEA, might enhance identification and intervening of early SEB problems in preventive child healthcare by guiding both professionals and parents to pay more attention to substantial aspects of young children's SEB development and encouraging them to discuss possible problems and worries.

Background: Inflammation contributes to the pathogenesis of colorectal cancer (CRC), and cytokine levels are altered during colorectal carcinogenesis. Methods: The serum levels of 13 cytokines and their relation to clinical and pathological parameters, and systemic inflammatory response (mGPS, CRP and neutrophil–lymphocyte ratio), were analysed from a prospective series of 148 CRC patients and 86 healthy age- and sex-matched controls. Results: CRC patients had higher serum platelet-derived growth factor, interleukin (IL)-6, IL-7, and IL-8 levels and lower monocyte chemotactic protein-1 (MCP-1) levels than the controls. A logistic regression model for discriminating the patients from the controls – including the five most predictive cytokines (high IL-8, high IL-6, low MCP-1, low IL-1ra, and low IP-10) – yielded an area under curve value of 0.890 in receiver operating characteristics analysis. Serum cytokines showed distinct correlation with other markers of systemic inflammatory response, and advanced CRCs were associated with higher levels of IL-8, IL-1ra, and IL-6. A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu. Conclusion: CRC is associated with extensive alterations in serum cytokine environment, highlighting the importance of studying relative cytokine level alterations. Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed.

Objective: To investigate the prevalence of ear diseases, other otological risk factors potentially affecting hearing, and noise exposure among adults. Furthermore, subject-related factors possibly associated with hearing impairment (HI), i.e. handedness, eye color, and susceptibility to sunburn, were studied. Design: A cross-sectional, unscreened, population-based, epidemiological study among adults. Study sample: The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. Results: Chronic middle-ear disease (both active and inactive) was the most common ear disease with a prevalence of 5.3%, while the prevalence of otosclerosis was 1.3%, and that of Menieres disease, 0.7%. Noise exposure was reported by 46% of the subjects, and it had no effect on hearing among those with no ear disease or other otological risk factors for HI. Dark eye color and non-susceptibility to sunburn were associated with HI among noise-exposed subjects. Conclusions: Common ear diseases and other otological risk factors constitute a major part of the etiologies of HI among adults. Contrary to previous studies, noise exposure turned out to have only marginal effect on hearing among those with no otological risk factors.

There are only a few population-based epidemiological studies on audiogram configurations among adults. The aim of this study was to investigate the prevalence of different audiogram configurations among older adults. In addition, audiogram configurations among subjects reporting hearing problems were examined.Cross-sectional, population-based, unscreened epidemiological study among older adults.The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed.The most prevalent audiogram configuration among men was high-frequency steeply sloping (65.3% left ear, 51.2% right ear) and among women, high-frequency gently sloping (33.0% left ear, 31.5% right ear). There were significantly more flat configurations among women than among men. Unclassified audiograms were common especially among women (17.5%). Subjects reporting hearing difficulties, difficulties in following conversation in noise, or tinnitus, more often had a high-frequency steeply sloping configuration than those not reporting.High-frequency sloping audiogram configurations were common among older adults, and a high-frequency steeply sloping configuration was common among those reporting hearing problems.

Background: There are not many population-based epidemiological studies on the association between self-reported hearing problems and measured hearing thresholds in older adults. Previous studies have shown that the relationship between self-reported hearing difficulties and measured hearing thresholds is unclear and, according to our knowledge, there are no previous population-based studies reporting hearing thresholds among subjects with hyperacusis. Purpose: The aim was to investigate the prevalence of self-reported hearing problems, that is, hearing difficulties, difficulties in following a conversation in noise, tinnitus, and hyperacusis, and to compare the results with measured hearing thresholds in older adults. Research Design: Cross-sectional, population-based, and unscreened. Study Sample: Random sample of subjects (n = 850) aged 54-66 yr living in the city of Oulu (Finland) and the surrounding areas. Data Collection and Analysis: Otological examination, pure tone audiometry, questionnaire survey Results: The prevalence of self-reported hearing problems was 37.1% for hearing difficulties, 43.3% for difficulties in following a conversation in noise, 29.2% for tinnitus, and 17.2% for hyperacusis. More than half of the subjects had no hearing impairment, or HI (BEHL[better ear hearing level]0.5–4 kHz < 20 dB HL) even though they reported hearing problems. Subjects with self-reported hearing problems, including tinnitus and hyperacusis, had significantly poorer hearing thresholds than those who did not report hearing problems. Self-reported hearing difficulties predicted hearing impairment in the pure-tone average at 4, 6, and 8 kHz, and at the single frequency of 4 kHz. Conclusions: The results indicate that self-reported hearing difficulties are more frequent than hearing impairment defined by audiometric measurement. Furthermore, self-reported hearing difficulties seem to predict hearing impairment at high frequencies (4–8 kHz) rather than at the frequencies of 0.5–4 kHz, which are commonly used to define the degree of hearing impairment in medical and legal issues.

Tumor hypoxia-inducible transcription factor (HIF) overexpression often associates with a poor prognosis. Stability of the HIF-α subunits is regulated by HIF prolyl 4-hydroxylases, PHD1-3. We assessed here immunohistochemical expression of PHD1-3 and HIF-1α and 2α in patients with invasive ductal breast carcinoma (n = 102) and correlated their expression levels with main clinical prognostic factors and survival. PHD1 expression correlated with high proliferation, and these tumors were mainly estrogen receptor-negative. PHD3 expression declined in tumors of large size, poor differentiation, and high proliferation. There was a tendency for increased breast cancer-specific survival and longer disease-free survival among patients with high tumor PHD2 expression. Surprisingly, PHD1-3 expression did not correlate with HIF-1α or HIF-2α downregulation. However, HIF-2α expression correlated independently with low tumor stage and HIF-1α expression had a tendency for decreased breast cancer-specific survival. PHD1 and 3 appear to be HIF-independent factors in breast cancer. Not all PHD1 associated proliferation is estrogen-dependent and it is associated with a poor prognosis of cancer. PHD3 may be an important regulator of apoptosis and it is mainly found in tumors with good prognosis. PHD2 expression is likely to be involved in increased survival.

Aim: The aim of the study is to describe the relationships among thermal environment, skin temperatures and infants’ daytime outdoor sleep duration in northern winter conditions. Methods: This study is a cross-over observational study. Skin temperatures of three-month-old infants were recorded from seven skin sites continuously throughout outdoor (n = 34) and indoor sleep (n = 33) in the families’ homes. The duration of the sleep was observed, and temperature and the air velocity of the environment were recorded. Results: Skin temperatures increased towards the end of indoor sleeping, whereas they decreased during outdoor sleeping. The cooling rate of mean skin temperature (Tsk) increased in lower outdoor temperatures (rs = 0.628, p

Background Despite the extensive literature on neuropsychological sequelae after treatment of childhood acute lymphoblastic leukemia (ALL), the very-long-term neurocognitive outcome of the survivors is poorly studied. We assessed neuropsychological functioning in a population-based cohort of young adult childhood ALL survivors. Procedure Neuropsychological testing was performed on 64 survivors an average of 20 years after the diagnosis. The test battery included verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ), memory function, orientation and attention as well as motor performance. Cranial irradiation had been administered to 44 survivors as part of ALL treatment, whereas 20 survivors had been treated solely with chemotherapy. A control group consisted of 45 healthy young adults. Earlier neuropsychological test results of 45 of the survivors were available for comparison. Results The ALL survivors attained significantly lower test scores than the controls in all the neuropsychological function areas. The mean VIQ test scores were 91, 100, and 109 (P