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Abstract Background Successful ageing is the term often used for depicting exceptional ageing and can be measured with multidimensional models including physical, psychological and social wellbeing. The aim of this study was to test multidimensional successful ageing models to investigate whether these models can predict successful ageing, and which individual subcomponents included in the models are most significantly associated with successful ageing. Methods Successful ageing was defined as the ability to live at home without daily care at the age of 84 years or over. Data on the participants’ physical, psychological and social wellbeing were gathered at baseline and the follow-up period was 20 years. Four successful ageing models were constructed. Backward stepwise logistic regression analysis was used to identify the individual subcomponents of the models which best predicted successful ageing. Results All successful ageing models were able to predict ageing successfully after the 20-year follow-up period. After the backward stepwise logistic regression analysis, three individual subcomponents of four models remained statistically significant and were included in the new model: having no heart disease, having good self-rated health and feeling useful. As a model, using only these three subcomponents, the association with successful ageing was similar to using the full models. Conclusions Multidimensional successful ageing models were able to predict successful ageing after a 20-year follow-up period. However, according to the backward stepwise logistic regression analysis, the three subcomponents (absence of heart disease, good self-rated health and feeling useful) significantly associated with successful ageing performed as well as the multidimensional successful ageing models in predicting ageing successfully.

Background In this study in a tertiary care hospital, we examined the characteristics of the different microbial etiologies of infective endocarditis (IE) and the factors associated with embolic events.Materials and methods We included patients (aged ≥18 years) hospitalized for IE in Turku University Hospital in Finland between 2004-2017. Patient data were derived retrospectively from the mandatory database and patient record system.Results Among 342 IE cases in 321 patients, Staphylococcus aureus was isolated in 33.9%, viridans group streptococci in 18.3% and enterococci in 8.8% of the cases. Patients with enterococcal IE had more often a prosthetic valve (p

Wheezing children infected with rhinovirus (RV) have a markedly increased risk of subsequently developing recurrencies and asthma. No previous studies have assessed the association between cytokine response and the severity of acute illness in the first wheezing episode in children infected with RV. Forty-seven children treated both as inpatients and as outpatients infected with RV only, aged 3–23 months, with severe first wheezing episodes were recruited. During acute illness, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with anti-CD3/anti-CD28 in vitro. A multiplex ELISA was used to quantitatively identify 56 different cytokines. The mean age of the children was 17 months, 74% were males, 79% were hospitalized, and 33% were sensitized. In adjusted analyses, the inpatient group was characterized by decreased expressions of interferon gamma (IFN-γ), interleukin 10 (IL-10), macrophage inflammatory protein 1 alpha (MIP-1α), RANTES (CCL5), and tumor necrosis factor-alpha (TNF-α) and an increased expression of ENA-78 (CXCL5) compared to the outpatient group. The cytokine response profiles from the PBMCs were different between the inpatient and outpatient groups. Our results support that firmly controlled interplay between pro-inflammatory and anti-inflammatory responses are required during acute viral infection to absolve the initial infection leading, to less severe illness.

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. Methods The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. Discussion Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. Trial registration ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Abstract Background Successful ageing is the term often used for depicting exceptional ageing but a uniform definition is lacking. The aim was to re-examine and describe the successful agers living at home at the age of 84 years or over after a 20-year follow-up. The purpose was also to identify possible factors leading to their successful ageing. Methods Successful ageing was defined as the ability to live at home without daily care. Data on the participants’ functional ability, objective health, self-rated health and satisfaction with life were gathered at baseline and after a 20-year follow-up period. A measurement of personal biological age (PBA) was established and the difference between the PBA and the chronological age (CA) was counted. Results The participants’ mean age was 87.6 years (Standard deviation 2.5, range 84–96). All analyzed variables depicted poorer physical ability and subjective health at re-examination than at baseline. Still, 99% of the participants were at least moderately satisfied with their lives. The PBA at baseline was 6.5 years younger than CA, and at re-examination, the difference was even more pronounced at 10.5 years. Discussion Even though the participants were chronologically older, had poorer physical ability and subjective health, they were still satisfied with their lives indicating possible psychological resilience. The difference between the PBA and CA was greater at re-examination than at baseline indicating that they were also biologically successful agers. Conclusions Successful agers were satisfied with life despite hardships and had a lower biological than chronological age. Further research is needed to evaluate causality.

Abstract Background Rhinovirus (RV)‐induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV‐induced immune responses in young children. We investigated cytokine profiles of sole RV‐ and dual RV‐HBoV1‐induced first wheezing episodes, and their association with severity and prognosis. Methods Fifty‐two children infected with only RV and nine children infected with dual RV‐HBoV1, aged 3–23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti‐CD3/anti‐CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years. Results The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL‐1b, MIP‐1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF‐a, TARC, and ENA‐78 in the RV‐HBoV1 group compared with the RV group. In the convalescence phase, the RV‐HBoV1 group was characterized by decreased expression of Fractalkine, MCP‐3, and IL‐8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p

Abstract Background Various indexes have been developed to estimate the risk for mortality, institutionalization, and other adverse outcomes for older people. Most indexes are based on a large number of clinical or laboratory parameters. An index based on only a few parameters would be more practical to use in every-day clinical practice. Our aim was to create an index to predict the risk for mortality and institutionalization with as few parameters as possible without compromising their predictive ability. Methods A prospective study with a 10-year follow-up period. Thirty-six clinical and fourteen laboratory parameters were combined to form an index. Cox regression model was used to analyze the association of the index with institutionalization and mortality. A backward statistical method was used to reduce the number of parameters to form an easy-to-use index for predicting institutionalization and mortality. Results The mean age of the participants (n = 1172) was 73.1 (SD 6.6, range 64‒97) years. Altogether, 149 (14%) subjects were institutionalized, and 413 (35%) subjects deceased during the follow-up. Institutionalization and mortality rates increased as index scores increased both for the large 50-parameter combined index and for the reduced indexes. After a backward variable selection in the Cox regression model, three clinical parameters remained in the index to predict institutionalization and six clinical and three laboratory parameters in the index to predict mortality. The reduced indexes showed a slightly better predictive value for both institutionalization and mortality compared to the full index. Conclusions A large index with fifty parameters included many unimportant parameters that did not increase its predictive value, and therefore could be replaced with a reduced index with only a few carefully chosen parameters, that were individually associated with institutionalization or death.

Background: Most Western adults do not meet the recommendations for sufficient activity, and obesity is a global problem. Similar trends are also seen among Western military personnel. Many successful physical training interventions have been carried out in military environments, but the interventions have been quite short term, and the training has been supervised. Therefore, the aim of this study was to investigate the effects of a 12-month voluntary motivational training intervention among the Finnish Defence Forces’ (FDF) Navy soldiers. Methods: In total, 77 FDF Navy soldiers, serving in missile patrol boats, took part in the study. The intervention group (IG) contained 45 participants and the control group (CG) contained 32 participants. The IG was divided into four teams that carried out the intervention, while the CG took part in only the measurements. Results: Most of the participants (65%) in the IG reported that they had increased their exercise volume during the intervention, but no major beneficial impacts on the physical fitness, body composition, or health markers were observed. Nevertheless, there was a clear diversity visible between the subgroups in the IG. The team that reported the most exercise had the best motivation and the most motivated team coach and also had the most improved physical fitness and body composition results. Conclusions: The present study points out that in military environments, long-term voluntary training interventions may not be as successful as short-term supervised interventions. The results also suggest that in voluntary training interventions among military personnel, the participants’ motivation to exercise is a key factor when improving physical fitness.

Abstract Objectives To analyze the long‐term side effects of radiation therapy (RT) for head and neck cancer (HNC). Methods Retrospective chart analysis of all 688 HNC patients treated during 2010–2015 at Turku University Hospital, Finland. All patients who survived for more than a year after RT/chemoRT were included (n = 233). Intensity modulated RT (IMRT) with standard fractionation was applied in each case. Results One hundred and six patients (45%) reported persisting dysphagia, for which neck RT increased risk. Definitive neck RT to high‐risk volume did not increase late toxicity risks compared to elective neck RT. Radiation‐induced hypothyroidism (29%, n = 67) was more common among younger patients and females. Osteoradionecrosis (12%, n = 29) was more common in the oral cavity cancer group (20.7%, n = 92) compared to all other subsites. Conclusions Late toxicities of RT for HNC are common. Age, gender, tumor subsite, and neck RT affect susceptibility to long‐term side effects. Level of evidence 4.

Abstract Background Older adults are more susceptible to respiratory tract infection than healthy working age adults. The increased susceptibility of older adults is thought to be interlinked with vitamin D status, nourishment, and immunological state in general. Data are scarce whether these parameters could serve as prognostic markers. Aim To study whether serum 25(OH)D, albumin, and LL-37 level could give prognostic value of long-term survival in the older adults with multimorbidity and acute respiratory infection. Methods Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory markers included serum levels of 25(OH)D, albumin and LL-37, C-reactive protein (CRP), white blood cell count (WBC) and polymerase chain reaction diagnostics for 14 respiratory viruses. Pneumonia was confirmed by chest radiographs. Respiratory illness severity, death at ward, length of hospital stays, and 5-year survival were used as outcomes. Results In total, 289 older adult patients with mean age of 83 years were included in the study. Serum 25(OH)D deficiency (

Background: This exploratory study aimed to investigate whether dexmedetomidine, propofol, sevoflurane, and S-ketamine affect oxylipins and bile acids, which are functionally diverse molecules with possible connections to cellular bioenergetics, immune modulation, and organ protection. Methods: In this randomised, open-label, controlled, parallel group, Phase IV clinical drug trial, healthy male subjects (n=160) received equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml−1; n=40), propofol (1.7 μg ml−1; n=40), sevoflurane (0.9% end-tidal; n=40), S-ketamine (0.75 μg ml−1; n=20), or placebo (n=20). Blood samples for tandem mass spectrometry were obtained at baseline, after study drug administration at 60 and 130 min from baseline; 40 metabolites were analysed. Results: Statistically significant changes vs placebo were observed in 62.5%, 12.5%, 5.0%, and 2.5% of analytes in dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively. Data are presented as standard deviation score, 95% confidence interval, and P-value. Dexmedetomidine induced wide-ranging decreases in oxylipins and bile acids. Amongst others, 9,10-dihydroxyoctadecenoic acid (DiHOME) –1.19 (–1.6; –0.78), P

Objective To evaluate the association between the concerns of parents, teachers, and nurses regarding each child’s well-being and the school doctor actions conducted in routine general health checks.Design A blinded, observational study. Prior to the health check parents, teachers, and nurses completed questionnaires assessing their concerns. Doctors, blinded to the responses, routinely examined all children accompanied by parents and reported their actions after each health check. Multilevel logistic regression was used to analyse the association of the concerns with the actions.Setting 21 primary schools in four municipalities in Finland.Participants Between August 2017 and August 2018, we randomly recruited 1341 children from grades 1 and 5, aged 7 and 11 years, respectively.Outcome measures Outcome measures were the respondents’ concerns and the school doctor actions. The extent of concerns was assessed on a five-point Likert scale. Concern refers to ‘Quite a lot or a great deal of concern’ by at least one respondent. The school doctor actions included instructions and/or significant discussions, prescriptions, laboratory tests and/or medical imaging, scheduling of follow-up appointments, referrals to other professionals, and referrals to specialised care.Results Altogether, respondents were concerned about 47.5% of children. The top three concerns comprised growth/and or physical symptoms (22.7%), emotions (16.2%), and concentration (15.1%). All concerns were associated with some type of school doctor action (ORs: 1.66–4.27, p≤0.05); but only concerns regarding growth and/or physical symptoms were associated with all actions. Almost all concerns were associated with referrals to other professionals (ORs: 1.80–4.52, p≤0.01); emotions had the strongest association OR 4.52 (95% CI 3.00 to 6.80, p

BackgroundCerebrovascular involvement of Kawasaki disease (KD) is poorly studied. White matter hyperintensities (WMH) indicate cerebral small vessel disease and increase the risk for stroke.PurposeTo investigate whether childhood KD is associated with WMHs and other cerebrovascular findings later in adulthood.Materials and methodsIn this case-control study, patients diagnosed with KD (cases) at our tertiary hospital between 1978 and 1995 were invited to brain magnetic resonance (MRI) between 2016 and 2017. Migraine patients (controls) with available brain MRI were matched with cases (ratio 4:1) by age (±2 years) and sex. Two blinded neuroradiologists evaluated independently cerebrovascular findings from the brain MRI scans. Modified Scheltens' visual rating scale was used to evaluate WMH burden and the total WMH volume was measured using manual segmentation.ResultsMean age [years, (SD)] at the time of brain MRI was 33.3 (3.8) and 32.8 (4.0) for cases (n = 40) and controls (n = 160), respectively (P = 0.53). Mean follow-up time for cases was 29.5 years (4.3). Total volume of WMHs (median) was 0.26 cm3 (IQR 0.34) for cases and 0.065 cm3 (IQR 0.075) for controls, P = 0.039. Cases had higher total WMH burden (P = 0.003), deep WMH burden (P = 0.003), and more periventricular WMHs (prevalence 7.5 vs. 0%, P = 0.008) than controls. Cases had greater risk of having total Scheltens' score ≥2 vs. < 2 (odds ratio, 6.88; 95% CI: 1.84–25.72, P = 0.0041) and ≥3 vs. < 3 (odds ratio, 22.71; 95% CI: 2.57–200.53, P = 0.0049). Diabetes type 1/type 2, hypertension, smoking status or hypercholesterolemia were not risk factors for WMH burden, p > 0.1. Myocarditis at the acute phase of KD increased the risk for periventricular WMHs (P < 0.05). Three cases (7.5%) and three controls (1.9%) had lacune of presumed vascular origin (P = 0.0096).ConclusionHistory of KD could be associated with an increased WMH burden. More studies are needed to confirm our results.

Abstract Background In Finland, school doctors examine all children at predetermined ages in addition to annual health checks by school nurses. This study explored the association of study questionnaire-assessed need for and school doctor-evaluated benefit of routine health checks conducted by doctors. Methods Between August 2017 and August 2018, we recruited a random sample of 1341 children in grades 1 and 5 (aged seven and eleven years, respectively) from 21 elementary schools in four Finnish municipalities. Children mainly studying in special education groups or whose parents needed an interpreter were excluded. School nurses performed their health check as usual. Parents, nurses, and teachers then completed study questionnaires that assessed the concerns of parents, school nurses, and teachers regarding each child’s physical, mental and social health. Doctors, blinded to the responses, routinely examined all the children. The primary outcome measures were (1) the need for a health check based on the study questionnaires and (2) the benefit/harm of the appointment as estimated by the doctors according to predetermined criteria, and (3) the patient-reported experience measures (PREMs) of benefit/harm of the appointment as estimated by the parents and children. We compared the need for a health check with the doctor-evaluated benefit using multilevel logistic regression. Results The participation rate was 75.5 %. According to all questionnaires, 20–25 % of the 1013 children had no need for a health check. The doctors regarded 410 (40.6 %) and the parents 812 (83.4 %) of the appointments as being beneficial. Respondents rarely reported harm. The children who were classified as needing a health check more often benefitted from the health check (assessed by the doctor) than children with no need for one (OR 3.53; 95 % CI 2.41–5.17). Conclusions The need for a health check is an important predictor of school-doctor evaluated benefit of the health check. This approach could allow school doctors to allocate time for the children who need them most. Trial registration ClinicalTrials.gov, Identifier NCT03178331, registration June 6th 2017.

Objective Although sexual problems are common, they are rarely brought up in appointments with general practitioners (GPs). We aimed to assess the barriers that hinder GPs from bringing up sexual health issues and to evaluate the need for education on sexual medicine. Design A web-based questionnaire was used. Setting Four fields were included: A) the self-reported competence in discussing sexual health and treating patients with these issues, B) the barriers to bringing up patients’ sexual health problems, C) the source of education on sexual medicine and D) the need for education on sexual medicine. Subjects A random sample of 1000 GPs in Finland (a response rate of 43.5%, n = 402). Main outcome measures GPs’ self-assessed competence in discussing and treating sexual health issues, related barriers to bringing up the topic and the reported need for education. Results The main reasons reported for not bringing up sexual health issues were shortness of the appointment time (85.6%), a lack of knowledge (83.6%) and a lack of experience with sexual medicine (81.8%). The male GPs reported better competence in discussing the issues and treating male patients, whereas the female GPs reported better competence in discussing the issues with female patients. No differences emerged between genders regarding treating female patients. Nearly 90% of the GPs expressed needing more education about sexual medicine. Conclusions Although the GPs reported good competence in discussing sexual health issues with their patients, several barriers to bringing up sexual health issues emerged. Continuing education was desired and could lessen these barriers.Key points Only a few studies have evaluated the competence of general practitioners (GPs) in addressing sexual health issues with their patients. In our study, the GPs reported a high competence in discussing patients’ sexual health issues regardless of the patient’s gender. However, several barriers to bringing up sexual health issues in appointments emerged. A majority of the GPs expressed a need for continuing education about sexual medicine.

Abstract Background Objective health measures, such as registered illnesses or frailty, predict mortality and institutionalization in older adults. Also, self-reported assessment of health by simple self-rated health (SRH) has been shown to predict mortality and institutionalization. The aim of this study was to assess the association of objective and subjective health with mortality and institutionalization in Finnish community-dwelling older adults. Methods In this prospective study with 10- and 18-year follow-ups, objective health was measured by registered illnesses and subjective health was evaluated by simple SRH, self-reported walking ability (400 m) and self-reported satisfaction in life. The participants were categorized into four groups according to their objective and subjective health: 1. subjectively and objectively healthy, 2. subjectively healthy and objectively unhealthy, 3. subjectively unhealthy and objectively healthy and 4. subjectively and objectively unhealthy. Cox regression model was used in the analyses. Death was used as a competing factor in the institutionalization analyses. Results The mean age of the participants (n = 1259) was 73.5 years (range 64.0–100.0). During the 10- and 18-year follow-ups, 466 (37%) and 877 (70%) died, respectively. In the institutionalization analyses (n = 1106), 162 (15%) and 328 (30%) participants were institutionalized during the 10- and 18-year follow-ups, respectively. In both follow-ups, being subjectively and objectively unhealthy, compared to being subjectively and objectively healthy, was significantly associated with a higher risk of institutionalization in unadjusted models and with death both in unadjusted and adjusted models. Conclusions The categorization of objective and subjective health into four health groups was good at predicting the risk of death during 10- and 18-year follow-ups, and seemed to also predict the risk of institutionalization in the unadjusted models during both follow-ups. Poor subjective health had an additive effect on poor objective health in predicting mortality and could therefore be used as part of an older individual’s health evaluation when screening for future adverse outcomes.

Abstract Background Chemotherapy-induced side effects may have a negative effect on nutrition intake, thus increasing the risk of malnutrition and consequently, other serious complications for patients with cancer. The prevalence of malnutrition is common among patients with colorectal cancer. Nurse-led empowering education may have a positive effect on self-care activity in this patient group. Therefore, our purpose is to develop an empowering educational nursing intervention and test its effect on self-care activation and knowledge level among patients with colorectal cancer during chemotherapy. Secondary outcomes are quality of life and risk of malnutrition. Methods An interdisciplinary expert group developed a face-to-face empowering educational intervention using teach-back method. A two-arm, single-centre, superiority trial with stratified randomisation (1:1) and pre-post measures will be used to assess the effect of the intervention compared to standard care. Patients (N = 40 + 40) will be recruited in one university hospital outpatient clinic in Finland. Eligibility criteria are adult patients diagnosed with colorectal cancer starting oral fluoropyrimidine or combination chemotherapy treatment. A registered nurse experienced in oncology will deliver the intervention 2 weeks after the first chemotherapy. Outcomes are measured before intervention (M0) and after a two-month follow-up period (M1). Discussion This study will assess whether nurse-led empowering education using teach-back method is effective on self-care activity among patients with colorectal cancer. If the intervention has a positive effect, it may be implemented into patient education in a corresponding context. Trial registration ClinicalTrials.gov : NCT04160650 Registered 12 November 2019 - retrospectively registered

Abstract Background Previously, several indexes based on a large number of clinical and laboratory tests to predict mortality and frailty have been produced. However, there is still a need for an easily applicable screening tool for every-day clinical practice. Methods A prospective study with 10- and 18-year follow-ups. Fourteen common laboratory tests were combined to an index. Cox regression model was used to analyse the association of the laboratory index with institutionalization and mortality. Results The mean age of the participants (n = 1153) was 73.6 (SD 6.8, range 64.0–100.0) years. Altogether, 151 (14.8%) and 305 (29.9%) subjects were institutionalized and 422 (36.6%) and 806 (69.9%) subjects deceased during the 10- and 18-year follow-ups, respectively. Higher LI (laboratory index) scores predicted increased mortality. Mortality rates increased as LI scores increased both in unadjusted and in age- and gender-adjusted models during both follow-ups. The LI did not significantly predict institutionalization either during the 10- or 18-year follow-ups. Conclusions A practical index based on routine laboratory tests can be used to predict mortality among older people. An LI could be automatically counted from routine laboratory results and thus an easily applicable screening instrument in clinical settings.

Background and purpose — Whole-blood (WB) chromium (Cr) and cobalt (Co) measurements are vital in the follow-up of metal-on-metal total hip replacement (MoM THR) patients. We examined whether there is a substantial change in repeated WB, Co, and Cr levels in patients with bilateral ReCap-M2A-Magnum THR. We also specified the number of patients exceeding the safe upper limit (SUL) of WB Co and Cr in the repeated measurement. Patients and methods — We identified 141 patients with bilateral ReCap-M2A-Magnum THR operated in our institution. 61 patients had repeated WB metal ion measurements with bilateral MoM implants still in situ in the second measurement. The mean time elapsing from the first measurement (initial measurement) to the second (control measurement) was 1.9 years (SD = 0.6, range 0.2–3.5). We used earlier established SUL levels for bilateral implants by Van Der Straeten et al. (). Results — The median (range) Co and Cr values decreased in the repeated measurement from 2.7 (0.6–25) to 2.1 (0.5–21) and 2.6 (0.8–14) to 2.1 (0.5–18) respectively. In 13% of the patients Co levels exceeded the SUL in the initial measurement and the proportion remained constant, at 13%, in the repeated measurement. In 5% of the patients, Cr levels were above SUL in the initial measurement and an equal 5% in the control measurement. Interpretation — Repeated WB metal ion levels did not increase in patients with bilateral ReCap-M2A-Magnum THR with a mean 1.9-year measurement interval. Long-term development of WB metal ion levels is still unclear in these patients.

Abstract Background Despite a non-specific nature of self-rated health (SRH), it seems to be a strong predictor of mortality. The aim of this study is to assess the association of SRH and objective health status (OH) with all-cause mortality in 70-year-old community-dwelling older people in Finland. Methods A prospective study with 5-, 10- and 27-year follow-ups. SRH (n = 1008) was assessed with a single question and OH (n = 962) by the Rockwood’s Frailty Index (FI). To assess the association of SRH and OH with mortality, Cox regression model was used. Results Of the 1008 participants, 138 (13.7%), 319 (31.6%), and 932 deceased (86.3%) during the 5-, 10- and 27-year follow-ups, respectively. In unadjusted models, subjects with poor SRH had almost eightfold risk for mortality compared to those with good SRH during the 5-year follow-up; among those with poor OH, the risk was fourfold compared to those with good OH. In the 10-year-follow up, both poor SRH and poor OH predicted about fourfold risk for mortality compared to those with good health. During the 27-year follow-up, OH was a stronger predictor of mortality than SRH. Poor SRH, compared to good SRH, showed 95% sensitivity and 34% specificity for 5-year mortality; corresponding figures for OH were 54 and 80%, respectively. Conclusions Single-item SRH seems to be able to capture almost the same as OH in predicting a short-term (less than 10 years) mortality risk among older adults in clinical settings. The use of SHR may also enhance the focus on patient-centered care.

The aim of this cross-sectional study was to investigate whether parental views on child feeding and its impact on health differ between those parents whose self-perception was that they followed a healthy diet to those who do not. Furthermore, differences in the child’s diet quality and weight were compared between the groups. Parents of 2−6-year-old children (n = 738), recruited from child health clinics throughout Finland, answered semi-structured questionnaires on their views on child feeding and health as well as their child’s diet quality. Participants were divided into two groups based on their self-perceived report of following a healthy diet: health-conscious (HC, n = 396) and non-health-conscious (non-HC, n = 342) parents. HC parents considered health, eating behavior, and nutrient-related factors more often when feeding their child than non-HC parents (p < 0.03). Moreover, they more commonly considered diet to have an important impact on their child’s long-term health than the non-HC parents (p < 0.05). Children of HC parents were more likely to have a good diet quality (p = 0.01) and lower BMI-SDS values (p = 0.015) than those of non-HC parents. Parental health consciousness was linked with better diet quality and healthier weight in their children. This information may be useful in the regular clinical monitoring of children’s health.

Abstract Background Surgery and diseases modify inflammatory responses and the immune system. Anesthetic agents also have effects on the human immune system but the responses they induce may be altered or masked by the surgical procedures or underlying illnesses. The aim of this study was to assess how single-drug dexmedetomidine and propofol anesthesia without any surgical intervention alter acute immunological biomarkers in healthy subjects. Methods Thirty-five healthy, young male subjects were anesthetized using increasing concentrations of dexmedetomidine (n = 18) or propofol (n = 17) until loss of responsiveness (LOR) was detected. The treatment allocation was randomized. Multi-parametric immunoassays for the detection of 48 cytokines, chemokines and growth factors were used. Concentrations were determined at baseline and at the highest drug concentration for each subject. Results The changes in the concentration of eotaxin (decrease after dexmedetomidine) and platelet-derived growth factor (PDGF, increase after propofol) were statistically significantly different between the groups. Significant changes were detected within both groups; the concentrations of monocyte chemotactic protein 1, chemokine ligand 27 and macrophage migration inhibitory factor were lower in both groups after the drug administration. Dexmedetomidine decreased the concentration of eotaxin, interleukin-18, interleukin-2Rα, stem cell factor, stem cell growth factor and vascular endothelial growth factor, and propofol decreased significantly the levels of hepatocyte growth factor, IFN-γ-induced protein 10 and monokine induced by IFN-γ, and increased the levels of interleukin-17, interleukin-5, interleukin-7 and PDGF. Conclusions Dexmedetomidine seemed to have an immunosuppressive effect on the immune system whereas propofol seemed to induce mixed pro- and anti-inflammatory effects on the immune system. The choice of anesthetic agent could be relevant when treating patients with compromised immunological defense mechanisms. Trial registration Before subject enrollment, the study was registered in the European Clinical Trials database (EudraCT number 2013–001496-21, The Neural Mechanisms of Anesthesia and Human Consciousness) and in ClinicalTrials.gov (Principal Investigator: Harry Scheinin, number NCT01889004, The Neural Mechanisms of Anesthesia and Human Consciousness, Part 2, on the 23rd of June 2013).

Background: If a pregnant woman is overweight, this can evoke metabolic alterations that may have health consequences for both mother and child. Methods: Pregnant women with overweight/obesity (n = 358) received fish oil+placebo, probiotics+placebo, fish oil+probiotics or placebo+placebo from early pregnancy onwards. The serum metabolome was analysed from fasting samples with a targeted NMR-approach in early and late pregnancy. GDM was diagnosed by OGTT. Findings: The intervention changed the metabolic profile of the women, but the effect was influenced by their GDM status. In women without GDM, the changes in nine lipids (FDR

OBJECTIVES:. This explorative substudy aimed at determining the effect of inhaled xenon on left ventricular function by echocardiography in comatose survivors of out-of-hospital cardiac arrest. DESIGN:. A randomized two-group single-blinded phase 2 clinical drug trial. SETTING:. A multipurpose ICU in two university hospitals. PATIENTS:. Of the 110 randomized comatose survivors after out-of-hospital cardiac arrest with a shockable rhythm in the xenon in combination with hypothermia after cardiac arrest trial, 38 patients (24–76 yr old) with complete echocardiography were included in this study. INTERVENTIONS:. Patients were randomized to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours or hypothermia treatment alone. Echocardiography was performed at hospital admission and 24 ± 4 hours after hypothermia. MEASUREMENTS AND MAIN RESULTS:. Left ventricular ejection fraction, myocardial longitudinal systolic strain, and diastolic function were analyzed blinded to treatment. There were 17 xenon and 21 control patients in whom echocardiography was completed. Clinical characteristics did not differ significantly between the groups. At admission, ejection fraction was similar in xenon and control patients (39% ± 10% vs 38% ± 11%; p = 0.711) but higher in xenon than control patients after hypothermia (50% ± 10% vs 42% ± 10%; p = 0.014). Global longitudinal systolic strain was similar in xenon and control patients at admission (–9.0% ± 3.8% vs –8.1% ± 3.6%; p = 0.555) but better in xenon than control patients after hypothermia (–14.4.0% ± 4.0% vs –10.5% ± 4.0%; p = 0.006). In patients with coronary artery disease, longitudinal strain improved in the nonischemic myocardial segments in xenon patients. There were no changes in diastolic function between the groups. CONCLUSIONS:. Among comatose survivors of a cardiac cause out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia was associated with greater recovery of left ventricular systolic function in comparison with hypothermia alone.

BackgroundSomatostatin receptors (SSTR) and chemokine receptor CXCR4 are expressed in lymphomas, while the abundance is known to be heterogeneous in different subtypes of lymphomas. Targeting tumor cells expressing these receptors might add to therapeutic opportunities while radiolabeled ligands for both imaging and therapy have been developed. The aim of this study was to establish SSTR subtype 2, 3 and 5 and also CXCR4 status immunohistochemically in six different lymphoma subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), mucosa-associated marginal B-cell lymphoma (MALT), Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL).Material and MethodsThis study included a total of 103 lymphoma patients (24 DLBCL, 22 FL, 18 HL, 9 MALT, 20 MCL and 10 PTCL) diagnosed in the Southwest hospital district of Finland during 2010-2019. SSTR 2, 3 and 5 and CXCR4 expression was analyzed immunohistochemically (IHC) in lymphoma samples obtained from local archival Biobank tissue repository. Immunopositivity of each receptor was scored on a four-point scale accounting for staining intensity and proportion of positively stained tumor cells.ResultsOf different SSTR subtypes SSTR2 immunopositivity was most common and seen predominantly at the cell membrane of the malignant cells in 46-56% of DLBCL, HL and FL. CXCR4 co-expression was frequently present in these cases. SSTR3 and SSTR5 IHC were negative in DLBCL and FL but in HL SSTR expression was more heterogenous and SSTR3 and SSTR5 positivity was found in cytoplasm in 35% and 25% of cases. 2/4 blastoid MCL variants and one pleomorphic MCL variant had positive CXCR4 IHC whilst all other MCL cases (85%) were negative for all receptors. 30% (n=3) of the PTCL patients had positive SSTR5 IHC and CXCR4. MALT lymphomas were negative for all receptors.ConclusionSSTR2 and CXCR4 are found in DLBCL, FL and HL and co-expression of these receptors is common. Although in general expression of SSTRs and CXCR4 is heterogenous and very low in some subtypes such as MCL and MALT there are also patients with abundant expression. The latter are candidates for trials studying SSTR2 and/or CXCR4 based treatments in the future.

Introduction: The proportion of patients who are frequent attenders (FAs) varies from few percent to almost 30% of all patients. A small group of patients continued to visit GPs year after year. In previous studies, it has been reported that over 15% of all 1-year FAs were persistent frequent attenders (pFAs). Objectives: This study aimed to identify typical features of pFAs from the textual content in their medical entries, which could help GPs to recognize pFAs easily and facilitated treatment.Methods: A retrospective register study was done, using 10 years of electronic patient records. The data were collected from Finnish primary health care centers and used to analyze chronic symptoms and diagnoses of pFAs and to calculate the inverse document frequency weight (IDF) of words used in the patient records. IDF was used to determine which words, if any, are typical for pFAs. The study group consisted of the 5-year pFAs and control group of 1-year FAs. The main background variables were age, gender, occupation, smoking habits, use of alcohol, and BMI. Results: Out of 4392 frequent attenders, 6.6% were pFAs for 3 years and 1.1% were pFAs for 5 years. Of the pFAs, 65% were female and 35% were male. The study group had significantly more depressive episodes ( P = .004), heart failure ( P = .019), asthma ( P = .032), COPD ( P = .036), epilepsy ( P = .035), and lumbago ( P = .046) compared to the control group. GPs described their 5-year pFAs by words related to lung and breathing issues, but there was no statistical difference to the 1-year FAs’ descriptions. Conclusion: A typical pFA seems to be a woman, aged about 55 years with depressive episodes, asthma or COPD, and lower back pain. Physicians describe pFAs with ordinary words in patient records. It was not possible to differentiate pFAs from 1-year FAs in this way.

Abstract Objective To evaluate the effect of active video games in promoting physical activity and motor performance, and reducing fatigue in children with cancer. A randomized controlled trial was conducted. The intervention included playing Nintendo Wii™Fit (Nintendo Co., Ltd., Kyoto, Japan) for 30 min/day for 8 weeks. Physical activity was estimated with accelerometers, physical activity diaries and questionnaires. Movement-ABC2 and PedsQL™ were used to examine motor performance and fatigue. Intervention experiences and fidelity were examined with an interview. Results Participants (n = 36 children with cancer, 3–16 years-old) were randomly assigned to the intervention and control groups. The median [min–max] accelerometer counts/h (500 [131–1130] vs 385 [116–1012], p = 0.63) and physical activity min/day (34 [0–150] vs 23 [0–260], p = 0.95) did not differ between the groups. Change between the pre-test and post-test regarding motor performance and fatigue was similar in both groups (motor performance p = 0.77; fatigue p = 1.00). Participants experienced playing active video games meaningful, but the intervention was not followed completely as instructed. Overall, the physical activity levels were low and one fourth of the children had or were at risk of having movement difficulties. Trial registration: ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012)

Abstract Background Coercive measures is a topic that has long been discussed in the field of psychiatry. Despite global reports of reductions in the use of restraint episodes due to new regulations, it is still questionable if practices have really changed over time. For this study, we examined the rates of coercive measures in the inpatient population of psychiatric care providers across Finland to identify changing trends as well as variations in such trends by region. Methods In this nationwide registry analysis, we extracted patient data from the national database (The Finnish National Care Register for Health Care) over a 20-year period. We included adult patients admitted to psychiatric units (care providers) and focused on patients who had faced coercive measures (seclusion, limb restraints, forced injection and physical restraints) during their hospital stay. Multilevel logistical models (a polynomial model of quadratic form) were used to examine trends in prevalence of any coercive measures as well as the other four specified coercive measures over time, and to investigate variation in such trends among care providers and regions. Results Between 1995 and 2014, the dataset contained 226,948 inpatients who had been admitted during the 20-year time frame (505,169 treatment periods). The overall prevalence of coercive treatment on inpatients was 9.8%, with a small decrease during 2011–2014. The overall prevalence of seclusion, limb restraints, forced injection and physical restraints on inpatients was 6.9, 3.8, 2.6 and 0.8%, respectively. Only the use of limb restraints showed a downward trend over time. Geographic and care provider variations in specific coercive measures used were also observed. Conclusions Despite the decreasing national level of coercive measures used in Finnish psychiatric hospitals, the overall reduction has been small during the last two decades. These results have implications on the future development of structured guidelines and interventions for preventing and more effectively managing challenging situations. Clinical guidelines and staff education related to the use of coercive measures should be critically assessed to ensure that the staff members working with vulnerable patient populations in psychiatric hospitals are ethically competent.

Abstract Background Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer. Methods In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome. Results We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative). Conclusions TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.

Background and purpose — Whole blood (WB) cobalt (Co) and chromium (Cr) ion levels have a major role in the follow-up of metal-on-metal total hip replacement (MoM THR). We investigated, first, if there was a change in WB Co or Cr levels over repeated measurements in patients with ReCap-M2A-Magnum THR, and, second, determined how many patients had WB Co or Cr levels that exceeded the safe upper limits (SUL) in the repeated whole blood metal ion assessment. Patients and methods — A Recap-M2A-Magnum THR was used in 1,329 operations (1,188 patients) at our institution between 2005 and 2012. We identified all patients (n = 319) with unilateral ReCap-M2A-Magnum implants who had undergone at least 2 repeated metal ion measurements with the first blood sample taken mean 5.5 years (1.8–9.3) after surgery and the second taken mean 2 years (0.5–3) after the first. Results — The median WB Co and Cr ion levels decreased in repeated measurements from 1.40 (0.40–63) ppb to 1.10 (0.20–68) ppb and from 1.60 (0.60–13.0) ppb to 1.10 (0.30–19.0) ppb, respectively. 7% of the Co ion values exceeded SUL at the initial measurement, and 7% at the control measurement. The proportion of Cr ion values exceeding the safe upper limit (SUL) decreased during the measurement interval from 5% to 4%. Interpretation — Repeated metal ion measurements in unilateral ReCap-M2A-Magnum patients in a mean 2-year time interval did not show any increase. Long-term ion levels are, however, not yet known.

Background and purpose — It has been suggested that cemented arthroplasty is associated with increased peri- and postoperative mortality due to bone cement implanting syndrome, especially in fracture surgery. We investigated such an association in elective total hip arthroplasty (THA) patients and hemiarthroplasty (HA) patients treated for femoral neck fracture. Patients and methods — All 10,677 patients receiving elective THA or HA for fracture in our hospital between 2004 and 2015 were identified. Mortality rates for cemented and uncemented THA and HA were compared at different times postoperatively using logistic regression analysis. Analysis was adjusted for age, sex, ASA class, and year of surgery. Results — Adjusted 10- and 30-day mortality after cemented THA was comparable to that of the uncemented THA (OR 1.7; 95% CI 0.3–8.7 and OR 1.6; CI 0.7–3.6, respectively). There was no statistically significant difference in the adjusted 2-day mortality in the cemented HA group when compared with the uncemented group. However, in a subgroup analyses of ASA-class IV HA patients there was a difference, statistically not significant, during the first 2 days postoperatively in the cemented HA group compared with the uncemented HA group (OR 2.1; CI 0.9–4.7). Interpretation — Cementing may still be a safe option in both elective and hip fracture arthroplasty. Excess mortality of cemented THA and HA in the longer term is comorbidity related, not due to bone cement implantation syndrome. However, in the most fragile HA patient group caution is needed at the moment of cementing.

Abstract Background Oral microbiome has significant impact on both oral and general health. Polyols have been promoted as sugar substitutes in prevention of oral diseases. We aimed to reveal the effect of candies containing erythritol, xylitol or control (sorbitol) on salivary microbiome. Methods Ninety children (11.3 ± 0.6 years) consumed candies during 3 years. Microbial communities were profiled using Illumina HiSeq 2000 sequencing and real-time PCR. Results The dominant phyla in saliva were Firmicutes (39.1%), Proteobacteria (26.1%), Bacteroidetes (14.7%), Actinobacteria (12%) and Fusobacteria (6%). The microbiome of erythritol group significantly differed from that of the other groups. Both erythritol and xylitol reduced the number of observed bacterial phylotypes in comparison to the control group. The relative abundance of the genera Veillonella, Streptococcus and Fusobacterium were higher while that of Bergeyella lower after erythritol intervention when comparing with control. The lowest prevalence of caries-related mutans streptococci corresponded with the lowest clinical caries markers in the erythritol group. Conclusions Daily consumption of erythritol, xylitol or control candies has a specific influence on the salivary microbiome composition in schoolchildren. Erythritol is associated with the lowest prevalence of caries-related mutans streptococci and the lowest levels of clinical caries experience. Trial registration ClinicalTrials.gov Identifier NCT01062633.

Aim: The aim of the study was to find out, if a single cognitive behavior treatment (CBT) session for long-term frequent attenders in primary care affects the attendance frequency and mental well-being of the patients. Methods: Out of 193 long-term frequent attenders, 56 participated and were randomized to receive either a one-session CBT intervention or usual care. The groups were compared to each other regarding change in general practitioner visits and change in depressive symptoms, sense of coherence, somatoform symptoms and hypochondriacal anxiety at six months’ follow-up. Results: The attendance frequency decreased in both groups, but there was no difference between the groups. Changes in mental functioning did not differ between the groups. When patients with no mental health disorder were analyzed separately, the decrease in GP visits was significantly higher in the intervention group than in the control group (p = .004). Conclusion: A single session of CBT is not useful in reducing GP visits or improving mental well-being of long-term frequent attenders. Frequent attenders without a psychiatric disorder may benefit from this kind of intervention.

Infective endocarditis (IE) is associated with high mortality. However, data on factors associated with length of stay (LOS) in hospital due to IE are scarce. In addition, long-term mortality of more than 1 year is inadequately known. In this large population-based study we investigated age and sex differences, temporal trends, and factors affecting the LOS in patients with IE and in-hospital, 1-year, 5-year and 10-year mortality of IE. Data on patients (≥18 years of age) admitted to hospital due to IE in Finland during 2005-2014 were collected retrospectively from nationwide obligatory registries. We included 2166 patients in our study. Of the patients 67.8% were men. Women were older than men (mean age 63.3 vs. 59.5, p

Abstract Background Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications. Methods 92 outpatients (≥55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9.9 ± 6.2 years), and willingness to withdraw from BZDAs each received either melatonin or a placebo nightly for one month. During this period, BZDAs were meant to be gradually withdrawn. Sleep hygiene counselling and psychosocial support were provided. Three years later, use of BZDAs and other medications was determined by interview and confirmed from medical records. Results Of the original 92 outpatients, 83 (90%) participated in the 3-year survey (mean follow-up 3.3 ± 0.2 years). The number of BZDA-free participants decreased from 34 (37%) at 6 months to 26 (28%; intention-to-treat) at 3 years, that of irregular BZDA users decreased from 44 (48%) at 6 months to 27 (29%) at 3 years, while that of regular users increased from 11 (12%) at 6 months to 30 (33%) at 3 years (P = 0.001). Those who were regular BZDA users at 3 years had at baseline (before withdrawal) higher BMI (P = 0.001) than did other participants. At 3 years, the total number of medications remained unchanged for non-users (P = 0.432), but increased for the irregular (P = 0.011) and regular users (P = 0.026) compared to baseline. At 3 years, compared to baseline, use of antidepressants, dopamine agonists, melatonin, and NSAIDs/paracetamol was significantly more common in the whole cohort, but their use did not differ between the BZDA-user subgroups. Randomization to melatonin or placebo during BZDA withdrawal was unrelated to BZDA-withdrawal result. Conclusions At 3 years after withdrawal, the number of BZDA-free participants had decreased, but still one-third of the subjects remained BZDA-free, and one-third had reduced their use. Successful BZDA withdrawal did not lead to any increase in total number of medications; use of symptomatic medications in the whole cohort, however, did increase.

Abstract Background Tonsils provide an innovative in vivo model for investigating immune response to infections and allergens. However, data are scarce on the differences in tonsillar virus infections and immune responses between patients with tonsillar hypertrophy or recurrent tonsillitis. We investigated the differences in virus detection and T cell and interferon gene expression in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis. Methods Tonsils of 89 surgical patients with tonsillar hypertrophy (n = 47) or recurrent tonsillitis (n = 42) were analysed. Patients were carefully characterized clinically. Standard questionnaire was used to asses preceding and allergy symptoms. Respiratory viruses were analysed in tonsils and nasopharynx by PCR. Quantitative real-time PCR was used to analyse intratonsillar gene expressions of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet. Results Median age of the subjects was 15 years (range 2–60). Patients with tonsillar hypertrophy were younger, smoked less often, had less pollen allergy and had more adenovirus, bocavirus-1, coronavirus and rhinovirus in nasopharynx (all P

Abstract Background Neurofibromatosis type 1 (NF1) is a dominantly inherited Rasopathy caused by mutations in the NF1 gene on chromosome 17. NF1 has been connected to congenital anomalies, e.g., in the skeletal and cardiovascular systems, but the overall incidence of anomalies is unknown. In this retrospective register-based total population study conducted in Finland, the congenital anomalies in NF1 were evaluated. Methods One thousand four hundred ten patients with NF1 were identified by searching the medical records related to inpatient and outpatient hospital visits of patients with an associated diagnosis for NF1 in 1987–2011. Each diagnosis was confirmed by a thorough review of the medical records. Ten non-NF1 control persons per NF1 patient were collected from the Population Register Centre. NF1 patients and controls were linked to the Medical Birth Register and the Register of Congenital Malformations. Odds ratios (OR) and 95% confidence intervals (95% CI) for major congenital anomalies (MCA) were calculated. Results The OR for at least one MCA among NF1 children was almost threefold (adjusted OR 2.78, 95% CI 1.71–4.54) compared to controls matched for age, sex and municipality. NF1 children had a significantly increased risk of congenital anomalies in the circulatory (adjusted OR 3.35, 95% CI 1.64–6.83), urinary (adjusted OR 4.26, 95% CI 1.36–13.35) and musculoskeletal (adjusted OR 2.77, 95% CI 1.09–7.02) systems. Also, anomalies of the eye, ear, head and neck were more common among NF1 children than controls (adjusted OR 4.66, 95% CI 1.42–15.31). Non-NF1 children of mothers with NF1 did not have more anomalies than controls (adjusted OR 0.53, 95% CI 0.13–2.21). Conclusions Children with NF1 have more MCAs than controls and close follow-up during pregnancy and the neonatal period is required if the mother or father has NF1. Non-NF1 children of mothers with NF1 do not have an increased risk for anomalies.

Idiopathic pulmonary fibrosis (IPF) is characterised by unpredictable disease course and poor survival. After the introduction of novel antifibrotic drugs, the prognosis of patients with IPF is probably changing. FinnishIPF, a nationwide registry of carefully characterised patients, was initiated in Finland in 2011. For the data analysis, we included 453 incident IPF patients diagnosed during 2011–2015. In this study, we describe the demographics and prognosis of these real-life patients. The median overall survival time of registered IPF patients was 4.5 years. The transplant-free survival at 1, 2, 3, 4 and 5 years was 95%, 83%, 70%, 58% and 45%, respectively. Smoking did not have any effect on survival. 117 (26%) patients received pirfenidone or nintedanib. Patients who received ≥6 months of treatment had better survival compared with those who did not receive treatment but this difference disappeared after age adjustment. The transplantation rate was 3%. Although IPF is diagnosed in Finland at a older age, the prognosis is better than expected due to a relatively well preserved lung function at diagnosis. Age and pulmonary function were identified as independent predictors of survival in the entire IPF patient population as well as in patients who had received antifibrotic treatment.

Recent studies have shown increased concentration of fetal hemoglobin (HbF) in pre-eclamptic women. Plasma hemopexin (Hpx) and alpha-1-microglobulin (A1M) are hemoglobin scavenger proteins that protect against toxic effects of free heme released in the hemoglobin degradation process. We used an enzyme-linked immunosorbent assay to analyze maternal plasma Hpx and A1M concentrations at 12-14, 18-20 and 26-28 weeks of gestation in three groups: 1) 51 women with a low risk for pre-eclampsia (LRW), 2) 49 women with a high risk for pre-eclampsia (PE) who did not develop PE (HRW) and 3) 42 women with a high risk for PE who developed PE (HRPE). The study had three aims: 1) to investigate whether longitudinal differences exist between study groups, 2) to examine if Hpx and A1M concentrations develop differently in pre-eclamptic women with small for gestational age (SGA) fetuses vs. pre-eclamptic women with appropriate for gestational age fetuses, and 3) to examine if longitudinal Hpx and A1M profiles differ by PE subtype (early-onset vs. late-onset and severe vs. non-severe PE). Repeated measures analysis of variance was used to analyze differences in Hpx and A1M concentrations between the groups. We found that the differences in longitudinal plasma Hpx and A1M concentrations in HRW compared to HRPE and to LRW may be associated with reduced risk of PE regardless of clinical risk factors. In women who developed PE, a high A1M concentration from midgestation to late second trimester was associated with SGA. There were no differences in longitudinal Hpx and A1M concentrations from first to late second trimester in high-risk women who developed early-onset or. late-onset PE or in women who developed severe or. non-severe PE.

Background: Recent epidemiologic studies have shown that the use of psychotropics is associated with many symptoms and may result in dependence and tolerance among elderly individuals. The aim of this study was to describe the symptoms related to withdrawal or dose reduction of long-term benzodiazepine (BZD) or BZD-related drugs (RDs) use and to compare them with nonuse of these drugs in community-dwelling individuals aged 65 and older. Methods: The study was a post hoc analysis embedded in a 12-month randomized, controlled fall-prevention trial that included withdrawal of BZDs and RDs. The participants (n = 248) in the intervention group were divided into the following four groups according to their use of BZDs/RDs at baseline and follow-up: (1) withdrawal (WG), (2) reduction (RG), (3) unchanged (UG), and (4) nonusers (NUG). Differences in symptom changes were compared between and within these four groups. Results: Using BZD/RD was associated with numerous symptoms at baseline and during the intervention. At follow-up, those symptoms reduced significantly among all participants. However, there were no significant differences between the groups in the changes of symptoms during the follow-up. Self-perceived health improved in only NUG (p

BackgroundObesity and smoking are strongly associated with worse cardiorespiratory fitness (CRF). Most previous studies that have examined the association of body composition with CRF have neither assessed non-linearity nor separately examined the effects of underweight. Thus, very little is known on how underweight affects CRF. Possible joint effects of obesity and smoking on CRF have not been adequately explored.AimsWe examined the association between body mass index (BMI) and smoking with CRF in 1,629 Finnish army conscripts. We focused on non-linear effects of BMI in order to assess the importance of underweight. We also examined whether the cooccurrence of obesity and smoking potentiates their deleterious effects on CRF.MethodsWe used the Cooper’s 12-minute run test (12MR) to measure CRF. The 12MR score was analyzed as continuous (linear, polynomial, and restricted cubic spline regression) and categorical. In categorical analyses, we used binary logistic regression with the 12MR score in two groups (low = lowest quintile vs. intermediate/high = quintiles 2–5) and multinomial logistic regression with the 12MR score in three groups (low = lowest quintile, intermediate = quintiles 2 and 3, and high = quintiles 4 and 5).ResultsNon-linearity in the spline model was statistically significant (p

Patient classification systems generate information for staff allocation based on a patient’s care needs. This study aims to test further the instrument for assessing nursing intensity (NI) in perioperative settings. Nine operating departments from five university hospitals were involved. The perioperative nurses gathered data from patients (N=876) representing different fields of surgery. Reliability was tested by parallel classifications (n=144). Also, the users’ (n=40) opinions were surveyed. The results support the predictive validity and interrater reliability of the instrument. The nurses considered the instrument feasible to use. The patients’ low ASA class did not automatically signify low NI; however, high ASA class was more frequently associated with high intraoperative NI. Intraoperative NI indicated the length of the postanaesthesia care and the type of the follow-up unit. Parallel classifications ensured the homogenous use of the instrument. The use of the instrument is recommended.

BACKGROUND:Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. METHODS:110 elective tonsillectomy patients participated. Serum levels of vitamins A, 25(OH)D, and E, LL-37 and allergen-specific IgE as well as nasopharyngeal/intratonsillar respiratory viruses were analyzed. The mRNA expression of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet in tonsils were analyzed by quantitative RT-PCR. RESULTS:The median age of the patients was 16 years (range 3-60), 28% of subjects had atopy, and 57% carried ≥1 respiratory virus in nasopharynx. Detection of viruses decreased by age. Higher vitamin A levels showed borderline significance with less viral detection (P = 0.056). Higher 25(OH)D was associated with less allergic rhinitis and atopy (P < 0.05) and higher vitamin E with less self-reported allergy (P < 0.05). In gene expression analyses, 25(OH)D was associated with higher IL-37, vitamin A with higher IFN-γ and vitamin E with less IL-28 (P < 0.05). LL-37 was associated with less FOXP3, RORC2 and IL-17 in tonsils (P < 0.05). CONCLUSIONS:Vitamin D and E levels were associated with less allergic disorders. Vitamin A was linked to antiviral and vitamin D with anti-inflammatory activity. LL-37 and was linked to T regulatory cell effects.

Background/Aims: Psychotropics and antiepileptics (AE) are medications commonly used among the aged with cognitive decline or dementia, although they may precipitate further cognitive decline. Our aim was to analyze the relationships between the use of (i) psychotropics (i.e. benzodiazepines or related drugs, BZD, antipsychotics, AP, or antidepressants, AD), opioids (Op), anticholinergics (ACh) or AEs or the concomitant use of two of these drugs, and (ii) the risk of precipitous cognitive decline in an older (≧65 years) cognitively disabled population. Methods: A longitudinal population-based study of general aged community-dwelling patients was executed in two phases (1990–1991 and 1998–1999) in Lieto, Finland. Fifty-two individuals cognitively disabled (MMSE score 0–23) at the 1990–1991 baseline form this study’s sample. Cognitive abilities were assessed in each phase with the Mini-Mental State Examination (MMSE) and medication utilization data were collected in both phases. The mean follow-up time was 7.6 years. Multivariate models were used to analyze the change in MMSE total score between medication users and non-users. Results: BZD or any psychotropic use was associated with greater cognitive decline in elders aged ≧75 years compared to non-users (change in MMSE sum score: –8.6 ± 7.0 vs. –3.3 ± 5.6 and –5.9 ± 7.0 vs. –2.7 ± 6.4, respectively). A greater decline was also associated specifically with the concomitant use of BZD and AP (–16 vs. –1.4 ± 7.8); as were BZD and any drug with CNS effects (–9.6 ± 9.9 vs. –1.3 ± 7.2) compared to non-users. The concomitant use of BZD and AD (–10.7 ± 4.7 vs. –3.2 ± 5.6) or ACh (–15.0 ± 8.5 vs. –3.3 ± 5.6) or any drug with CNS effects (–13.3 ± 6.5 vs. –3.3 ± 5.6) was associated with cognitive decline in patients ≧75 years compared to non-users of any drug with CNS effects. Conclusion: The use of a BZD or any psychotropic medication may be an independent risk factor for cognitive decline in the cognitively disabled aged, and patients co-prescribed psychotropic medications had greater cognitive decline. Studies with larger sample sizes and studies on possible pathophysiologic mechanisms are needed.

BackgroundEarly diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.MethodsThe study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA).ResultsThe median PTX3 levels in groups 1-5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (pConclusionsA high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.

ErbB4 is a receptor tyrosine kinase that can signal by a mechanism involving proteolytic release of intracellular and extracellular receptor fragments. Proteolysis-dependent signaling of ErbB4 has been proposed to be enhanced in breast cancer, mainly based on immunohistochemical localization of intracellular epitopes in the nuclei. To more directly address the processing of ErbB4 in vivo, an ELISA was developed to quantify cleaved ErbB4 ectodomain from serum samples. Analysis of 238 breast cancer patients demonstrated elevated quantities of ErbB4 ectodomain in the serum (≥ 40 ng/mL) in 21% of the patients, as compared to 0% of 30 healthy controls (P = 0.002). Significantly, the elevated serum ectodomain concentration did not correlate with the presence of nuclear ErbB4 immunoreactivity in matched breast cancer tissue samples. However, elevated serum ectodomain concentration was associated with the premenopausal status at diagnosis (P = 0.04), and estradiol enhanced ErbB4 cleavage in vitro. A 3.4 Å X-ray crystal structure of a complex of ErbB4 ectodomain and the Fab fragment of anti-ErbB4 mAb 1479 localized the binding site of mAb 1479 on ErbB4 to a region on subdomain IV encompassing the residues necessary for ErbB4 cleavage. mAb 1479 also significantly blocked ErbB4 cleavage in breast cancer cell xenografts in vivo, and the inhibition of cleavage was associated with suppression of xenograft growth. These data indicate that ErbB4 processing is enhanced in breast cancer tissue in vivo, and that ErbB4 cleavage can be stimulated by estradiol and targeted with mAb 1479.

Caries has traditionally been assessed with WHO criteria including only obvious caries lesions. ICDAS has been developed to detect also the enamel caries lesions. This study aims to study caries and the associations of the number of caries lesions between the permanent and primary molars with ICDAS in the mixed dentition of the first and second grade primary school children. The clinical examinations of 485 children were conducted by four examiners with high reproducibility (inter- and intraexaminer kappas >0.9). The mean number of caries lesions—especially dentine caries—seemed to be higher in the second primary molars than in the first permanent molars. There were significant correlations between the number of lesions on occlusal and lingual surfaces between the primary and permanent molars. Enamel caries lesions, restorations, and caries experience did not increase according to age. Therefore, caries might be increasing in this population. As a conclusion, ICDAS recording seems to give appropriate information from the occurrence of caries lesions and its correlations between the primary and permanent teeth and surfaces.