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Abstract Mortality in renal cell cancer (RCC) is high in the elderly population. Comorbidities have a greater impact on overall prognosis of RCC among elderly patients than in younger patients. All new RCC cases were collected in people over 74 years of age between 1995 and 2018 from the Finnish cancer registry. The comorbidities were identified from the Care Registry for Healthcare. Charlson Comorbidity Index (CCI) was used to evaluate the risk of death based on comorbidities. The overall risk of death was analyzed using the Cox regression model. The risk for RCC death was analyzed using Fine and Gray regression analysis. Individual prognostic role of CCI components was evaluated by adding each component separately into the multivariable Fine and Gray regression model. Using the most prognostic comorbidities we constructed a nomogram to predict RCC mortality. Statistically significant prognostic factors of RCC death were tumor morphology (clear cell, papillary and chromophobe), sex, operative treatment, age, primary tumor extent and CCI. The strongest prognostic factors for overall mortality were tumor extent, tumor morphology and operative treatment. Among the components of CCI, the most important comorbidities predicting mortality were dementia, heart failure and kidney disease. The limitation of this study is that the comorbidities have only been recorded at inpatient and outpatient hospital contacts, which is why the prevalence of comorbidities is probably underestimated. In addition, physical performance status was not available from registry data, but it significantly affects the treatment decisions. RCC mortality is high in the elderly population. Among comorbidities, dementia and heart failure have the greatest impact on the prognosis. Curative treatment in selected elderly patients is efficient and should be considered in patients who can tolerate it and have only limited comorbidities.

ABSTRACTBackground The adoption of avoidance diets by adult-onset asthmatics has not previously been studied. We hypothesized that avoidance diets would associate with adult-onset asthma, allergy, and aspirin-exacerbated respiratory disease (AERD).Methods A total of 1247 subjects with adult-onset asthma (age range: 31–91) from the Finnish national registry, and age- and sex-matched controls (n = 1970) participated in a questionnaire study in 1997. We estimated the association between asthma/allergy/AERD and avoidance diets, adjusting for potential confounding factors and validated the results in two retrospective cohorts of 5080 rhinitis/rhinosinusitis patients and 167 AERD patients from 2019 to 2020.Results The presence of asthma positively associated with adoption of any avoidance diet (adjusted OR [CI95%] 1.24 [1.02–1.51], p = 0.029) as did allergic disease and self-reported AERD within the asthmatic group (1.79 [1.29–2.48], p = 0.001 and 1.69 [1.15–2.49], p = 0.007, respectively). Asthmatics and allergic asthmatics were more likely to report avoidance of fish, fruits and vegetables, and spices (p ≤ 0.03) compared to controls and non-allergic asthmatics. The adjusted OR for multiple diets among AERD patients was 2.57 [1.34–4.95] p = 0.005. In the validation, 26.2% of the allergic asthmatics and 10.8% of AERD patients had documented avoidance diets.Conclusions Our study shows a positive association between avoidance diets and adult-onset asthma, and with allergic disease or AERD within asthmatic patients. Although we lack information on the reason patients chose to observe a specific diet, our results reinforce the importance of asking patients about their diet and if needed, giving dietary advice for adult asthma patients to help them avoid the adoption of unnecessarily restrictive diets.

Abstract Background The aim of this study was to evaluate how diagnostic practice in congenital ichthyoses has evolved during the years 2000–2020 and what kind of gene variants of congenital ichthyosis have been found. Methods The study cohort of this register‐based research consisted of a total of 88 patients, whose diagnostic testing was conducted, and ichthyosis diagnoses set at the Department of Dermatology and the Department of Clinical Genetics at Tampere University Hospital during the years 2000–2020. Results Diagnosis of ichthyosis was confirmed with genetic testing in 33 cases, and with conventional diagnostic methods, such as clinical findings, skin biopsy and family history of ichthyoses, in 55 cases. We observed four novel variants in patients with the clinical diagnoses of congenital ichthyoses. Conclusion When genetic testing became available, it was offered primarily to patients with severe forms of ichthyosis. During the study period next‐generation sequencing became the genetic testing method of choice providing new opportunities in diagnostics.

BackgroundBased on Finnish LDLR-founder variations, the prevalence of familial hypercholesterolemia (FH) in Finland is estimated to be at least 1:600. Patients with FH have increased risk of premature coronary artery disease (CAD) and thus the prevalence of FH is expected to be higher in this subgroup.ObjectiveTo assess the prevalence of monogenic FH in a Finnish cohort of patients with premature CAD and elevated low-density lipoprotein cholesterol (LDL-C) levels.MethodsAmong 28,295 patients undergoing angiography at Heart Hospital at Tampere University Hospital between 2007 and 2017, we identified 162 patients diagnosed with premature CAD (men aged

Background The influence of burden of atherosclerosis in the brain supplying arteries on mortality in patients with acute ischemic stroke or transient ischemic attack is poorly known. We assessed whether total burden of atherosclerosis within cervicocerebral arteries is associated with long‐term mortality. Methods and Results A total of 406 patients (median age, 71.8 years; 57.9% male) with acute ischemic stroke or transient ischemic attack were included and their cervicocerebral arteries imaged with computed tomography angiography. The presence of atherosclerotic findings was scored for 25 artery segments and points were summed as a Cervicocerebral Atherosclerosis Burden (CAB) score, analyzed as quartiles. Data on all‐cause mortality came from Statistics Finland. After a median follow‐up of 7.3 years, 147 (33.5%) patients had died. Compared with surviving patients, those who died had a higher median CAB score (5, interquartile range 2–10 versus 11, 7–16; P

Abstract Background The predictive accuracies of screening instruments for identifying home-dwelling old people at risk of hospitalization have ranged from poor to moderate, particularly among the oldest persons. This study aimed to identify variables that could improve the accuracy of a Minimum Data Set for Home Care (MDS-HC) based algorithm, the Detection of Indicators and Vulnerabilities for Emergency Room Trips (DIVERT) Scale, in classifying home care clients’ risk for unplanned hospitalization. Methods In this register-based retrospective study, factors associated with hospitalization among home care clients aged ≥ 80 years in the City of Tampere, Finland, were analyzed by linking MDS-HC assessments with hospital discharge records. MDS-HC determinants associated with hospitalization within 180 days after the assessment were analyzed for clients at low (DIVERT 1), moderate (DIVERT 2–3) and high (DIVERT 4–6) risk of hospitalization. Then, two new variables were selected to supplement the DIVERT algorithm. Finally, area under curve (AUC) values of the original and modified DIVERT scales were determined using the data of MDS-HC assessments of all home care clients in the City of Tampere to examine if addition of the variables related to the oldest age groups improved the accuracy of DIVERT. Results Of home care clients aged ≥ 80 years, 1,291 (65.4%) were hospitalized at least once during the two-year study period. Unplanned hospitalization occurred following 15.9%, 22.8%, and 33.9% MDS-HC assessments with DIVERT group 1, 2–3 and 4–6, respectively. Infectious diseases were the most common diagnosis within each DIVERT groups. Many MDS-HC variables not included in the DIVERT algorithm were associated with hospitalization, including e.g. poor self-rated health and old fracture (other than hip fracture) (p 0.001) in DIVERT 1; impaired cognition and decision-making, urinary incontinence, unstable walking and fear of falling (p

Abstract Background Vomiting and nausea seem to be relatively specific symptoms related to gluten ingestion in treated celiac disease. However, the overall prevalence and associated factors of these symptoms after chronic gluten exposure at celiac disease diagnosis and acute re-exposure during gluten challenge remain obscure. Methods Medical data on 815 adult celiac disease patients were collected at diagnosis from the medical records and through supplementary interviews. An additional 74 patients underwent a three-day (10 g/day) gluten challenge (wheat, barley, rye or a combination of the three grains) while in remission. Prevalence of vomiting/nausea and associated factors were evaluated in both cohorts. A literature review was conducted to summarize earlier studies. Results Twenty-eight (3%) patients presented with vomiting at diagnosis. They were less often screen-detected and suffered from extra-intestinal symptoms, and had more often abdominal pain (71% vs. 49%, p = 0.021), diarrhea (61% vs. 40%, p = 0.031), weight loss (36% vs. 17%, p = 0.019) and childhood symptoms (61% vs. 33%, p = 0.002) than those without vomiting (n = 787). The groups were comparable in other clinical-demographic data and in genetic, serological, and histological findings. Short-term gluten challenge provoked vomiting/nausea in 14/74 (19%) patients. They consumed gluten-free oats less often than those without these symptoms (64% vs. 92%, p = 0.017), whereas the groups did not differ in clinical-demographic features at diagnosis, presence of comorbidities, duration of gluten-free diet, or in other symptoms or grain used ingested during the challenge. According to the literature, prevalence of vomiting/nausea at celiac disease diagnosis has varied 3–46% and during gluten challenge 13–61%. Conclusions In chronic gluten exposure at celiac disease diagnosis, vomiting was associated with other gastrointestinal symptoms and onset of symptoms already in childhood, whereas regular consumption of oats may increase the tolerance against vomiting/nausea after acute re-exposure in treated celiac disease.

Abstract Background Breast radiotherapy (RT) induces diffuse myocardial changes, which may increase the incidence of heart failure with preserved ejection fraction. This study aimed to evaluate the early signs of diffuse fibrosis after RT and their evolution during a six-year follow-up. Methods Thirty patients with early-stage left-sided breast cancer were studied with echocardiography and electrocardiography (ECG) at baseline, after RT, and at three-year and six-year follow-up visits. Echocardiography analysis included an off-line analysis of integrated backscatter (IBS). ECG was analysed for fragmented QRS (fQRS). In addition, cardiac magnetic resonance (CMR) imaging was performed at the six-year control. The left ventricle 16-segment model was used in cardiac imaging, and respective local radiation doses were analysed. Results Regional myocardial reflectivity in inferoseptal segments increased by 2.02 (4.53) dB (p = 0.026) and the percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. In CMR imaging, abnormal extracellular volume (ECV) and T1 mapping values were found with anteroseptal and apical localization in a median of 3.5 (1.00–5.75) and 3 (1.25–4.00) segments, respectively. A higher left ventricle radiation dose was associated with an increased likelihood of having changes simultaneously in CMR and echocardiography (OR 1.26, 95% Cl. 1.00–1.59, p = 0.047). Conclusions After radiotherapy, progressive changes in markers of diffuse myocardial fibrosis were observed in a multimodal manner in ECG and echocardiography. Changes in echocardiography and abnormal values in CMR were localized in the septal and apical regions, and multiple changes were associated with higher radiation doses.

Background/aims To analyse long-term outcomes of antivascular endothelial growth factor (anti-VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD) using pro re nata (PRN) regimen in a single-centre clinical practice.Methods All patients receiving intravitreal injection (IVI) for nAMD between 1 January 2008 and 31 December 2020 were searched from electronic medical records. All 3844 treatment-naïve eyes of 3008 patients were included with a total of 50 146 IVIs (87% bevacizumab) administered. Main outcome measures were mean change in visual acuity (VA) from baseline, proportion of eyes within 15 letters of baseline, proportion of eyes with VA ≥20/40 Snellen and ≤20/200 Snellen, number of annual visits and number of annual IVIs.Results The mean baseline VA was 55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the mean change in VA from baseline was +2, +2, ±0, –2, −2 and −4 ETDRS letters at year 1, 2, 3, 5, 7 and 10, respectively. Proportions of eyes within 15 letters of baseline were 88%, 87%, 82%, 80%, 76% and 72% at the end of years 1, 2, 3, 5, 7 and 10, respectively. The median number of annual IVI was 6 at years 1–7 and 5 at year 10. The median number of annual total visits was 10 at year 1, 9 at years 2–7 and 8 at year 10, respectively.Conclusions VA was maintained short-term and long-term with anti-VEGF therapy using PRN treatment regimen.

AbstractIntroduction Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed.Methods The study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR).Results The median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91–1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16–1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47–0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07–1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22–2.16) but not in DH.Conclusions The risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation.

ABSTRACTAcute respiratory infections (ARinf) are one of the leading causes that prevent athletes from training and competing. The aim of this study was to investigate the burden of ARinfs during one season among cross-country skiers. All Finnish cross-country skiers enrolled in the largest national competitions in winter 2019 (n = 1282) were sent a postal questionnaire. A higher proportion of skiers with than without asthma had to refrain from competitions because of ARinf (76.9% vs. 62.2%, p = 0.011) but there was no significant difference in refraining from training (91.2% vs. 83.8%, p = 0.084). In skiers with asthma, the median duration of a single ARinf episode was longer (5.0 days, IQR 3.8–6.8 vs. 4.0 days, IQR 3.0–6.7, p = 0.017), and they had more days of absence because of ARinf throughout the season (median 15 days (IQR 8–28) vs. 10 days (IQR 6–18), p = 0.006) in comparison to non-asthmatics. However, many of the skiers either trained (54.4%) or competed (22.5%) during an ARinf.

Background Acute ischemic stroke may be due to embolism from ruptured atherosclerotic carotid arteries. DNA of oral bacteria, mainly the viridans streptococci group, has been detected in thrombus aspirates of patients with ischemic stroke as well as in carotid endarterectomy samples. Because viridans streptococci are known to possess thrombogenic properties, we studied whether their presence in thrombus aspirates and in carotid artery specimens can be confirmed using bacterial immunohistochemistry. Methods and Results Thrombus aspirates from 61 patients with ischemic stroke (70.5% men; mean age, 66.8 years) treated with mechanical thrombectomy, as well as carotid endarterectomy samples from 20 symptomatic patients (65.0% men; mean age, 66.2 years) and 48 carotid artery samples from nonstroke autopsy cases (62.5% men; mean age, 66.4 years), were immunostained with an antibody cocktail against 3 species (Streptococcus sanguinis, Streptococcus mitis, and Streptococcus gordonii) of viridans streptococci. Of the thrombus aspirates, 84.8% were immunopositive for viridans streptococci group bacteria, as were 80.0% of the carotid endarterectomy samples, whereas immunopositivity was observed in 31.3% of the carotid artery samples from nonstroke autopsies. Most streptococci were detected inside neutrophil granulocytes, but there were also remnants of bacterial biofilm as well as free bacterial infiltrates in some samples. Conclusions Oral streptococci were found in aspirated thrombi of patients with acute ischemic stroke as well as in carotid artery samples. Our results suggest that viridans streptococci group bacteria may play a role in the pathophysiology of ischemic stroke.

Abstract Aims and objectives The aim of this quasi-experimental longitudinal intervention study was to investigate new graduate nurses’ professional competence development after preceptors’ participation in an education intervention. Background New graduate registered nurses are expected to be competent in many areas of nursing. Expectations that are sometimes unrealistic may cause a sense of inadequacy and stress, and this may in turn prevent them from fully deploying their competencies. Competence development is related to practice environment, occupational commitment, empowerment, and work experience. Orientation or transition programs have been designed to ensure new graduate nurses’ competence, and preceptors and preceptorship could also have significant influence on their competence development. Design A quasi-experimental longitudinal intervention study. Methods The data was collected from October 2015 to November 2017. Participating wards were randomized into intervention and control groups. The intervention group preceptors had an eight-hour education intervention that focused on new employees’ orientation, particularly from new graduates’ point of view. Wards in the control group continued to precept as before. The Nurse Competence Scale was used for new graduates’ self-assessment at baseline and at three-month and nine-month follow-up. This study is reported in accordance with the TREND Statement Checklist. Results The education intervention aimed at preceptors did not have impact on the intervention group NGRNs’ competence development. There were no statistically significant differences between the groups and effect size remained small. Conclusions The preceptors’ education intervention was not effective enough to develop new graduates’ professional competence so that it would have differed from that of the graduates receiving conventional orientation at the university hospital. This study confirmed that competence development is a complex and multidimensional phenomenon and organizations should invest in new graduate registered nurses’ competence development during their early career. Preceptors’ education and development of preceptorship and transition programs are an important part of overall competence development in complex health care environments. Trial registration Retrospectively registered

Abstract Background Asthma with NSAID‐exacerbated respiratory disease (NERD) is associated with uncontrolled or severe asthma. NERD patients are more prone to severe allergic reactions and their asthma exacerbations lead to hospitalisations twice as often compared to patients with non‐NERD‐asthma. NERD patients are prone to recurrent nasal polyposis requiring frequent endoscopic sinus surgeries. However, the early risk factors of NERD are not fully understood. The aim was to identify risk factors of NERD among patients with adult‐onset asthma. Methods We used data from 1350 population‐based adult asthmatics with adult‐onset asthma from Finnish national registers. NERD was defined as self‐reported wheeze or other typical respiratory symptoms after ingestion of NSAIDs. Thirty‐six covariates covering several domains (personal characteristics, life‐style, early life factors, asthma characteristics and multimorbidities) were selected based on literature and were studied in association with NERD using logistic regressions. Results The study population included 153 (11.3%) asthmatics with NERD. Thirty‐six covariates were entered in univariate logistic regression analysis, in which 23 were associated with NERD (p

IntroductionData on the prevalence of pediatric fatty liver disease remain limited, partly due to challenges in diagnosis. A novel concept of metabolic-associated fatty liver disease (MAFLD) makes it possible to establish the diagnosis in overweight children with sufficiently elevated alanine aminotransferase (ALT). We investigated the prevalence, risk factors, and metabolic co-morbidities of MAFLD in a large group of overweight children.MethodsData on 703 patients aged 2-16 years examined due to overweight in different levels of healthcare in 2002-2020 were collected retrospectively from patient records. MAFLD was here defined as ALT >2x reference (>44 U/l in girls and >50 U/l in boys) in overweight children according to recently updated definition. Patients with MAFLD and without it were compared, and subgroup analyses were conducted among boys and girls.ResultsMedian age was 11.5 years, and 43% were girls. Altogether 11% were overweight, 42% obese and 47% severely obese. Abnormal glucose metabolism was present in 44%, dyslipidemia in 51%, hypertension in 48% and type 2 diabetes (T2D) in 2%. MAFLD prevalence varied between 14-20% in examined years without significant change (p=0.878). The pooled prevalence over the years was 15% (boys 18%, girls 11%; p=0.018), peaking in girls at early puberty and increasing in boys with age and puberty. Associated factors in boys were T2D (OR 7.55, 95% CI 1.23-46.2), postpubertal stage (5.39, 2.26-12.8), increased fasting insulin (3.20, 1.44-7.10), hypertriglyceridemia (2.97, 1.67-5.30), hyperglycemia (2.88, 1.64-5.07), decreased high-density lipoprotein (HDL) cholesterol (2.16, 1.18-3.99), older age (1.28, 1.15-1.42) and higher body-mass-index (1.01, 1.05-1.15), and in girls T2D (18.1, 3.16-103), hypertriglyceridemia (4.28, 1.99-9.21), and decreased HDL (4.06, 1.87-8.79).ConclusionPrevalence of MAFLD was 15%, with no statistically significant increase in the 2000s. The condition was associated in general with male gender, puberty stage and disturbances in glucose and lipid metabolism, and higher age and BMI in boys.

Abstract Background Emergency medical dispatchers typically use the dispatch code for suspected stroke when the caller brings up one or more symptoms from the face-arm-speech triad. Paramedics and emergency department physicians are trained to suspect large vessel occlusion stroke when the stroke patient presents with hemiparesis and cortical symptoms: neglect, aphasia, and conjugate eye deviation (CED). We hypothesized that these symptoms could be evident in the emergency call. In this study, we aimed to describe common symptoms mentioned in the emergency calls for paramedic-suspected thrombectomy candidates. Secondly, we wanted to explore how the question about CED arises in the Finnish suspected stroke dispatch protocol. Our third aim was to find out if the symptoms brought up in suspected stroke and non-stroke dispatches differed from each other. Methods This was a retrospective study with a descriptive analysis of emergency calls for patients with paramedic-suspected large vessel occlusion stroke. We listened to the emergency calls for 157 patients transported to Tampere University Hospital, a Finnish comprehensive stroke centre. Two researchers listened for symptoms brought up in these calls and filled out a pre-planned case report form. Results Speech disturbance was the most common symptom brought up in 125 (80%) calls. This was typically described as an inability to speak any words (n = 65, 52% of calls with speech disturbance). Other common symptoms were falling down (n = 63, 40%) and facial asymmetry (n = 41, 26%). Suspicion of stroke was mentioned by 44 (28%) callers. When the caller mentioned unconsciousness the emergency dispatcher tended to use a non-stroke dispatch code. The dispatchers adhered poorly to the protocol and asked about CED in only 57% of suspected stroke dispatches. We found CED in 12 emergency calls and ten of these patients were diagnosed with large vessel occlusion. Conclusion In cases where paramedics suspected large vessel occlusion stroke, typical stroke symptoms were described during the emergency call. Speech disturbance was typically described as inability to say anything. It is possible to further develop suspected stroke dispatch protocols to recognize thrombectomy candidates from ischemic cortical signs such as global aphasia and CED.

Background Cross-country skiers train and compete during the winter for long periods of time in subfreezing conditions, which strains the airways and provokes respiratory symptoms. This study aimed to compare the prevalence of exercise-related symptoms and prolonged cough in competitive cross-country skiers versus the general population and to investigate the association between these symptoms and asthma.Methods A questionnaire was sent to Finnish cross-country skiers (n=1282) and a random sample of the general population (n=1754), with response rates of 26.9% and 19.0%, respectively.Results Both groups were mostly asymptomatic at rest, but symptoms were increased in both groups during and after exercise. Cough was more prevalent after exercise in skiers and phlegm production was more common during and after exercise in skiers. Asthma did not provoke specific symptoms, but symptom prevalence was higher in asthmatic individuals. Skiers had a higher prevalence of cough after exercise (60.6% vs 22.8%, p

Aims: To assess the prognosis and risk factors for diabetic ketoacidosis (DKA) in Tampere University Hospital (Tays) in a retrospective case-control study. Methods: All 282 patients (age ≥15 years) treated for DKA in Tays during the period 2014–2020 were included. A total of 846 controls adjusted for age, gender, diabetes type and municipality, and without any DKA during follow-up were collected from the Finnish National Diabetes Registry. HbA1c, mental and behavioural disorders, and mortality obtained from the Finnish National Diabetes Registry were compared between patients with and without DKA. Results: Patients’ median age was 36 years. Ten percent of the patients with DKA died during the median follow-up time of three years. Mortality rate was sixfold higher in patients with DKA than among the controls (OR 6.28; 95% CI 3.17–12.42). Patients with DKA had higher rates of substance abuse (OR 4.68; 95% CI 3.23–6.78) and depression (OR 2.24; 95% CI 1.58–3.18), and higher median HbA1c levels (84 vs. 61 mmol/mol, p

Abstract Background Pseudoxanthoma elasticum (PXE, OMIM# 264800) is an inborn error of metabolism causing ectopic soft tissue calcification due to low plasma pyrophosphate concentration. We aimed to assess the prevalence of PXE in Finland and to characterize the Finnish PXE population. A nationwide registry search was performed to identify patients with ICD-10 code Q82.84. Information was gathered from available medical records which were requisitioned from hospitals and health centers. Misdiagnosed patients and patients with insufficient records were excluded. Results The prevalence of PXE in Finland was 1:260,000 with equal sex distribution. Patients with high conventional cardiovascular risk had more visual and vascular complications than patients with low risk. Four patients (19%) had at least one vascular malformation. A high proportion (33%) of ABCC6 genotypes were of the common homozygous c.3421C > T, p.Arg1141Ter variant. Nine other homozygous or compound heterozygous allelic variants were found. Conclusions The prevalence of diagnosed PXE appears to be lower in Finland than in estimates from other countries. Decreased visual acuity is the most prevalent complication. We suggest that various vascular malformations may be an unrecognized feature of PXE.

Background and aims: To validate an automated screening tool for patients with premature coronary artery disease (CAD) and high total cholesterol or LDL-C levels and assess if it would provide clinicians with additional support in identifying patients with Familial Hypercholesterolemia (FH). Methods: An IT-based automated screening tool based on coronary angiography data recorded in the KARDIO registry and laboratory values was validated among patients undergone coronary angiography in the Heart Hospital at Tampere University Hospital between 2007 and 2017 fulfilling the criteria of premature CAD (men 8 mmol/l) or LDL-cholesterol (>5 mmol/l) levels. Electronic health records were retrospectively analyzed to determine if these patients had been diagnosed with FH based on clinical features and whether genetic testing had been conducted. Results: The automated screening tool identified 0.7% (211/28295) of all patients undergone coronary angiography and revealed history of high cholesterol in 8% (211/2678) of patients with premature CAD during the study period. Fifty-one percent (107/211) of these patients fulfilled the clinical criteria for probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria.None of the patients had been diagnosed with FH based on clinical criteria before or after diagnosis of CAD. Thirteen percent of patients (n = 14) with probable/definite FH had been tested for genetic mutations of FH before or after CAD, five (36%) of them having a pathogenic FH variant. Two patients were referred to cascade screening. Conclusions: FH was underdiagnosed among the population studied. An automated screening tool in cardiac care could provide additional support for clinicians in diagnosing patients potentially having FH.

Abstract Background We investigated paramedic-initiated consultation calls and advice given via telephone by Helicopter Emergency Medical Service (HEMS) physicians focusing on limitations of medical treatment (LOMT). Methods A prospective multicentre study was conducted on four physician-staffed HEMS bases in Finland during a 6-month period. Results Of all 6115 (mean 8.4/base/day) paramedic-initiated consultation calls, 478 (7.8%) consultation calls involving LOMTs were included: 268 (4.4%) cases with a pre-existing LOMT, 165 (2.7%) cases where the HEMS physician issued a new LOMT and 45 (0.7%) cases where the patient already had an LOMT and the physician further issued another LOMT. The most common new limitation was a do-not-attempt cardiopulmonary resuscitation (DNACPR) order (n = 122/210, 58%) and/or ‘not eligible for intensive care’ (n = 96/210, 46%). In 49 (23%) calls involving a new LOMT, termination of an initiated resuscitation attempt was the only newly issued LOMT. The most frequent reasons for issuing an LOMT during consultations were futility of the overall situation (71%), poor baseline functional status (56%), multiple/severe comorbidities (56%) and old age (49%). In the majority of cases (65%) in which the HEMS physician issued a new LOMT for a patient without any pre-existing LOMT, the physician felt that the patient should have already had an LOMT. The patient was in a health care facility or a nursing home in half (49%) of the calls that involved issuing a new LOMT. Access to medical records was reported in 29% of the calls in which a new LOMT was issued by an HEMS physician. Conclusion Consultation calls with HEMS physicians involving patients with LOMT decisions were common. HEMS physicians considered end-of-life questions on the phone and issued a new LOMT in 3.4% of consultations calls. These decisions mainly concerned termination of resuscitation, DNACPR, intubation and initiation of intensive care.

Abstract Background Undelayed diagnosis is thought to be a major determinant for good prognosis in pediatric inflammatory bowel disease (PIBD). However, factors predicting diagnostic delay and the consequences of this remain poorly defined. We investigated these issues in a well-defined cohort of PIBD patients. Methods Comprehensive electronic data were collected from 136 PIBD patients retrospectively. Diagnostic delay was further classified into 6 months in all PIBD (OR 2.07, 95% CI 1.00–4.31) and in UC patients (3.15, 1.14–8.7), while bloody stools predicted a shorter delay in all PIBD (0.28, 0.14–0.59) patients and in CD (0.10, 0.03–0.41) patients. A delay > 6 months was associated with a higher frequency of complications (2.28, 1.01–5.19). Conclusions Delay occurred mostly before specialist consultation, was longer in children presenting with abdominal pain and in CD and was associated with risk of complications. These findings emphasize the roles of active case-finding and prompt diagnostic evaluations.

Abstract Aims The aim of this study was to determine what kinds of unmet information needs people with COPD have and whether there are differences in information needs between genders or based on the time since COPD diagnosis. Design A descriptive cross‐sectional study. Methods Data on people with COPD (N = 169) were collected from a two‐part questionnaire distributed via website. On the first part, information needs concerning the medical aspects of self‐management were measured by the Lung Information Needs Questionnaire (LINQ). On the second part, which was developed specifically for this study, a more holistic view of self‐management counselling was sought. Statistical methods were used to analyse the data. Results The respondents had wide‐ranging information needs in many areas of COPD self‐management. The most often reported areas of unmet information needs included exacerbations, diet, fatigue, stress and anxiety, palliative care and sexual life. The information needs varied by gender and time since COPD diagnosis.

Abstract Background Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs. Methods ASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m2) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells. Results ASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins. Conclusions Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically.

BackgroundCeliac disease (CeD) is often accompanied by other autoimmune diseases (AID). However, the association of co-existing autoimmunity with the presentation and treatment success in CeD is unclear. We investigated these issues with a large and well-defined cohort of Finnish patients.MethodsAdult CeD patients (n = 806) were collected from multiple heath care sites via nationwide recruitment. They were interviewed, underwent measurement of CeD autoantibodies, and filled out questionnaires to ascertain quality of life (PGWB) and gastrointestinal symptoms (GSRS) after a median of 9.7 years on a gluten-free diet. Data were supplemented retrospectively from patient records. The results were compared between CeD patients with and without a coexisting AID.ResultsAltogether 185 patients had CeD+AID and 621 had CeD only. At CeD diagnosis, patients with CeD+AID were older (median 42 vs. 36 years, p = 0.010) and had more joint symptoms (9.1 vs. 4.2%, p = 0.011), whereas the groups were comparable in sex, family history of CeD, other presenting symptoms, proportion of screen-detected subjects, and severity of duodenal lesion. During follow-up on gluten-free diet, CeD+AID patients experienced poorer general health (median score 12 vs. 14, p < 0.001) in PGWB, more overall gastrointestinal symptoms (2.1 vs. 1.9, p = 0.001), and constipation (2.0 vs. 1.7, p < 0.001) in GSRS, whereas there was no difference in histological and serological recovery, dietary adherence, use of gluten-free oats, smoking, and presence of regular follow-up.ConclusionsCo-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support.

BackgroundDuodenal histology remains the diagnostic reference standard in celiac disease. However, traditional methods have suboptimal sensitivity and reproducibility for early mucosal changes and research purposes. We validated a recently introduced micro-CT imaging method for an accurate digital evaluation of duodenal histomorphometry and mucosal surface areas.MethodsEndoscopic biopsies from 58 individuals were utilized for the micro-CT imaging, selecting histological changes ranging from normal to severely damaged mucosa. The imaging protocol was optimized for practicability and resolution. The Bland–Altman method was applied to test intra- and interobserver variations in the blinded measurements.ResultsThe 3D micro-CT reconstructions enabled easy and precise digital cutting with optimal orientation and computer-assisted measurement of the surface area. Intraobserver analysis of morphological measurements showed a mean difference of 0.011 with limits of agreement (LA) from -0.397 to 0.375 and a standard deviation (SD) of 0.197. The corresponding figures for interobserver analysis were 0.080, from -0.719 to 0.537 and 0.320, respectively. The intraclass correlation coefficients (ICC) for the intraobserver and interobserver variations were 0.981 and 0.954, respectively. Intraobserver surface area analysis yielded a mean difference of 0.010, LA from -0.764 to 0.785 and an SD of 0.395, and an interobserver analysis mean difference of 0.028, LA from -0.642 to 0.698 and SD of 0.342. The respective ICCs for the intra- and interobserver variations were 0.963 and 0.972.ConclusionsMicro-CT showed excellent accuracy and reproducibility in the evaluation of mucosal morphometry and surface areas. The improved sensitivity for histological changes is a powerful tool for the diagnosis of celiac disease and for clinical and pharmacological studies.

Abstract Background and aims The incidence of total knee arthroplasty (TKA) is increasing, especially among younger working-age patients. However, dissatisfaction rates in this population are higher than among older patients. The aim of this study was to assess the rates of dissatisfaction and persistent pain after TKA and to evaluate those factors that predict these outcomes. Material and methods In total, 186 patients undergoing unilateral TKA aged 65 years or less were enrolled into this prospective observational study with 2-year follow-up. To assess the outcome, the visual analogue scales regarding satisfaction and persistent pain at rest and during exercise were used. In addition, the association between patients´ demographics, radiographic severity of knee osteoarthritis (OA), patient-reported outcome measures (PROMs) and dissatisfaction and persistent pain were tested by univariate logistic regression analysis. Mild OA was defined as Kellgren-Lawrence (KL) grade 2 and severe OA as KL grade 3–4. Furthermore, multiple logistic regression analysis was also conducted to test statistically significant relations. Results After 2 years, 12 % (n = 23) of patients were dissatisfied with the outcome of TKA, 27 % (n = 50) reported persistent pain during exercise and 10 % (n = 18) at rest. Patients with mild knee OA were significantly more dissatisfied (28.6 %) than patients with more severe OA (8.7 %) (p = 0.003). Younger patients had an increased risk for both dissatisfaction and persistent pain. Apart from KOOS Quality of Life, poor preoperative KOOS subscores were also predictive for these outcomes. Conclusion Mild radiographic knee OA was the main predicting factor for dissatisfaction after TKA. Thus, performing TKA for such patients should be carefully considered. Furthermore, these patients should be informed about the increased risk for dissatisfaction and the same seems to apply to younger patients. Interestingly, when TKA is performed for patients with more severe knee OA, the satisfaction rates seem to be somewhat higher than those previously reported. Trial registration The study was retrospectively registered with ClinicalTrials.gov (registration number NCT03233620 ) on 28 July 2017.

Abstract Background Despite the steady improvements in survival and operative safety, postoperative complications still remain a significant cause of morbidity and mortality after coronary artery bypass grafting (CABG). However, less is known on the impact of postoperative complications on health-related quality of life (QoL). The main objective of our study was to investigate the impact of postoperative complications on long-term QoL and survival after CABG surgery. Methods Data of 508 patients, who underwent isolated CABG was prospectively collected. The RAND-36 Health Survey (RAND-36) was used to evaluate patients’ QoL status preoperatively, 1 year and 12 years after the surgery. Predefined postoperative complications were reported during primary and secondary hospital stay. QoL and survival analysis were performed primarily on three patient groups: patients with and without complications and patients with major adverse cardiac and cerebrovascular events (MACCE). Results In total 205(40%) of 508 patients had at least one postoperative complication and 73 (14%) experienced MACCE. Patients’ thirty-day, 1-year and 10-year survival rates were, 99, 98, 84% without complications, 97, 95, 72% with complications, and 90, 89, 64% with MACCE, respectively (log-rank p

Abstract Background The number of colorectal cancer patients increases with age. The decision to go through major surgery can be challenging for the aged patient and the surgeon because of the heterogeneity within the older population. Differences in preoperative physical and cognitive status can affect postoperative outcomes and functional recovery, and impact on patients’ quality of life. Methods / design A prospective, observational, multicentre study including nine hospitals to analyse the impact of colon cancer surgery on functional ability, short-term outcomes (complications and mortality), and their predictors in patients aged ≥80 years. The catchment area of the study hospitals is 3.88 million people, representing 70% of the population of Finland. The data will be gathered from patient baseline characteristics, surgical interventional data, and pre- and postoperative patient-questionnaires, to an electronic database (REDCap) especially dedicated to the study. Discussion This multicentre study provides information about colon cancer surgery’s operative and functional outcomes on older patients. A further aim is to find prognostic factors which could help to predict adverse outcomes of surgery. Trial registration ClinicalTrials.gov ( NCT03904121 ). Registered on 1 April 2019.

Objectives and studyGastrointestinal endoscopy is often performed when investigating abdominal complaints in children. While atrophic changes of the duodenal mucosa are usually caused by celiac disease, the prevalence and clinical significance of non-atrophic duodenal changes are less clear. We studied these issues in a large pediatric endoscopic cohort.MethodsComprehensive data on clinical features, diagnostic findings and long-term outcomes of children who had undergone upper gastrointestinal endoscopy with systematic duodenal sampling were collected. Study variables were compared between children with non-atrophic changes and normal histology, and between those with non-atrophic changes who did and did not receive a diagnosis.ResultsThe study comprised 1,170 consecutive children, of whom 51 (4.4%) had non-atrophic and 315 (26.9%) atrophic duodenal changes and 804 (68.7%) normal histology. The most common non-atrophic findings were non-specific inflammation (n = 19) and intraepithelial lymphocytosis (n = 14). Patients with non-atrophic changes presented more often with blood in stools (23.5 vs. 11.3%; p = 0.009), anemia (43.2 vs. 36.5%; p = 0.028) and positive celiac serology (34.3 vs. 12.9%; p < 0.001) than those with a normal duodenum. Twenty-four (44%) of those with non-atrophic changes received an initial diagnosis, the most common of which were inflammatory bowel disease (IBD) (n = 8), Helicobacter pylori infection (n = 3) and food allergy (n = 3). The prevalence of the diagnoses did not differ from those with a normal duodenum. Those who received a diagnosis had more often blood in stools (37.5 vs. 11.1%; p = 0.027), anemia (70.6 vs. 20.0%; p = 0.002) and negative celiac serology (50.0 vs. 7.7%; p = 0.013) than those without diagnosis. During a follow-up of 6.1–13.3 years, five of the 12 initially undiagnosed seropositive patients developed celiac disease, and one patient also developed ulcerative colitis.ConclusionNon-atrophic duodenal changes are relatively common and associated with anemia, blood in stools, and positive celiac disease serology. Excluding potential celiac disease, those without an initial diagnosis have a favorable long-term prognosis.

Abstract Background Anaphylaxis has increased over the last two decades in Europe, reaching an estimated prevalence of 0.3% and an incidence of 1.5–7.9 per 100,000 person‐years. Allergic multimorbidity is associated with asthma severity, yet its role in anaphylaxis is not fully understood. Our aim was to study association between allergic multimorbidity and anaphylaxis in adults. Methods We used population‐based data from the Finnish Allergy Barometer Study (n = 2070, age range: 5–75). Food allergy (FA), atopic dermatitis (AD), allergic rhinitis (AR) and allergic conjunctivitis (AC), were defined from a self‐completed questionnaire. A logistic regression adjusted on potential confounders (sex, age, smoking status) was applied to estimate the anaphylaxis risk associated with allergic multimorbidity. Results 1319 adults with at least one allergic disease (FA, AD, AR, AC) with/without asthma (AS) were included. Of these, 164 had self‐reported anaphylaxis [mean (SD, min‐max) 54 (14, 22–75) years, 17% men]. AS, FA, AR, AC, or AD were reported by 86.0%, 62.2%, 82.3%, 43.3%, and 53.7% of subjects with anaphylaxis and respectively by 67.8%, 29.5%, 86.2%, 29.4%, and 34.4% of subjects without anaphylaxis. Compared with subjects exhibiting only one allergic disease, the risk of anaphylaxis increased with the number of allergic diseases; adjusted odds ratios (OR) [CI95%] for two, three, four and five coinciding allergic diseases were 1.80 [0.79–4.12], 3.35 [1.47–7.66], 7.50 [3.25–17.32], and 13.5 [5.12–33.09], respectively. The highest risk of anaphylaxis (6.47 [4.33–9.92]) was associated with FA + AS or their various variations with AR/AC/AD embodied, when compared with AR, AC, and AS separately or their combinations. Conclusions Anaphylaxis was positively associated with the number of allergic diseases a subject exhibited and with subgroups including FA and/or AS. The results can be applied when estimating the risk of anaphylaxis for individual patients.

Objectives Basic tools that measure a hospital’s performance are required in order to benchmark or compare hospitals, but multispecialty institutional registries are rarely reported, and there is no consensus on their standard definitions and methodology. This study aimed to describe the setting up and first results of a hospital-wide surgical complication register that uses a minimal set of patient-related risk factors based on bedside data and produces outcomes data based on severity of complications.Design Cohort study.Setting Perioperative data related to all adult surgical procedures in a tertiary referral centre in Finland for 3 years (2016–2018) were included in the study. Complications were recorded according to a modified Clavien-Dindo classification, and the preoperative risk factors were compiled based on the literature and coded as numerical measures. The associations of preoperative risk factors with postoperative complications were analysed using the χ2 test or Fisher’s exact test.Results In total, 19 158 operations were performed between 2016 and 2018. Data on complications (Clavien 0–9) were recorded for 4529 surgical patients (23.6%), and 779 complications were reported (Clavien 1–9), leading to an overall complication rate of 17.2%. Of these, 4.6% were graded as major (Clavien 4–7). Patient-related risk factors with the strongest association with complications were growing American Society of Anesthesiologists Physical Status Classification System score (p

Aims: To assess glycaemic control in ≥15-year-old patients with type 1 diabetes treated in Tampere University Hospital in a real-life cross-sectional registry study. Methods: Glycaemic control was assessed with HbA1c, time in range (TIR) and the incidence of acute complications. The effect of age, BMI, gender, duration of diabetes, daily insulin dose, and device group on the glycaemic control was studied. Results: The study included 1,132 patients. Eighty-four percent of the patients had TIR≤70%. Two percent of patients had an episode of diabetic ketoacidosis and 0,2% had severe hypoglycemia within the last 12 months. Intermittently scanned CGM (IsCGM) with MDI was used in 59%, continuous subcutaneous insulin infusion (CSII) with glucose sensor in 15%, and sensor-augmented/hybrid closed-loop pump (SAP/HCL) in 9% of the patients. In the logistic regression analysis, TIR≤70% was associated with young age group (OR 2.70; 95% CI 1.43–5.09) and daily insulin dose per weight (OR 6.66; 95% CI 3.53–12.57). CSII with glucose sensor and IsCGM with MDI were associated with poor glycaemic control compared to SAP/HCL. Conclusion: There is room for improvement in the glycaemic control in our area although serious acute complications are rare. Closed insulin pump system was more effective than open system.

Abstract Ischemic heart disease is a major cause of death worldwide, and the only available therapy to salvage the tissue is reperfusion, which can initially cause further damage. Many therapeutics that have been promising in animal models have failed in human trials. Thus, functional human based cardiac ischemia models are required. In this study, a human induced pluripotent stem cell derived-cardiomyocyte (hiPSC-CM)-based platform for modeling ischemia–reperfusion was developed utilizing a system enabling precise control over oxygen concentration and real-time monitoring of the oxygen dynamics as well as iPS-CM functionality. In addition, morphology and expression of hypoxia-related genes and proteins were evaluated as hiPSC-CM response to 8 or 24 h hypoxia and 24 h reoxygenation. During hypoxia, initial decrease in hiPSC-CM beating frequency was observed, after which the CMs adapted to the conditions and the beating frequency gradually increased already before reoxygenation. During reoxygenation, the beating frequency typically first surpassed the baseline before settling down to the values close the baseline. Furthermore, slowing on the field potential propagation throughout the hiPSC-CM sheet as well as increase in depolarization time and decrease in overall field potential duration were observed during hypoxia. These changes were reversed during reoxygenation. Disorganization of sarcomere structures was observed after hypoxia and reoxygenation, supported by decrease in the expression of sarcomeric proteins. Furthermore, increase in the expression of gene encoding glucose transporter 1 was observed. These findings indicate, that despite their immature phenotype, hiPSC-CMs can be utilized in modeling ischemia–reperfusion injury.

PurposeWe evaluated adherence to a gluten-free diet and associated factors in adult celiac disease patients diagnosed in childhood.MethodsComprehensive medical data on 955 pediatric celiac disease patients was collected and study questionnaires sent to 559 who were now adults. All variables were compared between strictly adherent and non-adherent patients.ResultsAltogether 237 adults (median age 27 years, 69% women) responded to the questionnaires a median of 18 (range 3–51) years after the childhood diagnosis. Altogether 78% were reportedly adherent and 22% non-adherent. The non-adherent patients had more concomitant type 1 diabetes (18% vs. 4%, p = 0.003), whereas the groups did not differ in demographic data or clinical and histological features at diagnosis, or in short-term dietary adherence. In adulthood, non-adherent patients found gluten-free diet more challenging (39% vs. 17%, p < 0.001) and had higher prevalence (39% vs. 19%, p = 0.004) and severity of symptoms. The main motivation factors for dietary adherence were attempts to avoid symptoms and complications, but these were considered less important and price of gluten-free products more important among non-adherent patients. Adherent and non-adherent patients did not differ in socioeconomic or lifestyle factors, comorbidities other than type 1 diabetes, self-reported general health, health concerns, follow-up, or in quality of life.ConclusionMost originally pediatric celiac disease patients reported strict dietary adherence in adulthood. However, particularly those with concomitant type 1 diabetes, persistent symptoms or financial issues may require attention during the transition from pediatric to adult care.

Abstract Background Introduction of nitisinone and newborn screening (NBS) have transformed the treatment of type 1 tyrosinemia, but the effects of these changes on the long-term outcomes remain obscure. Also, the predictors for later complications, the significance of drug levels and the normalization of laboratory and imaging findings are poorly known. We investigated these issues in a nationwide study. Results Type 1 tyrosinemia was diagnosed in 22 children in 1978–2019 in Finland. Incidence was 1/90,102, with a significant enrichment in South Ostrobothnia (1/9990). Median age at diagnosis was 5 (range 0.5–36) months, 55% were girls and 13 had homozygotic Trp262X mutation. Four patients were detected through screening and 18 clinically, their main findings being liver failure (50% vs. 100%, respectively, p = 0.026), ascites (0% vs. 53%, p = 0.104), renal tubulopathy (0% vs. 65%, p = 0.035), rickets (25% vs. 65%, p = 0.272), growth failure (0% vs. 66%, p = 0.029), thrombocytopenia (25% vs. 88%, p = 0.028) and anaemia (0% vs. 47%, p = 0.131). One patient was treated with diet, seven with transplantation and 14 with nitisinone. Three late-diagnosed (6–33 months) nitisinone treated patients needed transplantation later. Kidney dysfunction (86% vs. 7%, p = 0.001), hypertension (57% vs. 7%, p = 0.025) and osteopenia/osteoporosis (71% vs. 14%, p = 0.017) were more frequent in transplanted than nitisinone-treated patients. Blood/serum alpha-fetoprotein decreased rapidly on nitisinone in all but one patient, who later developed intrahepatic hepatocellular carcinoma. Liver values normalized in 31 months and other laboratory values except thrombocytopenia within 18 months. Imaging findings normalized in 3–56 months excluding five patients with liver or splenic abnormalities. Low mean nitisinone concentration was associated with higher risk of severe complications (r = 0.758, p = 0.003) despite undetectable urine succinylacetone. Conclusions Prognosis of type 1 tyrosinemia has improved in the era of nitisinone, and NBS seems to provide further benefits. Nevertheless, the long-term risk for complications remains, particularly in the case of late diagnosis and/or insufficient nitisinone levels.

Background: Periodontal diseases are a major public health problem with a 70% prevalence in adults. This retrospective controlled study aimed at studying radiologic periodontal findings in chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (sNP). Methodology: Radiologic and patient record data of CRSsNP (n=66) and CRSwNP (n=78) patients undergoing sinus surgery consultation in 2005-18 were used. Chronic rhinitis/oral disease patients served as a control group (n=52). Radiologic periodontal findings referring to chronic periodontitis of maxillary premolar and molar region and Lund-Mackay (LM) scores were analyzed blinded from sinus computed tomography (CT) scans. Results: The prevalence of ≥1 periapical radiolucency was 4.0 % in controls, 14.5% in CRSsNP and 25.4% in CRSwNP group, however this difference became insignificant when adjusted by age. In multivariable linear regression model, the presence of ≥1 other radiologic periodontal finding than periapical radiolucency, was significantly associated with high Total LM score. About half (47%) of the sinus CT scans did not visualize cemento-enamel-junction because of limiting radiation. Conclusions: Radiologic periodontal findings were significantly associated with an increment of Total LM score. Detection of radiologic periodontal findings in CRS patients seems to be possible, if adding the maxillary bone region in sinus CT scans.

Abstract Background Geriatric assessment upon admission may reveal factors that contribute to adverse outcomes in hospitalized older patients. The purposes of this study were to derive a Frailty Index (FI-PAC) from the interRAI Post-Acute Care instrument (interRAI-PAC) and to analyse the predictive ability of the FI-PAC and interRAI scales for hospital outcomes. Methods This retrospective cohort study was conducted by combining patient data from interRAI-PAC with discharge records from two post-acute care hospitals. The FI-PAC was derived from 57 variables that fulfilled the Frailty Index criteria. Associations of the FI-PAC and interRAI-PAC scales (ADLH for activities of daily living, CPS for cognition, DRS for mood, and CHESS for stability of health status) with hospital outcomes (prolonged hospital stay ≥90 days, emergency department admission during the stay, and in-hospital mortality) were analysed using logistic regression and ROC curves. Results The cohort included 2188 patients (mean age (SD) 84.7 (6.3) years) who were hospitalized in two post-acute care hospitals. Most patients (n = 1691, 77%) were discharged and sent home. Their median length of stay was 35 days (interquartile range 18–87 days), and 409 patients (24%) had a prolonged hospital stay. During their stay, 204 patients (9%) were admitted to the emergency department and 231 patients (11%) died. The FI-PAC was normally distributed (mean (SD) 0.34 (0.15)). Each increase of 0.1 point in the FI-PAC increased the likelihood of prolonged hospital stay (odds ratio [95% CI] 1.91 [1.73─2.09]), emergency admission (1.24 [1.11─1.37]), and in-hospital death (1.82 [1.63─2.03]). The best instruments for predicting prolonged hospital stay and in-hospital mortality were the FI-PAC and the ADLH scale (AUC 0.75 vs 0.72 and 0.73 vs 0.73, respectively). There were no differences in the predictive abilities of interRAI scales and the FI-PAC for emergency department admission. Conclusions The Frailty Index derived from interRAI-PAC predicts adverse hospital outcomes. Its predictive ability was similar to that of the ADLH scale, whereas other interRAI-PAC scales had less predictive value. In clinical practice, assessment of functional ability is a simple way to assess a patient’s prognosis.

Abstract Background According to the International Liaison Committee on Resuscitation (ILCOR), the trigger words used by callers that are associated with cardiac arrest constitute a scientific knowledge gap. This study was designed to find hypothetical trigger words in emergency calls in order to improve the specificity of out-of-hospital cardiac arrest recognition. Methods In this descriptive pilot study conducted in a Finnish hospital district, linguistic contents of 80 emergency calls of dispatcher-suspected or EMS-encountered out-of-hospital cardiac arrests between January 1, 2017 and May 31, 2017 were analysed. Spontaneous trigger words used by callers were transcribed and grouped into 36 categories. The association between the spontaneous trigger words and confirmed true cardiac arrests was tested with logistic regression. Results Of the suspected cardiac arrests, 51 (64%) were confirmed as true cardiac arrests when ambulance personnel met the patient. A total of 291 spontaneous trigger words were analysed. ‘Is not breathing’ (n = 9 [18%] in the true cardiac arrest group vs n = 1 [3%] in the non-cardiac arrest group, odds ratio [OR] 6.00, 95% confidence interval [CI] 0.72–50.0), ‘the patient is blue’ (n = 9 [18%] vs n = 1 [3%], OR 6.00, 95% CI 0.72–50.0), ‘collapsed or fallen down’ (n = 12 [24%] vs n = 2 [7%], OR 4.15, 95% CI 0.86–20.1) and ‘is wheezing’ (n = 17 [33%] vs n = 5 [17%], OR 2.40, 95% CI 0.78–7.40) were frequently used to describe true cardiac arrest. ‘Is snoring’ was associated with a false suspicion of cardiac arrest (n = 1 [2%] vs n = 6 [21%], OR 0.08, 95% CI 0.009–0.67). Conclusions In our pilot study, no trigger word was associated with confirmed cardiac arrest. ‘Is wheezing’ was a frequently used spontaneous trigger word among later confirmed cardiac arrest victims.

Objective: To find out how regularly the contents of patient education regarded as essential for COPD patients’ self-management are provided by healthcare professionals in specialised healthcare (SHC) and primary healthcare (PHC) in Finland. Design: A cross-sectional study based on an e-questionnaire with 42 items on the content of self-management education of COPD patients. Setting: The study sample included all public SHC units with pulmonary outpatient clinics (n = 29) and nine out of 160 health centres in Finland. Subjects: 83 doctors and 162 nurses. Main outcome measures: The respondents’ answers on how regularly they included the contents regarded as essential for COPD patients’ self-management in their education of COPD patients. Results: COPD patients were educated regularly on medical issues regarding COPD treatment, such as smoking cessation, exercise and pharmacological treatment. However, issues vital for coping with the disease, such as psychological well-being, stress management or fatigue, were often ignored. Patient education in SHC seemed to be more systematic than education in PHC. The education provided by the asthma/COPD nurses (n = 70) was more systematic than the education provided by the other nurses (n = 84). Conclusion: Healthcare professionals’ continuous education should cover not only the medical but also the psychosocial aspects of coping with COPD. The role of doctors and nurses should be considered to ensure that there is no gap in COPD patients’ education. Training asthma/COPD nurses and promoting specialised nurse-led asthma/COPD clinics in primary care could be beneficial while improving practices of patient education that enhance patients’ ability to cope with the disease.KEY POINTS Issues vital for coping with chronic obstructive pulmonary disease (COPD), such as psychological well-being, stress and fatigue, are irregularly included in self-management education both in primary and specialised healthcare. Patient education provided by asthma/COPD nurses is more regular than patient education provided by other nurses. The distribution of work between doctors and nurses should be considered to ensure that there is no gap in COPD patients’ education.

The 23-valent pneumococcal polysaccharide vaccine (PPV23) given alone is ineffective in patients with chronic lymphocytic leukemia (CLL) and better antibody response is achieved with pneumococcal conjugate vaccines (PCVs). In this study, we determine whether CLL patients would achieve a significant antibody response and broaden their serotype coverage against invasive pneumococcal disease (IPD) with PPV23 given five years after the 7-valent conjugate vaccine (PCV7). A total of 24 patients with CLL and eight controls were vaccinated with PPV23 five years after PCV7. Blood samples for evaluation of antibody response to PCV7 serotypes and PPV23 serotypes 5 and 7 were taken before vaccination and one month after it. Post-vaccination samples were available from 20 patients. IgG antibodies were measured with ELISA. Antibody concentrations after PPV23 were significantly lower in CLL patients for six of the PCV7 serotypes and for both PPV23 serotypes. Only 10% to 15% of CLL patients achieved an antibody response suggested to be protective against IPD. Hence, PCV7 given five years before PPV23 did not improve antibody response in patients with CLL. Based on our results, PPV23 given after a PCV primer is not useful against IPD in CLL patients.

Military pilots undergo rigorous selection compared with civilian professional pilots because of different operational requirements. There are no studies of military pilots’ subsequent civil aviation careers and fatal pilot aviation accidents. This study focuses on Vietnam War (VW) pilots and subsequent fatal aviation accidents in the U.S from 1965 to 2018. In total nine aviation accidents met the inclusion criteria and are described in detail, including the pilots’ previous civil aviation incidents. The VW pilots were healthy, had valid Medicals and continued to fly in demanding pilot positions after their military careers. Although the data are limited, this study suggests that previous military pilots may differ slightly from other pilots in their subsequent civil aviation careers.

Abstract Background Making ethically sound treatment limitations in prehospital care is a complex topic. Helicopter Emergency Medical Service (HEMS) physicians were surveyed on their experiences with limitations of care orders in the prehospital setting, including situations where they are dispatched to healthcare facilities or nursing homes. Methods A nationwide multicentre study was conducted among all HEMS physicians in Finland in 2017 using a questionnaire with closed five-point Likert-scale questions and open questions. The Ethics Committee of the Tampere University Hospital approved the study protocol (R15048). Results Fifty-nine (88%) physicians responded. Their median age was 43 (IQR 38–47) and median medical working experience was 15 (IQR 10–20) years. All respondents made limitation of care orders and 39% made them often. Three fourths (75%) of the physicians were often dispatched to healthcare facilities and nursing homes and the majority (93%) regularly met patients who should have already had a valid limitation of care order. Every other physician (49%) had sometimes decided not to implement a medically justifiable limitation of care order because they wanted to avoid conflicts with the patient and/or the next of kin and/or other healthcare staff. Limitation of care order practices varied between the respondents, but neither age nor working experience explained these differences in answers. Most physicians (85%) stated that limitations of care orders are part of their work and 81% did not find them especially burdensome. The most challenging patient groups for treatment limitations were the under-aged patients, the severely disabled patients and the patients in healthcare facilities or residing in nursing homes. Conclusion Making limitation of care orders is an important but often invisible part of a HEMS physician’s work. HEMS physicians expressed that patients in long-term care were often without limitations of care orders in situations where an order would have been ethically in accordance with the patient’s best interests.

Background and purpose — Previous small studies have suggested that delivery does not adversely affect the survivorship of total hip replacement (THR). We investigated whether delivery after primary THR affects hip implant survivorship in a large population-based study sample Patients and methods — In this register-based nationwide cohort study, all women aged 15–45 who underwent primary THR in Finland from 1987 to 2007 were included from the Finnish Arthroplasty Register. Data on deliveries were obtained from the medical birth register. After primary THR, 111 women (133 THRs) delivered and formed the delivery group. In the reference group, 1,878 women (2,343 THRs) had no deliveries. We used Kaplan–Meier analysis with 95% confidence intervals (CI) to study implant survivorship at 6 and 13 years, and Cox multiple regression to assess survival and hazard ratios (HRs), with revision for any reason as an endpoint with adjustment for age, rheumatoid arthritis, and stem and cup fixation. Results — 51 (38%) revisions were recorded in the delivery group and 645 (28%) revisions in the reference group. The 6-year implant survivorship was 91% (CI 85–96) in the delivery group and 88% (CI 87–90) in the reference group. The 13-year survival rates were 50% (CI 39–62) and 61% (CI 59–64). The adjusted HR for revision after delivery was 0.7 (CI 0.4–1.2) in ≤ 6.8 years’ follow-up and 1.1 (CI 0.8–1.6) in > 6.8 years’ follow-up. Interpretation — Based on the findings in this nationwide study of hip replacement in fertile-aged women, delivery does not seem to decrease THR implant survivorship; women should not be afraid of or avoid becoming pregnant after THR.

Introduction: Puumala hantavirus (PUUV) causes a mild type of hemorrhagic fever with renal syndrome characterized by acute kidney injury (AKI), increased capillary leakage, and thrombocytopenia. Albuminuria and hematuria in dipstick urine test at hospital admission are known to predict the severity of upcoming AKI. Methods: We analyzed dipstick urine glucose in 195 patients with acute PUUV infection at hospital admission, and divided them into 2 categories according to the presence or absence of glucose in the dipstick urine test. Determinants of disease severity were analyzed in glucosuric and nonglucosuric patients. Results: Altogether, 24 of 195 patients (12%) had glucosuria. The patients with glucosuria had more severe AKI than patients without glucosuria (median maximum creatinine concentration 459 μmol/l, range 78–1041 μmol/l vs. 166 μmol/l, range 51–1499 μmol/l; P < 0.001). The glucosuric patients had more severe thrombocytopenia (median minimum platelet count 41 × 109/l, range 5–102 × 109/l vs. 62 × 109/l, range 3–249 × 109/l; P = 0.006), and more pronounced signs of increased capillary leakage (change in weight, maximum plasma hematocrit, minimum plasma albumin). The glucosuric patients were more often in clinical shock at admission (20.8% vs. 1.2%; P < 0.001) and the length of hospital stay was longer (median 7.5 days, range 4–22 days vs. 6 days, range 2–30 days; P = 0.009). Conclusion: Glucosuria is relatively rare, but when present it predicts a more severe disease course in patients with acute PUUV infection. Keywords: acute kidney injury, glucosuria, hantavirus, Puumala virus, thrombocytopenia

Abstract Background Patients with isolated traumatic brain injury (TBI) are likely to benefit from effective prehospital care to prevent secondary brain injury. Only a few studies have focused on the impact of advanced interventions in TBI patients by prehospital physicians. The primary end-point of this study was to assess the possible effect of an on-scene anaesthetist on mortality of TBI patients. A secondary end-point was the neurological outcome of these patients. Methods Patients with severe TBI (defined as a head injury resulting in a Glasgow Coma Score of ≤8) from 2005 to 2010 and 2012–2015 in two study locations were determined. Isolated TBI patients transported directly from the accident scene to the university hospital were included. A modified six-month Glasgow Outcome Score (GOS) was defined as death, unfavourable outcome (GOS 2–3) and favourable outcome (GOS 4–5) and used to assess the neurological outcomes. Binary logistic regression analysis was used to predict mortality and good neurological outcome. The following prognostic variables for TBI were available in the prehospital setting: age, on-scene GCS, hypoxia and hypotension. As per the hypothesis that treatment provided by an on-scene anaesthetist would be beneficial to TBI outcomes, physician was added as a potential predictive factor with regard to the prognosis. Results The mortality data for 651 patients and neurological outcome data for 634 patients were available for primary and secondary analysis. In the primary analysis higher age (OR 1.06 CI 1.05–1.07), lower on-scene GCS (OR 0.85 CI 0.79–0.92) and the unavailability of an on-scene anaesthetist (OR 1.89 CI 1.20–2.94) were associated with higher mortality together with hypotension (OR 3.92 CI 1.08–14.23). In the secondary analysis lower age (OR 0.95 CI 0.94–0.96), a higher on-scene GCS (OR 1.21 CI 1.20–1.30) and the presence of an on-scene anaesthetist (OR 1.75 CI 1.09–2.80) were demonstrated to be associated with good patient outcomes while hypotension (OR 0.19 CI 0.04–0.82) was associated with poor outcome. Conclusion Prehospital on-scene anaesthetist treating severe TBI patients is associated with lower mortality and better neurological outcome.

Abstract Background In coeliac disease, ingestion of gluten induces the production of transglutaminase 2 (TG2)-targeted autoantibodies by TG2-specific plasma cells present at high frequency in the small intestinal mucosa in untreated disease. During treatment with a gluten-free diet (GFD), the number of these cells decreases considerably. It has not been previously investigated whether the cells are also present prior to development of villous atrophy, or in non-responsive patients and those with dietary lapses. We aimed to define the frequency of small bowel mucosal TG2-specific plasma cells in coeliac disease patients with varying disease activity, and to investigate whether the frequency correlates with serum and small intestinal TG2-targeting antibodies as well as mucosal morphology and the number of intraepithelial lymphocytes. Results Mucosal TG2-specific plasma cells were found in 79% of patients prior to development of mucosal damage, in all patients with villous atrophy, and in 63% of the patients after 1 year on GFD. In these disease stages, TG2-specific plasma cells accounted for median of 2.3, 4.3, and 0.7% of all mucosal plasma cells, respectively. After long-term treatment, the cells were present in 20% of the patients in clinical remission (median 0%) and in 60% of the patients with poor dietary adherence (median 5.8%). In patients with non-responsive coeliac disease despite strict GFD, the cells were found in only one (9%) subject; the cells accounted for 2.4% of all plasma cells. A positive correlation between the percentage of TG2-specific plasma cells and serum TG2 antibody levels (rS = 0.69, P

Chronic ulcers cause a significant burden to patients and society. This study evaluated long-term mortality among patients with chronic ulcers diagnosed at a dermatology clinic between 1980 and 2010. The mortality risk and causes of death of 3,489 patients with ulcers were compared with a matched reference group of 10,399 individuals, and factors associated with increased mortality risk were examined. Long-term mortality was increased in patients with chronic ulcers (hazard ratio (HR) 1.74) and in both males and females (HR 1.99 and 1.62, respectively). Diabetes was the most relevant underlying cause of death (HR 8.98), and of the immediate causes of death, sepsis was strongly associated with mortality (HR 5.86). The mortality risk was highest among those with arterial ulcers (HR 2.85), but also increased in patients with atypical, mixed and venous leg ulcers. In conclusion, patients with chronic ulcers are at an increased mortality risk irrespective of age, sex and ulcer aetiology.