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Background: Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown. Methods: We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up. Results: Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%–15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%–19.1%) in those without (χ 2 =1.834, P =0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%–21.0%) versus 6.3% (95% CI, 0.7%–54.0%; χ 2 =0.814, P =0.367) in definite CS and 7.6% (95% CI, 3.8%–15.1%) versus 3.3% (95% CI, 0.5%–22.9%; χ 2 =0.680, P =0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis ( P =0.033) but not by Class I or IIa ICD indications ( P =0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%–71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation. Conclusions: Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.

Background Etanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN. Methods In this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum. Results Ninety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33–0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups – in MTX group [r = 0.35 (95% CI: 0.14–0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39–0.67)]. Conclusion In the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) procedures may result in remarkable radiation doses to patients and staff. The aim of this prospective study was to determine occupational exposures in gastrointestinal endoscopy procedures, with a special emphasis on eye lens dose in ERCP. Methods Altogether 604 fluoroscopy-guided procedures, of which 560 were ERCPs belonging to four American Society for Gastrointestinal Endoscopy procedural complexity levels, were performed using two fluoroscopy systems. Personal deep-dose equivalent Hp(10), shallow-dose equivalent Hp(0.07), and eye lens dose equivalent Hp(3) of eight interventionists and Hp(3) for two nurse dosimeters were measured. Thereafter, conversion coefficients from kerma-area product (KAP) for Hp(10), Hp(0.07), and Hp(3) were determined and dose equivalents per procedure to an operator and assisting staff were estimated. Further, mean conversion factors from Hp(10) and Hp(0.07) to Hp(3) were calculated. Results The median KAP in ERCP was 1.0 Gy·cm2, with mobile c-arm yielding higher doses than a floor-mounted device (P Conclusions Occupational dose limits are unlikely to be exceeded in gastrointestinal endoscopy practice when following radiation-hygienic working methods and focusing on dose optimization. The eye lens dose equivalent Hp(3) may be estimated with sufficient agreement from the Hp(10) and Hp(0.07).

Background Long-term functional limitations are common after hip fractures. Exercise may alleviate these negative consequences but there is no consensus on an optimal training program. The objective was to study the effects of a 12-month home-based supervised, progressive exercise program on functioning, physical performance, and physical activity. Methods Secondary analysis of a randomized controlled trial targeting patients with surgical repair of a hip fracture, aged >= 60 years, Mini-Mental State Examination (MMSE) score of >= 12. The participants were randomized into Exercise (n = 61) or Usual care (n = 60). Assessments at baseline, 3, 6, and 12 months included Lawton's Instrumental Activities of Daily Living (IADL), Short Physical Performance Battery (SPPB), handgrip strength, and self-reported frequency of sessions of leisure-time physical activity. Analyzed using mixed-effects models. Results Participants' (n = 121) mean age was 81 years (SD 7), and 75% were women. The mean IADL score at baseline was 17.1 (SD 4.5) in the exercise group, and 17.4 (5.1) in the usual care group. The mean SPPB scores were 3.9 (1.6) and 4.2 (1.8), and handgrip strength was 17.7 (8.9) kg and 20.8 (8.0) kg, respectively. The age- and sex-adjusted mean changes in IADL over 12 months were 3.7 (95% CI 2.8-4.7) in the exercise and 2.0 (1.0-3.0) in the usual care group (between-group difference, p = 0.016); changes in SPPB 4.3 (3.6-4.9) and 2.1 (1.5-2.7) (p < 0.001); and changes in handgrip strength 1.2 kg (0.3-2.0) and 1.0 kg (-1.9 to -0.2) (p < 0.001), respectively. We found no between-group differences in changes in the frequency of leisure-time activity sessions. Conclusion A 12-month home-based supervised, progressive exercise program improved functioning and physical performance more than usual care among patients with hip fractures. However, the training did not increase leisure-time physical activity.

OBJECTIVE: To assess the safety of senior residents performing trochanteric hip fracture surgery without immediate consultant supervision DESIGN: A retrospective chart review of trochanteric hip fractures (AO-OTA 31-A) operated in a single center between years 2011 and 2016 (inclusive). Operations were divided into three groups: Group 1 surgeon was a senior resident without any immediate supervision; Group 2 surgeon was a consultant and Group 3surgeon was a senior resident supervised by a consultant. The follow-up period was a minimum of 2 years or until death. All re-operations and surgical related mortality were assessed. SETTING: Helsinki University Hospital, Finland. A tertiary level trauma center. PARTICIPANTS: 987 consecutive trochanteric fractures on 966 patients treated by operative fixation of an intertrochanteric fracture with an intramedullary nail between 2011and 2016 (inclusive). RESULTS: The total number of reoperations was smaller in Group 1 where the surgeon was a senior resident without any immediate supervision compared to Group 2 where the surgeon was a consultant (5.5 % vs 8.8 %, p < 0.05). There were no significant differences in mortality or length of surgery. The total rate of mechanical complications was 2.0 %, with no significant differences between groups. The observed blade cut-out rate was low: 1.3 %, suggesting a good overall quality of surgery. CONCLUSIONS: Senior residents can safely perform intramedullary nailing of trochanteric fractures without immediate supervision. (C) 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Aim: To determine the ability of serum glial fibrillary acidic protein (GFAp) and tau protein to predict neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods: We measured plasma concentrations of GFAp and tau of patients included in the previously published COMACARE trial (NCT02698917) on intensive care unit admission and at 24, 48, and 72 h after OHCA, and compared them to neuron specific enolase (NSE). NSE concentrations were determined already during the original trial. We defined unfavourable outcome as a cerebral performance category (CPC) score of 3-5 six months after OHCA. We determined the prognostic accuracy of GFAp and tau using the receiver operating characteristic curve and area under the curve (AUROC). Results: Overall, 39/112 (35%) patients had unfavourable outcomes. Over time, both markers were evidently higher in the unfavourable outcome group (p < 0.001). At 48 h, the median (interquartile range) GFAp concentration was 1514 (886-4995) in the unfavourable versus 238 (135-463) pg/ ml in the favourable outcome group (p < 0.001). The corresponding tau concentrations were 99.6 (14.5-352) and 3.0 (2.2-4.8) pg/ml (p < 0.001). AUROCs at 48 and 72 h were 0.91 (95% confidence interval 0.85-0.97) and 0.91 (0.85-0.96) for GFAp and 0.93 (0.86-0.99) and 0.95 (0.89-1.00) for tau. Corresponding AUROCs for NSE were 0.86 (0.79-0.94) and 0.90 (0.82-0.97). The difference between the prognostic accuracies of GFAp or tau and NSE were not statistically significant. Conclusions: At 48 and 72 h, serum both GFAp and tau demonstrated excellent accuracy in predicting outcomes after OHCA but were not superior to NSE. Clinical trial registration: NCT02698917 (https://www.clinicaltrials.gov/ct2/show/NCT02698917).

Numerous studies have described specific metabolites as biomarkers ofsevere liver diseases, but very few have measured gut microbiota (GM)-produced metab-olites in fatty liver disease. We aimed atfinding GM signatures and metabolite markersin plasma and feces related to high liver fat content. Based on imaging, we dividedstudy participants into low (,5%, LF,n= 25) and high (.5%, HF,n= 39) liver fatgroups. Fecal (LFn= 14, HFn= 25) and plasma (LFn= 11, HFn= 7) metabolomes ofsubsets of participants were studied using liquid chromatography/high resolution massspectrometry. The GM were analyzed using 16S rRNA gene sequencing. Additionally,blood clinical variables and diet were studied. Dyslipidemia, higher liver enzymes and in-sulin resistance characterized the HF group. No major differences in diet were foundbetween the groups. In the GM, the HF group had lower abundance ofBacteroidesandPrevotellaceae NK3B31 group than the LF group after adjusting for metformin use orobesity. In feces, the HF group had higher levels of lysine and histidine degradationproducts, while 6-hydroxybetatestosterone (metabolized by CYP3A4) was low. Higherplasma levels of caffeine and its metabolites in the HF group indicate that the activity ofhepatic CYP1A2 was lower than in the LF group. Our results suggest, that low fecalPrevotellaceae NK3B31 andBacteroidesabundance, and increased lysine and histidinedegradation may serve as GM biomarkers of high liver fat. Altered plasma caffeinemetabolites and lowered testosterone metabolism may specify decreased CYP activities,and their potential utility, as biomarkers of fatty liver disease. peerReviewed

Background Myocardial perfusion SPECT (MPS) images often suffer from artefacts caused by low-count statistics. Poor-quality images can lead to misinterpretations of perfusion defects. Deep learning (DL)-based methods have been proposed to overcome the noise artefacts. The aim of this study was to investigate the differences among several DL denoising models. Methods Convolution neural network (CNN), residual neural network (RES), UNET and conditional generative adversarial neural network (cGAN) were generated and trained using ordered subsets expectation maximization (OSEM) reconstructed MPS studies acquired with full, half, three-eighths and quarter acquisition time. All DL methods were compared against each other and also against images without DL-based denoising. Comparisons were made using half and quarter time acquisition data. The methods were evaluated in terms of noise level (coefficient of variation of counts, CoV), structural similarity index measure (SSIM) in the myocardium of normal patients and receiver operating characteristic (ROC) analysis of realistic artificial perfusion defects inserted into normal MPS scans. Total perfusion deficit scores were used as observer rating for the presence of a perfusion defect. Results All the DL denoising methods tested provided statistically significantly lower noise level than OSEM without DL-based denoising with the same acquisition time. CoV of the myocardium counts with the different DL noising methods was on average 7% (CNN), 8% (RES), 7% (UNET) and 14% (cGAN) lower than with OSEM. All DL methods also outperformed full time OSEM without DL-based denoising in terms of noise level with both half and quarter acquisition time, but this difference was not statistically significant. cGAN had the lowest CoV of the DL methods at all noise levels. Image quality and polar map uniformity of DL-denoised images were also better than reduced acquisition time OSEM’s. SSIM of the reduced acquisition time OSEM was overall higher than with the DL methods. The defect detection performance of full time OSEM measured as area under the ROC curve (AUC) was on average 0.97. Half time OSEM, CNN, RES and UNET provided equal or nearly equal AUC. However, with quarter time data CNN, RES and UNET had an average AUC of 0.93, which was lower than full time OSEM’s AUC, but equal to quarter acquisition time OSEM. cGAN did not achieve the defect detection performance of the other DL methods. Its average AUC with half time data was 0.94 and 0.91 with quarter time data. Conclusions DL-based denoising effectively improved noise level with slightly lower perfusion defect detection performance than full time reconstruction. cGAN achieved the lowest noise level, but at the same time the poorest defect detection performance among the studied DL methods.

Recent longitudinal studies in youth have reported MRI correlates of prospective anxiety symptoms during adolescence, a vulnerable period for the onset of anxiety disorders. However, their predictive value has not been established. Individual prediction through machine-learning algorithms might help bridge the gap to clinical relevance. A voting classifier with Random Forest, Support Vector Machine and Logistic Regression algorithms was used to evaluate the predictive pertinence of gray matter volumes of interest and psychometric scores in the detection of prospective clinical anxiety. Participants with clinical anxiety at age 18–23 (N = 156) were investigated at age 14 along with healthy controls (N = 424). Shapley values were extracted for in-depth interpretation of feature importance. Prospective prediction of pooled anxiety disorders relied mostly on psychometric features and achieved moderate performance (area under the receiver operating curve = 0.68), while generalized anxiety disorder (GAD) prediction achieved similar performance. MRI regional volumes did not improve the prediction performance of prospective pooled anxiety disorders with respect to psychometric features alone, but they improved the prediction performance of GAD, with the caudate and pallidum volumes being among the most contributing features. To conclude, in non-anxious 14 year old adolescents, future clinical anxiety onset 4–8 years later could be individually predicted. Psychometric features such as neuroticism, hopelessness and emotional symptoms were the main contributors to pooled anxiety disorders prediction. Neuroanatomical data, such as caudate and pallidum volume, proved valuable for GAD and should be included in prospective clinical anxiety prediction in adolescents.

Objectives: To investigate tympanostomy tube (TT) treatment in young children, with special interest in bloodless surgical methods (laser and radiofrequency), myringosclerosis formation and tympanometric testing.Methods: This prospective study includes 76 children whose 121 ears with middle ear effusion were treated with tympanostomy tubes. Myringotomy was performed with CO2 laser in 37, radiofrequency in 40 and myringotomy knife in 44 ears. The ears were evaluated with otomicroscopy and tympanometry preoperatively and post-operatively every 3-4 months until spontaneous tube extrusion.Results: All tubes extruded spontaneously (mean 12.8 months, range 3-36 months), with no persistent perfora-tions or cholesteatomas. CO2 laser and radiofrequency inserted tympanostomy tubes extruded faster (mean 11 months) compared to incisional myringotomy (mean 15 months, p = 0.002). Myringosclerosis was noted in 25 (21%) ears after treatment. There was a tendency to less myringosclerosis with bloodless techniques, but the difference was not significant. Flat tympanograms on the day of procedure predicted continuation of ventilation problems also after TT treatment (p = 0.003). Ears with preoperative type B tympanogram had significantly more myringosclerosis 21/75 (28%) compared with type A and C tympanograms 4/41 (10%) (p = 0.032).Conclusions: While all myringotomy methods were effective and safe, the traditional incisional myringotomy with a tympanostomy knife is still a good, feasible and cost-effective myringotomy method. No surgical removal of tympanostomy tubes is needed before 3 years of uncomplicated tympanostomy treatment. Tympanometry turned out to be a useful tool in prediction of post TT treatment ventilation problems of the middle ear.

Background In a chronic pain-causing disease such as juvenile idiopathic arthritis, the quality of coping with pain is crucial. Parents have a substantial influence on their children’s pain-coping strategies. This study aimed to develop scales for assessing parents’ strategies for coping with their children’s pain and a shorter improved scale for children usable in clinical practice. Methods The number of items in the Finnish version of the pain-coping questionnaire for children was reduced from 39 to 20. A corresponding reduced scale was created for parental use. We recruited consecutive patients from nine hospitals evenly distributed throughout Finland, aged 8–16 years who visited a paediatric rheumatology outpatient clinic and reported musculoskeletal pain during the past week. The patients and parents rated the child’s pain on a visual analogue scale from 0 to 100 and completed pain-coping questionnaires and depression inventories. The selection process of pain questionnaire items was performed using factor analyses. Results The average (standard deviation) age of the 130 patients was 13.0 (2.3) years; 91 (70%) were girls. Four factors were retained in the new, improved Pain-Coping Scales for children and parents. Both scales had 15 items with 2–5 items/factor. The goodness-of-fit statistics and Cronbach’s alpha reliability coefficients were satisfactory to good in both scaled. The criterion validity was acceptable as the demographic, disease related, and the depression and stress questionnaires correlated with the subscales. Conclusions We created a shorter, feasible pain-coping scale for children and a novel scale for caregivers. In clinical work, the pain coping scales may serve as a visualisation of different types of coping strategies for paediatric patients with pain and their parents and facilitate the identification of families in need of psychological support.

Background Because of the premalignant nature of intraductal papillary mucinous neoplasms (IPMNs), patients should undergo surveillance as long as they remain fit for surgery. This surveillance, with imaging and laboratory tests every 6 to 12 months, is expensive and may psychologically burden patients. This study aimed to determine the effects of IPMN surveillance on patients´ health-related quality of life (HRQoL) and anxiety levels. Methods We included a random subgroup of all IPMN patients undergoing a follow-up check-up at Helsinki University Hospital (HUH) between August 2017 and November 2018. Patients were asked to complete the 15D HRQoL and state-trait anxiety inventory (STAI) questionnaires just before and three months after an IPMN control. Results Among 899 patients in IPMN follow-up, 232 participated. The 15D HRQoL results showed differences in some IPMN patients’ 15 analyzed dimensions compared to a sex- and age-standardized general population cohort, but the clinical relevance of these differences appear doubtful. We detected no significant difference in the anxiety levels determined using the STAI questionnaires before or three months after the IPMN control. Conclusion Surveillance should be less harmful than the risk of disease. Among our patients, the recommended IPMN follow-up carried minimal negative impact on patients’ HRQoL or anxiety levels. This result is important, because the number of patients under IPMN surveillance is rapidly increasing and the cancer risk among the majority of these patients remains small. Trial registration: The Surgical Ethics Committee of Helsinki University Hospital approved this study (Dnro HUS 475/2017) and it was registered at ClinicalTrials.gov (NCT03131076) before patient enrollment began.

Vertaisarvioitu. • Terrorististen iskujen ja muiden joukkosurmien määrä on lisääntynyt Euroopassa ja Suomessa 2000-luvulla. • Poliisi ja muut turvallisuusviranomaiset ovat panostaneet merkittävästi ratkaisumallien kehittämiseen näitä tilanteita varten. • Terveydenhuollon pitää osallistua joukkosurmatilanteiden moniammatillisen vasteen kehittämiseen ja parantaa lääketieteellistä valmiutta. • Toimintavalmiutta parantavat esimerkiksi potilasluokittelujärjestelmät ja taktisen lääketieteen toimintamallit ensihoidossa ja päivystyksessä.

BackgroundContinued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies.MethodsThe EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014–2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined.FindingsAmong 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions.InterpretationResults from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors. Background: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies. Methods: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014–2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined. Findings: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions. Interpretation: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.

Take Home Message In terms of clinically relevant outcomes, such as overall survival, prostate cancer–specific survival, metastasis-free survival, and treatment-free survival, a strict follow-up protocol does not provide benefit for men with low-risk prostate cancer on active surveillance., Background Active surveillance (AS) is the preferred option for initial management for low-risk prostate cancer (PC). Although many AS protocols exist, there is little evidence to support one over another. Objective To assess whether there is difference in overall (OS), prostate cancer–specific (CSS), metastasis-free (MFS), or treatment-free (TFS) survival between a strict (Prostate cancer Research International: Active Surveillance [PRIAS]) and a loose (European Randomized study of Screening for Prostate Cancer [ERSPC]) AS protocol. Design, setting, and participants This study included two cohorts of men (n = 518) with low-risk, localized, Gleason score ≤7 PC. The ERSPC cohort included 241 men followed for 9.5 yr (median) with a non–protocol-based follow-up. The PRIAS cohort included 277 men followed for 5 yr (median) with a strict protocol. Outcome measurements and statistical analysis OS, CSS, MFS, and TFS were compared by the Kaplan-Meier method, competing risk analysis, and Cox proportional hazard regression. Results and limitations As expected, due to the difference in median follow-up time between the cohorts, a difference in the absolute number of events was seen. However, no difference in any of the survival outcomes was evident in the Kaplan-Meier or competing risks analysis. Furthermore, in Cox proportional hazard regression analysis, cohort (ERSPC vs PRIAS) was not associated with any of the outcomes. Results are limited by the retrospective study design, limited statistical power, and inability to match the cohorts for predictive factors. Conclusions There was no difference in survival outcomes between a non–protocol-based follow-up and a protocol-based contemporary AS follow-up of patients with low-risk PC. However, a longer follow-up is needed. Patient summary We compared survival outcomes of two cohorts of patients with low-risk prostate cancer: a strict and a loose follow-up protocol. We found no differences in survival measures between the cohorts.

Background: Zoledronic acid is an intravenous, highly potent aminobisphosphonate for use in patients with primary or secondary osteoporosis. Zoledronic acid-induced prolonged side-effects are well known and quite common. However, severe side-effects can be a threat to life. We report a case of severe side-effects induced by zoledronic acid infusion, and its positive effect on long-term back pain. Case presentation: In 2012, a 62-year-old white native Finnish woman was operated on for an estrogen and progesterone receptor-positive breast cancer. After radiotherapy, an aromatase inhibitor (letrozole) was started. Nine months after the operation, the patient suffered a low-energy compression fracture of Th XII. She received denosumab to prevent fragility fractures and to improve bone mineral density. Letrozole was discontinued after 5.5 years, and the last denosumab injection was given after 7 years. Six months later, at the age of 71 years, the patient received a single intravenous zoledronic acid infusion. Suddenly, at 10 hours from the infusion, she complained of severe trismus, muscle twitching, spasms, and tingling, matching hypocalcemia and several other symptoms. Her serum 25-hydroxyvitamin D concentration was high (163 nmol/L), the concentration of serum calcium and calcium-ion was normal (2.32 mmol/L and 1.23 mmol/L, respectively). However, the neutrophil to lymphocyte ratio (NLR) was low (1.6). A complete recovery took 2 months. Zoledronic acid infusion also had a positive effect: for many years, the patient had suffered low back pain and strain, which came to an end after this single infusion. Conclusion: It is important that the potential patients receive sufficient information about the possibility of side-effects following the administration of intravenous zoledronic acid. To ensure that a zoledronic acid infusion is given as safely as possible, the safety information should include that the patient should not be left without monitoring for a minimum 24 hours after the infusion. Being alone and experiencing serious side-effects may lead to acute cardiac problems. Furthermore, the chronic low back pain and strain that our patient suffered for many years has clearly reduced for 16 months after infusion, so far. We conclude that this is a positive effect of zoledronic acid.

Background: Low ferritin without anaemia has been linked to adverse health effects. Objectives: To investigate the prevalence and clinical significance of low ferritin in screen-detected coeliac disease. Methods: Seventy-six screen-detected coeliac disease patients were enrolled in the prospective collection of comprehensive clinical, laboratory and histological data at diagnosis and after 1–2 years on a gluten-free diet (GFD). All variables were compared between patients with different ferritin levels. Results: At coeliac disease diagnosis, six patients had anaemia. Of the 70 nonanaemic patients, ferritin levels were

IntroductionConstitutional delay of growth and puberty (CDGP) is the most common reason for delayed puberty in healthy male adolescents. The main indication for medical treatment for this condition is psychosocial burden. However, to the best of our knowledge, no previous study has addressed the impact of puberty-promoting treatment on health-related quality of life (HRQoL) among boys with CDGP.MethodsWe investigated HRQoL in 22 boys with CDGP, who participated in a randomized controlled trial in four Finnish pediatric endocrinology outpatient clinics between 2013 and 2017. The boys were randomized to receive either aromatase inhibitor letrozole (2.5mg/day; n=11) or intramuscular testosterone (1mg/kg/every 4 weeks; n=11) for 6 months and followed up to 12 months. HRQoL was assessed with a generic self-assessment 16D© instrument developed and validated for adolescents aged 12 to 15 years. The 16D includes 16 dimensions (vitality, sight, breathing, distress, hearing, sleeping, eating, discomfort and symptoms, speech, physical appearance, school and hobbies, mobility, friends, mental function, excretion and depression). The results were compared with an age-matched reference population that included 163 boys from the Finnish capital-city area. The study protocol is registered to ClinicalTrials.gov (registration number: NCT01797718).ResultsAt baseline, the mean 16D score of the CDGP boys was similar to the age-matched reference population (0.95 vs 0.96, p=0.838). However, the physical appearance score (satisfaction with general appearance, height and weight) was significantly lower in the CDGP boys (0.75 vs 0.92, p=0.004) than their peers. Twelve months after treatment, Appearance had improved significantly (0.75 vs 0.87, p=0.004) and no HRQoL dimension was inferior compared to the age-matched reference population.DiscussionIn terms of HRQoL, the main impact of delayed puberty was dissatisfaction with physical appearance. Puberty promoting therapy was associated with a positive change in perceived appearance, with no clear difference between low-dose testosterone and letrozole treatments.

PurposeTo compare intra- and postoperative complications in combined phacoemulsification and pars plana vitrectomy surgeries performed in patients with non-proliferative diabetic retinopathy (NPDR) vs. proliferative diabetic retinopathy (PDR).MethodsRetrospective, case series of patients with diabetic retinopathy who underwent combined phacovitrectomy surgery between 2008 and 2017. We compared intraoperative complications including posterior capsular rupture and retinal tear, and postoperative complications including corneal edema, macular edema (ME), epiretinal membrane (ERM), neovascular glaucoma and persistent inflammation.ResultsA total of 104 eyes of 104 patients were included in this study. Twenty-four eyes (23.1%) were categorized as NPDR and 80 eyes (76.9%) as PDR. The most common indications for surgery in the NPDR group were ERM (67%) and rhegmatogenous retinal detachment (12.5%), while in the PDR group, indications were vitreous hemorrhage (56%) and tractional retinal detachment (19%). The most common intraoperative complication was retinal tear (8% in NPDR and 19% in PDR, p = 0.195) and postoperative complication was ME (29% in NPDR and 26% in PDR, p = 0.778). There were no statistically significant differences in intra- and postoperative complication rates between the NPDR and PDR groups, even after adjusting for confounders; patient age at surgery and indication for surgery.ConclusionAfter combined phacovitrectomy in NPDR and PDR patients, new-onset ME was found in about a quarter of eyes in both groups. Intraoperative anti-VEGF or steroid administration, and intense postoperative anti-inflammatory medication and follow-up should be regarded after phacovitrectomy regardless of the DR level.

Purpose Recent studies have suggested that higher postmenopausal follicle stimulating hormone (FSH) may be associated with lower risk of diabetes. However, relatively little is known about postmenopausal FSH levels, including the level of variation between women and whether reproductive factors are associated with this variation. Methods We assessed the relationship of multiple reproductive factors with FSH levels among 588 postmenopausal women in the Kuopio Ischaemic Heart Disease Risk Factor Study. Participants were aged 53 to 73 years and not using hormone therapy at study enrollment (1998–2001) when reproductive factors were assessed and FSH was measured. Results After adjustment for age, menopause timing, sex steroid levels, adiposity and behavioral factors, we observed numbers of pregnancies and age at first birth were each inversely associated with FSH levels. For example, women with ≥ 3 births and an age at first birth ≥ 25 years had mean FSH levels that were 7.8 IU/L lower than those of women with 1–2 births and an age at first birth ≤ 24 years (P = 0.003). Number of miscarriages was inversely associated with FSH levels (-2.7 IU/L per miscarriage; P = 0.02). Women reporting 4 or more years of past hormone therapy use had significantly higher mean FSH levels than women who had never used hormone therapy (P for trend = 0.006). Conclusion Multiple reproductive factors were associated with postmenopausal FSH, independent of estradiol, adiposity and other confounders. These findings warrant replication and further exploration of potential underlying mechanism.

Introduction: The current manuscript presents a protocol for a systematic review and meta-analysis of the evidence regarding the determinants of responsiveness to multidisciplinary management of chronic pain, with pain intensity, pain-related interference, physical functioning and health-related quality of life as the main outcomes, with consideration to multiple secondary outcomes. Methods and analysis: To identify relevant studies, the Ovid MEDLINE, PubMed, Ovid PsycINFO, EBSCO CINAHL and Scopus databases will be searched for all studies exploring factors associated with responsiveness to multidisciplinary pain management from study inception to the present. Cohorts, case-control studies and randomised controlled trials will be included. Independent screening for eligible studies will be completed by a total of four researchers using defined criteria. Data extraction will be executed by two researchers. Study heterogeneity will be estimated using the I2 index. A meta-analysis will be performed using random effects models. Publication bias will be evaluated by means of funnel plots and Egger's test. Ethics and dissemination: The proposed study does not involve collection of primary data. Therefore, no ethical approval is required. The results of the systematic review and meta-analysis will be presented in a peer-reviewed journal and at conferences. Prospero registration number: CRD42021236424.

Key messages Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Abstract Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1–2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Purpose: An important outcome measure of patient care is the impact on the patient's health-related quality of life (HRQoL). Current ear-specific HRQoL instruments are designed for one diagnosis and emphasize different subdivisions such as symptoms, hearing problems, psychosocial impact, and the need for care. The optimal length of the recall period has not been studied. For these reasons, a new survey is needed that would cover most chronic ear diseases. Methods: A preliminary 24-item survey (EOS-24) was created. Untreated adult patients (included n = 186) with one of seven different chronic otologic conditions from all university hospitals in Finland were recruited to respond to EOS-24 and the 15D general HRQoL instrument. The recruiting otologists evaluated the severity of the disease and the disability caused by it. A control group was recruited. Based on the patients' responses in different diagnosis groups, the items were reduced according to pre-defined criteria. The resulting survey was validated using a thorough statistical analysis. Results: The relevance and necessity of the original 24 items were thoroughly investigated, leading to the exclusion of 8 items and the modification of 1. The remaining 16 items were well-balanced between subdivisions and were useful in all seven diagnosis groups, thus constituting the final instrument, EOS-16. The most suitable recall period was three months. Conclusions: EOS-16 has been created according to the HRQoL survey guidelines with a versatile nationwide patient population. The survey has been validated and can be used for a wide range of chronic ear diseases as a HRQoL instrument. (C) 2021 PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.

Context Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden. Objective To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders. Design, Setting and Participants A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women. Main Outcome Measures We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation. Results Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders. Conclusions This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.

OBJECTIVES To assess long-term survival of pulpotomized primary molars and factors related to the survival of the teeth. MATERIALS AND METHODS This retrospective longitudinal study was based on electronic dental health records of children who attended public health service. Eligible children were

Importance: Blue light-filtering (BLF) intraocular lenses (IOLs) have been widely used in clinical practice for more than 20 years and have been implanted in millions of patients with cataracts worldwide. However, little evidence on the association of BLF IOLs with injuries is available. Objective: To assess the association of BLF IOLs with all-cause and traffic accident-related injuries and quality of vision while driving after bilateral cataract surgery. Design, Setting, and Participants: This retrospective registry-based cohort study included patients who underwent bilateral cataract surgery between September 3, 2007, and December 14, 2018, and were followed until December 14, 2021. Surgery was performed at the Department of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland. The 4986 participants received non-BLF IOLs (n = 2609) or BLF IOLs (n = 2377) in both eyes. Patients undergoing bilateral surgery between 2015 to 2016 with non-BLF IOLs (n = 102) or BLF IOLs (n = 91) and currently driving a car were interviewed using a structured questionnaire for visual performance while driving. Exposures: Follow-up for a mean (SD) of 2166 (1110) days after second eye surgery. Main Outcomes and Measures: Kaplan-Meier and multivariable Cox proportional hazards regression analyses for the risk of all-cause and traffic accident-related injuries after surgery in the second eye obtained from the patient medical records were assessed. To improve follow-up precision, both death and the end of the follow-up were used as censoring events. Results: A total of 4986 patients were included in the analysis (1707 [34.2%] men and 3279 [65.8%] women; mean [SD] age, 73.2 [8.6] years at the first surgery and 74.3 [8.8] years at the second). Injury-free survival rates preceding the first eye surgery were comparable between the non-BLF and BLF IOL groups (hazard ratio adjusted for age and sex, 0.95 [95% CI, 0.81-1.13; P = .57]). In multivariable Cox proportional hazards regression analysis controlling for age and sex, the use of BLF IOLs showed no advantage in overall injuries compared with the use of non-BLF IOLs (hazard ratio, 0.99 [95% CI, 0.88-1.11]; P = .85) or in any injury subtype. Subjective visual performance parameters for driving were all comparable between the non-BLF and BLF IOL groups except for glare when driving in the dark (evening or night), which occurred among 9 of 80 patients with BLF IOLs compared with 0 of 83 non-BLF IOLs (P

PurposeSelf-fixed mesh is an alternative to suture mesh fixation in inguinal hernia repair. The aim of this study was to evaluate postoperative pain after open inguinal hernia surgery using self-fixed meshes.MethodsA randomized clinical trial comparing self-adhesive mesh (Adhesix™) and self-gripping mesh (Progrip™) was conducted from November 2018 through March 2021. Patients included were male, 18–85 years old, and suitable for day case surgery. The primary endpoint was the number of patients needing follow-up visits due to postoperative pain during the first 3 postoperative months. Secondary endpoints included the intensity of pain, the time of return to work and normal daily activities, quality of life measures and postoperative complications.Results270 patients were enrolled, 132 received Adhesix™ mesh (A group) and 138 Progrip™ mesh (P group), 231 (85.6%) completed 1- or 3-month follow-up. The number of patients needing follow-up for postoperative pain was significantly higher in the P group (19 vs. 4,p= 0.001). The P group had higher numeric rating scale of pain while coughing (P 0.50 vs. A 0.20,p= 0.024) and during exercise (P 1.02 vs. A 0.60,p= 0.057) at 3 months postoperatively. The time of return to normal activity was 16.6 days in the A group and 22.9 days in the P group, (p= 0.004). The postoperative day being fit for work was sooner for the A group (14.3 days vs 17.8 days,p= 0.009).ConclusionThis study demonstrated an advantage of self-adhesive mesh over self-gripping mesh with respect to acute postoperative pain and thus faster recovery after surgery.

Purpose: Unstable forearm shaft fractures in children are preferably treated surgically using elastic stable intramedullary nails. The radius is nailed retrograde from the distal metaphysis. There is a risk of surgery-related soft-tissue complications during the operation. Close evaluation of occult surgery-related soft-tissue lesions has not been possible previously, due to the titanium alloy hardware used in the process. The aim of the present study was to evaluate the potential findings in the surrounding soft tissues after intramedullary nailing of the radius, by using magnetic resonance imaging. Methods: The study population comprised 15 pediatric patients with forearm shaft fractures treated by polylactide-co-glycolide biodegradable intramedullary nails and postoperatively evaluated via magnetic resonance imaging. The main outcome was signal abnormality in any tendon at the entry point postoperatively. Secondarily, other changes in the soft tissues related to nailing were determined. Furthermore, the precise location of the entry point and the anatomic characteristics of the soft-tissue tunnel were described. Results: In total, 5 of 15 patients (33.3%) had transient signal pathology in a tendon postoperatively. Edema around the superficial radial nerve was detected in 13 of 15 patients (86.7%). The most common surgical approach was between the extensor pollicis brevis and the extensor carpi radialis longus tendons, which was applied in 10 of 15 patients (66.7%). Conclusions: One in three patients exhibited transient and occult surgery-related intraparenchymal signal pathology in a tendon, after forearm intramedullary nailing. Caution with surgical prepare of the soft-tissue cleavage is recommended. Level of evidence: IV

Introduction: The European Association of Urology committee in 2020 suggested a new classification, intraoperative adverse incident classification (EAUiaiC), to grade intraoperative adverse events (IAE) in urology. Aims: We applied and validated EAUiaiC, for kidney tumor surgery. Patients and methods: A retrospective multicenter study was conducted based on chart review. The study group comprised 749 radical nephrectomies (RN) and 531 partial nephrectomies (PN) performed in 12 hospitals in Finland during 2016–2017. All IAEs were centrally graded for EAUiaiC. The classification was adapted to kidney tumor surgery by the inclusion of global bleeding as a transfusion of ≥3 units of blood (Grade 2) or as ≥5 units (Grade 3), and also by the exclusion of preemptive conversions. Results: A total of 110 IAEs were recorded in 13.8% of patients undergoing RN, and 40 IAEs in 6.4% of patients with PN. Overall, bleeding injuries in major vessels, unspecified origin and parenchymal organs accounted for 29.3, 24.0, and 16.0% of all IEAs, respectively. Bowel (n = 10) and ureter (n = 3) injuries were rare. There was no intraoperative mortality. IAEs were associated with increased tumor size, tumor extent, age, comorbidity scores, surgical approach and indication, postoperative Clavien–Dindo (CD) complications and longer stay in hospital. 48% of conversions were reactive with more CD-complications after reactive than preemptive conversion (43 vs. 25%). Conclusions: The associations between IAEs and preoperative variables and postoperative outcome indicate good construct validity for EAUiaiC. Bleeding is the most important IAE in kidney tumor surgery and the inclusion of transfusions could provide increased objectivity. publishedVersion

Introduction: The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. Material and methods: This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Results: Treatment interruptions were associated with immunisation in patients using infliximab (p

publishedVersion

Background Treating hemorrhaging patients with prehospital blood product transfusions (PHBT) narrows transfusion delays and potentially benefits the patient. We describe our initial experiences of PHBT in a ground-based emergency medical service (EMS), where the transfusion protocol covers both traumatic and nontraumatic hemorrhaging patients. Methods A descriptive retrospective analysis was performed on the records of all the patients receiving red blood cells, freeze-dried plasma, or both during prehospital care from September 2016 to December 2020. The delays of PHBT and the effects on patients’ vital signs were analyzed and reported as the median and interquartile range (IQR) and analyzed using a Wilcoxon Signed rank test. Results 65 patients received prehospital blood product transfusions (PHBT), 29 (45%) were non-traumatic, and 36 (55%) traumatic. The main two reasons for PHBT were blunt trauma (n = 30, 46%) and gastrointestinal hemorrhage (n = 20, 31%). The median time from the emergency call to the start of PHBT was 54 min (IQR 38), and the transfusion began on a median of 61 min (IQR 42) before arrival at the hospital. The median systolic blood pressure improved from a median 76.5 mmHg (IQR 36.5) before transfusion to a median of 116.60 mmHg (IQR 26.5) (p Conclusions Starting PHBT in ground-based EMS is a feasible and viable option. The PHBT began significantly earlier than it would have started on arrival to the hospital, and it seems to be safe and improve patients’ physiology. Study approval D/2603/07.01.04.05/2019.

To evaluate the accuracy of heart rate variability (HRV) parameters obtained with a wrist-worn photoplethysmography (PPG) monitor in patients recovering from minimally invasive colon resection to investigate whether PPG has potential in postoperative patient monitoring. 31 patients were monitored for three days or until discharge or reoperation using a wrist-worn PPG monitor (PulseOn, Finland) with a Holter monitor (Faros 360, Bittium Biosignals, Finland) as a reference measurement device. Beat-to-beat intervals (BBI) and HRV information collected by PPG were compared with RR intervals (RRI) and HRV obtained from the ECG reference after removing artefacts and ectopic beats. The beat-to-beat mean error (ME) and mean absolute error (MAE) of good quality heartbeat intervals obtained by wrist PPG were estimated as − 1.34 ms and 10.4 ms respectively. A significant variation in the accuracy of the HRV parameters was found. In the time domain, SDNN (9.11%), TRI (11.4%) and TINN (11.1%) were estimated with low relative MAE, while RMSSD (34.3%), pNN50 (139%) and NN50 (188%) had higher errors. The logarithmic parameters in the frequency domain (VLF Log, LF Log and HF Log) exhibited the lowest relative error, and for non-linear parameters, SD2 (7.5%), DFA α1 (8.25%) and DFA α2 (4.71%) were calculated much more accurately than SD1 (34.3%). The wrist PPG shows some potential for use in a clinical setting. The accuracy of several HRV parameters analyzed post hoc was found sufficient to be used in further studies concerning postoperative recovery of patients undergoing laparoscopic colon resection, although there were large errors in many common HRV parameters such as RMSSD, pNN50 and NN50, rendering them unusable.ClinicalTrials.gov Identifier: NCT04996511, August 9, 2021, retrospectively registered

Publisher Copyright: © 2022 Heart Rhythm Society Background: Poor R-wave progression (PRWP) is a common clinical finding on the standard 12-lead electrocardiogram (ECG), but its prognostic significance is unclear. Objective: The purpose of this study was to examine the prognosis associated with PRWP in terms of sudden cardiac death (SCD), cardiac death, and all-cause mortality in general population subjects with and without coronary artery disease (CAD). Methods: Data and 12-lead ECGs were collected from a Finnish general population health examination survey conducted during 1978–1980 with follow-up until 2011. The study population consisted of 6854 subjects. Main end points were SCD, cardiac death, and all-cause mortality. PRWP was defined as R-wave amplitude ≤ 0.3 mV in lead V3 and R-wave amplitude in lead V2 ≤ R-wave amplitude in lead V3. Results: PRWP occurred in 213 subjects (3.1%). During the follow-up period of 24.3 ± 10.4 years, 3723 subjects (54.3%) died. PRWP was associated with older age, higher prevalence of heart failure and CAD, and β-blocker medication. In multivariate analyses, PRWP was associated with SCD (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.34–3.39), cardiac death (HR 1.75; 95% CI 1.35–2.15), and all-cause mortality (HR 1.29; 95% CI 1.08–1.54). In the subgroup with CAD, PRWP had a stronger association with cardiac mortality (HR 1.71; 95% CI 1.19–2.46) than in the subgroup without CAD, while the association with SCD was significant only in the subgroup with CAD (HR 2.62; 95% CI 1.38–4.98). Conclusion: PRWP was associated with adverse prognosis in the general population and with SCD in subjects with CAD.

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Funding Information: Funding for this research was provided by the Finnish Cultural Foundation ( 00181077 ), Finnish Pediatric Foundation, the Finnish Academy ( 313242 , 288220 , 321235 ), Aivosäätiö, Neuroscience Center at University of Helsinki , Helsinki University Hospital, Helsinki University Hospital Research Funds, HUS and University of Helsinki Researcher position, Sigrid Juselius Foundation and European Union's Horizon 2020 Research and Innovation Programme ( H2020-MCSA-ITN-813483 and H2020-MCSA-IF-656131 ). The study sponsors had no involvement in the study design, nor in the collection, analysis or interpretation of data. Additionally we acknowledge the computational resources provided by the Aalto Science-IT project. Publisher Copyright: © 2022 The Authors Neonatal seizure detection algorithms (SDA) are approaching the benchmark of human expert annotation. Measures of algorithm generalizability and non-inferiority as well as measures of clinical efficacy are needed to assess the full scope of neonatal SDA performance. We validated our neonatal SDA on an independent data set of 28 neonates. Generalizability was tested by comparing the performance of the original training set (cross-validation) to its performance on the validation set. Non-inferiority was tested by assessing inter-observer agreement between combinations of SDA and two human expert annotations. Clinical efficacy was tested by comparing how the SDA and human experts quantified seizure burden and identified clinically significant periods of seizure activity in the EEG. Algorithm performance was consistent between training and validation sets with no significant worsening in AUC (p > 0.05, n = 28). SDA output was inferior to the annotation of the human expert, however, re-training with an increased diversity of data resulted in non-inferior performance (Δκ = 0.077, 95% CI: −0.002-0.232, n = 18). The SDA assessment of seizure burden had an accuracy ranging from 89 to 93%, and 87% for identifying periods of clinical interest. The proposed SDA is approaching human equivalence and provides a clinically relevant interpretation of the EEG.

Purpose: The aim of this study was to investigate the eye lens and whole-body radiation doses to interventional radiology and cardiology staff in two Finnish hospitals. Methods: Simultaneous measurements of personal dose equivalent quantities H-p(3) and H-p(10) were conducted in clinical conditions during different radiological and cardiological interventional procedures. In order to study the feasibility to estimate eye lens dose with H-p(10) measured over the protective apron or thyroid shield, the ratio between measured H-p(3) and H-p(10) was investigated. Results and conclusions: Applying the obtained ratio on H-p(10) records from national dose register showed that only a small number of interventional radiologists and cardiologists in Finland may exceed eye lens equivalent dose levels of 20 mSv per year or 100 mSv in five consecutive years, but likely do not exceed 50 mSv in a single year. For the most Finnish interventionalists, the eye lens dose is well below 10 mSv per year. Nurses and radiographers assisting in interventions are, on average, less exposed than interventionalists, and will not exceed 20 mSv per year. Based on our results, H-p(10) measured over the protective apron or thyroid shield provides a conservative estimate of the eye lens dose for interventional radiologists and cardiologists, provided that appropriate protective glasses are used.

We have followed the clinical course of a 45-year-old man with a severe form of alpha-thalassemia X-linked intellectual disability syndrome for 40 years. The most challenging health issue is the combination of rumination, drooling, and vomiting. The patient achieved present adaptive and motor skills in his teenage years. He is able to move on the floor in a sitting position. He seems happy and has not shown any behavioral or psychiatric symptoms. New signs not described in the literature before are accelerated growth after puberty and atypical sleeping position with upper body resting on legs. Non

Objective Mechanochemical ablation (MOCA) is a nonthermal nontumescent method of treating saphenous vein insufficiency. The feasibility and short-term results of MOCA are good, but its long-term results are unknown. A randomized study was performed to compare MOCA with endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in the setting of unilateral great saphenous vein (GSV) insufficiency. Methods Venous outpatient clinic patients with varicose veins (CEAP class C2-C4) caused by GSV insufficiency were invited to participate in the study; in total, 132 patients met the inclusion criteria and were willing to participate. Patients were randomized to treatment (2:1:1 for MOCA, EVLA, and RFA, respectively). The state of the GSV with duplex Doppler ultrasound examination and the disease-specific quality of life were assessed at 1 month, 1 year, and 3 years after the treatment. Results Some patients declined to continue in the study after randomization; in total, 117 patients underwent treatment. At 3 years, the occlusion rate was significantly lower with MOCA than with either EVLA or RFA (82% vs 100%; P = .005). Quality of life was similar between the groups. In the MOCA group, GSVs that were larger than 7 mm in diameter preoperatively were more likely to recanalize during the follow-up period. The partial recanalizations of proximal GSV observed at 1 year progressed during the follow-up. Conclusions MOCA is a feasible treatment option in an outpatient setting, but its technical success rates are inferior compared with endovenous thermal ablation. Its use in large-caliber veins should be considered carefully.

Background Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0–1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0–1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Objective To investigate the long-term outcomes of patients with RA after myocardial infarction (MI). Methods All-comer, real-life MI patients with RA (n = 1614, mean age 74 years) were retrospectively compared with propensity score (1:5) matched MI patients without RA (n = 8070) in a multicentre, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients’ outcomes were also studied. The median follow-up was 7.3 years. Results RA was associated with an increased 14-year mortality risk after MI compared with patients without RA [80.4% vs 72.3%; hazard ratio (HR) 1.25; CI: 1.16, 1.35; P Conclusion RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population.

Objectives: The aim of this controlled follow-up study was to compare the need for revision surgery, long-term efficacy, and satisfaction in chronic rhinosinusitis patients who had undergone maxillary sinus operation with either balloon sinuplasty or traditional endoscopic sinus surgery (ESS) technique. Methods: Thirty-nine ESS patients and 36 balloon patients of our previously described cohort, who had been primarily operated in 2008 to 2010, were contacted by phone. Symptoms, satisfaction, and need for revision surgery were asked. In addition, we collected data of patients who had undergone primary maxillary sinus balloon sinuplasty in the Helsinki University Hospital during the years 2005 to 2019. As a control group, we collected data of patients who had undergone primary maxillary sinus ESS at 3 Finnish University Hospitals, and 1 Central Hospital in years 2005, 2008, and 2011. Results: Altogether, 77 balloon patients and 82 ESS patients were included. The mean follow-up time was 5.3 years in balloon group and 9.8 years in ESS group. Revision surgery was performed on 17 balloon patients and 6 ESS patients. In the survival analysis, the balloon sinuplasty associated significantly with a higher risk of revision surgery compared to ESS. According to the phone interviews, 82% of ESS patients and 75% of balloon patients were very satisfied with the primary operation. Conclusion: Although the patient groups expressed equal satisfaction and change in symptoms after the operations, the need for revision surgery was higher after balloon sinuplasty than after ESS. This should be emphasized when counselling patients regarding surgical options.

Background Knowledge of arrhythmias in patients with end-stage renal disease (ESRD) is mainly based on ambulatory electrocardiography (ECG) studies and observations during haemodialysis (HD). We used insertable cardiac monitors (ICMs) to define the prevalence of arrhythmias, focusing on bradyarrhythmias, in ESRD patients treated with several dialysis modes including home therapies. Moreover, we assessed whether these arrhythmias were detected in baseline or ambulatory ECG recordings. Methods Seventy-one patients with a subcutaneous ICM were followed for up to 3 years. Asystole (≥4.0 s) and bradycardia (heart rate Results At recruitment, 44 patients were treated in in-centre HD, 12 in home HD and 15 in peritoneal dialysis. During a median follow-up of 34.4 months, 18 (25.4%) patients had either an asystolic or a bradycardic episode. The median length of each patient’s longest asystole was 6.6 s and that of a bradycardia 13.5 s. Ventricular tachyarrhythmias were detected in 16 (23%) patients, and AF in 34 (51%) patients. In-centre HD and Type II diabetes were significantly more frequent among those with bradyarrhythmias, whereas no bradyarrhythmias were found in home HD. No bradyarrhythmias were evident in baseline or ambulatory ECG recordings. Conclusions Remarkably many patients with ESRD had bradycardia or asystolic episodes, but these arrhythmias were not detected by baseline or ambulatory ECG.

Background Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. Methods All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007–2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. Results In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007–2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0–146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. Conclusion The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.

Background Nonsteroidal anti‐inflammatory drug (NSAID) exacerbated respiratory disease (N‐ERD) is a triad with asthma, chronic rhinosinusitis with nasal polyps, and NSAID intolerance. Uncontrolled N‐ERD forms a major public health problem due to frequent and difficult‐to‐treat exacerbations and/or requiring putatively frequent endoscopic sinus surgeries (ESS). Our aim was to study factors affecting control of N‐ERD. Methods Retrospective patient record data (patient characteristics, prior sinus surgeries, follow‐up data in 2020) from 167 N‐ERD patients undergoing consultation at three tertiary hospitals from 2001 to 2017 was used. Outcome measurements reflecting uncontrolled N‐ERD were revision ESS, corticosteroids/biological therapy, and antibiotic courses during 2016–2020. Associations were analyzed by using nonparametric tests, Cox's proportional hazard, and binary logistic regression models. Results Nasal polyp eosinophilia increased the risk of revision surgery during the follow‐up (adjusted hazard ratio [aHR] 3.21, confidence interval 1.23–8.38). Also baseline oral corticosteroids (OCS; HR, 1.73, 1.04–2.89) and baseline surgery without total ethmoidectomy increased the risk of revision ESS (HR, 2.17, 1.07–4.42) in unadjusted models. In addition, both baseline OCS (adjusted odds ratio [aOR] 2.78, 1.23–6.26) and a history of ≥4 previous ESS (aOR, 2.15, 0.98–4.70) were associated with the use of OCS/biological therapy during the follow‐up, but not with high number of antibiotics. Conclusions Nasal polyp eosinophilia, baseline OCS, and a history of recurrent ESS predict uncontrolled N‐ERD. These factors might be clinically useful in risk‐estimation of uncontrolled disease and for organizing follow‐ups. Prospective cohort studies with larger sample size are needed to further study the factors affecting the upper airway control of N‐ERD., The patient record data of 167 patients with NSAID‐exacerbated respiratory disease was analyzed to study factors affecting the disease control. Nasal polyp eosinophilia increased the risk of revision surgery, and baseline oral corticosteroids and a history of four or more endoscopic sinus surgeries were associated with poor disease control during the follow‐up.

IntroductionOral infectious diseases are common chronic oral diseases characterized by a chronic inflammatory condition. We investigated chronic oral diseases as potential risk factors for systemic chronic diseases, diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis, and Crohn's disease, as well as severe psychotic and other severe mental disorders.MethodsThe cohort comprised 68,273 patients aged ≥ 29 years with at least one dental visit to the Helsinki City Health Services between 2001 and 2002. The cohort was linked to the data on death (Statistics Finland), cancer (Finnish Cancer Registry), and drug reimbursement (Finnish Social Insurance Institution) and followed until death or the end of 2013. The outcomes of interest were the incidences of chronic diseases measured starting with special refund medication, which means Social Insurance Institution partly or fully reimburses medication costs. Outcomes of interest were diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis and Crohn's disease, and severe mental disorders.ResultsThe mean follow-up time was 9.8 years. About 25% of the study population had periodontitis, 17% caries, over 70% apical periodontitis, and 9% ConclusionOur epidemiological 10 years follow-up study suggests that the association exists between chronic oral diseases and diabetes, warranting close collaboration among patient's healthcare professionals.

Objective The aim of this study was to compare reprojected bone SPECT/CT (RBS) against planar bone scintigraphy (BS) in the detection of bone metastases in breast and prostate cancer patients. Methods Twenty-six breast and 105 prostate cancer patients with high risk for bone metastases underwent Tc-99m-HMDP BS and whole-body SPECT/CT, 1.5-T whole-body diffusion-weighted MRI and F-18-NaF or F-18-PSMA-1007 PET/CT within two prospective clinical trials (NCT01339780 and NCT03537391). Consensus reading of all imaging modalities and follow-up data were used to define the reference standard diagnosis. The SPECT/CT data were reprojected into anterior and posterior views to produce RBS images. Both BS and RBS images were independently double read by two pairs of experienced nuclear medicine physicians. The findings were validated against the reference standard diagnosis and compared between BS and RBS on the patient, region and lesion levels. Results All metastatic patients detected by BS were also detected by RBS. In addition, three metastatic patients were missed by BS but detected by RBS. The average patient-level sensitivity of two readers for metastases was 75% for BS and 87% for RBS, and the corresponding specificity was 79% for BS and 39% for RBS. The average region-level sensitivity of two readers was 64% for BS and 69% for RBS, and the corresponding specificity was 96% for BS and 87% for RBS. Conclusion Whole-body bone SPECT/CT can be reprojected into more familiar anterior and posterior planar images with excellent sensitivity for bone metastases, making additional acquisition of planar BS unnecessary.

Concerns over future healthcare capacity along with continuing demands for sustainability call for novel solutions to improve citizens’ health and wellbeing through effective prevention and improved diagnosis and treatment. Part of the solution to tackle the challenge could be making the most of the exploitation of genomic data in personalized risk assessment, creating new opportunities for data-driven precision prevention and public health. Presently, the utilization of genomic data in the Finnish healthcare system is limited to a few medical specialty areas. To successfully extend the use of genomic information in everyday healthcare, evidence-based and feasible strategies are needed. The national actions that Finland is taking towards this goal are 1) providing scientific evidence for the utility of genomic information for healthcare purposes; 2) evaluating the potential health-economic impact of implementing precision healthcare in Finland; 3) developing a relevant legal framework and infrastructures for the utilization of genomic information; 4) building a national multidisciplinary expert network bringing together relevant professionals and initiatives to achieve consensus among the different stakeholders on specific issues vital for translating genomic data into precision healthcare; 5) building competence and genomic literacy skills among various target groups; and 6) public engagement (informing and educating the public). Taken together, these actions will enable building a roadmap towards the expedient application of genomic data in Finnish healthcare and promoting the health of our citizens.