Organisation of paediatric echocardiography laboratories and governance of echocardiography services and training in Europe: current status, disparities, and potential solutions. A survey from the Association for European Paediatric and Congenital Cardiology (AEPC) imaging working group.

BACKGROUND: There is limited data on the organisation of paediatric echocardiography laboratories in Europe. METHODS: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs. RESULTS: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%). CONCLUSION: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

Multicenter cohort study on duration of antiarrhythmic medication for supraventricular tachycardia in infants.

Antiarrhythmic medication (AM) is commonly used to prevent supraventricular tachycardia (SVT) recurrence in infants. Our aim was to determine whether a shorter duration of AM is sufficient to prevent atrioventricular reentrant tachycardia (AVRT) recurrence and evaluate risk factors for recurrence of SVT after discontinued AM.This multicenter cohort study included all infants diagnosed with SVT in the five university hospitals in Finland between 2005 and 2017. Those diagnosed between 2005 and 2012 received AM for 12 months (group 1), and those diagnosed between 2013 and 2017 received AM for 6 months (group 2). A total of 278 infants presented with AVRT (group 1, n = 181; group 2, n = 97), and the median AM duration was 12.0 months (interquartile range [IQR] 11.4-13.4) and 7.0 months (IQR 6.0-10.2), respectively. Propranolol was the most frequently used first-line AM (92% and 95%). Recurrence-free survival rates were over 88% until 12 months after AM prophylaxis in both groups, without any statistically significant difference between them. Independent risk factors for recurrence of SVT after discontinuation of AM were need of combination AM (HR 2.2, 95% CI 1.14-4.20), Wolff-Parkinson-White (WPW) syndrome (HR 2.4, 95% CI 1.25-4.59), and age over 1 month at admission (HR 2.2, 95% CI 1.12-4.48).    Conclusion: Shortening AM duration in infants from 12 to 6 months does not seem to lead to more frequent SVT recurrence. The risk factors for recurrence of SVT were WPW syndrome, need of combination AM, and age over 1 month.

Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial.

OBJECTIVE: To study the biologic effect of paracetamol, an inhibitor of prostaglandin synthase, on early closure of ductus arteriosus, and to evaluate possible adverse effects associated with the drug. STUDY DESIGN: In a controlled, double-blind, phase I-II trial, very low gestational age (<32 weeks) infants requiring intensive care were randomly assigned to intravenous paracetamol or placebo (0.45% NaCl). A loading dose of 20 mg/kg was given within 24 hours of birth, followed by 7.5 mg/kg every 6 hours for 4 days. Daily cardiac ultrasound examinations of ductal calibers were performed before the first dose, and until 1 day after the last dose. The main outcome was a decrease in the ductal caliber without side effects. RESULTS: Of 63 screened infants, 48 were randomized: 23 were assigned to paracetamol and 25 to placebo. Before the intervention, their ductal calibers were similar. During the intervention, the ductus closed faster in the paracetamol group (hazard ratio 0.49, 95% CI 0.25-0.97, P = .016). The mean (95% CI) postnatal ages for ductal closure were 177 hours (31.1-324) for the paracetamol-treated vs 338 hours (118-557) for controls (P = .045). Paracetamol serum levels were within the therapeutic range, and no adverse effects were evident. CONCLUSIONS: Prophylactic paracetamol induced early closure of the ductus arteriosus without detectable side effects. Further trials are required to determine whether intravenous paracetamol may safely prevent symptomatic patent ductus arteriosus. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01938261; European Clinical Trials Database: EudraCT 2013-008142-33.

Term neonates with infection and shock display high cortisol precursors despite low levels of normal cortisol.

AIM: Neonatal therapy-resistant septic shock is a common problem in middle and low-income countries. We investigated whether newborn infants with infection and therapy-resistant hypotension showed evidence of abnormal levels of cortisol or cortisol precursors. METHODS: A total of 60 term or near term neonates with evidence of infection were enrolled after informed consent. Of these, 30 had an infection and refractory shock and 30 had an infection without shock. There were no detectable differences between the groups in the length of gestation, birth weight or gender distribution. Serum was obtained during days four and 14 after birth. Cortisol and cortisol precursor concentrations were analysed using liquid chromatography-tandem mass spectrometry. RESULTS: The cortisol concentrations were low considering the expected responses to stress and they did not differ between the groups. The infants with infection and shock had higher serum dehydroepiandrosterone (DHEA) levels than those without shock (319.0 ± 110.3 µg/dL, versus 22.3 ± 18.3 µg/dL; p < 0.0001) and they also had higher 17-hydroxy-pregnenolone, pregnenolone and progesterone concentrations. There were no detectable differences in the levels of 17-hydroxy-progesterone, 11-deoxy-cortisol, cortisol or cortisone. CONCLUSION: Septic newborn infants with therapy-resistant hypotension had very high DHEA levels, suggesting that 3-beta-hydroxysteroid dehydrogenase activity limited the rate of cortisol synthesis.

Heart Rate and Heart Rate Variability in Healthy Preterm-Born Young Adults and Association with Vitamin D: A Wearable Device Assessment.

Prematurity has been associated with impaired parasympathetic cardiac regulation later in life. Changes in heart rate (HR) and heart rate variability (HRV) may indicate a risk for future cardiac dysfunction. The putative role of Vitamin D on cardiac autonomic function in individuals born preterm (PT) remains unknown. This study involves monitoring autonomic cardiac regulation and Vitamin D concentrations in 30 PT and 16 full-term (FT) young adults in a free-living context. The PT subjects were born between 1994 and 1997 at Oulu University Hospital. The inclusion criteria were (1) being born ≤ 32 gestation weeks or (2) being born < 34 gestation weeks with a birth weight under 1500 g. Participants wore an Oura ring sleep tracer, a smart ring device, for 2 weeks to monitor cardiac autonomic function. Parameters related to autonomic cardiac regulation, lowest nighttime resting HR, and the root mean square of successive differences (RMSSD) to describe HRV were collected. PT males exhibited a tendency toward lower RMSSD (71.8 ± 22.6) compared to FT males (95.63 ± 29.0; p = 0.10). Female participants had a similar mean RMSSD in the FT and PT groups at 72.04 ± 33.2 and 74.0 ± 35.0, respectively. Serum 25-hydroxyvitamin D concentration did not correlate with cardiac autonomic function parameters. When assessing the lowest resting nighttime HRs and HRVs in a long-term, real-world context, healthy female PT young adults performed similarly to their FT peers. In contrast, the present study's results suggest that male PT young adults exhibit impaired autonomic cardiac function, potentially putting them at risk for cardiovascular disease later in adulthood.

Preterm-Born Young Women Have Weaker Hand Grip Strength Compared to Their Full-Term-Born Peers.

Prematurity has been linked to lower muscular fitness and increased morbidity across the human lifespan. Hand grip strength is widely used as a measure of muscle strength. Previous studies have shown inconsistent results regarding the role of vitamin D in hand grip strength. Here, we investigated hand grip strength and the effects of a yearlong vitamin D supplementation in healthy preterm-born young adults. We recruited 38 young adults born preterm at either ≤32 weeks' gestation or <34 weeks' gestation and weighing <1500 g, as well as 39 gender- and age-matched controls, for this study. Anthropometric measurements, hand grip strengths, and vitamin D concentrations were recorded. These investigations were repeated after a yearlong vitamin D supplementation intervention. There was a significant difference in the age- and gender-specific hand grip strength ranks between the preterm- and full-term-born young adults: 57.9% and 30.7%, respectively, were below average (p = 0.009). In the preterm-born group, the females had significantly lower hand grip strengths compared to their full-term-born peers, with a mean difference of -3.46 kg (95% CI: -6.68 to -0.247; p = 0.035). In a linear regression analysis, the preterm-born female adult height was negatively associated with hand grip strength (R2 = 0.24, F (1.43) = 13.61, p < 0.001). The vitamin D concentrations were increased after the supplementation period, with no association with hand grip strength. According to our results, preterm-born young females are at risk for lower muscle strength, independent of their current vitamin D status.

[Prostatic pain]. / Eturauhasen kiputilat--miehen krooninen lantiokipu.

Prostatic pain usually refers to male chronic pelvic pain syndrome (CPPS), chronic abacterial prostatitis. It has a prevalence of 14% among Finnish men, and it is characterised by chronic pain in the pelvis, genital and inguinal area, lower abdomen and perineum, often accompanied by various urinary symptoms. The aetiology and pathophysiology of CPPS are poorly understood. Most likely, the aetiology is multifactorial and there is evidence of neuroinflammation in the development of the chronic pain associated with CPPS. Alpha-blockers, 5-alpha reductase inhibitors and possibly extracorporeal shock wave therapy (ESWT) are beneficial for treating CPPS. Antibiotics and antiinflammatory agents seem to be beneficial only in short-term treatment.

Benefits of Integrating an Explicit Self-Efficacy Intervention With Calculation Strategy Training for Low-Performing Elementary Students.

This study examined the malleability of math self-efficacy (SE) among children with poor calculation fluency via an intervention that targeted four sources of SE (mastery experiences, vicarious experiences, social persuasions, and emotional and physiological states). The effect of pure strategy training was contrasted with an intervention that integrated strategy training and explicit SE support. Moreover, the changes in SE source experiences and their relation with math SE, as well as the relation between math-SE profiles and calculation fluency development, were examined. In a quasi-experimental design, 60 Finnish children with calculation fluency problems in Grades 2 to 4 participated in strategy training (N = 38) or in an intervention that integrated SE support with strategy training (N = 32) for 12 weeks. The results showed that the explicit SE intervention integrated with strategy training enhanced math SE among children with poor calculation fluency and low SE (effect size, r = 0.61). Changes in mastery experiences and social persuasions were positively associated with changes in math SE among children who received the explicit SE intervention. An initially high math-SE profile and a profile indicating an increase from low to high math SE were related to growth in calculation fluency that approached the children's average age level during the interventions. In conclusion, an integrated approach that combined skill training and SE intervention was especially beneficial for children with poor calculation fluency and low math SE.

Inflammatory biomarkers in very preterm infants during early intravenous paracetamol administration.

BACKGROUND: Paracetamol promotes early closure of patent ductus arteriosus (PDA), and it may affect inflammation after preterm birth. OBJECTIVE: The aim of this study was to evaluate the association between paracetamol treatment and serum inflammatory biomarkers in very preterm infants with respiratory distress. STUDY DESIGN: The infants were randomly assigned to intravenous paracetamol or placebo during the first 4 days of life, and others received a lower dose of paracetamol unblinded. Serum samples were used for the analysis of 10 cytokines, C-reactive protein (CRP) and malondialdehyde (MDA). The impact of paracetamol on the biomarkers was evaluated, based on the levels during the early (<60 h) and the later (60-120 h) postnatal age. RESULTS: Altogether, 296 serum samples from 31 paracetamol and 25 placebo group infants were analysed. Paracetamol had no effect on cytokine levels during the first 60 h when most induced PDA contractions took place. Later paracetamol treatment was associated with lower serum levels of several cytokines, including interleukin (IL-) 10, interferon gamma-induced protein (IP-) 10, and monocyte chemoattractant protein-1. CRP levels were lower in the paracetamol group during the early treatment. Amongst the infants who had severe morbidities, MDA was higher (p = .045), regardless of paracetamol treatment. CONCLUSION: No significant differences in the cytokine levels were evident between the treatment and placebo groups. However, during early treatment, CRP levels were lower in the paracetamol group. To clarify whether this was due to a decrease in cardiopulmonary distress, or a distinct anti-inflammatory effect, requires further studies.

Subjective quality of life among youth with severe physical disabilities during the transition to adulthood in Finland.

Purpose: This study examined the subjective quality of life among youth with severe physical disabilities during the transition to adulthood.Method: A purposive sample of 74 youths (mean age 20.19) with severe physical disabilities completed World Health Organization Quality of Life - Brèf (WHOQOL-BREF) to measure the quality of life; the Severely Disabled Youths' Life Situation and Functioning of Service Systems in Finland to measure health issues. The data were analyzed using one-sample and independent-samples t-tests, and sequential multiple regression analysis.Results: Compared to youth without disabilities, the study youth scored lower values in physical, social, and environmental quality of life. No gender differences were found in the quality of life among youth with severe physical disabilities. Age, gender, and intensity of pain were associated with quality of life.Conclusions: This evidence-based knowledge can be used to provide guidance for policy issues such as providing health and social services for youth with severe physical disabilities in Finland.

Subgroup analysis of the early paracetamol trial to preterm infants found haemodynamic changes and improved oxygenation.

BACKGROUND: We previously reported in a randomised trial that early intravenous paracetamol accelerated contraction of ductus arteriosus in very preterm infants (<32 gestation weeks). AIMS: To monitor sequentially paracetamol effects on the blood pressure and brain tissue oxygenation in the infants participating the trial. METHODS: In a double-blind trial, intravenous paracetamol or placebo was infused to 48 very premature infants starting within 24 h of birth for four days. Besides the ductus arteriosus, we systematically measured blood pressure, peripheral (spO2) and regional cerebral oxygen saturation (rcSO2), and cerebral fractional tissue oxygen extraction (cFTOE) during the study period. RESULTS: Compared to the placebo, the paracetamol loading dose transiently decreased the arterial blood pressure. During treatment, the paracetamol-treated infants had higher spO2 (p = .042) and rcSO2 (p = .036) values than the placebo group infants. Additionally, the cFTOE values were lower in the paracetamol group during the study without statistical significance. All infants with closed ductus had higher tissue oxygenation and a lower cFTOE than infants with open ductus. CONCLUSIONS: Paracetamol caused modest haemodynamic effects and increased cerebral oxygenation. They were mostly due to early contraction of ductus. Additional direct drug-effects in brain are not ruled-out.

Biweekly Cabazitaxel Is a Safe Treatment Option for Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients After Docetaxel - A Final Analysis of the Prosty II Trial.

BACKGROUND/AIM: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. PATIENTS AND METHODS: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. RESULTS: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. CONCLUSION: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.

[Scrotal masses in adulthood]. / Kivespussin resistenssit aikuisilla.

GPs often encounter patients with scrotal masses. Most of these are easily diagnosed by means of palpation and transillumination. Scrotal ultrasound is the primary radiological investigation, and should be done in cases of uncertain clinical diagnosis or when a solid mass in the scrotum is suspected. Benign processes such as hydrocele, spermatocele and varicocele are the most common causes for scrotal abnormalities. Symptomatic cases are treated with surgery or percutaneous sclerotherapy/embolization. Malignant testicular tumours, although less frequently seen, need prompt and accurate diagnosis and treatment. Radical orchidectomy is the primary treatment, followed by radiochemotherpy in selected cases.

Fetal nuchal translucency in severe congenital heart defects: experiences in Northern Finland.

OBJECTIVE: To evaluate the performance of first-trimester measurement of fetal nuchal translucency (NT) in the detection of severe congenital heart defects (CHDs). METHODS: During the study period of 1 January 2008 - 31 December 2011, NT was measured in 31,144 women as a part of voluntary first-trimester screening program for Down's syndrome in Northern Finland. NT was measured by personnel trained on the job by the experienced staff. No certification or annual audits are required in Finland. However, the recommendation is that the examiner should perform 200 scans on average per year. Severe CHD was classified as a defect requiring surgery in the first year of life or a defect that led to the termination of the pregnancy. All severe CHDs diagnosed during the study period in Northern Finland could not be included in this study since all women did not participate in the first-trimester screening and some cases were missing important data. RESULTS: Fourteen (17.7%) out of 79 severe CHDs were found with NT cutoff of 3.5 mm. Amongst the 79 severe CHD cases, there were 17 chromosomal abnormalities. With NT cutoffs of 2.0 and 1.5 mm the detection rates would have increased to 25.3% (n = 20) and 46.8% (n = 37). Using a randomly selected control group of 762 women with normal pregnancy outcomes, false positive rates (FPRs) were calculated. For NT cutoffs of 1.5, 2.0 and 3.5 mm, the FPRs were, 18.5, 3.3 and 0.4%, respectively. CONCLUSIONS: A greater than 3.5 mm NT measurement in the first-trimester ultrasound is an indication to suspect a fetal heart defect but its sensitivity to detect severe CHD is poor. In our study, only 17.7% of severe CHDs would have been detected with an NT cutoff of 3.5 mm.

First trimester combined screening biochemistry in detection of congenital heart defects.

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fß-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Results: Both PAPP-A and fß-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fß-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fß-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fß-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.

Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial.

BACKGROUND: Docetaxel combined with androgen deprivation therapy (ADT) has improved patient survival for advanced prostate cancer (PCa). OBJECTIVE: This randomised trial aimed to evaluate whether six courses of docetaxel improved biochemical disease-free survival (BDFS) after radical radiotherapy (RT) for intermediate- or high-risk PCa patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 376 patients were randomised in this multinational phase III study, and received either six cycles of adjuvant docetaxel 75 mg/m2 every 3 wk without continuous prednisone (arm A, n = 188) or surveillance (arm B, n = 188) after RT (NTC006653848). Neoadjuvant/adjuvant ADT was mandatory for all the patients. The primary endpoint was rising prostate-specific antigen (PSA) ≥2 ng/ml above the nadir PSA value. Intermediate- or high-risk PCa was defined as T2 with a Gleason score (GS) of 4 + 3, PSA > 10; T2, GS 8-10, ≤ 70 ng/ml; or any T3. The patients were followed for 5 yr by assessing PSA levels every 3 mo for 2 yr and every 6 mo thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study power was 89% to detect a difference in BDFS between groups, and the sample size calculation accounted for the T2/T3 distribution, where a 12%/15% difference in BDFS was assumed for the T2/T3 patients. RESULTS AND LIMITATIONS: All six cycles were completed in 147 (78%) of the patients in arm A. The median age was 67 yr in both treatment groups, 75% had T3 disease, and 47% had GS 8-10. The median follow-up was 59 mo (range 1-111 mo). The primary endpoint was observed for 58 patients in arm A (docetaxel) and for 57 patients in arm B (surveillance). The Kaplan-Meier analysis showed no difference in the BDFS curves (p = 0.6) between the treatment groups. The 5-yr estimated biochemical progression rates were 31% for arm A and 28% for arm B. Febrile neutropenia occurred in 16% of the docetaxel patients. No deaths were related to the docetaxel treatment. There were 43 deaths during the trial, including 20 in arm A and 23 in arm B, of which nine and seven, respectively, were due to PCa. The hazard ratio from Cox multivariate analysis for PSA progression of arm A (docetaxel) versus arm B (surveillance) was 1.14 (95% confidence interval 0.79-1.64, p = 0.5). CONCLUSIONS: Adjuvant docetaxel without prednisone did not improve BDFS after radical RT with ADT for intermediate- or high-risk PCa. PATIENT SUMMARY: We compared six cycles of adjuvant docetaxel given after radical external radiotherapy plus androgen deprivation therapy to surveillance in intermediate- and high-risk localised prostate cancer. We found no overall benefit in this setting.

Intravesical Bacillus Calmette-Guérin Versus Combination of Epirubicin and Interferon-α2a in Reducing Recurrence of Non-Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study.

BACKGROUND: Patients with non-muscle-invasive bladder cancer (NMIBC) belonging to the intermediate-risk group should be treated with intravesical instillations to prevent recurrence and progression. OBJECTIVE: We compared the outcome of a monthly maintenance bacillus Calmette-Guérin (BCG) regimen with that of epirubicin (EPI) and interferon-α2a (IFN) in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Our prospective randomized multicenter study comprised 229 eligible patients with frequently recurrent TaT1 grade 1-2 or low-grade NMIBC enrolled between 1997 and 2008. INTERVENTIONS: The four-arm study involved a single perioperative instillation of EPI plus five weekly instillations of BCG or EPI/IFN, followed by 11 monthly instillations in the 1-yr BCG or EPI/IFN maintenance arms, further followed by four additional quarterly instillations in the two 2-yr maintenance arms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence, progression, disease-specific survival, and overall mortality were analyzed using the Kaplan-Meier and cumulative incidence analyses plus the Cox and proportional subdistribution hazards models. RESULTS AND LIMITATIONS: The median follow-up time was 7.5 and 7.4 yr in the BCG and EPI/IFN groups, respectively. The probability of recurrence was significantly lower in the BCG group than in the EPI/IFN group. The probability was 39% versus 72% at 7.4 yr, respectively (hazard ratio [HR]: 0.41; 95% confidence interval [CI], 0.28-0.60; p<0.001). There was no significant difference in the probability of progression or in overall survival. However, there was a significant difference in disease-specific mortality in favor of the BCG group (HR: 0.20; 95% CI, 0.04-0.91; p=0.04). CONCLUSIONS: The monthly maintenance BCG regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of EPI/IFN-α2a. PATIENT SUMMARY: A monthly bacillus Calmette-Guérin (BCG) regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of epirubicin and interferon-α2a. TRIAL REGISTRATION: Registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1997, before the current requirements concerning study registrations were implemented.