Development of Real-Time Surveillance for Serious Adverse Events in a Pragmatic Clinical Trial Using National Registers in Finland.

Purpose: We developed a hybrid safety surveillance approach for a large, pragmatic clinical trial of a high-dose quadrivalent influenza vaccine (QIV-HD), using both active and passive data collection methods. Here, we present the methods and results for the passive register-based surveillance of serious adverse events (SAEs), which replaced conventional SAE reporting during the trial.

Patients And Methods: The trial recruited over 33,000 older adults of whom 50% received the QIV-HD while the rest received a standard-dose vaccine (QIV-SD) as a control vaccine.

High-Dose Quadrivalent Influenza Vaccine for Prevention of Cardiovascular and Respiratory Hospitalizations in Older Adults.

Background: We assessed the relative vaccine effectiveness (rVE) of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing respiratory or cardiovascular hospitalizations in older adults.

Methods: FinFluHD was a phase 3b/4 modified double-blind, randomized pragmatic trial. Enrolment of 121,000 adults ≥65 years was planned over three influenza seasons (October to December 2019-2021).

Is vaccination against measles, mumps, and rubella associated with reduced rates of antibiotic treatments among children below the age of 2 years? Nationwide register-based study from Denmark, Finland, Norway, and Sweden.

Objectives: Previous studies have shown that vaccination against measles, mumps, and rubella (MMR) may have beneficial non-specific effects, reducing the risk of infections not targeted by the vaccine. We investigated if MMR vaccine given after the third dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP3), was associated with reduced rates of antibiotic treatments.

Methods: Register-based cohort study following children from the age of recommended MMR vaccination until age 2 years.

Cohort Profile: Childhood morbidity and potential non-specific effects of the childhood vaccination programmes in the Nordic countries (NONSEnse): register-based cohort of children born 1990-2017/2018.

Purpose: The aim of the NONSEnse project is to investigate the non-specific effects of vaccines and immunisation programmes on the overall health of children by using information from the extensive nationwide registers on health and sociodemographic factors in Denmark, Finland, Norway and Sweden.

Participants: The cohort covers 9 072 420 children aged 0-17 years, born 1990-2017/2018 and living in Denmark, Finland, Norway or Sweden. All countries use a unique identification number for its permanent residents, which makes it possible to link individual-level information from different registers.

A retrospective nationwide register-based study to evaluate the non-specific effects of first MMR vaccination among children in Finland.

Background: According to earlier studies, live vaccines like measles-mumps-rubella (MMR) vaccine could reduce also other infections than only the infections they are targeted against. This non-specific effect has been seen especially in studies in low-income countries and results from high-income countries have not been unambiguous. In 2011 Finland changed the recommended schedule for the first MMR vaccination from 18 months to 12 months of age.

Time and labour costs of preventive health care, including vaccinations, in Finnish child health clinics.

In Finland all children are entitled to regular health check-up visits at child health clinics (CHC). During the visits public health nurses and physicians follow-up the growth and development of the child, evaluate the welfare of the family, give health counselling and vaccinate the children. The aim of this study was to measure the time used by the nurses and physicians for different tasks during the visits and evaluate the costs of preventive health care procedures.

Lower incidence of hospital-treated infections in infants under 3 months of age vaccinated with BCG.

Background: Live vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design.

Trends in Antibiotic Use in Danish, Finnish, Norwegian and Swedish Children.

Objective: To compare the use of antibiotics in children in four Northern European countries.

Methods: We conducted a register-based study based on individual-level prescription data from national prescription registers. We identified all redeemed outpatient prescriptions for systemic antibiotics in children aged 0-14 years from July 2006 to June 2017 in Denmark, Finland, Norway, and Sweden.

Hospital Contacts for Infectious Diseases Among Children in Denmark, Finland, Norway, and Sweden, 2008-2017.

Purpose: Comparing rates of childhood infectious disease hospitalisations across countries may uncover areas for improvement in the prevention of severe childhood infections. We compared rates of childhood infectious disease hospital contacts across Denmark, Finland, Norway, and Sweden with the overall objective to elucidate potential differences in burden of disease and in organisational and registration practices.

Methods: Using national registries, we estimated incidence rates for infectious disease hospital contacts between 2008 and 2017 among children aged 0-14 years.

Prescription medication use after congenital heart surgery.

Background: Improvements in mortality after congenital heart surgery have necessitated a shift in focus to postoperative morbidity as an outcome measure. We examined late morbidity after congenital heart surgery based on prescription medication use.

Methods: Between 1953 and 2009, 10,635 patients underwent congenital heart surgery at <15 years of age in Finland.

Evaluation of the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine in a cluster-randomised trial.

Background: In the nation-wide double-blind cluster-randomised Finnish Invasive Pneumococcal disease trial (FinIP, ClinicalTrials.gov NCT00861380, NCT00839254), we assessed the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against five pneumococcal disease syndromes.

Methods: Children 6 weeks to 18 months received PHiD-CV10 in 48 clusters or hepatitis B/A-vaccine as control in 24 clusters according to infant 3+1/2+1 or catch-up schedules in years 2009-2011.

Revaccination with measles-mumps-rubella vaccine and hospitalization for infection in Denmark and Sweden - An interrupted time-series analysis.

Background: In a previous cohort study of 4-year-old Danish children, revaccination with the live measles-mumps-rubella vaccine (MMR) was associated with a 16% reduction in the rate of hospitalization lasting two days or longer for non-measles-mumps-rubella infections.

Aim: To examine if the introduction of revaccination with MMR at 4 years of age in Denmark (spring 2008) and at 7-9 years of age in Sweden (autumn 2009), at a time when there was virtually no measles, mumps or rubella cases, was associated with a reduction in the rate of hospitalization-for-infection lasting two days or longer at the population level.

Methods: We included 4-year-olds in Denmark and 7-9-year-olds in Sweden.

Long-term Social Outcomes After Congenital Heart Surgery.

Background: Patients are surviving decades after congenital heart surgery (CHS), raising the importance of postoperative quality of life as an outcome measure. We determined the long-term social outcomes after CHS performed during childhood.

Methods: Between 1953 and 2009, 10 635 patients underwent surgery for congenital heart defects at <15 years of age in Finland.

Chronic Disease Burden After Congenital Heart Surgery: A 47-Year Population-Based Study With 99% Follow-Up.

Background Postoperative morbidity is an increasingly important outcome measure of patients who have undergone congenital heart surgery (CHS). We examined late postoperative morbidity after CHS on the basis of patients' government-issued medical special reimbursement rights. Methods and Results Between 1953 and 2009, 10 635 patients underwent CHS at <15 years of age in Finland.

Vaccine-preventable disease incidence of pneumococcal conjugate vaccine in the Finnish invasive pneumococcal disease vaccine trial.

Estimation of the full disease burden caused by Streptococcus pneumoniae is challenging due to the difficulties in assigning the aetiology especially in lower and upper respiratory infections. We estimated the pneumococcal disease burden by using the vaccine-preventable disease incidence (VPDI) of PHiD-CV10 vaccine (GSK) in our clinical trial setting. Finnish Invasive Pneumococcal disease (FinIP) trial was a cluster-randomized, double-blind trial in children <19 months who received PHiD-CV10 in 52 clusters or hepatitis B/A vaccine as control in 26 clusters according to 3+1 or 2+1 schedules (infants < 7 months) or catch-up schedules (children 7-18 months).

Direct and Indirect Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine Against Carriage in a Cluster Randomized Trial.

Finnish invasive pneumococcal disease (FinIP) vaccine trial was designed to evaluate effectiveness of 10-valent pneumococcal conjugate vaccine (PHiD-CV10; GSK; Rixensart, Belgium). We conducted 2 satellite studies to evaluate ten-valent Pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) effectiveness against pneumococcal carriage in FinIP-vaccinated children (long-term direct and indirect effectiveness combined) and in their unvaccinated siblings (indirect effectiveness within the family). FinIP was a cluster randomized trial, where >47,000 children <19 months of age were recruited in 2009-2010.

Outcomes after the Mustard, Senning and arterial switch operation for treatment of transposition of the great arteries in Finland: a nationwide 4-decade perspective.

Objectives: We analysed nationwide early and late results after the Mustard, Senning and arterial switch operation.

Methods: We included all paediatric patients (<18 years) who underwent a Senning, a Mustard or an arterial switch operation for transposition of the great arteries from 1968 to 2009 in Finland. Data were obtained retrospectively from a paediatric cardiac surgical database and population data from the Finnish national registry.

Late Causes of Death After Pediatric Cardiac Surgery: A 60-Year Population-Based Study.

Background: Comprehensive information regarding causes of late post-operative death following pediatric congenital cardiac surgery is lacking.

Objectives: The study sought to analyze late causes of death after congenital cardiac surgery by era and defect severity.

Methods: We obtained data from a nationwide pediatric cardiac surgery database and Finnish population registry regarding patients who underwent cardiac surgery at <15 years of age at 1 of 5 universities or 1 district hospital in Finland from 1953 to 2009.

Effectiveness of the Ten-valent Pneumococcal Conjugate Vaccine Against Tympanostomy Tube Placements in a Cluster-randomized Trial.

Background: We evaluated the impact of the new pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10, GSK Vaccines) on tympanostomy tube placements (TTPs).

Methods: Finnish Invasive Pneumococcal disease vaccine trial was a nationwide phase III/IV cluster-randomized, double-blind trial. Children younger than 19 months received PHiD-CV10 in two thirds of clusters (N = 52) or hepatitis B or A vaccine as control in 26 clusters according to 3 + 1 or 2 + 1 schedules (infants younger than 7 months) or catch-up schedules.

Progress in late results among pediatric cardiac surgery patients: a population-based 6-decade study with 98% follow-up.

Background: Surgical treatment of congenital cardiac defects in Finland started >60 years ago. We analyzed the survival of all the pediatric cardiac surgery patients operated on before 2010.

Methods And Results: Data were obtained retrospectively from a pediatric cardiac surgery database.

Need of transannular patch in tetralogy of Fallot surgery carries a higher risk of reoperation but has no impact on late survival: results of Fallot repair in Finland.

Objectives: Our study is a population-based evaluation of the long-term results after surgical repair for tetralogy of Fallot (TOF). All patients operated on in the country since the first procedure were identified via the Finnish research database of paediatric cardiac surgery and the Finnish population register. The follow-up was 99% completed due to comprehensive coverage of the registers.

Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial.

Background: The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was designed to assess the effectiveness of a pneumococcal vaccine containing ten serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) against invasive pneumococcal disease.

Methods: In this cluster-randomised, double-blind trial, children aged younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants aged younger than 7 months at the first vaccination received either a 3+1 or a 2+1 vaccination schedule, children aged 7-11 months received a 2+1 schedule, and those 12-18 months of age received a two-dose schedule.

Morbidity after paediatric cardiac surgery assessed with usage of medicines: a population-based registry study.

Objective: To examine the overall morbidity of patients who underwent surgery for congenital cardiac defect during childhood.

Background: A congenital cardiac defect treated with surgery is seldom totally cured. The incidence of residua, sequelae, and comorbidity is quite high.