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). Participants received a single injection of QIV-HD or QIV-SD. The primary endpoint was first occurrence of an unscheduled acute respiratory or cardiovascular hospitalization (ICD-10 primary discharge J/I codes), from ≥14 days post-vaccination until May 31. The study was terminated after one season due to COVID-19; follow-up data for 2019-2020 are presented. RESULTS: 33,093 participants were vaccinated (QIV-HD, n = 16,549; QIV-SD, n = 16,544); 529 respiratory or cardiovascular hospitalizations (QIV-HD, n = 257; QIV-SD, n = 272) were recorded. The rVE of QIV-HD versus QIV-SD to prevent respiratory/cardiovascular hospitalizations was 5.5% (95% CI, -12.4 to 20.7). When prevention of respiratory and cardiovascular hospitalizations were considered separately, rVE estimates of QIV-HD versus QIV-SD were 5.4% (95% CI, -28.0 to 30.1) and 7.1% (95% CI, -15.0 to 25.0), respectively. Serious adverse reactions were <0.01% in both groups. CONCLUSIONS: Despite insufficient statistical power due to the impact of COVID-19, rVE point estimates demonstrated a trend toward a benefit of QIV-HD over QIV-SD. QIV-HD was associated with lower respiratory or cardiovascular hospitalization rates than QIV-SD, with a comparable safety profile. Adequately powered studies conducted over multiple influenza seasons are needed to determine statistical significance of QIV-HD compared with QIV-SD against preventing respiratory and cardiovascular hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04137887.

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. We included 831,287 children born in Denmark, Finland, Norway, and Sweden who had received DTaP3 but not yet MMR vaccine. Cox proportional hazards regression with age as the underlying timescale and vaccination status as a time-varying exposure was used to estimate covariate-adjusted Hazard Ratios (aHRs) and inverse probability of treatment weighted (IPTW) HRs of antibiotic treatments. Summary estimates were calculated using random-effects meta-analysis. RESULTS: Compared with only having received DTaP3, receipt of MMR vaccine after DTaP3 was associated with reduced rates of antibiotic treatments in all countries: the aHR was 0.92 (0.91-0.93) in Denmark, 0.92 (0.90-0.94) in Finland, 0.84 (0.82-0.85) in Norway, and 0.87 (0.85-0.90) in Sweden, yielding a summary estimate of 0.89 (0.85-0.93). A stronger beneficial association was seen in a negative control exposure analysis comparing children vaccinated with DTaP3 vs two doses of DTaP. CONCLUSIONS: Across the Nordic countries, receipt of MMR vaccine after DTaP3 was associated with an 11% lower rate of antibiotic treatments. The negative control analysis suggests that the findings are affected by residual confounding. Findings suggest that potential non-specific effects of MMR vaccine are of limited clinical and public health importance for the milder infections treated out-of-hospital in the Nordic setting.

Reductive Thermal Atomic Layer Deposition Process for Gold.

In this work, we developed an atomic layer deposition (ALD) process for gold metal thin films from chloro(triethylphosphine)gold(I) [AuCl(PEt3)] and 1,4-bis(trimethylgermyl)-1,4-dihydropyrazine [(Me3Ge)2DHP]. High purity gold films were deposited on different substrate materials at 180 °C for the first time with thermal reductive ALD. The growth rate is 1.7 Å/cycle after the film reaches full coverage. The films have a very low resistivity close to the bulk value, and a minimal amount of impurities could be detected. The reaction mechanism of the process is studied in situ with a quartz crystal microbalance and a quadrupole mass spectrometer.

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. FINDINGS TO DATE: Data collection and harmonisation according to a common data model was completed in March 2022. As a prerequisite for comparing the effects of childhood vaccinations on the overall health of children across the Nordic countries, we have identified indicators measuring similar levels of infectious disease morbidity across these settings. So far, studies pertaining to non-specific effects of vaccines are limited to investigations that could be undertaken using aggregated data sets that were available before the NONSEnse cohort with individual-level information was completely set up. FUTURE PLANS: We are currently performing several studies of the effects on non-targeted infectious disease morbidity across the countries following vaccination against measles, mumps, rubella, diphtheria, tetanus, pertussis, human papillomavirus, rotavirus and influenza. Multiple studies are planned within the next years using different study designs to facilitate triangulation of results and enhance causal inference. REGISTRATION: No clinical trials will be conducted within the NONSEnse project.

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. This change created a natural experiment for evaluating the potential non-specific effects. METHODS: This is a retrospective nationwide register-based cohort study of Finnish children born between 2008 and 2012. Children were divided into two cohorts by age at MMR vaccination: children administered early MMR vaccination (11 through 12 months of age) and late MMR vaccination (18 through 19 months of age). Morbidity was evaluated during the main follow-up period (from 13 to 17 months of age) and before any MMR vaccination (3 to 10 months) and after all were vaccinated with MMR (20 to 35 months) as control follow-up periods. We analyzed all infections and did additional analyzes for urinary tract infections (UTI) and bronchitis. Injuries were analyzed as a control outcome. RESULTS: Early MMR vaccinated children (N = 79949) had fewer infections compared to late MMR vaccinated (N = 60965) during the main follow-up period. The incidence rate ratio (IRR) was 0.84 (95 % confidence interval (95 % CI) 0.81-0.87). However, similar differences were also observed during the control follow-up periods. MMR vaccinated children had less UTI in the main follow-up period (IRR 0.73, 0.60-0.89) but not in the control follow-up periods. When stratified by sex, the difference was observed among girls but not in boys. CONCLUSION: No clear evidence was found for non-specific effects in infectious diseases morbidity. However, there could be a nonspecific effect on UTI. Confirmation is needed from other studies, especially from high-income countries.

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. Special emphasis was on time and costs used for administering vaccinations. The study was conducted in four CHCs. Trained observers measured the time used for predefined tasks with a stopwatch application operating on a tablet computer. Labour costs of visits and vaccinations were evaluated by using the gross average salary costs of health care personnel. Time used for vaccine logistics and other administrative tasks was obtained by interviewing the nurses in charge of the vaccine logistics at each CHC. Altogether 325 CHC visits of children <13 months were followed. Public health nurse used for a visit in average 49 (range 12-101) minutes, and the corresponding labour costs were 17 (4-35) Euros. Vaccines were administered at 183 visits. Children got on average 2.4 (1-4) vaccine doses per visit. The observed time used for vaccinations was 10.2 (1.6-25) minutes and the costs 3.58 (0.57-8.62) Euros per visit. The observed time included guidance, preparation, administration, and documentation of vaccinations. Adding one dose into a visit increased the time spent on vaccination on average 2.8 minutes (0.99 Euros). The mean non-observed time used for vaccine logistics outside the visits was 3.4 minutes and cost 1.19 Euros per dose. Administering of the vaccines of the Finnish vaccination programme is relatively simple and inexpensive because Finnish children have regular scheduled visits to CHCs.

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. METHODS: We compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome. RESULTS: The incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86-0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4-12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01-1.06). CONCLUSIONS: BCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies.

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. We computed incidence rates and incidence rate ratios of treatment episodes with any antibiotic and different antibiotic classes. Results: In 2016/2017, the rates of antibiotic treatment episodes per 1000 person-years in children aged 0-14 years were 429, 284, 219, and 184 in Finland, Denmark, Sweden, and Norway, respectively, and the rate ratios (95% confidence intervals) compared with Norway were 2.33 (2.33-2.34), 1.54 (1.54-1.55), and 1.19 (1.19-1.20) in Finland, Denmark, and Sweden, respectively. The rate of antibiotic treatment episodes declined over time in all countries. The relative reductions in 2016/2017 compared with 2006/2007 were 36% in Finland, 40% in Denmark, 49% in Sweden, and 29% in Norway. Treatment episodes peaked between age 12 and 18 months. The most used antibiotic class was beta-lactamase sensitive penicillins among all children in Norway and Sweden and among children above two years in Denmark, while penicillins with extended spectrum were most used in Finland and among the youngest children in Denmark. Conclusion: In all countries, the use of antibiotics in children declined between 2006 and 2017. However, there were still considerable differences in antibiotic use between otherwise quite similar Nordic countries, with a more than 2-fold difference between the countries with the lowest and highest rates. Interventions to reduce the number of antibiotic treatment episodes in the countries with higher rates could reduce the total antibiotic use.

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. We investigated the rates for different types of contacts (inpatient or outpatient including emergency room), duration of admission, and by sex. Results: During the study period, the rate of all hospital contacts per 1000 person-years was highest in Sweden (125.2) followed by Finland (87.1), Denmark (79.0), and Norway (62.1). The rates aligned for inpatient contacts with overnight stays; 19.3 (Denmark), 16.6 (Finland), 16.3 (Norway), and 13.0 (Sweden); these were highest in early infancy in all countries. A peak around 1 year of age was seen in all countries except in Sweden. The rates were higher among boys compared with girls in early childhood, after 13 years of age the rates among girls surpassed the boys. Conclusion: Large cross-country differences were observed for outpatient and short-term hospital contacts for infectious diseases, affected by differences in organisational structures and coding practices across and within countries over time. Inpatient contacts requiring overnight stays reflected more comparable levels of severe infections across countries. Childhood infectious disease morbidity was greatest among boys and before 2 years of age.

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. Outcome data were collected from national health registers and included laboratory-confirmed and clinically suspected invasive pneumococcal disease (IPD), hospital-diagnosed pneumonia, tympanostomy tube placements (TTP) and outpatient antimicrobial prescriptions. Incidence rates in the unvaccinated population in years 2010-2015 were compared between PHiD-CV10 and control clusters in age groups <5 and ≥5 years (5-7 years for TTP and outpatient antimicrobial prescriptions), and in infants <3 months. PHiD-CV10 was introduced into the Finnish National Vaccination Programme (PCV-NVP) for 3-month-old infants without catch-up in 9/2010. RESULTS: From 2/2009 to 10/2010, 45398 children were enrolled. Vaccination coverage varied from 29 to 61% in PHiD-CV10 clusters. We detected no clear differences in the incidence rates between the unvaccinated cohorts of the treatment arms, except in single years. For example, the rates of vaccine-type IPD, non-laboratory-confirmed IPD and empyema were lower in PHiD-CV10 clusters compared to control clusters in 2012, 2015 and 2011, respectively, in the age-group ≥5 years. CONCLUSIONS: This is the first report from a clinical trial evaluating the indirect impact of a PCV against clinical outcomes in an unvaccinated population. We did not observe consistent indirect effects in the PHiD-CV10 clusters compared to the control clusters. We consider that the sub-optimal trial vaccination coverage did not allow the development of detectable indirect effects and that the supervening PCV-NVP significantly diminished the differences in PHiD-CV10 vaccination coverage between the treatment arms.

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. We obtained 4 age-, sex-, birth-time, and hospital district-matched controls per patient. The Social Insurance Institution of Finland provided data on all prescription medications obtained between 1999 and 2012 by patients and controls. Patients were assigned one diagnosis based on a hierarchical list of cardiac defects and dichotomised into simple and severe groups. Medications were divided into short- and long-term based on indication. Follow-up started at the first operation and ended at death, emigration, or 31 December, 2012. RESULTS: Totally, 8623 patients met inclusion criteria. Follow-up was 99.9%. In total, 8126 (94%) patients required prescription medications. Systemic anti-bacterials were the most common short-term prescriptions among patients (93%) and controls (88%). Patients required betablockers (simple hazard ratio 1.9, 95% confidence interval 1.7-2.1; severe hazard ratio 6.5, 95% confidence interval 5.3-8.1) and diuretics (simple hazard ratio 3.2, 95% CI 2.8-3.7; severe hazard ratio 38.8, 95% CI 27.5-54.7) more often than the general population. Both simple and severe defects required medication for cardiovascular, gastrointestinal, psychiatric, neurologic, metabolic, autoimmune, and infectious diseases more often than the general population. CONCLUSIONS: The significant risk for postoperative cardiovascular and non-cardiovascular disease warrants close long-term follow-up after congenital heart surgery for all defects.

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. We obtained the number of hospitalization-for-infection lasting two days or longer from nationwide hospital registers. Person-years at risk were approximated from population statistics for each season and year. We performed an interrupted time series analysis using Poisson regression to estimate the change in hospitalization incidence rates following the introduction of MMR revaccination, adjusting for seasonality. We also performed analyses with control series (3-year-olds in Denmark and 4-year-olds in Sweden). RESULTS: Comparing the incidence of hospitalization-for-infection lasting two days or longer after the introduction of MMR revaccination with the expected level without an introduction of MMR revaccination resulted in an incidence rate ratio of 1.07 (95% confidence interval [CI] = 0.89-1.28) for 4-year-olds in Denmark and 0.89 (95% CI = 0.77-1.02) for 7-9-year-olds in Sweden in analyses without controls. Analyses with controls gave similar results. CONCLUSION: This population-level study of the introduction of MMR revaccination in Denmark and Sweden had inadequate power to confirm or refute the findings from an individual-level Danish study of an association between MMR revaccination and a lower incidence rate of hospitalization-for-infection lasting two days or longer.

Synchronizing gas injections and time-resolved data acquisition for perturbation-enhanced APXPS experiments.

An experimental approach is described in which well-defined perturbations of the gas feed into an Ambient Pressure X-ray Photoelectron Spectroscopy (APXPS) cell are fully synchronized with the time-resolved x-ray photoelectron spectroscopy data acquisition. These experiments unlock new possibilities for investigating the properties of materials and chemical reactions mediated by their surfaces, such as those in heterogeneous catalysis, surface science, and coating/deposition applications. Implementation of this approach, which is termed perturbation-enhanced APXPS, at the SPECIES beamline of MAX IV Laboratory is discussed along with several experimental examples including individual pulses of N2 gas over a Au foil, a multi-pulse titration of oxygen vacancies in a pre-reduced TiO2 single crystal with O2 gas, and a sequence of alternating precursor pulses for atomic layer deposition of TiO2 on a silicon wafer substrate.

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. We obtained 4 control subjects per patient, matched by age, sex, birth time, and hospital district, from Statistics Finland, which also provided data on the highest education level, employment status, marital status, and progeny for both patients and control subjects. We included patients who were alive and ≥18 years of age at the end of the follow-up on December 31, 2017. RESULTS: A total of 7308 patients met inclusion criteria. Patients had on average similar high school or vocational education rates as the general population but lower undergraduate or higher education rates (female patients: risk ratio [RR] 0.8 [95% confidence interval (CI) 0.8-0.9]; male patients: RR 0.8 [95% CI 0.7-0.9]). Patients were less likely to be married or have progeny compared with the general population. The rate of employment was significantly lower (female patients: RR 0.8 [95% CI 0.8-0.9]; male patients: RR 0.8 [95% CI 0.8-0.9]) and the rate of retirement (female patients: RR 2.1 [95% CI 2.0-2.3]; male patients RR 3.1 [95% CI 2.9-3.5]) significantly higher among patients. CONCLUSIONS: Patients who undergo CHS at childhood age are, on average, more disadvantaged from both an educational and professional standpoint compared with the general population, regardless of the severity of the defect.

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. We excluded early deaths and mental disabilities. Noncyanotic and cyanotic defects were divided into simple and severe groups, respectively. We obtained 4 age-, sex-, birth time-, and hospital district-matched control subjects per patient. The Social Insurance Institution of Finland provided data on all medical special reimbursement rights granted between 1966 and 2012. Follow-up started at the first operation and ended at death, date of emigration, or December 31, 2012. A total of 8623 patients met inclusion criteria. Follow-up was 99.9%. A total of 3750 patients (43%) required special reimbursements rights for a chronic disease. Cardiovascular disease was the most common late morbidity among patients (28%), followed by obstructive pulmonary disease (9%), neurologic disease (3%), and psychiatric disease (2%). Heart failure (simple hazard ratio [HR], 56.3 [95% CI, 35.4-89.7]; severe HR, 918.0 [95% CI, 228.9-3681.7]) and arrhythmia (simple HR, 11.0 [95% CI, 7.1-17.0]; severe HR, 248.0 [95% CI, 61.3-1002.7]) were the most common cardiovascular morbidities. Hypertension was common among patients with coarctation of the aorta (13%; incidence risk ratio [RR], 8.9; 95% CI, 7.5-10.7). Psychiatric disease was more common among simple defects, particularly ventricular septal defects. Conclusions Chronic cardiac and noncardiac sequelae are common after CHS regardless of the severity of the defect, underscoring the importance of long-term follow-up of all patients after CHS.

Atomic Layer Deposition of Photoconductive Cu2O Thin Films.

Herein, we report an atomic layer deposition (ALD) process for Cu2O thin films using copper(II) acetate [Cu(OAc)2] and water vapor as precursors. This precursor combination enables the deposition of phase-pure, polycrystalline, and impurity-free Cu2O thin films at temperatures of 180-220 °C. The deposition of Cu(I) oxide films from a Cu(II) precursor without the use of a reducing agent is explained by the thermally induced reduction of Cu(OAc)2 to the volatile copper(I) acetate, CuOAc. In addition to the optimization of ALD process parameters and characterization of film properties, we studied the Cu2O films in the fabrication of photoconductor devices. Our proof-of-concept devices show that approximately 20 nm thick Cu2O films can be used for photodetection in the visible wavelength range and that the thin film photoconductors exhibit improved device characteristics in comparison to bulk Cu2O crystals.

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). Outcome data were collected using Finnish routine health-care registers, consisting of THL National Infectious Diseases Register, THL Care register, and Benefits Register of Social Insurance Institution of Finland. Blinded follow-up lasted from the date of first vaccination (trial enrolment Feb-2009 through Aug-2010) to January 31, 2012 for Invasive Pneumococcal Disease (IPD) and to end of December 2011 for four other outcomes: non-laboratory-confirmed IPD, hospital-diagnosed pneumonia, tympanostomy tube placements, and antimicrobial purchases. VPDI was estimated as difference in disease incidences between PHiD-CV10 clusters and control clusters. Altogether >47,000 children were enrolled. In 30,527 vaccinated infants <7 months at first dose, the VPDIs per 100,000 person-years were 75 for laboratory-confirmed IPD, 210 for non-laboratory-confirmed IPD, 271 for hospital-diagnosed pneumonia, 1143 for any tympanostomy tube placements and 11,381 for antimicrobial outpatient prescription, mainly due to otitis media. In a European developed-country setting, over 95% of the disease episode reductions in vaccinated children were seen in mild upper respiratory infections. The VPDIs of severe diseases are underestimated, because the majority of invasive disease goes undetected with routine blood-culture-based definitions. Evaluation of the absolute reduction achievable with vaccinations using sensitive case detection is essential for understanding the full disease burden, for valid cost-effectiveness analyses and for appropriate vaccination policy decisions. Registration: ClinicalTrials.gov, NCT00861380 and NCT00839254.

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. Children received PHiD-CV10 in 2/3, and control vaccine in 1/3 of clusters according to age-specific infant and catch-up schedules. We obtained nasopharyngeal samples from subgroups of FinIP-vaccinated children at 3-5 years of age in 2013 and their unvaccinated older siblings in 2011 and 2013, and compared carriage in PHiD-CV10 clusters to control clusters in parallel. National Vaccination Programme with PHiD-CV10 for all 3-month-old children started in 2010 resulting in 92% vaccination coverage. To investigate indirect effects, over 2200 nasopharyngeal swabs were obtained during each round from unvaccinated older siblings. In 2011, we observed a 29% (95% confidence interval: 6-47) reduction in vaccine-type carriage in siblings of PHiD-CV10 participants vaccinated according to infant schedules. Vaccine-type carriage prevalences were low with no differences observed in 2013, 3 years after PHiD-CV10 introduction. For estimation of combined direct and indirect effectiveness, 1550 swabs from FinIP-vaccinated children were obtained in 2013. We observed a reduction of 54% (95% confidence interval: 34-68) in vaccine-type carriage in PHiD-CV10-vaccinated children. This study was the first randomized trial to show the indirect effect of extended valency pneumococcal conjugate vaccination on carriage. Also, long-term effectiveness against vaccine-type carriage was demonstrated in vaccinated children.

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. RESULTS: Early mortality (<30 days) was 11% after Mustard and 5% after Senning operation, while the rate decreased from 19% during 1976-1999 to 2% during 2000-2009 for arterial switch patients (P < 0.0001). The 43-year survival rate was 75% [95% confidence interval (CI) 70-80%] for all patients and 97% (95% CI 94-98%) for the general population. Late survival improved during later eras, with a 10-year survival of 96% (95% CI 92-99%) for those operated during 2000-2009 vs 81% (95% CI 74-88%) in the 1990s (hazard ratio 3.7, 95% CI 1.4-9.6, P = 0.008). Twenty-year survival rates (without 30-day mortality) after arterial switch operation, Mustard and Senning were 97% (95% CI 95-100%), 78% (95% CI 68-87%) and 84% (95% CI 77-90%), respectively. No late sudden deaths or fatal heart failures occurred after the arterial switch operation. CONCLUSIONS: Outcome after surgery for transposition of the great arteries has improved, mostly due to the arterial switch operation but also due to improvements in perioperative care and follow-up. Operative deaths after the arterial switch operation have diminished, and no late sudden deaths or fatal heart failures occurred during the first 25-30 years after the procedure.

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. Noncyanotic and cyanotic defects were classified as simple and severe, respectively. Causes of death were determined using International Classification of Diseases diagnostic codes. Deaths among the study population were compared to a matched control population. RESULTS: Overall, 10,964 patients underwent 14,079 operations, with 98% follow-up. Early mortality (<30 days) was 5.6% (n = 613). Late mortality was 10.4% (n = 1,129). Congenital heart defect (CHD)-related death rates correlated with defect severity. Heart failure was the most common mode of CHD-related death, but decreased after surgeries performed between 1990 and 2009. Sudden death after surgery for atrial septal defect, ventricular septal defect, tetralogy of Fallot, and transposition of the great arteries decreased to zero following operations from 1990 to 2009. Deaths from neoplasms, respiratory, neurological, and infectious disease were significantly more common among study patients than controls. Pneumonia caused the majority of non-CHD-related deaths among the study population. CONCLUSIONS: CHD-related deaths have decreased markedly but remain a challenge after surgery for severe cardiac defects. Premature deaths are generally more common among patients than the control population, warranting long-term follow-up after congenital cardiac surgery.