Detecting epinephrine auto-injector shortages in Finland 2016-2022: Log-data analysis of online information seeking.

INTRODUCTION: Medicine shortages prevail as a worldwide problem causing life-threatening situations for adults and children. Epinephrine auto-injectors are used for serious allergic reactions called anaphylaxis, and alternative auto-injectors are not always available in pharmacies. Healthcare professionals in Finland use the dedicated internet source, Physician's Database (PD), when seeking medical information in practice, while Health Library (HL) provides health information for citizens (S1 Data). The objectives were to assess whether (1) professionals' searches for epinephrine auto-injectors and (2) citizens' anaphylaxis article openings relate to epinephrine shortages in Finland. METHODS: Monthly log data on epinephrine auto-injectors (EpiPen®, Jext®, Emerade®) from PD and on openings of anaphylaxis articles from HL were collected during 2016-2022. Professionals' searches of seven auto-injectors and citizens' openings of four anaphylaxis articles were compared to information on epinephrine shortages reported by Finnish Medicines Agency. Professionals' auto-injector prescriptions provided by Social Insurance Institution were also assessed. RESULTS: Total searches in EpiPen® (N = 111,740), Jext® (N = 25,631), and Emerade® (N = 18,329) could be analyzed during 2016-2022. EpiPen® only could visually show seasonal patterns during summertime, peaking vigorously in the summer of 2018 when the major EpiPen® shortage appeared worldwide. Anaphylaxis articles equaled 2,030,855 openings altogether. Openings of one anaphylaxis article ("Bites and Stings") peaked during summertime, while another article ("Anaphylactic Reaction") peaked only once (three-fold increase) at the end of 2020 when COVID-19 vaccinations started, and auto-injector prescriptions were lowest. Fifty EpiPen®, one Jext®, and twelve Emerade® shortages were reported. Almost a two-fold increase in peaks of auto-injector prescriptions was found during summertime. CONCLUSION: This study shows that (1) epinephrine shortages related to professionals' searching for auto-injectors, and (2) citizens' information seeking on anaphylaxis related to summertime and shortages with lesser prescriptions. Therefore, the dedicated internet databases aimed at professionals and citizens could be used as additional information sources to detect anaphylactic reactions and auto-injector shortages.

Albumin and Cardioprotection in On-Pump Cardiac Surgery-A Post Hoc Analysis of a Randomized Trial.

OBJECTIVES: To study the quantitative potency of plasma albumin on cardioprotection in terms of creatinine kinase-myocardial band mass (CK-MBm) in on-pump cardiac surgery. DESIGN: Post hoc analysis of a double-blinded randomized clinical trial. SETTING: Single-center study in the Helsinki University Hospital. PARTICIPANTS: A total of 1,386 adult on-pump cardiac surgical patients. INTERVENTION: Administration of 4% albumin (n = 693) or Ringers acetate (n = 693) for cardiopulmonary bypass priming and volume replacement intraoperatively and postoperatively during the first 24 hours. MEASUREMENTS AND MAIN RESULTS: Albumin concentration was measured preoperatively and intraoperatively (after protamine administration), and CK-MBm on the first postoperative morning. Multivariate linear regression analyses were measured in the whole cohort and the Ringer group. Plasma albumin concentration did not differ between the groups preoperatively (Ringer v albumin: 38.3 ± 5.0 g/L v 38.6 ± 4.5 g/L; p = 0.171) but differed intraoperatively (29.5 ± 5.2 g/L v 41.5 ± 6.0 g/L; p < 0.001). Creatinine kinase-myocardial band mass was higher in the Ringer (32.0 ± 34.8 µg/L) than in the albumin group (24.3 ± 33.0 µg/L) (p < 0.001). Aortic cross-clamping time associated with CK-MBm in the whole cohort (standardized ß = 0.376 [95% CI 0.315-0.437], p < 0.001) and the Ringer group (ß = 0.363 [0.273-0.452]; p < 0.001). Albumin administration in the whole cohort (ß = -0.156 [-0.201 to -0.111]; p < 0.001) and high intraoperative albumin concentration in the Ringer group (ß = -0.07 [-0.140 to -0.003]; p = 0.04) associated with reduced CK-MBm. Compared with ischemia-induced increase in CK-MBm, albumin's potency to reduce CK-MBm was 41% in the whole cohort (ß-value ratio of -0.156/0.376) and 19% in the Ringer group (ß-value ratio of -0.07/0.363). CONCLUSION: Both endogenous and exogenous albumin appear to be cardioprotective regarding CK-MBm release in on-pump cardiac surgery.

Highly pathogenic avian influenza A(H5N1) virus infection on multiple fur farms in the South and Central Ostrobothnia regions of Finland, July 2023.

Since mid-July 2023, an outbreak caused by highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b genotype BB is ongoing among farmed animals in South and Central Ostrobothnia, Finland. Infections in foxes, American minks and raccoon dogs have been confirmed on 20 farms. Genetic analysis suggests introductions from wild birds scavenging for food in farm areas. Investigations point to direct transmission between animals. While no human infections have been detected, control measures are being implemented to limit spread and human exposure.

Policies on children and schools during the SARS-CoV-2 pandemic in Western Europe.

During the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigation policies for children have been a topic of considerable uncertainty and debate. Although some children have co-morbidities which increase their risk for severe coronavirus disease (COVID-19), and complications such as multisystem inflammatory syndrome and long COVID, most children only get mild COVID-19. On the other hand, consistent evidence shows that mass mitigation measures had enormous adverse impacts on children. A central question can thus be posed: What amount of mitigation should children bear, in response to a disease that is disproportionally affecting older people? In this review, we analyze the distinct child versus adult epidemiology, policies, mitigation trade-offs and outcomes in children in Western Europe. The highly heterogenous European policies applied to children compared to adults did not lead to significant measurable differences in outcomes. Remarkably, the relative epidemiological importance of transmission from school-age children to other age groups remains uncertain, with current evidence suggesting that schools often follow, rather than lead, community transmission. Important learning points for future pandemics are summarized.

Implementing and Maintaining a SARS-CoV-2 Exposure Notification Application for Mobile Phones: The Finnish Experience.

Exposure notification applications (ENAs) or digital proximity tracing apps were used in several countries during the COVID-19 pandemic. In this viewpoint, we share our experience of implementing and running the Finnish ENA (Koronavilkku), one of the national ENAs with the highest proportion of users during the pandemic. With the aim of strengthening public trust and increasing app uptake, there was a strong prioritization of privacy and data security for the end user throughout the ENA development. This, in turn, limited the use of the app as a tool for health care professionals and deeper insight into its potential effectiveness. The ENA was designed to supplement conventional contact tracing, rather than replace it, and to serve as an early warning system and a trigger for action for the user in case of potential exposure. The predefined target of 40% uptake in the population was achieved within 3 months of the ENA launch. We consider easy-to-understand information produced together with communication experts crucial during the changing pandemic situation. This information educated people about the app as one component in mitigating the pandemic. As the pandemic and its mitigation evolved, the ENA also needed adapting and updating. A few months after its launch, Finland joined European interoperability, which allowed the ENA to share information with ENAs of other countries. We added automatic token issuing to the ENA as of mid-2021. If added earlier and more comprehensively, automatization could have more effectively saved resources in health care services and prevented overburdening contact tracing teams, while also notifying potentially exposed individuals quicker and more reliably. In the spring of 2021, the number of active apps started to gradually decline. Quarantine and testing practices for asymptomatic vaccinated individuals following exposure to the virus were eased and home tests became more common, eventually replacing laboratory testing for much of the population. Taken together, this led to decreased token issuance, which weakened the potential public health usefulness of the app. A self-service option for token issuance would likely have prolonged the lifespan of the app. The ENA was discontinued in mid-2022. Regularly conducted surveys would have helped gain timely knowledge on the use and effectiveness of the app for better responding to the changing needs during the pandemic.

Face mask recommendations in schools did not impact COVID-19 incidence among 10-12-year-olds in Finland - joinpoint regression analysis.

BACKGROUND: In autumn 2021 in Finland, a recommendation to use face masks was implemented nationwide in schools for pupils ages 12 years and above. While national guidelines were in form of recommendations, cities implemented mandatory masking in schools. Some cities extended this mandate for younger pupils as well. Our aim was to compare COVID-19 incidence among 10-12-year-olds between cities with different recommendations on the use of face masks in schools. METHODS: COVID-19 case numbers, defined as positive laboratory verified SARS-CoV-2 test results, were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare. Helsinki, Turku and Tampere were selected for comparison since the baseline COVID-19 incidence in the cities had been similar in August and September 2021. Helsinki and Tampere implemented the national recommendation on face mask use at schools, while Turku extended this to include those 10 years old and above, starting from the beginning of semester in early August. Age groups of 7-9-year-olds, 10-12-year-olds and 30-49-year-olds were included in the statistical analysis and moving averages of 14-day incidences per 100 000 inhabitants were used as a dependent variable. Joinpoint regression was used to estimate average percent changes (APC) and average daily percent changes (ADPC) in the 14-day incidences. Differences in the ADPC values between the cities were compared in one-month periods. We also calculated cumulative incidences from the beginning of August to the end of November in the cities by age group. RESULTS: In August, the ADPC was highest in Turku (3.9) and lowest in Tampere (2.0), while in September, the ADPC was highest in Turku (-0.3) and lowest in Helsinki (-3.2) among 10-12-year-olds. In October, the ADPC was highest in Helsinki (2.1) and lowest in Turku (-0.2) and in November, the ADPC was highest in Turku (4.1) and lowest in Tampere (-0.5) among 10-12-year-olds. We also calculated cumulative incidences from the beginning of August to the end of November in the cities by age groups of 7-9 years, 10-12 years, and 30-49 years. The cumulative incidence was highest in Turku in all age groups and lowest in Tampere. CONCLUSIONS: According to our analysis, no additional effect was gained from mandating face masks, based on comparisons between the cities and between the age groups of the unvaccinated children (10-12 years versus 7-9 years).

Albumin Infusion and Blood Loss After Cardiac Surgery.

BACKGROUND: In the recent ALBICS (ALBumin In Cardiac Surgery) trial, 4% albumin used for cardiopulmonary bypass priming and volume replacement increased perioperative bleeding compared with Ringer acetate. In the present exploratory study, albumin-related bleeding was further characterized. METHODS: Ringer acetate and 4% albumin were compared in a randomized, double-blinded fashion in 1386 on-pump adult cardiac surgery patients. The study end points for bleeding were the Universal Definition of Perioperative Bleeding (UDPB) class and its components. RESULTS: The UDPB bleeding grades were higher in the albumin group than the Ringer group: "insignificant" (albumin vs Ringer: 47.5% vs 62.9%), "mild" (12.7% vs 8.9%), "moderate" (28.7% vs 24.4%), "severe" (10.2% vs 3.2%), and "massive" (0.9% vs. 0.6%; P < .001). Patients in the albumin group received red blood cells (45.2% vs 31.5%; odds ratio [OR], 1.80; 95% CI, 1.44-2.24; P < .001), platelets (33.3% vs 21.8%; OR, 1.79; 95% CI, 1.41-2.28; P < .001), and fibrinogen (5.6% vs 2.6%; OR, 2.24; 95% CI, 1.27-3.95; P < .05), and underwent resternotomy (5.3% vs 1.9%; OR, 2.95; 95% CI, 1.55-5.60, P < .001) more often than patients in the Ringer group. The strongest predictors of bleeding were albumin group allocation (OR, 2.18; 95% CI, 1.74-2.74) and complex (OR, 2.61; 95% CI, 2.02-3.37) and urgent surgery (OR, 1.63; 95% CI, 1.26-2.13). In interaction analysis, the effect of albumin on the risk of bleeding was stronger in patients on preoperative acetylsalicylic acid. CONCLUSIONS: Perioperative administration of albumin, compared with Ringer's acetate, resulted in increased blood loss and higher UDBP class. The magnitude of this effect was similar to the complexity and urgency of the surgery.

When schools were open for in-person teaching during the COVID-19 pandemic - the nordic experience on control measures and transmission in schools during the delta wave.

BACKGROUND: Extensive measures to control spread of SARS-CoV-2 have led to limited access to education for millions of children and adolescents during the COVID-19 pandemic. Education and access to schools is vital for children and adolescents' learning, health, and wellbeing. Based on high vaccine uptake and low incidence levels, the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) decided to start the academic year 2021/22 with schools open for in-person teaching and moderate mitigation measures. We describe trends in SARS-CoV-2 infections and vaccination coverage among students during the first 12 weeks of the fall semester. METHODS: In this multinational, retrospective, observational study, we have used surveillance and registry data from each of the Nordic countries to describe vaccine uptake (≥12 years), infection incidence (whole population) and transmission of SARS-CoV-2 among students. The study period, week 30 to 41 (Jul 26th - Oct 17th), represents the autumn semester from immediately before school started until fall break. In addition, we collected information on mitigation measures applied by the respective countries. RESULTS: There were slight variations between the countries regarding existing infection prevention and control (IPC) measures, testing strategies and vaccination start-up among adolescents. All countries had high vaccine uptake in the adult population, while uptake varied more in the younger age groups. Incidence in the school-aged population differed between countries and seemed to be influenced by both vaccine uptake and test activity. Infection clusters among school-aged children were described for Denmark and Norway, and the number of clusters per week reflected the incidence trend of the country. Most events consisted of only 1-2 cases. Larger clusters appeared more frequently in the higher grades in Norway and in lower grades in Denmark. CONCLUSION: Data from the Nordic countries indicate that vaccination of adults and adolescents, in addition to mitigation measures, enabled full in-person learning. As SARS-CoV-2 infection does not represent a severe medical risk for most children as previously thought, measures targeting this group should be carefully adjusted and kept at a minimum. Our data add to the evidence on incidence and transmission of SARS-CoV-2 among students in schools open for in-person teaching, and may be valuable for decision makers worldwide.

Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial.

BACKGROUND: A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life- a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system. METHODS: Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother's stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4 weeks, then at the ages of 8 weeks, 3, 6, 12 and 24 months. The parents fill in questionnaires until the age of 24 months. Blood samples are taken at the age of 2-3 days and 3, 6, 12 and 24 months to assess development of major immune cell populations and plasma proteins throughout the first years of life. DISCUSSION: This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04173208 , registration date 21.11.2019.

Online searches of children's oseltamivir in public primary and specialized care: Detecting influenza outbreaks in Finland using dedicated databases for health care professionals.

INTRODUCTION: Health care professionals working in primary and specialized care typically search for medical information from Internet sources. In Finland, Physician's Databases are online portals aimed at professionals seeking medical information. As dosage errors may occur when prescribing medication to children, professionals' need for reliable medical information has increased in public health care centers and hospitals. Influenza continues to be a public health threat, with young children at risk of developing severe illness and easily transmitting the virus. Oseltamivir is used to treat children with influenza. The objective of this study was to compare searches for children's oseltamivir and influenza diagnoses in primary and specialized care, and to determine if the searches could aid detection of influenza outbreaks. METHODS: We compared searches in Physician's Databases for children's oral suspension of oseltamivir (6 mg/mL) for influenza diagnoses of children under 7 years and laboratory findings of influenza A and B from the National Infectious Disease Register. Searches and diagnoses were assessed in primary and specialized care across Finland by season from 2012-2016. The Moving Epidemic Method (MEM) calculated seasonal starts and ends, and paired differences in the mean compared two indicators. Correlation was tested to compare seasons. RESULTS: We found that searches and diagnoses in primary and specialized care showed visually similar patterns annually. The MEM-calculated starting weeks in searches appeared mainly in the same week. Oseltamivir searches in primary care preceded diagnoses by -1.0 weeks (95% CI: -3.0, -0.3; p = 0.132) with very high correlation (τ = 0.913). Specialized care oseltamivir searches and diagnoses correlated moderately (τ = 0.667). CONCLUSION: Health care professionals' searches for children's oseltamivir in online databases linked with the registers of children's influenza diagnoses in primary and specialized care. Therefore, database searches should be considered as supplementary information in disease surveillance when detecting influenza epidemics.

Decrease in paediatric emergency room visits during the COVID-19 pandemic restrictions: A population-based study.

AIM: To investigate paediatric emergency room (ER) visits to evaluate the immediate health effects of COVID-19 pandemic restrictions on children. METHODS: We retrospectively examined paediatric ER visits in the Helsinki University Hospital (HUH) district during the first wave of the pandemic (1 March to 31 May 2020), and a 2-month period immediately before and after. These periods were compared to the corresponding time periods in 2015-2019 ('reference period'). RESULTS: The total number of ER visits decreased by 23.4% (mean 6474 during the reference period, 4960 during the pandemic period (incidence rate ratio [IRR] 0.75, 95% confidence interval 0.72-0.77; p < 0.001). This was due to a decrease in visits related to infectious diseases; visits due to surgical reasons did not decrease. The amount or proportion of patients triaged to the most urgent class (Emergency Severity Index 1) did not increase. Paediatric ER visits returned to baseline after lifting of restrictions. CONCLUSIONS: Although paediatric ER visits substantially decreased during the pandemic restrictions, children seen at the ER were not more severely ill. Our results do not indicate immediate detrimental health effects of pandemic control measures on children.

Election promises on children's wellbeing and health 2015 to 2021 - a study of Finnish voting advice applications database.

BACKGROUND: According to the UN Convention on the Rights of the Child, children's views should be heard in policymaking. But it remains unclear to what extent children's wellbeing is considered in election promises. METHODS: We investigated the extent to which Finnish political candidates consider children and their wellbeing in their election promises. We used YLE, the national broadcaster's voting advice application database, and analysed some 35,000 politicians' election promises made in the 2015 and 2019 parliamentary and the 2017 and 2021 municipal elections. We calculated the proportion of candidates who mentioned children and examined the content of the election promises in which children were mentioned. Logistic regression models were used to examine the role of the background of the characteristics of candidates. RESULTS: In the 2015 and 2019 elections, some 12% and 19% of candidates, respectively, mentioned children in their election promises. The figures for the 2017 and 2021 municipal elections were higher at 19% and 24%, respectively. In the 2021 election, the candidates considering children in their election promises were younger and had higher education qualifications. Inspection of a random set of 350 promises indicated that common issues mentioned in respect of children were education and hobby activities. Concrete proposals to improve the wellbeing of children were rarely put forward. CONCLUSIONS: Political candidates are increasingly considering children in their election promises but concrete proposals to improve the wellbeing and health of children are rare. Effective policy solutions to improve the health of children should be discussed in election debates.

Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages, Finland, December 2021.

Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.

Nasal expression of SARS-CoV-2 entry receptors in newborns.

BACKGROUND: SARS-CoV-2 infection is typically mild in children. Lower expression of SARS-CoV-2 entry receptors in the nasal epithelia have been described in children compared with adults. However, data from newborns are lacking. We compared nasal expression of four SARS-CoV-2 entry receptors between term and preterm newborns and adults. METHODS: Nasal scrape samples were obtained from 28 newborns (17 term and 11 preterm) and 10 adults. Reverse-transcription quantitative PCR was used to measure mRNA expression of ACE2, transmembrane serine protease 2 (TMPRSS2), neuropilin 1 (NRP1) and neuropilin 2 (NRP2) and insulin-like growth factor 1 receptor (IGF1R). RESULTS: Expression levels of ACE2, TMPRSS2, NRP1 and NRP2 were lower in term and preterm newborns and IGF1R lower in term newborns compared with adults (p<0.05). CONCLUSIONS: Both term and preterm newborns, compared with adults, have lower expression of SARS-CoV-2 entry receptors in nasal epithelium.

A gamified mobile health intervention for children in day surgery care: Protocol for a randomized controlled trial.

AIMS: To describe a study protocol for a randomized controlled trial which will evaluate the effectiveness of a gamified mobile health intervention for children in whole day surgery care. DESIGN: A study protocol for a two-arm randomized controlled trial. METHODS: Participants will be randomly assigned to the intervention group (N = 62), in which patients receive routine care and play a mobile game designed for children or the control group (N = 62), in which patients receive routine care, including a mobile phone application that supports parents during the care path. The primary outcome is children's pre-operative anxiety, while the secondary outcome measures included fear and postoperative pain, along with parental satisfaction and anxiety. Data collection started in August 2020. RESULTS: The results of the ongoing randomized controlled trial will determine whether the developed gamified mobile health intervention can be recommended for hospital use, and whether it could be used to educate children about their surgical treatment to decrease anxiety.

Analyzing Citizens' and Health Care Professionals' Searches for Smell/Taste Disorders and Coronavirus in Finland During the COVID-19 Pandemic: Infodemiological Approach Using Database Logs.

BACKGROUND: The COVID-19 pandemic has prevailed over a year, and log and register data on coronavirus have been utilized to establish models for detecting the pandemic. However, many sources contain unreliable health information on COVID-19 and its symptoms, and platforms cannot characterize the users performing searches. Prior studies have assessed symptom searches from general search engines (Google/Google Trends). Little is known about how modeling log data on smell/taste disorders and coronavirus from the dedicated internet databases used by citizens and health care professionals (HCPs) could enhance disease surveillance. Our material and method provide a novel approach to analyze web-based information seeking to detect infectious disease outbreaks. OBJECTIVE: The aim of this study was (1) to assess whether citizens' and professionals' searches for smell/taste disorders and coronavirus relate to epidemiological data on COVID-19 cases, and (2) to test our negative binomial regression modeling (ie, whether the inclusion of the case count could improve the model). METHODS: We collected weekly log data on searches related to COVID-19 (smell/taste disorders, coronavirus) between December 30, 2019, and November 30, 2020 (49 weeks). Two major medical internet databases in Finland were used: Health Library (HL), a free portal aimed at citizens, and Physician's Database (PD), a database widely used among HCPs. Log data from databases were combined with register data on the numbers of COVID-19 cases reported in the Finnish National Infectious Diseases Register. We used negative binomial regression modeling to assess whether the case numbers could explain some of the dynamics of searches when plotting database logs. RESULTS: We found that coronavirus searches drastically increased in HL (0 to 744,113) and PD (4 to 5375) prior to the first wave of COVID-19 cases between December 2019 and March 2020. Searches for smell disorders in HL doubled from the end of December 2019 to the end of March 2020 (2148 to 4195), and searches for taste disorders in HL increased from mid-May to the end of November (0 to 1980). Case numbers were significantly associated with smell disorders (P<.001) and taste disorders (P<.001) in HL, and with coronavirus searches (P<.001) in PD. We could not identify any other associations between case numbers and searches in either database. CONCLUSIONS: Novel infodemiological approaches could be used in analyzing database logs. Modeling log data from web-based sources was seen to improve the model only occasionally. However, search behaviors among citizens and professionals could be used as a supplementary source of information for infectious disease surveillance. Further research is needed to apply statistical models to log data of the dedicated medical databases.

Closing lower secondary schools had no impact on COVID-19 incidence in 13-15-year-olds in Finland.

School lockdowns have been widely used to control the COVID-19 pandemic. However, these lockdowns may have a significant negative impact on the lives of young people. In this study, we have evaluated the impact of closing lower secondary schools for COVID-19 incidence in 13-15-year-olds in Finland, in a situation where restrictions and recommendation of social distancing were implemented uniformly in the entire country. COVID-19 case numbers were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare, in which clinical microbiology laboratories report all positive SARS-CoV-2 tests with unique identifiers in a timely manner. The NIDR is linked to population data registry, enabling calculation of incidences. We estimated the differences in trends between areas with both restaurant and lower secondary school closures and areas with only restaurant closures in different age groups by using joinpoint regression. We also estimated the differences in trends between age groups. Based on our analysis, closing lower secondary schools had no impact on COVID-19 incidence among 13-15-year-olds. No significant changes on COVID-19 incidence were observed in other age groups either.

Incidence Trends for SARS-CoV-2 Alpha and Beta Variants, Finland, Spring 2021.

Severe acute respiratory syndrome coronavirus 2 Alpha and Beta variants became dominant in Finland in spring 2021 but had diminished by summer. We used phylogenetic clustering to identify sources of spreading. We found that outbreaks were mostly seeded by a few introductions, highlighting the importance of surveillance and prevention policies.

Effect of High-Dose vs Standard-Dose Vitamin D Supplementation on Neurodevelopment of Healthy Term Infants: A Randomized Clinical Trial.

Importance: Vitamin D may be important for neurodevelopment. The optimal daily dose of vitamin D for early brain development is not known. Objectives: To test whether a higher (1200 IU) vs standard (400 IU) dose of vitamin D3 has beneficial effects on neurodevelopment in the first 2 years of life and whether serum 25-hydroxyvitamin D concentration is associated with neurodevelopment. Design, Setting, and Participants: This double-blind, interventional randomized clinical trial involved healthy infants born full-term between January 1, 2013, and June 30, 2014, at a maternity hospital in Helsinki, Finland, at the 60th northern latitude. Two-year follow-up was conducted by May 30, 2016. Data analysis was by the intention-to-treat principle. Data were analyzed from November 1, 2020, to May 31, 2021. Interventions: Randomization of 404 infants to receive 400 IU of oral vitamin D3 supplementation daily and 397 infants to receive 1200 IU of oral vitamin D3 supplementation daily from 2 weeks to 24 months of age. Main Outcomes and Measures: Primary outcomes were child total developmental milestone scores at 12 and 24 months of age measured using the Ages and Stages Questionnaire (total score is calculated as a mean of the 5 subscale scores: total score range, 0-60, where 0 indicates delay in all developmental domains and 60 indicates that the child can master all age-specific skills) as well as externalizing, internalizing, and dysregulation problems and competencies scores at 24 months measured using the Infant-Toddler Social and Emotional Assessment (range 0-2, where 0 indicates no problems or no competencies and 2 indicates a high level of problems or a high level of competencies; variables were standardized to the mean [SD] of 0 [1]). Secondary outcomes were specific skills, problems, and competencies derived from these questionnaires. Results: Of the 987 families recruited, 495 children were randomly assigned to receive 400 IU of vitamin D3, and 492 children were randomly assigned to receive 1200 IU of vitamin D3. A total of 801 families participated in the follow-up at 12 and/or 24 months, with 404 children (207 girls [51.2%]) in the 400-IU group and 397 children (198 girls [49.9%]) in the 1200-IU group. All children were of Northern European ethnicity. No differences were found between the 400-IU group and the 1200-IU group in the mean (SD) adjusted Ages and Stages Questionnaire total score at 12 months (45.0 [7.1] vs 46.2 [7.9]; mean difference [MD], 1.17 [95% CI, -0.06 to 2.38]) or 24 months (50.9 [5.3] vs 51.5 [5.5]; MD, 0.48 [95% CI, -0.40 to 1.36]). No differences were found between the 400-IU group and the 1200-IU group at 24 months in the mean (SD) adjusted Infant-Toddler Social and Emotional Assessment externalizing domain score (-0.07 [1.00] vs 0.07 [0.98]; MD, 0.15 [95% CI, -0.01 to 0.31]), internalizing domain score (0.04 [1.06] vs -0.02 [0.98]; MD, -0.07 [95% CI, -0.24 to 0.1.0]), dysregulation domain score (-0.00 [1.04] vs 0.02 [0.96]; MD, 0.02 [95% CI, -0.14 to 0.18]), or competencies score (-0.02 [1.02] vs 0.01 [1.02]; MD, 0.03 [95% CI, -0.13 to 0.20]). The 1200-IU group did have a higher risk in the adjusted model of scoring 1.5 SDs or more on the externalizing domain score (odds ratio, 2.33 [95% CI, 1.19-4.56]; P = .01). Levels of serum 25-hydroxyvitamin D were not associated with the primary outcomes. Conclusions and Relevance: Higher-than-standard vitamin D3 doses provide no systematic benefits for child neurodevelopment up to 2 years of age. However, the potential disadvantageous effects of higher doses could not be fully excluded; even if minimal, the potential nonbeneficial effects of higher-than-standard doses warrant further studies in which both safety and benefits should be evaluated. Trial Registration: ClinicalTrials.gov Identifier: NCT01723852.

Detection of SARS-CoV-2 Infection in Gargle, Spit, and Sputum Specimens.

The gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is reverse transcription (RT)-PCR from a nasopharyngeal swab specimen (NPS). Its collection involves close contact between patients and health care workers, requiring a significant amount of workforce and putting them at risk of infection. We evaluated self-collection of alternative specimens and compared their sensitivity and cycle threshold (CT) values to those of NPS. We visited acute coronavirus disease 2019 (COVID-19) outpatients to collect concomitant NPS and gargle specimens and had patients self-collect gargle and either sputum or spit specimens the next morning. We included 40 patients and collected 40 concomitant NPS and gargle specimens, as well as 40 gargle, 22 spit, and 16 sputum specimens the next day (2 patients could not produce sputum). All specimens were as sensitive as NPS. Gargle specimens had a sensitivity of 0.97 (95% confidence interval [CI], 0.92 to 1.00), whether collected concomitantly with NPS or the next morning. Next-morning spit and sputum specimens showed sensitivities of 1.00 (95% CI, 1.00 to 1.00) and 0.94 (95% CI, 0.87 to 1.00]), respectively. The gargle specimens had significantly higher mean CT values of 29.89 (standard deviation [SD], 4.63; P < 0.001) and 29.25 (SD, 3.99; P < 0.001) when collected concomitantly and the next morning, respectively, compared to NPS (22.07 [SD, 4.63]). CT values obtained with spit (23.51 [SD, 4.57]; P = 0.11) and sputum (25.82 [SD, 9.21]; P = 0.28) specimens were close to those of NPS. All alternative specimen collection methods were as sensitive as NPS, but spit collection appeared more promising, with a low CT value and ease of collection. Our findings warrant further investigation. IMPORTANCE Control of the COVID-19 pandemic relies heavily on a test-trace-isolate strategy. The most commonly used specimen for diagnosis of SARS-CoV-2 infection is a nasopharyngeal swab. However, this method is quite uncomfortable for the patient, requires specific equipment (nose swabs and containers), and requires close proximity to health care workers, putting them at risk of infection. Developing alternative sampling strategies could decrease the burden for health care workers, help overcome potential shortages of equipment, and improve acceptability of testing by reducing patient discomfort.