Monoclonal antibody therapies in respiratory syncytial virus prophylaxis-An umbrella review.

The aim was to gather an overview of the evidence of monoclonal antibody therapies in respiratory syncytial virus (RSV) prophylaxis in children. For this umbrella review of previous meta-analyses, we searched PubMed, Scopus, and Web of Science databases in August 2023. We included systematic reviews with meta-analyses of randomized controlled trials. One author extracted the data, and another author validated the data. We extracted all analyses focusing on clinical outcomes and comparing prophylaxis to placebo. Risk of bias in systematic reviews (ROBIS) tool was used to analyze the risk of bias in the included reviews. AMSTAR-2 was used to evaluate the quality of the included reviews. After screening of 323 abstracts and 22 full reports, a total of seven systematic reviews with meta-analyses were included. The risk of bias was rated to be low in four and high in three of these. Three reviews were of moderate quality, one low, and three very low quality according to AMSTAR-2 classification. Six of the meta-analyses were direct comparisons, and one was a network meta-analysis. Five of the reviews focused on palivizumab, one in nirsevimab, and one included all monoclonal antibodies. Six reviews focused on preterm neonates and consisted of 42 comparisons to placebo of which 21 showed efficacy, and 21 had no evidence of a difference. The positive effect was seen in all reviews against RSV infection and RSV hospitalization in palivizumab and nirsevimab groups compared to placebo. None of the mortality comparisons showed efficacy. One meta-analysis focused on cystic fibrosis patients and had eight comparisons, but it was underpowered to detect any results. The overall evidence from previous meta-analyses shows that monoclonal antibodies are effective in preventing RSV infections and RSV hospitalizations in preterm infants. However, no effect on mortality was seen in these studies. Evidence certainty has been ranked mainly from low to moderate.

Pneumonia, wheezing and asthma were more common in children after thymectomy due to open-heart surgery.

AIM: This nationwide study evaluated the clinical impact that an early thymectomy, during congenital heart defect (CHD) surgery, had on the health of children and adolescents. METHODS: The subjects were patients aged 1-15 years who had undergone CHD surgery at the University Children's Hospital, Helsinki, where all CHD surgery in Finland is carried out, from 2006 to 2018. The parents or the cases and population-based controls, matched for sex, age and hospital district, completed electronic questionnaires. We excluded those with low birth weights or a known immunodeficiency. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for prespecified outcomes. RESULTS: We received responses relating to 260/450 (58%) cases and 1403/4500 (31%) controls and excluded 73 cases with persistent cardiac or respiratory complaints after surgery. The CHD group reported more recurrent hospitalisations due to infections (aOR 6.3, 95% CI 3.0-13) than the controls and more pneumonia episodes (aOR 3.5, 95% CI 2.1-5.6), asthma (aOR 2.5, 95% CI 1.5-4.1) and wheezing (aOR 2.1, 95% CI 1.5-2.9). CONCLUSION: Hospitalisation due to infections, pneumonia, wheezing and asthma was more common in children after a thymectomy due to open-heart surgery than population-based controls, underlining the importance of immunological follow-ups.

Tonsillotomy for Periodic Fever Syndrome: A Randomized and Controlled Trial.

OBJECTIVE: Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Tonsillotomy has a milder operative risk profile and postoperative morbidity in children than tonsillectomy. We aimed to compare the efficacy of tonsillotomy to observation-only in children with PFAPA syndrome at a 3-month follow-up. METHODS: This was a randomized multicenter trial with sequential design. Participants were randomized into a tonsillotomy group and a control group that was only observed. The trial started in 1/2017 and was accomplished in 12/2021 with 16 patients (10 boys, six girls, the mean age 4.2 years). The symptoms were monitored with daily symptom diaries. RESULTS: After the 3-month follow-up, 7/8 patients (87.5%) in the tonsillotomy group and 2/8 (25%) patients in the control group were free from PFAPA symptoms (95% CI 13% to 87%; p = 0.0021). The mean number of days with fever was 2.6 (SD 3.7) in the tonsillotomy group and 8.0 (SD 6.5) days in the control group (n = 8) (p = 0.06). Mean number of fever days compatible with PFAPA syndrome was 0.8 (SD 1.4) in the tonsillotomy group and 6.5 (SD 6.0) in the control group (95%CI -10% to -1%; p = 0.007). Rescue tonsillectomy was needed for all patients in the control group and none of the patients in the tonsillotomy group. CONCLUSIONS: Tonsillotomy might be an effective treatment option for children with PFAPA syndrome. Further studies are needed to clarify the long-term efficacy of tonsillotomy for treating PFAPA. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:968-972, 2024.

Respiratory virus circulation in children after relaxation of COVID-19 restrictions in fall 2021-A nationwide register study in Finland.

Social restrictions interrupted the normal respiratory virus circulation in Spring 2020. This report describes virus circulation in the pediatric population before and after the restrictions ended in Finland in September 2021. We used data from the Finnish Infectious Disease Register. Nationwide influenza A and B, rhinovirus, severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), and respiratory syncytial virus (RSV) findings from January 2018 to December 2021. Age stratified (0-4, 5-9, and 10-14 years) weekly incidences per 100 000 children were calculated. School and day-care closures interrupted completely the circulation of all other respiratory viruses than rhinovirus in spring 2020. After restrictions were relaxed in September 2021, SARS-Cov-2 detections increased majorly. We observed high RSV season atypically early. SARS-Cov-2 was detected in older children whereas RSV season peaked especially among children aged under 5. Influenza seemed to return to normal circulation. In conclusion, we report that the ending of social restrictions in September 2021 led to an increase in SARS-Cov-2 detections and high epidemic peaks of RSV and parainfluenza in atypical timing in children. Our results highlight the importance of continuous pathogen surveillance during the pandemic, as atypical surges of non-COVID-19 respiratory viruses were observed.

Record high parainfluenza season in children after relaxation of COVID-19 restrictions in fall 2021-A nationwide register study in Finland.

Social restrictions interrupted the circulation of common respiratory viruses among children in spring 2020. In the winter season 2020-2021, only rhinovirus spread in Finland. As the restrictions were ended in September 2021, we saw record high epidemic peak of parainfluenza. Typically, the epidemic peak is in springtime, but now, it started in the early fall 2021. The monthly incidence among children aged 0-4 years (120 per 100,000 children) was six times higher than the second highest reported monthly incidence (21 per 100,000 children) during the last 10 years. Our finding highlights the importance of active surveillance of viral respiratory pathogens during the pandemic.

Urinary tract infections decreased in Finnish children during the COVID-19 pandemic.

Social restrictions reduced the rates of respiratory infections in 2020, but studies on the rates of urinary tract infections (UTIs) during lockdown have had conflicting results. This study aimed to report UTI incidence during the first and second waves of COVID-19 pandemic in Finland. We conducted a retrospective register-based cohort study. The whole Finnish pediatric population (children under the age of 15 years, N = 860,000) was included. The yearly and monthly incidences of UTIs per 100,000 children in 2020 were compared to that of three previous years (2017-2019) by incidence rate ratios (IRRs) with 95% confidence intervals (CIs). A total of 10,757 cystitis and 4873 pyelonephritis cases were included. The yearly incidence of cystitis was 12% lower (IRR 0.88, CI 0.83-0.94) among children aged 1-6 in 2020 and 11% (IRR 0.89, CI 0.83-0.95) lower among children aged 7-14 in 2020 compared with previous years. The yearly incidence of pyelonephritis was 16% lower (IRR 0.84, CI 0.76-0.94) among children aged 1-6. No significant decrease were observed among children aged < 1 and 7-14. CONCLUSION: The incidence of cystitis and pyelonephritis during a period of social restrictions was lower than during 2017-2019, especially in children aged 1-6 years. These results raise the possibility of reducing the occurrence of urinary tract infections in children by improving hygiene measures. WHAT IS KNOWN: • Social restrictions have reduced the rate of common respiratory infections globally. • Previous studies have presented a decreased or unchanged incidence of urinary tract infections during the COVID-19 pandemic. WHAT IS NEW: • During the pandemic, there was a decrease in the incidence of urinary tract infections in Finnish children and the most prominent decrease was in daycare-aged children. • Improved hygiene measures and social restrictions may have influenced the transmission of uropathogens.

Tympanostomies and tonsillar surgery in children during the COVID-19 pandemic in Finland.

OBJECTIVE: To assess the impact of social restrictions due to COVID-19 on the number of tympanostomies and tonsillar surgeries in children. METHODS: Incidences were calculated per 100 000 children for tonsillar surgery and tympanostomies in 2020 and compared to the mean incidence of referral years 2017 to 2019 by incidence rate ratios (IRR) with 95% confidence intervals (CIs). Median waiting times were also compared. RESULTS: Before the lockdown, tonsillar surgery incidence was 33.4/100000 (IRR 1.14, CI 0.76-1.71) in February 2020. After the lockdown began, the incidence of tonsillar surgery was 1.4/100000 (IRR 0.04, CI 0.01-0.15) in April. In June, tonsillar operation incidence started to increase (20.4 per 100 000). The incidence of tympanostomies was 81% lower (IRR 0.19, CI 0.09-0.39) in April 2020 and 61% lower (IRR 0.39, CI 0.22-0.69) in August 2020 than in 2017-2019. These incidence rates remained lower all year (December 2020 IRR 0.13, CI 0.05-0.33). Median waiting time for tonsillar surgery was 3.3 months in 2020 and 1.6 months in 2017 to 2019; P <.001, and for tympanostomies 1.3 months in 2020 and 1.0 months in 2017 to 2019, P <.001. The referral rate to otorhinolaryngology during the severest restrictions was 35% lower in April and May 2020 compared with the reference years. CONCLUSION: This study suggests that the restrictions against COVID-19 reduced the incidence rates of tonsil surgery and tympanostomies in children. Also, the lockdown and cancellations of elective operations in spring 2020 led to increased waiting times. These findings may help in preparing for future pandemics.Level of evidence: Level 3.

The impact of the lockdown and the re-opening of schools and day cares on the epidemiology of SARS-CoV-2 and other respiratory infections in children - A nationwide register study in Finland.

BACKGROUND: Nationwide restrictions started in Finland in March to prevent the spread of COVID-19, leading to school and day care closures. The aim of this study is to describe the effect of closures and re-openings on the respiratory pathogen epidemiology. METHODS: Laboratory-confirmed cases of SARS-CoV-2; respiratory syncytial virus (RSV); influenza (A & B); parainfluenza-, adeno-, and rhinoviruses; Mycoplasma pneumoniae; and Streptococcus pneumoniae in children were collected from the National Infectious Disease Register over the period of 2017-2020. Weekly incidences (weeks 1 to 35) with 95% confidence intervals (CIs) were calculated per 100 000 children in 2020 and compared by incidence rate ratios (IRRs) to corresponding periods in 2017-2019. FINDINGS: The lockdown had immediate impact on the incidences of respiratory pathogens except SARS-CoV-2. Week after the lockdown began IRR was 0•3 (CI 0•3-0•4) and next week the IRR was 0•1 (0•1-0•2). The incidence of SARS-CoV-2 started to decline eight weeks after the lockdown began. The highest recorded weekly incidence of SARS-CoV-2 was 7•2/100 000 children. The effect of the lockdown lasted until late summer. Rhinovirus and SARS-CoV-2 began to increase before the schools or day cares opened in August. The re-opening of schools seemed to have no impact on the incidence of any pathogen. INTERPRETATION: Our results suggest that general social distancing, including school and day care closures, played a crucial role in reducing infections, and the effect lasted for several weeks. The re-opening of schools and day care centres seems to have had no immediate impact on the incidences of any respiratory pathogens. FUNDING: This study had no funding source.

Loss of DIAPH1 causes SCBMS, combined immunodeficiency, and mitochondrial dysfunction.

BACKGROUND: Homozygous loss of DIAPH1 results in seizures, cortical blindness, and microcephaly syndrome (SCBMS). We studied 5 Finnish and 2 Omani patients with loss of DIAPH1 presenting with SCBMS, mitochondrial dysfunction, and immunodeficiency. OBJECTIVE: We sought to further characterize phenotypes and disease mechanisms associated with loss of DIAPH1. METHODS: Exome sequencing, genotyping and haplotype analysis, B- and T-cell phenotyping, in vitro lymphocyte stimulation assays, analyses of mitochondrial function, immunofluorescence staining for cytoskeletal proteins and mitochondria, and CRISPR-Cas9 DIAPH1 knockout in heathy donor PBMCs were used. RESULTS: Genetic analyses found all Finnish patients homozygous for a rare DIAPH1 splice-variant (NM_005219:c.684+1G>A) enriched in the Finnish population, and Omani patients homozygous for a previously described pathogenic DIAPH1 frameshift-variant (NM_005219:c.2769delT;p.F923fs). In addition to microcephaly, epilepsy, and cortical blindness characteristic to SCBMS, the patients presented with infection susceptibility due to defective lymphocyte maturation and 3 patients developed B-cell lymphoma. Patients' immunophenotype was characterized by poor lymphocyte activation and proliferation, defective B-cell maturation, and lack of naive T cells. CRISPR-Cas9 knockout of DIAPH1 in PBMCs from healthy donors replicated the T-cell activation defect. Patient-derived peripheral blood T cells exhibited impaired adhesion and inefficient microtubule-organizing center repositioning to the immunologic synapse. The clinical symptoms and laboratory tests also suggested mitochondrial dysfunction. Experiments with immortalized, patient-derived fibroblasts indicated that DIAPH1 affects the amount of complex IV of the mitochondrial respiratory chain. CONCLUSIONS: Our data demonstrate that individuals with SCBMS can have combined immune deficiency and implicate defective cytoskeletal organization and mitochondrial dysfunction in SCBMS pathogenesis.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome: Relapse and Tonsillar Regrowth After Childhood Tonsillectomy.

OBJECTIVES/HYPOTHESIS: Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, but the role of adenoidectomy, as well as later tonsillar regrowth, is unclear. To find out if the volume of lymphoid tissue is pivotal to the efficacy, we analyzed the association between the relapse of the symptoms of PFAPA syndrome and regrowth of tonsillar tissue after tonsillectomy or adenotonsillectomy. STUDY DESIGN: Prospective cohort study of operated PFAPA pateints. METHODS: We invited all patients that had undergone tonsillectomy or adenotonsillectomy due to PFAPA syndrome at the Oulu University Hospital, Oulu, Finland, between the years 1990 and 2007, at the age of ≤12 years, to a follow-up visit, after an average period of 9.8 years after their diagnoses. Out of the 132 invited, 94 (71%) participated in the follow-up study. RESULTS: At the follow-up study visit, 5 (5%) of the 94 PFAPA syndrome cases experienced recurrent fevers. The regrowth of palatine tonsillar tissue was seen in four of them (80%) as compared to 19/89 (21%) of symptom-free patients (P = .006). Two of the patients with clear PFAPA relapse at the time of the study visit were reoperated with clear effect on the symptoms. At the time of the study visit, 59/63 (94%) of the patients who had undergone adenotonsillectomy and 30/31 of the patients (97%) who had undergone tonsillectomy earlier were free of fever flares (P = .99). CONCLUSION: Palatine tonsil regrowth was associated with PFAPA syndrome relapse after tonsillectomy. Reoperation might be a treatment option in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2149-E2152, 2021.

Risk of Electrolyte Disorders in Acutely Ill Children Receiving Commercially Available Plasmalike Isotonic Fluids: A Randomized Clinical Trial.

Importance: The use of isotonic fluid therapy is currently recommended in children, but there is limited evidence of optimal fluid therapy in acutely ill children. Objective: To evaluate the risk for electrolyte disorders, including hyponatremia, hypernatremia, and hypokalemia, and the risk of fluid retention in acutely ill children receiving commercially available plasmalike isotonic fluid therapy. Design, Setting, and Participants: This unblinded, randomized clinical pragmatic trial was conducted at the pediatric emergency department of Oulu University Hospital, Finland, from October 3, 2016, through April 15, 2019. Eligible study subjects (N = 614) were between 6 months and 12 years of age, required hospitalization due to an acute illness, and needed intravenous fluid therapy. Exclusion criteria included a plasma sodium concentration of less than 130 mmol/L or greater than 150 mmol/L on admission; a plasma potassium concentration of less than 3.0 mmol/L on admission; clinical need of fluid therapy with 10% glucose solution; a history of diabetes, diabetic ketoacidosis, or diabetes insipidus; a need for renal replacement therapy; severe liver disease; pediatric cancer requiring protocol-determined chemotherapy hydration; and inborn errors of metabolism. All outcomes and samples size were prespecified except those clearly marked as exploratory post hoc analyses. All analyses were intention to treat. Interventions: Acutely ill children were randomized to receive commercially available plasmalike isotonic fluid therapy (140 mmol/L of sodium and 5 mmol/L potassium in 5% dextrose) or moderately hypotonic fluid therapy (80 mmol/L sodium and 20 mmol/L potassium in 5% dextrose). Main Outcomes and Measures: The primary outcome was the proportion of children with any clinically significant electrolyte disorder, defined as hypokalemia less than 3.5 mmol/L, hypernatremia greater than 148 mmol/L, or hyponatremia less than 132 mmol/L during hospitalization due to acute illness. The main secondary outcomes were the proportion of children with severe hypokalemia and weight change. Results: There were 614 total study subjects (mean [SD] age, 4.0 [3.1] years; 315 children were boys [51%] and all 614 were Finnish speaking [100%]). Clinically significant electrolyte disorder was more common in children receiving plasmalike isotonic fluid therapy (61 of 308 patients [20%]) compared with those receiving moderately hypotonic fluid therapy (9 of 306 patients [2.9%]; 95% CI of the difference, 12%-22%; P < .001). The risk of developing electrolyte disorder was 6.7-fold greater in children receiving isotonic fluid therapy. Hypokalemia developed in 57 patients (19%) and hypernatremia developed in 4 patients (1.3%) receiving plasmalike isotonic fluid therapy. Weight change was greater in children receiving isotonic, plasmalike fluid therapy compared with those receiving mildly hypotonic fluids (mean weight gain, 279 vs 195 g; 95% CI, 16-154 g; P = .02). Conclusions and Relevance: In this randomized clinical trial, commercially available plasmalike isotonic fluid therapy markedly increased the risk for clinically significant electrolyte disorders, mostly due to hypokalemia, in acutely ill children compared with previously widely used moderately hypotonic fluid therapy containing 20 mmol/L of potassium. Trial Registration: ClinicalTrials.gov identifier: NCT02926989.

A nearly fatal primary Epstein-Barr virus infection associated with low NK-cell counts in a patient receiving azathioprine: a case report and review of literature.

BACKGROUND: Symptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab. CASE PRESENTATION: An 11-year-old girl presented with chronic, bloody diarrhea. Endoscopic biopsies confirmed a diagnosis of chronic ulcerative colitis with features of Crohn's disease. Azathioprine was initiated after one year due to active colitis. She responded well and remission was achieved. At the age of 16 years she developed a life-threatening Epstein-Barr virus infection including severe multiple organ failure and was critically ill for 4 weeks in the intensive care unit. Natural killer cells were virtually absent in the lymphocyte subset analysis. Azathioprine was stopped on admission. She was initially treated with corticosteroids, acyclovir and intravenous immunoglobulin. Approximately 30 days after admission, she developed signs of severe hepatitis and pneumonitis and received weekly rituximab infusions for 8 weeks. Primary immunodeficiency was excluded by whole exome sequencing in two independent laboratories. Persistent viremia stopped when the natural killer cell count started to rise, approximately 90 days after the cessation of azathioprine. CONCLUSIONS: We found 17 comparable cases in the literature. None of the previous cases reported in the literature, who had been treated with azathioprine and developed either a severe or a fatal Epstein-Barr virus infection, underwent full genetic and prospective immunological workup to rule out known primary immunodeficiencies. Recently, azathioprine has been shown to cause rather specific immunosuppression, resulting in natural killer cell depletion. Our case demonstrates that slow recovery from azathioprine-induced natural killer cell depletion, 3 months after the stopping of azathioprine, coincided with the clearance of viremia and clinical recovery. Finally, our choice of treating the patient with rituximab, as previously used for patients with a severe immunosuppression and Epstein-Barr virus viremia, appeared to be successful in this case. We suggest testing for Epstein-Barr virus serology before starting azathioprine and measuring natural killer cell counts during the treatment to identify patients at risk of developing an unusually severe primary Epstein-Barr virus infection.

National treatment guidelines decreased the use of racemic adrenaline for bronchiolitis in four Finnish university hospitals.

AIM: Inhaled racemic adrenaline was used for bronchiolitis in many hospitals in Finland prior to new national current care guidelines for bronchiolitis in 2014, which limited its recommendations to on-demand rescue therapy. We studied the drug's use before and after the new guidelines to gauge changes in prescribing habits. METHODS: This 2012-2016 study analysed how many 0.5 mL doses of racemic adrenaline were used for children by emergency rooms, paediatric wards and paediatric intensive care units at four university hospitals and estimated drug and staff costs. RESULTS: There were substantial differences in the yearly consumption of racemic adrenaline between the hospitals before and after the bronchiolitis guidelines were published, with reductions in drug costs and staff time. The overall use more than halved during the study period, particularly in two hospitals where baseline consumptions were highest, but not in a third where baseline consumption was already low. In the fourth, the baseline consumption was modest and there was a constant decrease during the study years. CONCLUSION: The current care guidelines for bronchiolitis had some impact on clinical practice, as the overall use of racemic adrenaline more than halved, but considerable differences remained in the four study hospitals after their publication.

Risk factors for periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a case-control study.

The etiology and pathogenesis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome are unclear. We performed a case-control study to evaluate potential environmental or lifestyle factors associated with PFAPA morbidity. We enrolled 119 patients with PFAPA syndrome who had undergone tonsillectomy in Oulu University Hospital between 1987 and 2007. We recruited 230 controls, matched for sex, birth date, and place from the database of the Population Register Center of Finland. All the patients and controls completed a questionnaire regarding exposure to environmental triggers during early childhood. Maternal smoking was more common among PFAPA syndrome patients than controls (23 vs. 14%; P = 0.005). PFAPA patients had lower breastfeeding rates than controls (94 vs. 99%; P = 0.006). No other environmental factors were associated with PFAPA syndrome, except having an aquarium at home (P = 0.007). The patient group also used natural or herbal medicines more often than the controls (P = 0.01). CONCLUSION: Maternal smoking and lack of breastfeeding, known risk factors for common childhood infections, were more common in patients with PFAPA syndrome than in matched controls. Environmental factors may be important in the pathogenesis of PFAPA syndrome and should be evaluated in future studies. What is Known: • The pathogenesis and genetics of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome remain unsolved. • PFAPA syndrome has been shown to cluster in families. What is New: • Maternal smoking and lack of breastfeeding are more common in patients with PFAPA syndrome than in the controls. • Environmental risk factors may be important in the pathogenesis of the syndrome.

Aetiology of neonatal conjunctivitis evaluated in a population-based setting.

AIM: Our aim was to study prospectively the aetiology of neonatal conjunctivitis in a population-based setting. METHODS: Altogether 173 neonates with clinical conjunctivitis aged on average 20 (SD 10) days were recruited from child welfare clinics in Oulu, Finland, in 2010-2015. Conjunctival specimens were collected from 167 neonates for multiplex polymerase chain reaction to detect 16 respiratory viruses, from 163 for polymerase chain reaction to detect Chlamydia trachomatis and Neisseria gonorrhoeae and from 160 for bacterial culture studies. The cases were followed up until the age of 18 months. RESULTS: Viral conjunctivitis was diagnosed in 8/167 (4.8%; 95% CI 2.1-9.2%), chlamydial or gonococcal conjunctivitis in 0/163 cases (0%; 95% CI 0-2.2%) and other bacterial conjunctivitis in 58/160 (36%; 95% CI 29-44%). Rhinovirus was found at the ocular site in 4/167 (2.4%) neonates, adenovirus in 3/167 (1.8%) and bocavirus in 1/167 (0.6%). The most commonly isolated bacteria included Staphylococcus aureus (16%), Moraxella catarrhalis (9.4%) and Streptococcus pneumoniae (3.1%). None of these pathogens was associated with the 4/173 (2.3%) cases later operated on for persistent nasolacrimal duct obstruction. CONCLUSION: Chlamydia trachomatis was a rare pathogen in neonatal conjunctivitis in a population-based setting, but respiratory viruses were detected more frequently than indicated earlier.

Triclosan-containing sutures versus ordinary sutures for reducing surgical site infections in children: a double-blind, randomised controlled trial.

BACKGROUND: Surgical site infections (SSIs) are a pervasive problem in surgery. Sutures coated or impregnated with triclosan might reduce the occurrence of SSIs, but evidence of their efficacy is limited, especially in children. METHODS: We designed a randomised, double-blind, controlled trial in patients who underwent elective or daytime emergency surgery at Oulu University Hospital (Oulu, Finland). We included children younger than 18 years staying in the paediatric surgery and orthopaedics ward for any elective or emergency surgery during the daytime and with anticipated use of absorbing sutures. Children were randomly allocated (1:1) to receive either triclosan-containing sutures or ordinary absorbing sutures. The primary outcome was the occurrence of superficial or deep surgical site infections according to the Centers for Disease Control and Prevention criteria within 30 days after surgery. The primary analysis was with modified intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01220700. FINDINGS: Between September, 2010, and December, 2014, 1633 children were recruited. In the modified intention-to-treat group, SSIs occurred in 20 (3%) of 778 patients allocated to receive triclosan-containing sutures and in 42 (5%) of 779 patients allocated to receive control sutures (risk ratio 0·48, 95% CI 0·28-0·80). To prevent one SSI, triclosan-containing sutures had to be used in 36 children (95% CI 21-111). One patient died from suspected mitochondrial disease; no other expected or unexpected adverse events were reported in either of the groups. INTERPRETATION: Use of triclosan-containing sutures effectively reduced the occurrence of all SSIs compared with normal sutures. The results accord with the results of meta-analyses of previous studies in adults. Use of triclosan-containing sutures is a simple way to reduce SSIs in children. FUNDING: The Alma and K A Snellman Foundation.

Invasive Group A Streptococcal Infections in Children: A Nationwide Survey in Finland.

BACKGROUND: The incidence of invasive group A streptococcus (iGAS) infections varies in time and geographically for unknown reasons. We performed a nationwide survey to assess the population-based incidence rates and outcomes of children with iGAS infections. METHODS: We collected data on patients from hospital discharge registries and the electronic databases of microbiological laboratories in Finland for the period 1996-2010. We then recorded the emm types or serotypes of the strains. The study physician visited all university clinics and collected the clinical data using the same data entry sheet. RESULTS: We identified 151 children with iGAS infection. Varicella preceded iGAS infection in 20% of cases and fasciitis infection in 83% of cases. The annual incidence rate of iGAS infection was 0.93 per 100,000 in 1996-2000, 1.80 in 2001-2005 and 2.50 in 2006-2010. The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in 2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of the patients were severe soft-tissue infection (46%), sepsis (28%), empyema (10%), osteoarticular infection (9%) and primary peritonitis (5%). Severe pain was the most typical symptom for soft-tissue infections. More than half of the patients underwent surgery and received clindamycin. The readmission rate was 7%, and the case fatality rate was 2%. CONCLUSIONS: The incidence rate of pediatric iGAS infections tripled during our study. The increase was not, however, the result of a change in the strain types causing iGAS. Varicella immunization would likely have prevented a significant number of the cases.

Microbes of the tonsils in PFAPA (Periodic Fever, Aphtous stomatitis, Pharyngitis and Adenitis) syndrome - a possible trigger of febrile episodes.

Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis (PFAPA) is a childhood febrile syndrome that is often cured by tonsillectomy (TE). We hypothesized that microbes present in the tonsils may act as a trigger for the activation of inflammasomes and investigated the microbiology of the tonsils in PFAPA patients and controls. We recruited 31 consecutive children who underwent TE due to PFAPA; 24 children who underwent TE due to other reasons served as controls. We cultured all the samples for bacteria, mycobacteria, yeasts, and viruses and used PCR for 15 viruses. Also biofilm formation and histologic findings were identified. The samples of the patients yielded Candida albicans more often than did the controls (16 vs 0%, p = 0.003). Staphylococcus aureus occurred in only 10% of the patients, but in 38% of the controls (p = 0.01). Varicella zoster and Herpes simplex viruses occurred less often in patients than in controls. Biofilm was present in 55% of PFAPA tonsils, but in only 24% of the controls (p = 0.03). The microbes found in the tonsils of PFAPA patients showed significant differences from those of controls. This may in part explain the efficacy of TE in PFAPA.

Quality of life after surgery for recurrent otitis media in a randomized controlled trial.

BACKGROUND: Tympanostomy with or without adenoidectomy is effective in preventing recurrences of acute otitis media (RAOM), but little is known about the effect of these operations on the quality of life (QOL). We evaluated the efficacy of insertion of tympanostomy tubes with and without adenoidectomy for improving QOL in young children in a controlled, randomized trial. METHODS: QOL was evaluated in the 159 children aged 10 months to 2 years participating in our larger study in which children with RAOM were randomly assigned to receive tympanostomy tubes, tympanostomy tubes with adenoidectomy or neither. The caregiver of the child completed otitis media-specific QOL questionnaires (Otitis Media-6) at entry and after 4 months and 12 months of follow up. RESULTS: Scores on the global ear-related QOL and the subsets of caregiver concern, emotional distress and physical suffering in the questionnaires improved with time during the follow up, but the groups did not differ from each other. CONCLUSIONS: QOL in children with RAOM improves with time when the subjects are closely followed. Tympanostomy with adenoidectomy does not provide any additional QOL benefit for children with RAOM, even though these operations are effective in preventing further otitis media episodes.