Background. Human rhinoviruses (HRVs), human enteroviruses (HEVs) and human parechoviruses (HPeVs) have been linked to acute otitis media (AOM). We evaluated this association in a prospective birth cohort setting. Methods. A total of 324 healthy infants were followed up from birth to age 3 years. Nasal swab samples were collected at age 3, 6, 12, 18, 24, and 36 months and screened for HRV and HEV using real-time reverse-transcription quantitative polymerase chain reaction. Stool samples were collected monthly and analyzed for HRV, HEV, and HPeV. AOM episodes diagnosed by physicians were reported by parents in a diary. The association of viruses with AOM was analyzed using generalized estimation equations, and their relative contributions using population-attributable risk percentages. Results. A clear association was found between AOM episodes and simultaneous detection of HEV (adjusted odds ratio for the detection of virus in stools, 2.04; 95% confidence interval, 1.06-3.91) and HRV (1.54; 1.04-2.30). HPeV showed a similar, yet nonsignificant trend (adjusted odds ratio, 1.44; 95% confidence interval, .81-2.56). HRV and HEV showed higher population-attributable risk percentages (25% and 20%) than HPeV (11%). Conclusions. HEVs and HRVs may contribute to the development of AOM in a relatively large proportion of cases.

Sickle cell disease (SCD) was found in 10% of children with bacterial meningitis (BM) in Luanda, 5-fold more than in the general population. BM children with SCD versus BM children without SCD had higher inflammatory markers, more often had pneumococcal meningitis (71% vs. 39%), and either died (39% vs. 22%) or had a longer hospital stay (15 vs. 11 days).

Chimeric antigen receptor T-cell therapy (CAR-T) targeting CD19 has been associated with remarkable responses in paediatric patients and adolescents and young adults (AYA) with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). Tisagenlecleucel, the first approved CD19 CAR-T, has become a viable treatment option for paediatric patients and AYAs with BCP-ALL relapsing repeatedly or after haematopoietic stem cell transplantation (HSCT). Based on the chimeric antigen receptor molecular design and the presence of a 4-1BB costimulatory domain, tisagenlecleucel can persist for a long time and thereby provide sustained leukaemia control. "Real-world" experience with tisagenlecleucel confirms the safety and efficacy profile observed in the pivotal registration trial. Recent guidelines for the recognition, management and prevention of the two most common adverse events related to CAR-T - cytokine release syndrome and immune-cell-associated neurotoxicity syndrome - have helped to further decrease treatment toxicity. Consequently, the questions of how and for whom CD19 CAR-T could substitute HSCT in BCP-ALL are inevitable. Currently, 40-50% of R/R BCP-ALL patients relapse post CD19 CAR-T with either CD19(-) or CD19(+) disease, and consolidative HSCT has been proposed to avoid disease recurrence. Contrarily, CD19 CAR-T is currently being investigated in the upfront treatment of high-risk BCP-ALL with an aim to avoid allogeneic HSCT and associated treatment-related morbidity, mortality and late effects. To improve survival and decrease long-term side effects in children with BCP-ALL, it is important to define parameters predicting the success or failure of CAR-T, allowing the careful selection of candidates in need of HSCT consolidation. In this review, we describe the current clinical evidence on CAR-T in BCP-ALL and discuss factors associated with response to or failure of this therapy: product specifications, patient- and disease-related factors and the impact of additional therapies given before (e.g., blinatumomab and inotuzumab ozogamicin) or after infusion (e.g., CAR-T re-infusion and/or checkpoint inhibition). We discuss where to position CAR-T in the treatment of BCP-ALL and present considerations for the design of supportive trials for the different phases of disease. Finally, we elaborate on clinical settings in which CAR-T might indeed replace HSCT.

Patient experience (PX) is an important evaluation criterion for quality in healthcare. Compared to patient satisfaction, however less research has focused on the development of instruments to measure experiences of patients and their families. In the article, we describe the process of developing a PX questionnaire for the parents of pediatric patients in the context of children's hospital and illustrate the questionnaire items for measuring PX. The phases of the development process included retrospective interviews, description of the themes influencing PX and the metrics for measuring PX, as well as iterative development of three versions of questionnaires including data gathering and factor analysis. The final versions of the surveys suggested for implementation at the hospitals include eight PX statements for the outpatient clinic and five statements for the ward. Compared to satisfaction surveys, the developed surveys emphasize the aspects of parent's attitude towards the illness, support for families, and daily arrangements with a child patient. © 2019 American Psychological Association Inc. All rights reserved.

Context Development of the typical growth phenotype in juvenile acquired hypothyroidism (JHT), the faltering linear growth with increasing weight, has not been thoroughly characterized. Objective To describe longitudinal growth pattern in children developing JHT and investigate how their growth differs from the general population in systematic growth monitoring. Design Retrospective case-control study. Setting JHT cases from 3 Finnish University Hospitals and healthy matched controls from primary health care. Patients A total of 109 JHT patients aged 1.2 to 15.6 years (born 1983-2010) with 554 height and weight measurements obtained for 5 years preceding JHT diagnosis. Each patient was paired with 100 healthy controls (born 1983-2008) by sex and age. Longitudinal growth pattern was evaluated in mixed linear models. Growth monitoring parameters were evaluated using receiver operating characteristics analysis. Results At diagnosis, JHT patients were heavier (mean adjusted body mass index-for-age [BMISDS] difference, 0.65 [95% CI, 0.46-0.84]) and shorter (mean adjusted height-for-age deviation from the target height [(THSDS)-S-DEV] difference, -0.34 [95% CI, -0.57 to -0.10]) than healthy controls. However, 5 years before diagnosis, patients were heavier (mean BMISDS difference, 0.33 [95% CI, 0.12-0.54]) and taller (mean (THSDS)-S-DEV difference, 0.29 [95% CI, 0.06-0.52]) than controls. JHT could be detected with good accuracy when several growth parameters were used simultaneously in screening (area under the curve, 0.83 [95% CI, 0.78-0.89]). Conclusions Abnormal growth pattern of patients with JHT evolves years before diagnosis. Systematic growth monitoring would detect abnormal growth at an early phase of JHT and facilitate timely diagnosis of JHT.

Background: Post-mortem (PM) ethanol production may hamper the interpretation of blood alcohol concentration (BAC) in victims of drowning. Different exclusion criteria (e.g. cases with low BAC or with protracted interval between death and toxicological analysis) have been proposed with no factual figures to reduce the potential bias due to PM ethanol production when examining the prevalence rates for alcohol-related drowning. The aim of this study is to verify the extent to which PM alcohol production may affect the accuracy of studies on drowning and alcohol. Findings: Unintentional fatal drowning cases (n = 967) for which a full medico-legal autopsy and toxicological analysis was performed, in Finland, from 2000 to 2013, and relevant variables (demographic data of the victims, month of incident, PM submersion time, blood alcohol concentration, urine alcohol concentration (UAC), vitreous humour alcohol concentration (VAC) were available. Overall, out of 967 unintentional drownings, 623 (64.4%) were positive for alcohol (BAC > 0 mg/dL), 595 (61.5%) had a BAC ≥ 50 mg/dL, and 567 (58.6%) a BAC ≥ 100 mg/dL. Simultaneous measurements, in each victim, of BAC, UAC, and VAC revealed PM ethanol production in only 4 victims (BAC: 25 mg/dL – 48 mg/dL). These false positive cases represented 0.4% of drownings with BAC > 0 mg/dL and 14.3% of drownings with BAC > 0 mg/dL and <50 mg/dL. Conclusions: The present study suggests that PM ethanol production has a limited impact on research addressing the prevalence rate for alcohol-related drowning and that the use of too rigorous exclusion criteria, such as those previously recommended, may led to a significant underestimation of actual alcohol-positive drowning cases. © 2018, The Author(s).

Symptomatic venous thromboembolism (VTE) occurs in five percent of children treated for acute lymphoblastic leukemia (ALL), but whether a genetic predisposition exists across different ALL treatment regimens has not been well studied. Methods: We undertook a genome-wide association study (GWAS) meta-analysis for VTE in consecutively treated children in the Nordic/Baltic acute lymphoblastic leukemia 2008 (ALL2008) cohort and the Australian Evaluation of Risk of ALL Treatment-Related Side-Effects (ERASE) cohort. A total of 92 cases and 1481 controls of European ancestry were included. Results: No SNPs reached genome-wide significance (p <5 x 10(-8)) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (p <1 x 10(-6)), two loci had concordant effects in both cohorts: ALOX15B (rs1804772) (MAF: 1%; p = 3.95 x 10(-7)) that influences arachidonic acid metabolism and thus platelet aggregation, and KALRN (rs570684) (MAF: 1%; p = 4.34 x 10(-7)) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease. Conclusion: This represents the largest GWAS meta-analysis conducted to date associating SNPs to VTE in children and adolescents treated on childhood ALL protocols. Validation of these findings is needed and may then lead to patient stratification for VTE preventive interventions. As VTE hemostasis involves multiple pathways, a more powerful GWAS is needed to detect combination of variants associated with VTE.

Aim Bacterial meningitis (BM) is a common cause of hearing loss in childhood. Our aim was to investigate bacterial aetiology, hearing impairment and outcome in childhood BM with vs. without otitis media (OM) in Angola. Methods Hearing was tested by auditory brainstem response in 391 (76%) children with confirmed BM. The bacteria identified from the ear discharge were compared to those from cerebrospinal fluid (CSF). The hearing findings were compared among children with vs. without OM on days 1 and 7 of hospitalization, and at follow-ups of 1, 3 and 6 month(s). Results No correlation was found in bacteriology between the ear discharge and CSF. On day 7 in hospital, hearing impairment (>40 dB) was common, regardless of whether concomitant OM or not (in 27% vs. 30%, respectively). Any hearing deficit on day 7 was associated with a higher risk of complicated or fatal clinical course (OR 2.76, CI95% 1.43-5.29, p = 0.002). Conclusion No significant difference prevailed in hearing thresholds between children with or without OM in hospital on day 7 or at later follow-ups. Any hearing impairment during hospital stay associated with a higher risk for complicated clinical course or death.

Punasolusiirrot ovat tärkeä osa leukemiahoitoon ja kantasolusiirtoon liittyviä tukihoitoja. Runsaat punasolusiirrot altistavat rautaylimäärälle, jonka pitkäaikaisvaikutuksia kantasolusiirretyillä lapsilla on tutkittu suhteellisen vähän. Tutkimuksen tarkoituksena oli selvittää rautaylimäärän esiintyvyyttä sekä sen yhteyttä elinvaurioihin ja lapsuusiän pituuskasvuun potilailla, jotka olivat saaneet allogeenisen kantasolusiirron lapsuusiässä akuutin lymfaattisen leukemian vuoksi. Tutkimukseen osallistui 23 potilasta, jotka olivat mediaani-iältään 12.6 (vaihteluväli 7.5-21.4) vuotta. Kehon rautalastin suuruutta arvioitiin laboratoriokokeilla, sydämen ja maksan magneettikuvantamisella sekä laskemalla punasolusiirroista saadun raudan määrä. Käytimme monimuuttuja-analyysiä tutkiaksemme yhteyttä kehon rautalastin ja sydämen toiminnan, maksaentsyymitasojen, insuliiniresistenssin ja pituuskasvun välillä. Plasman ferritiini oli mediaaniarvoltaan 344 (vaihteluväli 40-3235) ng/ml ja ylitti tason 1000 ng/ml kolmella potilaalla (13%). Magneettikuvauksessa yhdellätoista potilaalla (48%) todettiin rautaylimäärä maksassa ja yhdellä potilaalla (4%) rautaylimäärä sydämessä. Sydämen magneettitutkimuksessa ejektiofraktio oli subkliinisesti alentunut kahdeksalla potilaalla (35%), mutta sydämen toiminta ei assosioitunut kehon rautalastiin. Maksaentsyymitaso korreloi punasolusiirroista saadun rautamäärän kanssa (p=0.001), mutta potilailla ei esiintynyt kohonneita maksaentsyymiarvoja tai merkkejä maksavauriosta mediaaniltaan 4.5 vuoden seurannan jälkeen. Rautalasti ei korreloinut pituuskasvun tai insuliiniresistenssin kanssa. Rautaylimäärä on yleinen akuutin leukemian vuoksi kantasoluriirretyillä lapsilla, mutta rautalastiin liittyviä elinvauriota ei esiinny nuorella iällä. Suosittelemme rautalastin arvioimista kaikille potilaille ainakin kerran kantasolusiirron jälkeisen seurannan aikana.

Tutkimuksen tarkoituksena oli kartoittaa Helsingin ja Uudenmaan sairaanhoitopiirin (HUS) sairaaloissa hoidettujen lasten kroonisten B- ja C-hepatiittien tartuntareittejä ja tartunnan riskitekijöitä sekä selvittää, miten hepatiittien seuranta ja hoito on HUS-piirissä toteutunut. Tutkimusaineisto kerättiin retrospektiivisesti strukturoitua tiedonkeruulomaketta käyttäen HUS-piirin sairaaloiden ja HUSLAB:n arkisto- ja sairauskertomustiedostoja. Potilaiden valintakriteereinä olivat alle 16 vuoden ikä ja laboratoriotutkimuksin varmennettu krooninen B- tai C-hepatiitti vuosien 1996-2006 aikana. B-hepatiittia sairastavista lapsista 61/66 oli syntynyt Suomen ulkopuolella, ja valtaosa heidän tartunnoistaan todettiin maahantulotarkastuksen yhteydessä. C-hepatiittia sairastavista lapsista 28/40 oli syntynyt Suomessa. Maahantulotarkastus sekä päihteiden käyttöön liittyvä seulonta olivat tärkeimmät diagnoosiin johtaneet tutkimustilanteet. Antiviraalisesta lääkehoidosta hyötyi 6/13 B-hepatiittia ja 2/4 C-hepatiittia sairastavista lapsista. HUS-piirissä B-hepatiittia esiintyy lähinnä maahanmuuttajataustaisilla lapsilla. Krooninen C-hepatiitti liittyi lapsen tai hänen vanhempiensa huumeiden käyttöön. Tutkimus korostaa lasten B- ja C-hepatiitin seulonta-, seuranta- ja hoitokäytäntöjä selkeyttävän ohjeistuksen tarvetta.