Non-TGFß profibrotic signaling in ulcerative colitis after in vivo experimental intestinal injury in humans.

Although impaired regeneration is important in many gastrointestinal diseases including ulcerative colitis (UC), the dynamics of mucosal regeneration in humans are poorly investigated. We have developed a model to study these processes in vivo in humans. Epithelial restitution (ER) and extracellular matrix (ECM) regulation after an experimental injury of the sigmoid colonic mucosa was assessed by repeated high-resolution endoscopic imaging, histological assessment, RNA sequencing, deconvolution analysis, and 16S rDNA sequencing of the injury niche microbiome of 19 patients with UC in remission and 20 control subjects. Human ER had a 48-h lag before induction of regenerative epithelial cells [wound-associated epithelial (WAE) and transit amplifying (TA) cells] along with the increase of fibroblast-derived stem cell growth factor gremlin 1 mRNA (GREM1). However, UC deconvolution data showed rapid induction of inflammatory fibroblasts and upregulation of major structural ECM collagen mRNAs along with tissue inhibitor of metalloproteinase 1 (TIMP1), suggesting increased profibrotic ECM deposition. No change was seen in transforming growth factor ß (TGFß) mRNA, whereas the profibrotic cytokines interleukin 13 (IL13) and IL11 were upregulated in UC, suggesting that human postinjury responses could be TGFß-independent. In conclusion, we found distinct regulatory layers of regeneration in the normal human colon and a potential targetable profibrotic dysregulation in UC that could lead to long-term end-organ failure, i.e., intestinal damage.NEW & NOTEWORTHY The study reveals the regulatory dynamics of epithelial regeneration and extracellular matrix remodeling after experimental injury of the human colon in vivo and shows that human intestinal regeneration is different from data obtained from animals. A lag phase in epithelial restitution is associated with induction of stromal cell-derived epithelial growth factors. Postinjury regeneration is transforming growth factor ß-independent, and we find a profibrotic response in patients with ulcerative colitis despite being in remission.

Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy.

BACKGROUND: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. METHODS: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. RESULTS: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 µg/mL (range 0.005-0.12 µg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] µg/mL) and without (3.1 [range 0.7-11.0] µg/mL) infections during the first year of life (P = .41). CONCLUSIONS: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.

Neonatal mortality and video assessment of resuscitation in four district hospitals in Pemba, Tanzania.

BACKGROUND: We aimed to assess risk factors for neonatal mortality, quality of neonatal resuscitation (NR) on videos and identify potential areas for improvement. METHODS: This prospective cohort study included women in childbirth and their newborns at four district hospitals in Pemba, Tanzania. Videos were analysed for quality-of-care. Questionnaires on quality-of-care indicators were answered by health workers (HW) and women. Risk factors for neonatal mortality were analysed in a binomial logistic regression model. RESULTS: 1440 newborns were enrolled. 34 newborns died within the neonatal period (23.6 per 1000 live births). Ninety neonatal resuscitations were performed, 20 cases on video. Positive pressure ventilation (PPV) was inadequate in 15 cases (75%). Half (10/20) did not have PPV initiated within the first minute, and in one case (5.0%), no PPV was performed. PPV was not sustained in 16/20 (80%) newborns. Of the 20 videos analysed, death occurred in 10 newborns: 8 after resuscitation attempts and two within the first 24 h. Most of HW 49/56 (87.5%) had received training in NR. CONCLUSIONS: Video analysis of NR revealed significant deviations from guidelines despite 87.5% of HW being trained in NR. Videos provided direct evidence of gaps in the quality of care and areas for future education, particularly effective PPV. IMPACT: Neonatal mortality in Pemba is 23.6 per 1000 livebirths, with more than 90% occurring in the first 24 h of life. Video assessment of neonatal resuscitation revealed deviations from guidelines and can add to understanding challenges and aid intervention design. The present study using video assessment of neonatal resuscitation is the first one performed at secondary-level hospitals where many of the world's births are conducted. Almost 90% of the health workers had received training in neonatal resuscitation, and the paper can aid intervention design by understanding the actual challenges in neonatal resuscitation.

Distinct clinical parameters were associated with shorter spontaneous resolution in children with non-tuberculous mycobacterial lymphadenitis.

AIM: Non-tuberculous mycobacteria (NTM) lymphadenitis typically resolves spontaneously, yet factors influencing the duration remain explored. We aimed to identify clinical parameters associated with shorter spontaneous resolution. METHODS: This cohort study included children with NTM lymphadenitis from 1 January 2015 to 1 March 2021 at Copenhagen University Hospital. Time-to-event analysis assessed clinical parameters associated with the duration of NTM lymphadenitis. RESULTS: Sixty children (57% boys) with a median age of 24 months (range 11-84) were included; 13 (22%) received primary surgery, 13 (22%) underwent surgery after a wait-and-see period and 34 (57%) received no intervention. In children without intervention, the median duration was 10 months (range 2-25). Faster resolution was associated with parental-reported lymph node enlargement within 2 weeks (HR 2.3, 95% CI 1.0-5.0; p = 0.044), abscess on ultrasound examination (HR 3.3, 95% CI 1.5-7.3; p = 0.003) and skin discoloration and/or perforation within 3 months of onset (HR 4.3, 95% CI 1.3-14.4; p = 0.017 and HR 3.7, 95% CI 1.5-9.1; p = 0.005). CONCLUSION: Knowledge of predictors for shorter spontaneous resolution of NTM lymphadenitis, such as rapid initial lymph node enlargement, abscess on ultrasound examination, and skin discoloration and/or perforation within 3 months of disease onset, may guide clinical management decisions concerning surgery versus a conservative approach.

Host RNA Expression Signatures in Young Infants with Urinary Tract Infection: A Prospective Study.

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.

Risk factors of stillbirths in four district hospitals on Pemba Island, Tanzania: a prospective cohort study.

BACKGROUND: More than 2 million third-trimester stillbirths occur yearly, most of them in low- and middle-income countries. Data on stillbirths in these countries are rarely collected systematically. This study investigated the stillbirth rate and risk factors associated with stillbirth in four district hospitals in Pemba Island, Tanzania. METHODS: A prospective cohort study was completed between the 13th of September and the 29th of November 2019. All singleton births were eligible for inclusion. Events and history during pregnancy and indicators for adherence to guidelines were analysed in a logistic regression model that identified odds ratios [OR] with a 95% confidence interval [95% CI]. RESULTS: A stillbirth rate of 22 per 1000 total births in the cohort was identified; 35.5% were intrapartum stillbirths (total number of stillbirths in the cohort, n = 31). Risk factors for stillbirth were breech or cephalic malpresentation (OR 17.67, CI 7.5-41.64), decreased or no foetal movements (OR 2.6, CI 1.13-5.98), caesarean section [CS] (OR 5.19, CI 2.32-11.62), previous CS (OR 2.63, CI 1.05-6.59), preeclampsia (OR 21.54, CI 5.28-87.8), premature rupture of membranes or rupture of membranes 18 h before birth (OR 2.5, CI 1.06-5.94) and meconium stained amniotic fluid (OR 12.03, CI 5.23-27.67). Blood pressure was not routinely measured, and 25% of women with stillbirths with no registered foetal heart rate [FHR] at admission underwent CS. CONCLUSIONS: The stillbirth rate in this cohort was 22 per 1000 total births and did not fulfil the Every Newborn Action Plan's goal of 12 stillbirths per 1000 total births in 2030. Awareness of risk factors associated with stillbirth, preventive interventions and improved adherence to clinical guidelines during labour, and hence improved quality of care, are needed to decrease the stillbirth rate in resource-limited settings.

Vaccination timeliness of preterm infants hospitalised in a neonatal intensive care unit in Denmark.

AIM: In Denmark, preterm infants are recommended to receive childhood vaccinations without correction for gestational age. This study aimed to describe the timeliness of the Danish Childhood Vaccination Program in preterm infants during the first 13 months of life and to evaluate possible determinants of delay. METHODS: This retrospective cohort study included preterm infants admitted to a level III neonatal intensive care unit between October 2019 and October 2020. Clinical data were retrieved from medical records and the Danish Vaccination Register. Timely vaccination was defined corresponding to chronological age of 3-, 5- and 12 months, within a time interval of 30 days before to 29 days after the expected date. RESULTS: Analyses included 365 infants. Timely vaccination occurred in 91%, 83% and 67% of preterm infants for the first, second and third vaccination, respectively, and timeliness was highest if born before gestational age 28 weeks. Gestational age 28-31 + 6 weeks and delayed former vaccinations negatively influenced the timeliness of the following vaccinations. CONCLUSION: Most preterm infants received the first vaccination timely; however, timeliness decreased with each subsequent vaccination. Efforts to improve timeliness should focus on counselling healthcare personnel and parents to follow the recommendations for the first and the following vaccinations.

The experiences of children, adolescents and their parents in isolation in a Danish paediatric unit: A qualitative study.

BACKGROUND: Previous studies on adult patients in hospital isolation show that it can be highly stressful, with some patients affected by depression and anxiety. This study aimed to explore how children, adolescents, and their parents perceive isolation and how it affects them physically, psychologically, and socially. METHODS: A qualitative approach was used comprising semi-structured interviews, participant observations, and field notes. FINDINGS: Two adolescents and 13 parents were selected to participate in the interviews, while three children and their parents participated in participant observation. Besides the participant observation one of the adolescents and one parent also participated in interviews. The children and adolescents were isolated at the hospital due to bacterial or viral infections or were carriers of an antibiotic resistant bacteria. After performing a thematic analysis to identify patterns in the data, four themes emerged: 1. Differing information provided about bacteria, virus, hygiene precautions, and isolation, 2. Dependence on healthcare professionals, 3. Impact of the environment, and 4. Coping and psychological reactions on isolation. DISCUSSION: The participants conveyed positive and negative experiences and emotions during isolation in relation to daily activities, psychological well-being, and social life. Adolescents and their parents requested clear comprehensible and consistent information on isolation from healthcare professionals. APPLICATION TO PRACTICE: To improve hospital isolation for children, adolescents, and their parents, well-written information on isolation and hygiene precautions is crucial, as are evolving strategies to minimise social exclusion and the emotional impact of isolation.

Response to pneumococcal conjugate and polysaccharide vaccination in children with rheumatic disease.

Children with rheumatic disease and compromised immune system have an increased risk of infection. Streptococcus pneumoniae is a frequent pathogen, and immunization is recommended. In this study, we investigated whether immunocompromised children with rheumatic disease do respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. The study was conducted at two tertiary referral hospitals in Denmark from 2015 to 2018. Patients with rheumatic disease and compromised immune system aged 2-19 years were eligible. Patients were vaccinated with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. A blood sample was collected before vaccination and after each vaccination. IgG antibodies were quantified for twelve serotypes. Seroprotection for each serotype was defined as IgG ≥0.35 µg/mL. A total of 27 patients were enrolled. After the conjugate vaccine, an increase in antibody titres compared with pre-vaccination was found for all serotypes and 9/12 were significant. After the polysaccharide vaccine, the antibody titres for all serotypes but one was seen to increase but none reached significance. The proportion of patients protected before immunization ranged from 20.8% to 100% for the individual serotypes. Odds ratio for achieving seroprotection after the conjugate vaccine was >1 for 10/12 serotypes but only significant for three serotypes. After the polysaccharide vaccine, the odds ratio was >1 for 9/12 serotypes but none reached significance. In conclusion, children with rheumatic disease and compromised immune system respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine and maintain antibody levels upon subsequent immunization with 23-valent pneumococcal polysaccharide vaccine.

Unexplained fever in children-Benefits and challenges of FDG-PET/CT.

AIM: To explore [fluorine-18]-fluoro-2-deoxy-d-glucose positron-emission-tomography/computed tomography (18 FDG-PET/CT) in patients where standard investigations were non-diagnostic. METHODS: We reviewed medical records of previously healthy children who had 18 FDG-PET/CT performed at Copenhagen University Hospital in 2015-2020 due to unexplained fever. RESULTS: Thirty-five of 819 paediatric 18 FDG-PET/CT were performed due to unexplained fever. The final diagnoses were malignancy (11%), infections (23%), inflammatory diseases (43%) and miscellaneous (26%). 18 FDG-PET/CT was diagnostic in six cases with Takayasu's arteritis, tuberculosis, Langerhans cell histiocytosis and Ewing sarcoma. Sixteen cases had focal 18 FDG-uptake, but 18 FDG-PET/CT could only differentiate malignancy, infection and inflammation in three cases. In six cases with inflammatory diseases and no focal signs, PET/CT was normal except increased non-specific 18 FDG-uptake in bone marrow and spleen in five cases. One case was false positive (suspicion of appendicitis) and two false negative (leukaemia and inflammatory disease). CONCLUSION: 18 FDG-PET/CT was diagnostic, or contributed to the diagnosis, in several children with unexplained fever referred to a tertiary centre. Challenges comprised (i) only increased non-specific 18 FDG-uptake in bone marrow and spleen in half of cases with inflammatory diseases, (ii) no differentiation between complicated infections, malignancy and inflammation in most cases with focal processes and (iii) a small risk of false positive and false negative results.

The right antibiotic for the right neonate? A prospective observational cohort study at a district hospital in Pemba, Tanzania.

BACKGROUND: The highest neonatal mortality is in Sub-Saharan Africa, where neonatal sepsis accounts for approximately 50%. At Pemba Island, Tanzania, we examined the use of prophylactic antibiotics in neonates and related it to WHO guidelines and compared clinical signs of infection with the use of antibiotic treatment; furthermore, we aimed to investigate all use of antibiotic treatment in the neonatal period. METHOD: This prospective observational cohort study was performed from 1 January 2022 to 15 April 2022 at a district hospital on Pemba Island, Tanzania. Women admitted in early established or active labour, and their neonates, were eligible for inclusion. We used questionnaires for mother and health worker and examined the neonates 2 h after birth. Follow-up was made at discharge or at 18 h of life, and days 7 and 28. RESULTS: We included 209 women and their 214 neonates. The neonatal mortality was 5 of 214 (23 per 1000 live births). According to WHO guidelines 29 (13.6%) had ≥ 1 risk factor for infection. Of these, three (10.3%) received prophylactic antibiotic treatment; only one (3.4%) received the correct antibiotic drug recommended in guidelines. Thirty-nine (18.2%) neonates had ≥ 1 clinical indicator of infection and 19 (48.7%) of these received antibiotic treatment. A total of 30 (14.0%) neonates received antibiotics during the study period. Twenty-three (76.7%) were treated with peroral antibiotics. CONCLUSION: Adherence to WHO guidelines for prophylactic antibiotic treatment to prevent neonatal infection was low. Further, only half of neonates with clinical signs of infection received antibiotics.

Pertussis in infants in Nordic countries.

AIM: A life-course immunisation approach is required to prevent and control pertussis. We aimed at reviewing pertussis incidence among infants in Denmark, Finland, Norway and Sweden, and at putting these data in the context of national surveillance systems and vaccination schedules. METHODS: We collected 2014-2018 data on pertussis incidence, on pertussis vaccination schedules and on coverage of the third dose of the diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine from publicly available sources. We gathered opinions on national surveillance systems from public health and paediatrics experts of the relevant countries. RESULTS: The pertussis vaccination schedules and coverage in infancy were similar across countries. All countries except Denmark recommended an additional booster vaccine dose for adolescents. None of the countries had maternal immunisation recommendation. Mean pertussis incidence in Denmark, Sweden and Finland was 168, 76 and 35 per 100,000 infant-years, respectively. Data were insufficient to derive a mean incidence in Norway. There were no systematic differences in the national surveillance systems across the countries. CONCLUSION: The higher mean pertussis incidence in Denmark may be explained by the lack of recommendations for adolescent pertussis booster vaccination. Further investigations are warranted.

Health screening among children newly granted asylum in Denmark.

AIM: To describe the findings and recommendations of the general health assessment (GHA) of newly resettled refugee children in Denmark. METHODS: This cross-sectional study included children (aged <18 years) undergoing GHA from 2017 to 2019 at a university hospital Section of Immigrant Medicine. GHA was offered to all refugees newly resettled in the Municipality of Copenhagen. It comprised of a structured questionnaire, clinical examination, blood test and recommendations. RESULTS: In the study period, 107 children were eligible, 100 children had a GHA performed and of whom all were included in the study. Trauma was reported in 61% (n = 61/100) of children. The median duration of the asylum-seeking process was 18 months (IQR: 8-24), and the highest number of relocations was nine. Latent tuberculosis (n = 2/100 [2%]) was the only infectious disease diagnosed. Specific recommendations for follow-up were frequent and included referral to specialist departments (n = 26/100 [26%]), suggestions for family doctor (n = 96/100 [96%]) and for municipality (n = 62/100 [62%]). CONCLUSION: Self-reported trauma was frequent among 100 newly resettled refugee children. For most children, the asylum process was protracted and included several relocations. Specific follow-up recommendations were given to the vast majority. GHA may contribute to improving health, which could possibly support integration for the child and family.

Immunity to vaccine-preventable diseases among paediatric healthcare workers in Denmark, 2019.

BackgroundHealthcare workers (HCW) have been identified as index cases in disease outbreaks of vaccine-preventable diseases (VPD) in hospitals.AimWe investigated whether Danish paediatric HCW were protected against selected serious VPD.MethodsWe included 90% of staff members from two paediatric departments. All 555 HCW (496 women) supplied a blood sample for serology and filled in a questionnaire. Antibodies were measured with enzyme immunoassay against measles, mumps, rubella (MMR), varicella zoster, pertussis toxin and diphtheria toxin.ResultsProtective levels of IgG were found for measles (90.3%), mumps (86.5%), rubella (92.3%), varicella (98.6%) and diphtheria (80.5%). We found seropositivity for all three MMR components in 421 (75.9%) HCW, lowest in those younger than 36 years (63.3%). Only 28 (5%) HCW had measurable IgG to pertussis. HCW with self-reported immunity defined as previous infection or vaccination, had protective levels of IgG against measles, mumps, rubella and varicella in 87.4-98.8% of cases, not significantly higher than in those not reporting immunity. Previous history of disease had a high positive predictive value (PPV) of 96.8-98.8%. The PPV for previous vaccination ranged from 82.5% to 90.3%. In contrast, negative predictive values of self-reported history of disease and vaccination were remarkably low for all diseases.ConclusionThe immunity gaps found primarily in young HCW indicate a need for a screening and vaccination strategy for this group. Considering the poor correlation between self-reported immunity and seropositivity, efforts should be made to check HCW's immune status in order to identify those who would benefit from vaccination.

Low-Cost Bubble-CPAP Treatment of a Severe Case of Pneumonia in a Low- and Middle-Income Country: A Case Report on the Importance of Optimizing Bubble-CPAP Setup.

A homemade low-cost bubble continuous positive airway pressure (bCPAP) setup can be created using resources available at most secondary healthcare facilities in low- and middle-income countries (LMICs). This setup has the potential of saving millions of children's lives worldwide; however, treatment failure due to bCPAP setup insufficiencies and lack of educated staff remains a significant obstacle. Here, we report a first-hand experience on the use of an established low-cost bCPAP setup to be used in LMICs and how optimization of two parameters was critical to effectively treat a severe case of lower respiratory disease in a 6-month-old infant in Tanzania. We report this case to strengthen that reducing the resistance in the tube system and minimizing air leakage at the nasal interface are crucial for efficient delivery of the CPAP therapy.

This case report describes how it is possible to successfully treat a 6-month-old infant with severe pneumonia in a low resource setting at a district hospital in Tanzania with a homemade low-cost oxygen therapy system called bubble continuous positive airway pressure (bCPAP). The construction was made of an oxygen concentrator, found in most secondary healthcare facilities in Africa, a nasal prong and a sterile water bottle. When optimized, this setup has the potential to mimic the therapeutic effect of an expensive and very effective therapy used in developed countries. The focus of this case report is how two adjustments of the bCPAP setup were necessary to achieve effective and safe treatment; however, we experienced that this homemade setup was very time-demanding and the quality of the treatment critically depended on the clinician to monitor and constantly optimize the equipment. So for this to be an effective and reliable treatment in secondary healthcare facilities in Tanzania, it requires sufficient staff education and nasal prongs that are suited for the purpose.

Health Workers' Practices in Assessment and Management of Children with Respiratory Symptoms in Primary Care Facilities in Uganda: A FRESH AIR Descriptive Study.

INTRODUCTION: Globally, acute lower respiratory infections are the leading cause of mortality among children under 5 years. Following World Health Organization primary care guidelines, pneumonia is diagnosed based on cough/difficult breathing and fast breathing. We aimed to describe the practices of healthcare workers in primary care health facilities in Uganda in the management of young children with respiratory symptoms especially regarding asthma as opposed to pneumonia. METHODS: Health workers were observed during clinical consultations with children 1-59 months of age presenting with cough and/or difficult breathing at recruitment. Afterward, an exit interview with the caregiver was conducted. Health center availability of clinical guidelines, equipment and supplies for management of children with respiratory symptoms was assessed systematically. RESULTS: A total of 218 consultations with 50 health workers at six health centers were included. Median consultation time was 4 min. Health workers asked history relevant to distinguishing asthma from pneumonia in 16% of consultations. The respiratory rate was counted in 10%. Antibiotics were prescribed to 32% of all the children and to 39% of children diagnosed with pneumonia. Caregivers reported being informed of findings and possible diagnosis in 5% of cases. Medicine and equipment needed for diagnosing and treating asthma were generally unavailable. CONCLUSION: Clinical practices among Ugandan health workers in primary care are insufficient to distinguish between main causes of respiratory symptoms, especially asthma as opposed to pneumonia, in children under five. Irrational use of antibiotics is widespread. Clear communication with caregivers is lacking. This could be due to lack of relevant competencies, medicines, time and supplies. LAY SUMMARY: Globally, the most frequent cause of death for children under five is infections in the lower airways. The World Health Organization recommends that in local health clinics this is defined as cough/difficult breathing and fast breathing. This article focuses on the practices of local health workers in Uganda and how they in practice diagnose and treat children under five with these symptoms. In addition, we try to estimate how much the caregivers of the children understand from the consultation. This is done by observing the healthcare workers (HCWs) and by interviewing the caregivers. In general, we found that the consultations were too short, that too few of the health workers looked for important signs for lower airways disease such as fast breathing and that antibiotics were prescribed in too many of the consultations. Also, the length and quality of the consultations and the supplies at the local health clinics were not sufficient to diagnose and treat asthma, which can often be mistaken for an infection. We believe that it is an important problem that too few children with asthma are being diagnosed correctly and that antibiotics are being prescribed too frequently, the latter being an important cause of antibiotic resistance. Relevant action must be taken to improve this.

Antibody response to vaccination after haematopoietic cell transplantation in children using a reduced dose schedule-A retrospective cohort study.

Children receiving HCT loose protective immunity to vaccines received pre-HCT. Therefore, revaccination post-HCT is of major importance. In Denmark, a vaccination schedule with fewer doses post-HCT has been used, including two doses for diphtheria, tetanus, polio, measles, mumps, and rubella, and one dose only for Haemophilus influenzae type B. The background for this was the presumption that post-HCT immunization constituted booster vaccination of donor immunity. Our objective was to evaluate the proportion of children protected after the scheduled vaccination programme. A nationwide retrospective cohort study of all children who have received an HCT in Denmark during 1994-2012. Antibody levels were analysed in blood samples drawn before and after vaccination, and the probability of achieving protection after the scheduled immunization programme was estimated. A total of 198 children were included. The protection post-immunization was as follows: diphtheria 75.3%, tetanus 89.1%, polio 97.7%, and Haemophilus influenzae type B 94.8%. For diphtheria and tetanus, the probability of achieving protection increased to 93.8% and 97.3%, respectively, after a third dose. For measles, mumps, and rubella, the probability of achieving protection was 89.4%, 80.9%, and 94.2%, respectively. In conclusion, our findings support a more extensive vaccination schedule including three doses for diphtheria and tetanus which are in line with current international guidelines.

Infectious diseases detected by screening after arrival to Denmark in internationally adopted children.

AIM: To show the prevalence of selected infectious diseases among internationally adopted children (IAC) in Denmark. BACKGROUND: Each year approximately 200 IAC arrive in Denmark. These are at increased risk of infectious diseases rarely seen in Danish children. Studies from the 1990s showed that 60% of IAC had infectious diseases and that the majority of these were undetected without screening. METHODS: The study is a prospective study of medical records from children seen in the adoption clinic at Copenhagen University Hospital in the period 2009-2013. Screening was done for hepatitis A (HAV), B (HBV) and C (HCV), syphilis, HIV, tuberculosis (TB) and intestinal parasites. RESULTS: In 245 IAC tested, 2% had evidence of recent HAV infection, 3% with HBV and one child with HCV, and no cases of HIV were found. One child had antibodies against syphilis (anti-Trpa AB positivity), and 2% were latently infected with tuberculosis. We found 30% infected with pathogenic intestinal parasites. Only 46% had serologic evidence of immunisation against HBV. CONCLUSION: The prevalence of infections in IAC was lower than previously reported but compared to the general population, a higher prevalence of intestinal parasites, hepatitis and tuberculosis was found. We recommend that IAC are offered screening shortly after arrival.

No time for change? Impact of contextual factors on the effect of training primary care healthcare workers in Kyrgyzstan and Vietnam on how to manage asthma in children - A FRESH AIR implementation study.

BACKGROUND: Training is a common and cost-effective way of trying to improve quality of care in low- and middle-income countries but studies of contextual factors for the successful translation of increased knowledge into clinical change are lacking, especially in primary care. The purpose of this study was to assess the impact of contextual factors on the effect of training rural healthcare workers in Kyrgyzstan and Vietnam on their knowledge and clinical performance in managing pediatric patients with respiratory symptoms. METHODS: Primary care health workers in Kyrgyzstan and Vietnam underwent a one-day training session on asthma in children under five. The effect of training was measured on knowledge and clinical performance using a validated questionnaire, and by direct clinical observations. RESULTS: Eighty-one healthcare workers participated in the training. Their knowledge increased by 1.1 Cohen's d (CI: 0.7 to 1.4) in Kyrgyzstan where baseline performance was lower and 1.5 Cohen's d (CI: 0.5 to 2.5) in Vietnam. Consultations were performed by different types of health care workers in Kyrgyzstan and there was a 79.1% (CI 73.9 to 84.3%) increase in consultations where at least one core symptom of respiratory illness was asked. Only medical doctors participated in Vietnam, where the increase was 25.0% (CI 15.1 to 34.9%). Clinical examination improved significantly after training in Kyrgyzstan. In Vietnam, the number of actions performed generally declined. The most pronounced difference in contextual factors was consultation time, which was median 15 min in Kyrgyzstan and 2 min in Vietnam. DISCUSSION AND CONCLUSION: The effects on knowledge of training primary care health workers in lower middle-income countries in diagnosis and management of asthma in children under five only translated into changes in clinical performance where consultation time allowed for changes to clinical practice, emphasizing the importance of considering contextual factors in order to succeed in behavioral change after training.

To Bubble or Not? A Systematic Review of Bubble Continuous Positive Airway Pressure in Children in Low- and Middle-Income Countries.

BACKGROUND: Bubble-continuous positive airway pressure (bCPAP) is a simple, low-cost ventilation therapy with the potential to lower morbidity and mortality in children in low- and middle-income countries (LMICs). AIM: To examine (i) whether bCPAP is a safe and effective treatment for children in all age-groups presenting with respiratory distress from any cause, (ii) LMIC-implemented bCPAP devices including their technical specifications and costs and (iii) the setting and level of health care bCPAP has been implemented in. METHOD: A systematic search was performed of Embase, PubMed and Web of Science. Inclusion criteria: bCPAP for children with respiratory distress in all age groups in LMICs. Database searches were performed up to 1 November 2018. RESULTS: A total of 24 publications were eligible for the review. For neonates bCPAP was superior in improving survival and clinical progression compared with oxygen therapy and mechanical ventilation (MV). In two studies bCPAP was superior to low flow oxygen in reducing mortality in children 29 days to 13 months. Respiratory rate reductions were significant across all ages. Only three of six studies in children of all ages evaluated serious adverse events. In 12 studies comprising 1338 neonates treated with bCPAP, pneumothorax was reported 27 times. The majority of studies were carried out at tertiary hospitals in middle-income countries and 50% implemented the most expensive bCPAP-device. CONCLUSION: In neonates and children below 13 months bCPAP is a safe treatment improving clinical outcomes and reducing the need for MV, without an increase in mortality. High-quality studies from non-tertiary settings in low-income countries are needed.