Treatment of Infants and Children With SARS-CoV-2 Monoclonal Antibodies: A European Case Series.

BACKGROUND: Although severe COVID-19 in children is rare, those with certain pre-existing health conditions are more prone to severe disease. Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potent antiviral agents that reduce adverse clinical outcomes in adults, but are commonly not approved for use in pediatric patients. METHODS: We retrospectively evaluated mAb treatment in children <12 years of age or <40kg with SARS-CoV-2 infection between January 1, 2021, and March 7, 2022, in 12 tertiary care centers in 3 European countries. RESULTS: We received data from 53 patients from Austria, Denmark and Germany. Median age was 5.4 years [0-13.8, interquartile range (IQR) = 6.2], and median body weight was 20 kg (3-50.1, IQR = 13). The most frequent SARS-CoV-2 variant in this study, if known, was Omicron, followed by Delta and Alpha. Pre-existing conditions included immunodeficiency, malignancy, hematologic disease, cardiac disease, chronic lung disease, chronic liver disease, kidney disease and diabetes. Forty-two patients received sotrovimab (79%), 9 casirivimab/imdevimab (17%) and 2 bamlanivimab (4%). All but 1 patient survived. Median duration of hospital stay was 3 days (0-56, IQR = 6). Seven patients required treatment in an intensive care unit, and 5 required high-flow nasal cannula treatment. Potential side effects included neutropenia (6/53, 11%), lymphopenia (3/53, 6%), nausea or vomiting (2/53, 4%), rise of alanine transaminase (1/53, 2%) and hypotonia (1/53, 2%). CONCLUSIONS: MAb treatment was well tolerated by children in this cohort.

A pilot study of evaluation of semi-rigid and flexible catheters for less invasive surfactant administration in preterm infants with respiratory distress syndrome-a randomized controlled trial.

BACKGROUND: In respiratory distress syndrome, many neonatology centers worldwide perform minimal invasive surfactant application in premature infants, using small-diameter catheters for endotracheal intubation and surfactant administration. METHODS: In this single-center, open-label, randomized-controlled trial, preterm infants requiring surfactant administration after birth, using a standardized minimal invasive protocol, were randomized to two different modes of endotracheal catheterization: Flexible charrière-4 feeding tube inserted using Magill forceps (group 1) and semi-rigid catheter (group 2). Primary outcome was duration of laryngoscopy. Secondary outcomes were complication rate (intraventricular hemorrhage, soft-tissue damage in first week of life) and vital parameters during laryngoscopy. Between 2019 and 2020, 31 infants were included in the study. Prior to in-vivo testing, laryngoscopy durations were studied on a neonatal airway mannequin in students, nurses and doctors. RESULTS: Mean gestational age and birth weight were 27 + 6/7 weeks and 1009 g; and 28 + 0/7 weeks and 1127 g for group 1 and 2, respectively. Length of laryngoscopy was similar in both groups (61.1 s and 64.9 s) overall (p.77) and adjusted for weight (p.70) or gestational age (p.95). Laryngoscopy failed seven times in group 1 (43.8%) and four times (26.7%) in group 2 (p.46). Longer laryngoscopy was associated with lower oxygen saturation with lowest levels occurring after failed laryngoscopy attempts. Secondary outcomes were similar in both groups. In vitro data on 40 students, 40 nurses and 12 neonatologists showed significant faster laryngoscopy in students and nurses group 2 (p < .0001) unlike in neonatologists (p.13). CONCLUSION: This study showed no difference in laryngoscopy duration in endotracheal catheterization when comparing semi-rigid and flexible catheters for minimal invasive surfactant application in preterm infants. In accordance with preliminary data and in contrast to published in-vitro trials, experienced neonatologists were able to perform endotracheal catheterization using both semi-rigid and flexible catheters at similar rates and ease, in vitro and in vivo. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05024435 Registered 27 August 2021-Retrospectively registered.

Breath-dependent pressure fluctuations in various constant- and variable-flow neonatal CPAP devices.

OBJECTIVE: In continuous positive airway pressure (CPAP) devices, pressure can be generated by two different mechanisms: either via an expiratory valve or by one or more jets. Valved CPAP devices are referred to as constant-flow devices, and jet devices are called variable-flow devices. Constant-flow CPAP devices are said to reduce the imposed work of breathing due to lower breath-dependent pressure fluctuations. The present study investigates the performance of various constant- and variable-flow CPAP devices in relation to breath-dependent pressure fluctuations. DESIGN: Experimental study comparing the pressure fluctuations incurred by seven neonatal CPAP devices attached to an active neonatal lung model. METHODOLOGY: Spontaneous breathing was simulated using a tidal volume of 6 ml at pressure levels of 5, 7, and 9 mbar. The main outcomes were respiratory pressure fluctuations, tidal volume, and end-expiratory pressure. RESULTS: All CPAP devices tested showed respiratory pressure fluctuations, varying from 0.631 to 3.466 mbar. The generated tidal volume correlated significantly with the pressure fluctuations (r = -0.947; p = 0.001) and varied between 5.550 and 6.316 ml. CPAP devices with jets showed no advantage over CPAP devices with expiratory valves. End-expiratory pressure in the nose deviated from the set pressure between -1.305 and 0.644 mbar and varied depending on whether the pressure was measured in the device or in the tube extending to the nose. CONCLUSION: During standard spontaneous breathing, breath-dependent pressure fluctuations in constant- and variable-flow devices are comparable. Pressure measurements taken in the tubing system can lead to a considerable deviation of the applied pressure.

When synchronized isn't synchronous- an experimental benchmarking study on the efficiency of SIMV in very-low-birth weight premature infants.

BACKGROUND: Synchronized ventilation promotes a patient's ability to breathe spontaneously by providing intermittent, mechanical-controlled respiration that is synchronized with the patient's own efforts. In "synchronized-intermittent-mandatory-ventilation" SIMV, assisted ventilation is regulated by frequency settings which dictate the interval at which the ventilator becomes sensitive to respiratory efforts and responds with an assisted breath. SIMV has become one of the most widely used modes of ventilation in neonates. Using a neonatal-active-lung-model (NALM), this in-vitro benchmark study investigated how well synchronization works in SIMV with several ventilators. METHODS: The competence of eight ventilators was tested using a NALM simulator representing a preterm infant weighing approximately 1500 grams. Two conditions were explored: first, the ventilators were set to a constant ventilation rate, while the NALM was adjusted to frequencies equal to and below this ventilation rate. The second condition varied the ventilators' rates while the NALM frequency was held constant. Correctly triggered breaths were counted and displayed as a percentage (%) of the total potential triggerable breaths. RESULTS: Performance among devices significantly differed, ranging from a low 38.9% competency to a max of 71.7% under the first condition, and 70.7% to 100% under the second condition. CONCLUSIONS: At high SIMV frequencies, synchronization between the patient and ventilator becomes increasingly limited. Despite their identical ventilator functions, SIMV algorithms of the various manufacturers and models tested, deliver ventilation rates with significantly different degrees of synchronization; not only in comparison to each other, but also in their own ability to continuously and effectively synchronize breaths under variable conditions, typical of preterm lungs.

Effects of an exclusive human-milk diet in preterm neonates on early vascular aging risk factors (NEOVASC): study protocol for a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial.

BACKGROUND: Preterm birth accounts for approximately 11% of all livebirths globally. Due to improvements in perinatal care, more than 95% of these infants now survive into adulthood. Research has indicated a robust association between prematurity and increased cardiovascular risk factors and cardiovascular mortality. While the innate adverse effects of prematurity on these outcomes have been demonstrated, therapeutic strategies on the mitigation of these concerning developments are lacking. The primary objective of the NEOVASC clinical trial is therefore to investigate whether the administration of a prolonged exclusive human-milk diet in preterm infants is capable of alleviating the harmful effects of preterm birth on the early development of cardiovascular risk factors. METHODS: The NEOVASC study is a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial conducted in four Austrian tertiary neonatal care facilities. The purpose of the present trial is to investigate the effects of a prolonged exclusive human-milk-diet devoid of bovine-milk-based food components on cardiovascular and metabolic risk factors at 1, 2, and 5 years of corrected age. Primary outcomes include assessments of fasting blood glucose levels, blood pressure levels, and the distensibility of the descending aorta using validated echocardiographic protocols at 5 years of corrected age. The test group, which consists of 200 preterm infants, will therefore be compared to a control group of 100 term-born infants and a historical control group recruited previously. DISCUSSION: Given the emerging implications of an increased cardiovascular risk profile in the potentially growing population of preterm infants, further research on the mitigation of long-term morbidities in formerly preterm infants is urgently warranted. Further optimizing preterm infants' nutrition by removing bovine-milk-based food components may therefore be an interesting approach worth pursuing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04413994 . Registered on 4 June 2020.

Introduction and feeding practices of solid food in preterm infants born in Salzburg!

BACKGROUND: It is shown that meeting the increased nutritional demand of preterm infants from birth is not only important for survival but essentially contributes to the infants` overall development and long-term health. While there are established guidelines for weaning term infants, evidence regarding preterm infants is scarce and less precise. The aim of this study was to identify the current practices on introducing solids to preterm infants amongst caregivers in Salzburg and determine potential reasons for early weaning. METHODS: Altogether 68 infants born between 24 0/7 and 36 6/7 weeks were recruited and detailed structured interviews with the caregivers were conducted at 17 weeks corrected age. Weight, height and head circumference were collected. RESULTS: 52% of the study group received solids before the recommended 17 weeks corrected age. For this group the mean age being 13.77 ± 1.11 weeks corrected age. Premature introduction of solids significantly correlates with exclusively and early formula-feeding. 34% were weaned due to recommendation by their paediatrician. 23% of the preterm infants even received solids before 12 weeks corrected age, putting them at risks for developing obesity, celiac disease and diabetes. CONCLUSIONS: This study shows the necessity for clear guidelines regarding the introduction of complementary feeding in preterm infants as well as the importance of their implementation. Caregivers should receive information on this topic early enough and they should fully understand the difference between chronological and corrected age.

Growth, Feeding Tolerance and Metabolism in Extreme Preterm Infants under an Exclusive Human Milk Diet.

BACKGROUND: For preterm infants, human milk (HM) has to be fortified to cover their enhanced nutritional requirements and establish adequate growth. Most HM fortifiers are based on bovine protein sources (BMF). An HM fortifier based on human protein sources (HMF) has become available in the last few years. The aim of this study is to investigate the impact of an HMF versus BMF on growth in extremely low birth weight (ELBW, <1000 g) infants. METHODS: This was a retrospective, controlled, multicenter cohort study in infants with a birthweight below 1000 g. The HMF group received an exclusive HM diet up to 32+0 weeks of gestation and was changed to BMF afterwards. The BMF group received HM+BMF from fortifier introduction up to 37+0 weeks. RESULTS: 192 extremely low birth weight (ELBW)-infants were included (HMF n = 96, BMF n = 96) in the study. After the introduction of fortification, growth velocity up to 32+0 weeks was significantly lower in the HMF group (16.5 g/kg/day) in comparison to the BMF group (18.9 g/kg/day, p = 0.009) whereas all other growth parameters did not differ from birth up to 37+0 weeks. Necrotizing enterocolitis (NEC) incidence was 10% in the HMF and 8% in the BMF group. CONCLUSION: Results from this study do not support the superiority of HFM over BMF in ELBW infants.

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3-3.2) as compared to controls (1.3; IQR 0.8-2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15-0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92-4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10-7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00-129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46-4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.

Gender differences and the role of parental education, school types and migration on the body mass index of 2930 Austrian school children : A cross-sectional study.

BACKGROUND: Austria faces increasing numbers of childhood overweight and obesity. Despite increasing numbers of studies, associations between parental body mass index (BMI) and education and the school type on overweight/obesity in students have not been reported. The objective of this study was to evaluate the influence of these parameters on the genesis of overweight/obesity in a large cohort representative of youth in Upper Austrian. METHODS: A cross-sectional analysis of data from 2930 children and adolescents aged 10, 14 or 17 years from 11 different state school types was conducted. Students and their parents completed a questionnaire and heights and weights were measured. RESULTS: Of the students 16.9% fulfilled the criteria for overweight and 5.6% for obesity, with the highest rates in the 10-year-olds (19.6% and 5.8%, respectively). While no gender differences were present in the youngest age group, the body mass index (BMI) during adolescence remained higher in boys but decreased significantly in girls. Male gender remained a risk factor through all calculations. Boys were overrepresented in schools with lower education levels and more often had BMIs ≥ 85th and ≥95th percentile. Higher parental education levels and lower parental BMIs were associated with lower BMIs of their offspring. Migration was an additional association factor for BMIs ≥ 85th percentile. CONCLUSION: Low parental education levels, higher parental BMIs and migration background were associated with overweight and obesity in 10-year-olds. In adolescence, male gender and higher parental BMIs remained risk factors.

Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea.

IFN-related pathways have not been studied in morphea, and biomarkers are needed. We sought to characterize morphea serum cytokine imbalance and IFN-related gene expression in blood and skin to address this gap by performing a case-control study of 87 participants with morphea and 26 healthy control subjects. We used multiplexed immunoassays to determine serum cytokine concentrations, performed transcriptional profiling of whole blood and lesional morphea skin, and used double-staining immunohistochemistry to determine the cutaneous cellular source of CXCL9. We found that CXCL9 was present at increased concentrations in morphea serum (P < 0.0001), as were other T helper type 1 cytokines. CXCL9 serum concentration correlated with the modified Localized Scleroderma Skin Severity Index (r = 0.44, P = 0.0001), a validated measure of disease activity. CXCL9 gene expression was also increased in inflammatory lesional morphea skin (fold change = 30.6, P = 0.006), and preliminary transcriptional profiling showed little evidence for IFN signature in whole blood. Double-staining immunohistochemistry showed CXCL9 co-localized with CD68+ dermal macrophages. In summary, inflammatory morphea is characterized by T helper type 1 cytokine imbalance in serum, particularly CXCL9, which is associated with disease activity. CXCL9 expression in lesional macrophages implicates the skin as the source of circulating cytokines. CXCL9 is a promising biomarker of disease activity in morphea.

Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients.

Adherence of patients to long-term medication: a cross-sectional study of antihypertensive regimens in Austria.

OBJECTIVE: The objective of this study was to evaluate adherence and causes for non-adherence to antihypertensive therapy in Austrian patients. A special focus was placed on social parameters and behavioural theories. METHODS: Patients were invited via advertisements in community pharmacies in Austria to complete an online survey. Inclusion criteria were an age of 18 years or older, a diagnosis of arterial hypertension and a current prescription of antihypertensive medication. Adherence was measured by the four-item Morisky scale. Non-adherence was defined by at least one point in the Morisky scale. Several demographic, social and behavioural parameters were analysed as potential co-variables associated with adherence. RESULTS: A total of 323 patients completed the online survey, of which 109 (33.7%) met the criteria for non-adherence. In a multivariable model, self-efficacy and age were associated with adherence, whereas intention and barriers were linked to non-adherence; 56 patients (17.3%) were classified as intentionally non-adherent. CONCLUSION: This study demonstrates that non-adherence affects an important proportion of patients in the treatment of arterial hypertension. Young age was a particularly important risk factor for non-adherence, and this patient population is, therefore, in need of special attention. Modifiable risk factors were identified that could help improving the treatment of arterial hypertension and potentially other chronic conditions.

Short report: premastication in rural Gabon--a cross-sectional survey.

Premastication-defined as pre-chewing of food for infants by their caregiver-is a common feeding practice in various societies. To date the impact of premastication on children's health including the potential for transmission of infectious diseases is not well understood. Since there are no epidemiologic data on premastication from resource poor regions in Central Africa, we investigated the epidemiology and demographic variables associated with premastication in Central Africa. Between 2011 and 2012, mothers were interviewed about child feeding behaviors in three rural communities in Gabon. A quarter (n = 20, 24%) of 82 participants stated to perform premastication regularly. Despite the small sample size, our study provides first baseline data for the epidemiology of premastication in Central Africa, indicating that this feeding practice is common in rural communities.

Current evidence and future of automated erythrocyte exchange in the treatment of severe malaria.

Despite the administration of antimalarial treatment, severe malaria still has a high mortality rate. Since overall survival is associated with total parasite biomass, whole blood exchange (e.g. blood exchange transfusions) has been proposed as a potential method to rapidly reduce peripheral parasitaemia. Automated red blood cell exchange has been advocated as a physical method to remove parasites. Compared to exchange transfusion, automated red blood exchange may avoid the risk of volume alterations and haemodynamic distress. Since 1984, there have been 37 published cases in which automated red blood cell exchange was used as an adjunctive treatment in severe malaria caused by Plasmodium falciparum. This short review summarizes current evidence and discusses problems, challenges and goals for future studies and research in order to assess the clinical benefit of automated erythrocyte exchange in severe malaria cases.

Automated red blood cell exchange as an adjunctive treatment for severe Plasmodium falciparum malaria at the Vienna General Hospital in Austria: a retrospective cohort study.

BACKGROUND: Severe falciparum malaria is associated with considerable rates of mortality, despite the administration of appropriate anti-malarial treatment. Since overall survival is associated with total parasite biomass, blood exchange transfusion has been proposed as a potential method to rapidly reduce peripheral parasitaemia. However, current evidence suggests that this treatment modality may not improve outcome. Automated red blood cell exchange (also referred to as "erythrocytapheresis") has been advocated as an alternative method to rapidly remove parasites from circulating blood without affecting patients' volume and electrolyte status. However, only limited evidence from case reports and case series is available for this adjunctive treatment. This retrospective cohort study describes the use of automated red blood cell exchange for the treatment of severe malaria at the Medical University of Vienna. METHODS: Epidemiologic data for imported malaria cases in Austria are reported and data of patients treated for malaria at the General Hospital/Medical University of Vienna were extracted from electronic hospital records. RESULTS: Between 2000 and 2010, 146 patients were hospitalized at the Medical University of Vienna due to malaria and 16 of those were classified as severe malaria cases. Eleven patients of this cohort were potentially eligible for an adjunctive treatment with automated red blood cell exchange. Five patients eventually underwent this procedure within a period of seven hours (range: 3-19 hours) after hospital admission. Six patients did not undergo this adjunctive treatment following the decision of the treating physician. The procedure was well tolerated in all cases and rapid reduction in parasite counts was achieved without occurrence of haemodynamic complications. One patient died within seven days, whereas four patients survived without any sequelae. DISCUSSION AND CONCLUSION: Automated red blood cell exchange was a safe and efficient procedure to rapidly clear peripheral parasitaemia. Whether the fast reduction in parasite biomass may ultimately improve patient survival remains however unclear. Randomized controlled trials are needed to conclusively appreciate the value of this adjunctive treatment.

The use of paediatric artemisinin combinations in sub-Saharan Africa: a snapshot questionnaire survey of health care personnel.

BACKGROUND: Paediatric drug formulations for artemisinin combination therapy (P-ACT) have been developed over the past few years and have been shown to improve the therapeutic management of young children with uncomplicated falciparum malaria. This process was however not equally paralleled by a timely adoption of P-ACT in national and international treatment recommendations. National malaria programmes in sub-Saharan Africa have not yet widely embraced this new therapeutic tool. To which extent P-ACT is used in the field in sub-Saharan Africa is not known to date. METHODS: This snapshot questionnaire survey aimed to provide an overview on the current routine practices for the availability and use of P-ACT as anti-malarial treatment for young children in sub-Saharan Africa. Health care personnel in seven countries in West-, Central, and East-Africa were invited to answer a structured questionnaire assessing use and availability of P-ACT. RESULTS: A total of 71 respondents including doctors, nurses and pharmacy personnel responsible for the anti-malarial treatment of young children were interviewed. P-ACT was used by 83% (95% confidence interval: 73-90%; n = 59) as first-line treatment for young children. Use of 15 different P-ACT products was reported among which only two have received WHO prequalification status and approval by a stringent registration authority. Use of a specific P-ACT product was not linked to consumer prices or availability of supporting clinical trial data, but may depend more on the marketing capacity of the manufacturer. Major differences in frequency and dosing of anti-malarial regimens with identical anti-malarial compounds and the marketing of loose combinations were recorded. CONCLUSION: Paediatric ACT is widely used for the treatment of uncomplicated malaria in young children. However, the majority of P-ACT formulations in use do not meet highest international quality standards evoking concerns for patients' safety and the induction of drug resistance. Improving the quality of currently marketed P-ACT should constitute a public health priority besides their adoption into official treatment recommendations.