Thrombotic events are common during COVID-19 infection. Aspirin might be beneficial. Objective: Systematic review and meta-analysis of deaths in users and non-users of aspirin. Data sources: Pubmed Medline, Google scholar, Clinicaltrials.gov, Cochrane, to June 8, 2021, Study selection: Studies providing adjusted or matched evaluation of association of exposure to aspirin and death in COVID-19 patients were included. Data extraction and synthesis: Data were used as published, as Odds ratio, hazard ratio or relative risks and 95% CI from which log(OR) and SE were recalculated. These were entered in an inverse variance odds ratios random-effects model, using RevMan 5.4 (the Cochrane Collaboration). Main outcomes and measure: The prespecified outcome studied was death. Results: Nine studies (8 observational, one interventional) included 14989 patients exposed to aspirin and 15857 unexposed. Overall Odds Ratio of death in aspirin exposed patients in a random effects model was 0.63, 95% confidence interval [0.40-0.99], I2 94%. Using a fixed-effect model did not change much the result (0.76 [0.71-0.81], removing the Recovery trial (OR 0.43 [0.38-0.49], I271%, or the two largest studies (0.66 [0.47-0.93], I2 38%) reduced heterogeneity without materially altering the results. The funnel plot showed no evident publication bias Conclusion: this meta-analysis suggests that the use of aspirin may be associated with a lower risk of death in COVID-19. Considering the results of the Recovery Study, it would appear preferable to continue aspirin in patients who have a non-covid indication, but possibly useless to add it if they don’t.

Foot-and-mouth disease (FMD) is widely distributed in Sudan where outbreaks occur on an annual basis especially during the winter months (December-February). This study aimed to increase our understanding of the epidemiological patterns of FMD in Sudan and connections to neighbouring countries by characterising the genetic sequences of FMD viruses (FMDV) collected from seven Sudanese states over a 10-year period (between 2009 and 2018). FMDV was detected in 91 of the 265 samples using an antigen-detection ELISA. Three serotypes were detected: O (46.2%), A (34.1%), and SAT 2 (19.8%). Fifty-three of these samples were submitted for sequence analyses, generating sequences that were characterised as belonging to O/EA-3 (n=18), A/AFRICA/G-IV (n=23) and SAT 2/VII/Alx-12 (n=12) viral lineages. Phylogenetic analyses provided evidence that FMDV lineages were maintained within Sudan, and also highlighted epidemiological connections to FMD outbreaks reported in neighbouring countries in East and North Africa (such as Ethiopia and Egypt). This study motivates continued FMD surveillance in Sudan to monitor the circulating viral lineages and broader initiatives to improve our understanding of the epidemiological risks in the region.

Objective There is a lack of studies comparing Procalcitonin (PCT), C-reactive protein (CRP) and white blood cell (WBC) levels in the differential diagnosis of acute bacterial, viral, and mycoplasmal respiratory infections. It is necessary to explore the correlation between above markers and different types of acute respiratory tract infections (ARTI). Methods 108 children with confirmed bacterial infection were regarded as group A, 116 children with virus infection were regarded as group B, and 122 children with mycoplasma infection were regarded as group C. The levels of PCT, CRP and WBC of the three groups were detected and compared. Results The levels of PCT, CRP and WBC in group A were significantly higher than those in groups B and C (P <0.05). The positive rate of combined detection of PCT, CRP and WBC was significantly higher than that of single detection. There was no significant difference of PCT, CRP and WBC levels between the group of Gram-positive (G+) bacteria infection and Gram-negative (G-) bacteria infection (P >0.05). ROC curve results showed that the area under the curve (AUC) of PCT, CRP and WBC for the diagnosis of bacterial respiratory infections were 0.65, 0.55, and 0.58, respectively. Conclusions PCT, CRP and WBC can be used as effective indicators for the identification of acute bacterial or no-bacterial infections in children. The levels of PCT and CRP have higher differential diagnostic value than that of WBC in infection, and the combined examination of the three is more valuable in clinic.

Background: Aspergillus fumigatus and other fungal species are common pathogens isolated in CF patients and they lead to a variety of diseases like ABPA and invasive aspergillosis. Aims and Objectives: To study the prevalence of Aspergillus colonization, sensitization and ABPA in our cohort of CF patients. Also, to study the various risk factors for Aspergillus colonization and ABPA in these patients. Methodology: This was a observational study in which 30 patients of cystic fibrosis between 0 to 18 years were enrolled visiting a tertiary care hospital in north India during January 2019 till December 2020. Data was collected on pre-structured proforma on cough swab and sputum c/s for bacteria and fungus, skin prick test for Aspergillus fumigatus, total IgE, Aspergillus specific IgE, Aspergillus specific IgG, galactomannan and CXR. Prevalence of Aspergillus colonization, sensitization and ABPA was calculated, Odds ratio for all the postulated risk factors for Aspergillus colonization and ABPA were calculated and further Chi square test was applied to check association of ABPA with pulmonary exacerbation. Results: Patients enrolled were between the age group of 4 months till 18 years of age with the median age being 4.75 years (IQR: 2.25 -11.75). 16.67% (n=5), 36.67% (n=11) of the patients enrolled in our study were colonized and sensitized with Aspergillus fumigatus respectively. While, 23.34% (n=7) of the patients had ABPA. We found positive association of Aspergillus colonization with multiple risk factors under study, in the following order of decreasing odds ratio, inhaled antibiotics (OR: 4.75) followed by use of azithromycin (OR: 3.5), inhaled corticosteroids (OR: 2.6), and atopy (OR: 1.3). Conclusion: Aspergillus fumigatus is a common colonizer in patients of cystic fibrosis (16.67%), and can lead to an inflammatory response and ABPA (23.34%). Use of azithromycin, inhaled antibiotics, inhaled corticosteroids and atopy increases the chances of Aspergillus colonization.

Background: Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies and the performance in clinical practice is essentially unclear.  Objectives: We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease-2019 (COVID-19) and (b) prediction of neutralizing antibodies against SARS-CoV-2 in real-life clinical settings.  Methods: We prospectively included 2’573 consecutive health-care workers and 1’085 inpatients with suspected or possible previous COVID-19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme-linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; lateral-flow immunoassay, LFI), epitopes of SARS-CoV-2 (nucleocapsid, N; receptor-binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan-Ig) were conducted. A positive real-time PCR test from a nasopharyngeal swab was defined as previous COVID-19. Neutralization assays with live SARS-CoV-2 were performed in a subgroup of patients to assess neutralization activity (n=201).  Results: The sensitivity to detect patients with previous COVID-19 was ≥85% in anti-N ECLIA (86.8%) and anti-S1 ELISA (86.2%). Sensitivity was 84.7% in anti-S1/S2 CLIA, 84.0% in anti-RBD+ LFI, 81.0% in anti-N CLIA, 79.2% in anti-RBD ELISA, and 65.6% in anti-N ELISA. The specificity was 98.4% in anti-N ECLIA, 98.3% in anti-N CLIA, 98.2% in anti-S1 ELISA, 97.7% in anti-N ELISA, 97.6% in anti-S1/S2 CLIA, 97.2% in anti-RBD ELISA, and 96.1% in anti-RBD+ LFI. The sensitivity to detect neutralizing antibodies was ≥85% in anti-S1 ELISA (92.7%), anti-N ECLIA (91.7%), anti-S1/S2 CLIA (90.3%), anti-RBD+ LFI (87.9%), and anti-RBD ELISA (85.8%). Sensitivity was 84.1% in anti-N CLIA, and 66.2% in anti-N ELISA. The specificity was ≥97% in anti-N CLIA (100%), anti-S1/S2 CLIA (97.7%), and anti-RBD+ LFI (97.9%). Specificity was 95.9% in anti-RBD ELISA, 93.0% in anti-N ECLIA, 92% in anti-S1 ELISA, and 65.3% in anti-N ELISA. Diagnostic accuracy measures were consistent among subgroups.  Conclusions: The diagnostic accuracy of serological tests for SARS-CoV-2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID-19 deviated substantially from the manufacturer’s specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re-infection.

Objective: To investigate the appropriate drug therapy based on a novel classification system for adenoids based on their appearance. Methods: We used fiberoptic nasal endoscopy to determine the degree and appearance of adenoid hypertrophy (AH). The adenoids were divided into three types: edematous type, common type, and fibrous type. In adenoid tissues, the eosinophils were counted. Immunohistochemistry and western blot were done to determine the expression of CysLTR1, CysLTR2, CGR-α, and CGR-β in different types of adenoids. Results: 70.67% (106/150) AH patients with AR, and of them 68% (72/106) of adenoids were the edematous type. The expression of CGR-α and CGR-β and eosinophil count were higher in the edematous type but not in common and fibrous types. The expression of the leukotriene receptor was stable in all types. There was a positive correlation between eosinophil count in the blood and in the adenoid tissue. Conclusion: AR was the risk factor for the development of AH. Leukotriene receptor antagonist was an important drug for the treatment of AH. The glucocorticoid was only useful in the edematous type. Therefore, for AH patients with AR, patients with edematous type adenoids and/or patients with increased eosinophils in blood routine choose nasal glucocorticoid combined with leukotriene receptor antagonist is appropriate. On the contrary, leukotriene receptor antagonists alone can be selected to treat AH.

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and ESR. In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of NT-proBNP, troponin and AST were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and ALT and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.

The dynamic of SARS-CoV-2 and other respiratory virus in children and adolescents is relevant in clinical context. There are few studies comparing clinical course in COVID-19 (coronavirus disease) and other respiratory virus in pediatric patients. The aim of this study was to compare demographics and clinical features, exams abnormalities, and outcomes in SARS-CoV-2 and other respiratory virus infections in a pediatric population. This was a single-center prospective study, between April 17 to September 30, 2020. We evaluated 76 pediatric COVID-19 and 157 other respiratory virus infections. Rhinovirus occurred in 132/157(84%). COVID-19 patients were significantly older, had more fever (69% versus 50%; p=0.01), pneumonia (22% versus 5%; p<0.01), myalgia (29% versus 8%; p=0.001), headache (31% versus 14%; p=0.01) and worse outcomes than those with other respiratory virus infections. Our data emphasizes differences in clinical presentation and outcomes between pediatric COVID-19 and rhinovirus infections.

Background: Air pollutants induce the increase of inflammatory components in the lungs and the decrease in pulmonary function. Genetic polymorphisms may modify the inflammatory and immunological response to the inhalation of those pollutants. Objective: To investigate effect modification by GST and TNF-α polymorphisms in the association between particulate matter (PM10) and lung function. Methods: This is a cross-sectional epidemiological study with 112 asthmatic children aged 6 to 14 years old. GSTM1, GSTT1, GSTP1, and TNF-α polymorphisms were genotyped using the polymerase chain reaction (PCR) technique. Spirometry tests were conducted. We tested associations using generalized linear models, adjusting for confounding variables. The effect modification of the genetic polymorphisms was assessed, including the genotypes and pollutants. Results: In carriers of the TNF-α-308 GA or AA genotypes, we found a reduction of 11.5% (95% CI: -19.08, -3.30) in FEV1 in the current exposure to PM10 and a reduction of 10.46% (95% CI: -14.91, -5.77) for the 5-day cumulative exposure. The TNF-α-1031 TT genotype was associated with a decline in FEV1 and FEF25-75% for the cumulative exposure to PM10. The GSTP1 wild-type genotype was associated with a decrease in FEF25-75% of 23.45% (95% CI; -30.6, -15.56) and in FEV1 of 13% (95% CI; -15.21, -10.74). We found that among GSTT1 null children, the cumulative exposure to PM10 was also associated with a reduction in FEV1, FVC, and FEF25-75%. Conclusion: Genetic polymorphism in GST and TNF-α may modify the association between particulate matter and pulmonary function in asthmatic children and adolescents.

Introduction. Dietary habits in developing countries are characterized in the last decades by low intake of fruits, vegetables, and high consumption of sweetened drinks. Most of the evidence linking carbohydrate intake and asthma comes from children over 6 years of age. The aim of this study was to examine the association of macronutrient intake with the severity of wheezing exacerbation in children aged 2 to 6 years Methods. We performed a prospective cohort study that included all children aged 2 to 6 years hospitalized by a wheezing exacerbation in two tertiary centers in Rionegro, Colombia. Dietary data were collected using a food frequency questionnaire (FFQ) validated in the Colombian population. Gina classification of acute wheezing in children 5 years and younger was to define the severity of the wheezing Results During the study period, 228 cases of patients with wheezing exacerbation were included. Wheezing severity was dose-dependently associated with protein and carbohydrate-rich intake. The variables included in the multivariable analysis included reactive C protein, smoking at home, atopic dermatitis, protein, and carbohydrate-rich food intake Conclusion High carbohydrate-rich food intake was associated with severity of wheezing exacerbation adjusted by other known risk factors such as atopic, smoking, and reactive C protein. Also, we found a negative association of severity of wheezing exacerbation with high protein-rich food intake adjusted by the factors mentioned above. This evidence should motivate the development of public health policies to control the consumption of sugar-rich products in children under 6 years of age.

A case of acute necrotising pancreatitis following the second dose of Pfizer-BioNTech COVID-19 mRNA vaccineAs of 22 June 2021, there have been about 400,000,000 doses of the Pfizer-BioNTech COVID-19 mRNA vaccine administered world-wide. At this time, 176 cases of pancreatitis have been reported in pharmacovigilance reports submitted to the WHO.1 No epidemiological link between the Pfizer-BioNTech COVID-19 mRNA vaccine and pancreatitis has been reported. We report a case of acute necrotising pancreatitis following the second dose of the Pfizer-BioNTech COVID-19 mRNA vaccine. This case has been reported to the New Zealand Pharmacovigilance Centre and the patient has consented to publication of the case report.A 43-year-old, NZ European male was diagnosed with acute necrotising pancreatitis 10 hours following the administration of his second Pfizer-BioNTech COVID-19 mRNA vaccine. He has a background of atopy with seasonal rhinitis, eczema and asthma, all of which are ‘mild’. He takes no regular medications and takes as needed melatonin 2 mg nocte, cetirizine 10 mg for hay fever, and betamethasone and emollient cream for dermatitis. He has no family history of note and works in a senior professional role. He drinks six standard units of alcohol per week, has never been a tobacco smoker and does not use recreational drugs – and his employer undertakes regular drug testing.He had a previous episode of pancreatitis in 2011, precipitated by high alcohol intake during a holiday abroad. He is otherwise previously well. There is no family history of note, his father was a smoker and died of lung cancer in his 60s, his mother is well, he has two siblings and three children all of whom are well. He is not aware of any diseases of note in his extended family.In May 2021 he received his second dose of Pfizer-BioNTech COVID-19 mRNA vaccine, he was well at that time. Four hours after the dose he had two 330ml bottles of 5% alcohol beer with his dinner. Six hours after the dose he became unwell with nausea, epigastric pain, and vomiting. Ten hours after the dose blood tests on admission to hospital included: white cell count 18.5 x109/L (4 - 11), neutrophils 15.5 x109/L (1.9 - 7.5), lymphocytes 0.8 x109/L (1.0 - 4.0), CRP <3 mg/L (<5), lipase 23,750 U/L (10 – 70), and triglycerides 3.3 mmol/L. Acute pancreatitis was diagnosed. An ultrasound scan showed pancreatitis without evidence of cholelithiasis. He subsequently deteriorated and a computer tomography (CT) scan on 17 May, day 9 of the illness, showed severe necrotising pancreatitis with collections.During the admission under a specialist hepatobiliary surgical team, known causes of pancreatitis were excluded including: steroid use, trauma, family history of autoimmune conditions, and infection. He did not have the risk factors of obesity, smoking or heavy alcohol consumption. He had the risk factor of a previous episode of acute pancreatitis. The incidence of pancreatitis in New Zealand Europeans in this age group is approximately 50 per 100,000 per year.2 Idiopathic cases represent about 15% of these.Using the Naranjo criteria, the pancreatitis being ’caused’ by the Pfizer-BioNTech COVID-19 mRNA vaccine score was 6 ‘probable’.3 Clinical case discussion (including a hepatobiliary surgeon, gastroenterologist and clinical pharmacologist) concluded that while idiopathic pancreatitis could not be excluded, the onset of symptoms and findings were consistent with an acute precipitating event around the time the second vaccine dose was administered.In addition to the 176 cases reported in VigiBase™, searches of PubMed and Google Scholar™ identified two published case reports of pancreatitis following the Pfizer-BioNTech COVID-19 mRNA vaccine. These were following administration of the first dose of the Pfizer-BioNTech COVID-19 mRNA vaccine. In one case symptoms developed several hours after vaccine administration and the other several days after vaccine administration.4,5Acute pancreatitis is a rare in patients with COVID-19 but characteristic patterns of illness have been reported.6 This raises the possibility that an immune response to either the virus or the vaccine could have common sequalae.This case of acute pancreatitis was temporally associated with the Pfizer-BioNTech COVID-19 mRNA vaccine suggesting a causal link. The characteristics of pancreatitis cases associated with the Pfizer-BioNTech COVID-19 mRNA vaccine should be examined to see if a consistent pattern is present.VigiAccess™ http://www.vigiaccess.org/ - accessed June 24, 2021.Pendharkar SA, Mathew J, Zhao J, Windsor JA, Exeter J, Petrov MS. Ethnic and geographic variations in the incidence of pancreatitis and post- pancreatitis diabetes mellitus in New Zealand: a nationwide population- based study. 2017;130(1450):14.Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther . 1981;30(2):239-245. doi:10.1038/clpt.1981.154Cieślewicz A, Dudek M, Krela-Kaźmierczak I, Jabłecka A, Lesiak M, Korzeniowska K. Pancreatic Injury after COVID-19 Vaccine—A Case Report. Vaccines . 2021;9(6):576. doi:10.3390/vaccines9060576Parkash O, Sharko A, Farooqi A, Ying GW, Sura P. Acute Pancreatitis: A Possible Side Effect of COVID-19 Vaccine. Cureus . Published online April 28, 2021. doi:10.7759/cureus.14741Bircakova B, Bruha R, Lambert L, Grusova G, Michalek P, Burgetova A. A bimodal pattern of the onset of COVID-19 related acute pancreatitis supports both the cytotoxic and immune-related pathogenesis – a systematic review. Scand J Gastroenterol . 2021;56(7):870-873. doi:10.1080/00365521.2021.1922751

Background: Uncontrolled chronic rhinosinusitis (CRS) needing consideration of surgery is a growing health problem yet its risk factors at individual level are not known. Our aim was to examine risk factors of revision endoscopic sinus surgery (ESS) at the individual level by using artificial intelligence. Methods: Demographic and visit variables were collected from electronic health records (EHR) of 790 operated CRS patients. The effect of variables on the prediction accuracy of revision ESS was examined at the individual level via machine learning models. Results: Revision ESS was performed to 114 (14.7%) CRS patients. The logistic regression, gradient boosting and random forest classifiers had similar performance (AUC values .746, .745 and .747, respectively) for predicting revision ESS. The best performance was yielded by using logistic regression and long predictor data retrieval time (AUC .809, precision 36%, sensitivity 70%) as compared with data collection time from baseline visit until 0, 3 and 6 months after the baseline ESS (AUC values .668, .717 and .746, respectively). The number of visits, number of days from the baseline visit to the baseline ESS, age, CRS with nasal polyps (CRSwNP), asthma, NERD and immunodeficiency or its suspicion were associated with revision ESS. Age and the number of visits before baseline ESS had non-linear effects for the predictions. Conclusions: Intelligent data analysis found important predictors of revision ESS at the individual level, such as visit frequency, age, Type 2 high diseases and immunodeficiency or its suspicion.

Objective: We developed a research usefulness tool collating published criteria and examined if randomised controlled trials (RCTs) addressing preterm birth were useful. Search Strategy: Cochrane library. Selection Criteria: Published RCTs within 56 preterm birth Cochrane reviews. Data Collection and Analysis: A usefulness tool was developed with eight criteria combining 13 items identified through literature searches and consensus. RCTs were evaluated for compliance with each item by multiple assessors (reviewer agreement 95-98%). Proportions with 95% confidence interval (CI) were calculated and compared for change over time using ≧ 2010 as a cut-off, with relative risks (RR). Main Results: Among 350 selected RCTs, only 38 (11%, 95% CI 8-15%) met half of the usefulness criteria. Compared to trials before 2010, recent trials used composite or surrogate (less informative) outcomes more often (13% vs 25%, RR 1.87, 95% CI 1.19-2.93). Only 17 trials reflected real life (pragmatism) in design (5%, 95% CI 3-8%), with no improvements over time. No trials reported involvement of mothers to reflect patients’ top priorities in question definition or outcomes selection. Recent trials were more transparent with prospective registration (0.5% vs 28%, RR 58, 95% CI 8-420%), availability of protocol (0.5% vs 15%, RR 32, 95% CI 4-237%) and data sharing statements (2% vs 8%, RR 3, 95% CI 1-10%). Conclusion: Clinical trials in preterm birth lacked many usefulness features, with one tenth of trials meeting half of the items evaluated. Use of informative outcomes, patient centeredness, pragmatism and transparency should be key targets for future research planning.

Objective: To describe the burden of influenza among pregnant women and their young infants. Design: Prospective cohort study. Setting: Rural western Kenya. Population: Pregnant women below 31 weeks of gestation and their infants aged 6 months and below Methods: We conducted weekly follow-up until 6 months postpartum to identify acute respiratory illnesses (ARI). We collected nasal/nasopharyngeal and oropharyngeal swabs from mothers/infants with ARI and tested for influenza A and B using polymerase chain reaction. We calculated incidence of laboratory-confirmed influenza per 1,000 person-months. Main outcome measure: Incidence of medically attended influenza illness among pregnant women and its impact on birth outcomes. Results: During June 2015–May 2020, we enrolled 3,026 pregnant women at a median gestational age of 16 weeks (interquartile range [IQR], 13, 18) and followed 2,550 infants. Incidence of laboratory-confirmed influenza during pregnancy (10.3 episodes per 1,000 person-months [95% CI 8.6–11.8]) was 2-fold higher than in the postpartum period (4.0 [95% CI 2.6–5.5]; p<0.01), and significantly higher among HIV-infected pregnant women (15.6 [95% CI 11.0–20.6] vs. 9.1 [95% CI 7.5–10.8]; p<0.01). Incidence among young infants was 4.4 (95% CI 3.0–5.9) and similar among HIV-exposed and HIV-unexposed infants. Conclusion: Our findings suggest a substantial burden of influenza illnesses during pregnancy, with a higher burden among HIV-infected mothers. Kenyan authorities should consider the value of vaccinating pregnant women, especially if HIV-infected. Funding: This work was supported by funding [Grant number GH002133] from the U.S. CDC, through the Influenza Division. Keywords: Burden, influenza, pregnant women, infants

Emergence of Congenital Chagas Disease in Ireland and the UK. Stone RG1, Gavin P1, Nolder D2, McGettrick P3, Keogh A4, Mc Entagart N4, Drew R5, Lambert J3, Ferguson W11. Paediatric Infectious Diseases, Rotunda Hospital and Children’s Health Ireland at Temple Street, Dublin2. Diagnostic Parasitology Laboratory, The London School of Hygiene and Tropical Medicine, London, UK3. Infectious Diseases, The Mater Misericordiae University Hospital, Dublin4. Histopathology, Rotunda Hospital, Dublin5. Microbiology, The Rotunda Hospital, Dublin

A document by Blair Wylie, written on Authorea.

Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Awareness of the multisystem concerns that face persons with CF (PwCF) has also continued to be recognized as an important aspect of the burden of the disease. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, an understanding of worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served, ranging from the advances in care in the United States (US) to the challenges of disease recognition and diagnosis in low-and-middle-income countries (LMIC). This review is the third in a three-part CF Year in Review 2020 series, focusing on the multi-system effects of CF. Part one focused on the literature related to CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators, while part two focused on pulmonary outcomes, radiographic and physiologic assessments, as well as infection and inflammation. Part three has been split into two individual parts, Part 3A presented here, and Part 3B related to CF specific nutrition and gastrointestinal publications will also be published this year. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.

Introduction: In the era of data-driven decision-making, an unacceptable haziness and inconsistency surrounds the yearlong scientific and public debate on the school closure policy in the COVID-19 pandemic mitigation efforts. Aim: The present literature review stems out of the need for a clear scaffold collecting in one place all current evidence, as well as helping organizing incoming future evidence, concerning both the role of schools in driving the Sars-CoV-2 community spread and the cost-effectiveness of school closure in containing such spread. Methods: References for this review were initially identified through searches of PubMed, Scopus and Cochrane Library for articles published from March, 2020, to March, 2021 by use of the terms “Schools” “COVID-19” “pandemic” “clusters” “outbreak” “seroprevalence”. Further search was undertaken through Google Scholar and ResearchGate, and finally through Google. Results: School closure at times of high background prevalence of COVID-19 should not be considered a measure implemented to protect the health of children. Children had lower secondary attack rates than adults and that they infrequently represented the index case. One year of pandemic has been sufficient for the emergence of one indication of concern: a potentially increased burden of paediatric mental health disorders. Conclusions: A fact-based understanding of what is currently known on such a consequential policy is required to provide a basis of evidence for an advocacy of either school closure or school opening at times of high intensity community transmission of Sars-CoV-2.

Objective: To explore the impact of risk factors from three different time periods on negative birth experience. Design: Register-based cohort study. Setting: Sweden. Population: Nulliparous women giving birth to singleton, term infants in 2013–2018 (n = 83 335), elective caesarean sections (CS) excluded. Methods: Hierarchical logistic regression was performed to calculate adjusted odds ratios (aOR) with 95% confidence intervals (CIs) in three blocks, each representing risk factors from one of three time periods: I) before pregnancy, II) pregnancy, III) labour. Main Outcome Measurement: Negative birth experience, defined as ratings of ≤ 4 on a ten-point scale. Results: Poor self-rated health (SRH) was the only pre-gestational factor remaining associated with negative birth experience after adjustment for pregnancy- and labour-related factors (aOR 1.22, 95% CI 1.10–1.36). Fear of childbirth and treatment for psychiatric disorder during pregnancy were both associated with negative birth experience (aOR 1.53, 95% CI 1.36–1.73; aOR 1.51, 95% CI 1.35–1.68), as were all labour-related factors included in the model. Women giving birth by operative vaginal delivery or unplanned CS under regional anaesthesia had three-fold higher ORs for rating their overall birth experience as negative (aOR 3.23, 95% CI 2.99–3.50; aOR 3.04, 95% CI 2.77–3.33). The highest OR, 5.38, was seen among women undergoing unplanned CS under general anaesthesia (95% CI 4.52–6.40). Conclusions: The main contributing factors to a negative birth experience are labour-related. Poor SRH, psychiatric treatment and fear of childbirth places the woman in a vulnerable position requiring extra attention.

A document by Isabella Annesi, written on Authorea.

Objective To estimate the pregnancy rates and outcomes for women with cystic fibrosis (wwCF) in the UK compared to the general population and to explore the impact of the introduction of disease modifying treatments on pregnancy rates. Design A population-based cross-sectional study. Setting Electronic records of UK CF Registry Data (~99% of all CF), and conceptions data for England and Wales (E&W). Population All women aged 15-44 years who were pregnant between 2003-2017. Methods We calculated 3-yearly crude and age-specific pregnancy rates per 1,000 women years (wys), pregnancy rates for wwCF with a G551D mutation before and after Ivacaftor was introduced in 2012 and compared live birth rates. Main outcome measures Crude rates, age specific fertility, and maternal morbidity. Results The overall pregnancy rate was 23.5 (95% CI 21.9-25.3) per 1,000 wys, ~3.4fold difference to E&W women (77.7). This pattern was evident in the age specific rates, except for those aged 40-44 years where the difference in rates was much less (wwCF 8.2 per 1,000 wys vs. 13.3 in E&W). LB rate differences mirrored pregnancy rates (wwCF 17.4 per 1000 wys vs. 61.4 E&W women). Following the introduction of Ivacaftor, pregnancy rates in wwCF with G551D increased from 29.5 to 56.9 per 1000wys (2012-2014 to 2015-2017). Conclusions Pregnancy rates in wwCF are about a third of the rates in the general population but on the rise following the introduction of Ivacaftor. There is no indication that there is a reduced chance of a live birth in wwCF who become pregnant.

AIM: Influenza infection poses a severe threat to pregnant mothers, and antiviral treatment is recommended. However, the safety of neuraminidase-inhibitor antiviral medications during pregnancy has not been well described. METHODS: A systematic review and meta-analysis were performed to evaluate the adverse neonatal outcomes associated with exposure to neuraminidase inhibitors during pregnancy. The PubMed, Embase, and Cochrane Library databases were searched to identify potential studies for inclusion. RESULTS: Nine cohort studies that estimated adverse neonatal outcomes associated with exposure to neuraminidase-inhibitor medication during pregnancy were included. Exposure to a neuraminidase inhibitor during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 0.9, 95% confidence interval [CI] 0.72–1.12, P = 0.341), low Apgar score (OR 0.96, 95% CI 0.77–1.2, P = 0.733), or preterm birth (OR 0.99, 95% CI 0.89–1.09, P = 0.771) compared with no exposure. However, exposure to a neuraminidase inhibitor was associated with a reduced risk of low birth weight (OR 0.79, 95% CI 0.68–0.92, P = 0.002) and giving birth to a small-for-gestational-age infant (OR 0.78, 95% CI 0.69–0.88, P < 0.001). Further analyses limited to oseltamivir exposure were consistent with the overall results. CONCLUSION: Exposure to neuraminidase-inhibitor medication during pregnancy does not appear to be associated with adverse neonatal outcomes. We recommend further studies to investigate this association, which will help clinicians determine whether to prescribe a neuraminidase inhibitor during pregnancy.

Background: Reaching early and definitive diagnosis in infants with cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID) is a priority of all CF newborn screening programs. Currently, sweat testing is the gold standard for CF diagnosis or exclusion. We assessed outcomes in a cohort of Italian CRMS/CFSPID infants who underwent repeat sweat testing in the first year of life. Methods: This multicentre, prospective study analysed clinical data and outcomes in CRMS/CFSPID infants born between September 1, 2018 and December 31, 2019, and followed until June 30, 2020. All subjects underwent CF transmembrane conductance regulator (CFTR) gene sequencing and the search for CFTR macrodeletions/macroduplications, and repeat sweat testing in the first year of life. Results: Fifty subjects (median age at end of follow-up, 16 months [range, 7–21 months]) were enrolled. Forty-one (82%) had the first sweat chloride in the intermediate range. During follow up, 150 sweat tests were performed (range, 1–7/infant). After a median follow-up of 8.5 months (range 1–16.2 months), 11 (22%) subjects were definitively diagnosed as follows: CF (n=2 [4%]) at 2 and 5 months, respectively; healthy carrier (n=8 [16%]), at a median age of 4 months (range 2–8 months); and healthy (n=1 [2%]) at 2 months of age. Inconclusive diagnosis remained in 39 (78%) infants. Conclusions: Early repeat sweat testing in the first year of life can shorten the time to definitive diagnosis in screening positive subjects with initial sweat chloride levels in the intermediate range.

Aim: With the widespread use of SGLT2i, various adverse events (AEs) have been reported. This study aimed to describe the distribution of SGLT2i-related AEs in different systems, quantify the association of important medical events (IMEs) and SGLT2i regimens, and build a signal profile of SGLT2i- induced IMEs. Methods: Data from 2015 Q1 to 2020 Q4 in the FDA Adverse Event Reporting System database (FAERS) were selected to conduct disproportionality analysis. Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to evaluate the correlation between SGLT2i and IMEs. The lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed a signal. For ROR, it was defined a signal if ROR025 over one, with at least 3 cases. Results: A total of 45,771,436 records were involved, including 111,564 records related to SGLT2i, with 38,366 records of SGLT2i-induced IMEs. Overall, SGLT2i was significantly associated with IMEs (IC=0.36, 95% CI: 0.35-0.38; ROR=1.44, 95% CI: 1.42-1.46). Most SGLT2i-related adverse events occurred in monotherapy (92.93%). Diabetic ketoacidosis was the most IMEs. Specifically, acute osteomyelitis has the strongest signal of all SGLT2i (IC025=7.83), and it was unique to canagliflozin. Diabetic ketoacidosis, acute kidney injury, ketoacidosis, Fournier’s gangrene, and euglycemic diabetic ketoacidosis were common to the four FDA-approved SGLT2i. Conclusion: Our study demonstrated that different SGLT2i regimens lead to different important adverse events, but there are overlapping events. Early identification and management of SGLT2i-associated IMEs are essential for clinical practice.