Lockdown during the COVID-19 pandemic: impact on infants with pyloric stenosis

The COVID-19 pandemic has posed challenges for the delivery of healthcare for infants with disruption to 6-week health checks and health visitor services.1 An area of particular concern is late presentation to the hospital.2 However, current data do not offer an objective picture of how significant a problem this may be, with other reports showing low rates of delays in presentation.3 Infantile hypertrophic pyloric stenosis (IHPS) is a common, non-infective infantile condition with a predictable clinical course and therefore a good indicator condition to assess for delays in presentation. We aimed to assess whether infants with IHPS presented later during ‘lockdown’ compared with the same period the preceding year

Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Background: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery

Factors associated with outcomes in congenital duodenal obstruction – a population based study

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The influence of the introduction of biologic agents on surgical intervention in paediatric inflammatory bowel disease

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Multi-centre prospective cohort study of diaphragmatic defect phenotype and repair in neonates with congenital diaphragmatic hernia: “The Defect Study”

Defect size and closure technique in neonates with congenital diaphragmatic hernia (CDH) has long-term consequences for morbidity in survivors. Although subjective operative reporting of the defect size has been standardized, objective evaluation is lacking. There is no reported optimum closure technique related to the size and position of the diaphragmatic defect. We aim to objectively describe diaphragmatic defects and repair methods, at the time of neonatal CDH repair, through a prospective multi-centre service evaluation project. We will evaluate all neonates born with CDH surviving to diaphragmatic repair. All specialist paediatric surgical centres in the UK, Ireland and New Zealand will be invited to participate. Non-identifiable patient data will be collected over a 24-month period using a REDCap database. Diaphragmatic defects and hemidiaphragm measurements will be recorded intra-operatively alongside standardized defect reporting. Closure technique and 1-year outcomes will be captured. Demographics and peri-operative data will be reported as median (interquartile range), mean (standard deviation) or categorical variables. Defect measurement will be calculated as an ellipse with area displayed as a histogram. Patch usage will be compared to the defect area using univariate logistic regression analysis. Univariate logistic regression analysis will also be used to assess for the association between peri-operative variables and complications. Where possible, a multi-variate regression analysis will be performed. Centres will register the project as service evaluation at each participating hospital site. The results will be submitted to an international peer reviewed journal and will be disseminated via appropriate international forums and through patient support networks (CDH-UK). <br/

Lockdown during the COVID-19 pandemic: impact on infants with pyloric stenosis

The COVID-19 pandemic has posed challenges for the delivery of healthcare for infants with disruption to 6-week health checks and health visitor services.1 An area of particular concern is late presentation to the hospital.2 However, current data do not offer an objective picture of how significant a problem this may be, with other reports showing low rates of delays in presentation.3 Infantile hypertrophic pyloric stenosis (IHPS) is a common, non-infective infantile condition with a predictable clinical course and therefore a good indicator condition to assess for delays in presentation. We aimed to assess whether infants with IHPS presented later during ‘lockdown’ compared with the same period the preceding year.Ten centres within the UK (England, Scotland and Northern Ireland) contributed data from babies with IHPS via a website (covidinchildren.co.uk) between 23 March 2020 and 31 May 2020 (the COVID-19 lockdown period) and between 23 March and 31 May 2019 (controls). A total of 87 eligible infants were included, comprising 40 controls (46%) and 47 cases (54%). The demographic and baseline characteristics of the two groups were similar (table 1 and figure 1).<br/

Discovery of BI 207524, an Indole Diamide NS5B Thumb Pocket 1 Inhibitor with Improved Potency for the Potential Treatment of Chronic Hepatitis C Virus Infection

The development of interferon-free regimens for the treatment of chronic HCV infection constitutes a preferred option that is expected in the future to provide patients with improved efficacy, better tolerability, and reduced risk for emergence of drug-resistant virus. We have pursued non-nucleoside NS5B polymerase allosteric inhibitors as combination partners with other direct acting antivirals (DAAs) having a complementary mechanism of action. Herein, we describe the discovery of a potent follow-up compound (BI 207524, <b>27</b>) to the first thumb pocket 1 NS5B inhibitor to demonstrate antiviral activity in genotype 1 HCV infected patients, BILB 1941 (<b>1</b>). Cell-based replicon potency was significantly improved through electronic modulation of the p<i>K</i>_a of the carboxylic acid function of the lead molecule. Subsequent ADME-PK optimization lead to <b>27</b>, a predicted low clearance compound in man. The preclinical profile of inhibitor <b>27</b> is discussed, as well as the identification of a genotoxic metabolite that led to the discontinuation of the development of this compound