Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy

Author version made available in accordance with the publisher's policy.ABSTRACT Background Esophageal impedance monitoring records changes in conductivity. During esophageal rest impedance baseline values may represent mucosal integrity. The aim of this study was to assess the influence of acid suppression on impedance baselines in a placebo controlled setting. Material and Methods Impedance recordings from 40 infants (0-6months) enrolled in randomized placebo controlled trials of proton pump inhibitor (PPI) were retrospectively analyzed. Infants underwent 24hr pH-impedance monitoring prior to and after two weeks of double blind therapy with placebo or a PPI. Typical clinical signs of gastroesophageal reflux (GER) were recorded and I-GERQ-R questionnaire was completed. Key results Median (IQR) impedance baseline increased on PPI treatment (from 1217 (826-1514) to 1903 (1560-2194) Ohm, p<0.001) but not with placebo (from 1445 (1033-1791) to 1650 (1292-1983) Ohm, p=0.13). Baselines before treatment inversely correlate with the number of GER, acid GER, weakly acid GER, acid exposure and symptoms. The change in baseline on treatment inversely correlates with acid exposure and acid GER. Patients with initial low baselines have no improved symptomatic response to treatment. Conclusions and Inferences Impedance baselines are influenced by GER and increase significantly more with PPI therapy than with placebo. Clinical impact of this observation remains undefined as targeting therapy at infants with low baselines does not improve symptomatic response to treatment

Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis

Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous kinases. By substituting a serine residue into cysteine at the DFG-1 position in the ATP-binding pocket, we sensitize the non-receptor tyrosine kinase FES towards covalent labeling by a complementary fluorescent chemical probe. This mutation is introduced in the endogenous FES gene of HL-60 cells using CRISPR/Cas9 gene editing. Leveraging the temporal and acute control offered by our strategy, we show that FES activity is dispensable for differentiation of HL-60 cells towards macrophages. Instead, FES plays a key role in neutrophil phagocytosis via SYK kinase activation. This chemical genetics strategy holds promise as a target validation method for kinases.Medicinal Chemistr

BMI and gastroesophageal reflux disease in children, is there an association?

Epidemiology in Pediatrics and Child Healt

Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy

BackgroundEsophageal impedance monitoring records changes in conductivity. During esophageal rest, impedance baseline values may represent mucosal integrity. The aim of this study was to assess the influence of acid suppression on impedance baselines in a placebo-controlled setting.MethodsImpedance recordings from 40 infants (0-6 months) enrolled in randomized placebo-controlled trials of proton pump inhibitor (PPI) were retrospectively analyzed. Infants underwent 24 h pH-impedance monitoring prior to and after 2 weeks of double blind therapy with placebo or a PPI. Typical clinical signs of gastro-esophageal reflux (GER) were recorded and I-GERQ-R questionnaire was completed.Key resultsMedian (IQR) impedance baseline increased on PPI treatment (from 1217 (826-1514) to 1903 (1560-2194) Ω, P Conclusions & inferencesImpedance baselines are influenced by GER and increase significantly more with PPI therapy than with placebo. Clinical impact of this observation remains undefined as targeting therapy at infants with low baselines does not improve symptomatic response to treatment.C. M. Loots, R. Wijnakker, M. P. van Wijk, G. Davidson, M. A. Benninga, & T. I. Omar

Limited MDRO related stigma in carriers exposed to isolation precautions: an exploratory quantitative questionnaire study.

Background: Isolation precautions are applied to control the risk of transmission of multi drug resistant organisms (MDROs). These precautions have been associated with adverse effects, such as anxiety and depression. This study aimed to quantify stigma among MDRO carriers and its association with perceived mental health and experienced quality of care.Methods: A quantitative questionnaire study was performed in MDRO carriers exposed to >= 3 days of isolation precautions during hospitalization. Items derived from the Consumer Quality Index questionnaire (CQI) were used to assess perception of care. Stigma scores were calculated using the recently modified Berger Stigma Scale for meticillin-resistant Staphylococcus aureus (MRSA). Mental health was measured with the RAND Mental Health Inventory. The Spearman rank correlation test was used to assess the association between stigma score and RAND mental health score.Findings: Of the 41 included carriers, 31 (75.6%) completed both questionnaires. The experienced quality of care was 'good' according to CQI score. Twenty-four percent reported not to have received proper explanation about MDRO carriership from healthcare workers (HCWs). MDRO-associated stigma was reported in 1/31 (3.2%). Poor mental health was self-reported in 3/31 (9.7%). There was no correlation between stigma score and RAND mental health score (Spearman correlation coefficient: 0.347).Conclusions: In this study, MDRO carriers exposed to >= 3 days of isolation precautions did not report stigma. This contrasts with a recent study that investigated MRSA-associated stigma and may be explained by contact plus airborne isolation protocols in MRSA compared with contact isolation alone in most other MDROs. Also, the psychological impact may be of a different magnitude due to as yet unknown reasons. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of The Healthcare Infection Society

The impact of an infectious disease expert team on outpatient parenteral antimicrobial treatment in the Netherlands

Immunogenetics and cellular immunology of bacterial infectious disease

Mortality after delay of adequate empiric antimicrobial treatment of bloodstream infection

Background: Timely empiric antimicrobial therapy is one of the cornerstones of the management of suspected bloodstream infection (BSI). However, studies about the effects of empiric therapy on mortality have reported inconsistent results. The objective of this study was to estimate the effect of delay of appropriate empiric therapy on early mortality in patients with BSI. Methods: Data for the propensity score matching (PSM) study were obtained from a cohort of patients with BSI. Inadequate empiric treatment was defined as in vitro resistance to the antimicrobial regimen administered < 6 h after blood cultures were taken. The primary outcome measure was 14-day mortality. Thirty-day mortality and median length of stay (LOS) were secondary outcomes. PSM was applied to control for confounding. Results: Of a total of 893 included patients with BSI, 35.7% received inadequate initial empiric treatment. In the PSM cohort (n = 334), 14-day mortality was 9.6% for inadequate antibiotic treatment, compared to. 10.2% in adequate empiric treatment (p = 0.85). No prolonged median LOS was observed in patients who initially received inadequate therapy (10.5 vs. 10.7 days, p = 0.89). Conclusions: In this study, we found no clear effect of inadequate empirical treatment on mortality in a low-risk BSI population. The importance of early empiric therapy compared to other determinants, may be limited. This may not apply for specific subpopulations, e.g., patients with sepsis