Pub Date : 2024-02-21DOI: 10.1101/2024.01.15.24301305
Joe D Piper, Clever Mazhanga, Marian Mwapaura, Gloria Mapako, Idah Mapurisa, Tsitsi Mashedze, Eunice Munyama, Maria Kuona, Thombizodwa Mashiri, Dzidzai Matemavi, Kundai Sibanda, Monica Tichagwa, Soneni Nyoni, Asinje Saidi, Manasa Mangwende, Dzivaidzo Chidhanguro, Eddington Mpofu, Joice Tome, Gabriel Mbewe, Batsirai Mutasa, Bernard Chasekwa, Handrea Njovo, Chandiwana Nyachowe, Mary Muchekeza, Kuda Mutasa, Virginia Sauramba, Ceri Evans, Melissa Gladstone, Jonathan Wells, Elizabeth Allen, Melanie Smuk, Jean Humphrey, Lisa Langhaug, Naume Tavengwa, Robert Ntozini, Andrew Prendergast
Background Globally, over 16 million children were exposed to HIV during pregnancy but remain HIV-free at birth and throughout childhood. Children born HIV-free (CBHF) have higher morbidity and mortality and poorer neurodevelopment in early life compared to children who are HIV-unexposed (CHU), but long-term outcomes remain uncertain. We characterized school-age growth, cognitive and physical function in CBHF and CHU previously enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Methods and Findings Children in SHINE who had been followed to age 18 months, were re-enrolled to this follow-up study if they were aged 7 years, resident in Shurugwi district, and had a known pregnancy HIV exposure status. From 5280 pregnant women originally enrolled, 264 CBHF and 990 CHU were evaluated at age 7 years using the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox. Cognitive function was evaluated using the Kaufman Assessment Battery for Children (KABC-II), with additional tools measuring executive function, literacy, numeracy, fine motor skills and socioemotional function. Physical function was assessed using standing broad jump and handgrip for strength, and the shuttle-run test for cardiovascular fitness. Growth was assessed by anthropometry. Body composition was assessed by bioimpedance analysis for lean mass and skinfold thicknesses for fat mass. A caregiver questionnaire measured demographics, socioeconomic status, nurturing, child discipline, food and water insecurity. We prespecified the primary comparisons and used generalized estimating equations (GEE) with an exchangeable working correlation structure to account for clustering. Adjusted models used covariates derived from directed acyclic graphs, with separate models adjusted for contemporary and early-life variables. We found strong evidence that cognitive function was lower for CBHF compared to CHU across multiple domains. The adjusted mean difference in the mental processing index (MPI), derived from KABC-II, was 3 points lower (95%CI 2, 4; P<0.001) in CBHF versus CHU. Similarly, the school achievement test (SAT) of literacy and numeracy was 7 points lower (95%CI 4, 11, P<0.001) and executive function, measured by the Plus-EF tablet-based test, was 5 points lower (95%CI 2, 8; P<0.001) in CBHF compared to CHU. CBHF also had smaller head circumferences by 0.3cm (95%CI 0.1, 0.5; P=0.009). CBHF had fewer years of schooling exposure and caregiver schooling, with higher rates of caregiver depression. CBHF had lower cardiovascular fitness from the shuttle-run test with a maximal oxygen consumption (VO2max) 0.8 ml/kg/min (95%CI 0.4, 1.2; P<0.001) lower than CHU. We found no evidence of differences in other growth, body composition or physical function outcomes. The main limitation of our study is that it was restricted to one of two previous study districts, with possible survivor bias and selection bias fr
{"title":"Growth, physical and cognitive function in children who are born HIV-free: school-age follow-up of a cluster-randomized trial in rural Zimbabwe","authors":"Joe D Piper, Clever Mazhanga, Marian Mwapaura, Gloria Mapako, Idah Mapurisa, Tsitsi Mashedze, Eunice Munyama, Maria Kuona, Thombizodwa Mashiri, Dzidzai Matemavi, Kundai Sibanda, Monica Tichagwa, Soneni Nyoni, Asinje Saidi, Manasa Mangwende, Dzivaidzo Chidhanguro, Eddington Mpofu, Joice Tome, Gabriel Mbewe, Batsirai Mutasa, Bernard Chasekwa, Handrea Njovo, Chandiwana Nyachowe, Mary Muchekeza, Kuda Mutasa, Virginia Sauramba, Ceri Evans, Melissa Gladstone, Jonathan Wells, Elizabeth Allen, Melanie Smuk, Jean Humphrey, Lisa Langhaug, Naume Tavengwa, Robert Ntozini, Andrew Prendergast","doi":"10.1101/2024.01.15.24301305","DOIUrl":"https://doi.org/10.1101/2024.01.15.24301305","url":null,"abstract":"Background\u0000Globally, over 16 million children were exposed to HIV during pregnancy but remain HIV-free at birth and throughout childhood. Children born HIV-free (CBHF) have higher morbidity and mortality and poorer neurodevelopment in early life compared to children who are HIV-unexposed (CHU), but long-term outcomes remain uncertain. We characterized school-age growth, cognitive and physical function in CBHF and CHU previously enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Methods and Findings\u0000Children in SHINE who had been followed to age 18 months, were re-enrolled to this follow-up study if they were aged 7 years, resident in Shurugwi district, and had a known pregnancy HIV exposure status. From 5280 pregnant women originally enrolled, 264 CBHF and 990 CHU were evaluated at age 7 years using the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox. Cognitive function was evaluated using the Kaufman Assessment Battery for Children (KABC-II), with additional tools measuring executive function, literacy, numeracy, fine motor skills and socioemotional function. Physical function was assessed using standing broad jump and handgrip for strength, and the shuttle-run test for cardiovascular fitness. Growth was assessed by anthropometry. Body composition was assessed by bioimpedance analysis for lean mass and skinfold thicknesses for fat mass. A caregiver questionnaire measured demographics, socioeconomic status, nurturing, child discipline, food and water insecurity. We prespecified the primary comparisons and used generalized estimating equations (GEE) with an exchangeable working correlation structure to account for clustering. Adjusted models used covariates derived from directed acyclic graphs, with separate models adjusted for contemporary and early-life variables. We found strong evidence that cognitive function was lower for CBHF compared to CHU across multiple domains. The adjusted mean difference in the mental processing index (MPI), derived from KABC-II, was 3 points lower (95%CI 2, 4; P<0.001) in CBHF versus CHU. Similarly, the school achievement test (SAT) of literacy and numeracy was 7 points lower (95%CI 4, 11, P<0.001) and executive function, measured by the Plus-EF tablet-based test, was 5 points lower (95%CI 2, 8; P<0.001) in CBHF compared to CHU. CBHF also had smaller head circumferences by 0.3cm (95%CI 0.1, 0.5; P=0.009). CBHF had fewer years of schooling exposure and caregiver schooling, with higher rates of caregiver depression. CBHF had lower cardiovascular fitness from the shuttle-run test with a maximal oxygen consumption (VO2max) 0.8 ml/kg/min (95%CI 0.4, 1.2; P<0.001) lower than CHU. We found no evidence of differences in other growth, body composition or physical function outcomes. The main limitation of our study is that it was restricted to one of two previous study districts, with possible survivor bias and selection bias fr","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139926379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-13DOI: 10.1101/2024.02.11.24302598
Facundo Jorro-Baron, Cecilia Echave, Viviana Monica Rodriguez, Maria Jose Aguilar-Fixman, Romina Balboa, Marina Guglielmino, Maria Florencia Garcia-Causarano, Veronica Del Negro, Patricia Dondoglio, Esteban Falcon, Luz Gibbons, Maria Celeste Guerrero, Ximena Juarez, Analia Lopez, Erika Matteucci, Ana Paula Rodriguez, Emilse Vitar, Javier Roberti, Ezequiel Garcia-Elorrio, Andrea Falaschi
Background: We aimed to test the feasibility of a multifaceted intervention to enhance the quality of antibiotic prescription by reducing its overuse and increasing the use of narrow-spectrum agents, comprising a range of antimicrobial stewardship strategies in LMIC pediatric hospitals. Methods: We implemented a quality improvement (QI) initiative for the treatment of three groups of infections: acute lower respiratory infections (ALRI), urinary tract infections (UTI), and skin and soft tissue infections (SSTI) in six units of two academic pediatric hospitals. We used an uncontrolled before-and-after design, preceded by a formative phase, to identify barriers and facilitators. The target population was Healthcare workers (HCWs). The strategy comprised an antibiotic audit and feedback, ward- or pathway-specific treatment guidelines, infection-based interventions focused on improving diagnostic accuracy, tailoring therapy to culture results, optimizing treatment duration (antibiotic time out), pharmacy-based interventions, and education. Results: We recruited 617 patients: 249 in the baseline period (BP) and 588 in the implementation period (IP). The patients in the IP group were younger, weighed less, had higher critical care requirements, and had higher ALRI. With implementation, we observed an increase in antibiotic days of therapy (1051 vs. 831; RR: 1.23 (1.14;1.33); p<0.001). After adjusting for age and place of hospitalization, the differences were significant. This increase was at the expense of a higher use of Access group antibiotics (382 vs. 310; RR: 1.23 (1.14;1.33); p<0.001) and lower use of the Watch group according to the WHO classification (552 vs. 623; RR: 0.89 (0.84; 0.94); p<0.001). We observed a decrease in antibiotic resistance in the IP group (5% vs. 13%; p<0.001) at the expense of extended-spectrum β-lactamase. We found no differences in mortality rates between the two periods. Conclusion: Through a QI initiative, the use of antibiotic stewardship programs in pediatric hospitals was shown to be feasible and may improve antibiotic use. We observed a decrease in antibiotic resistance, which may be due to an increase in antibiotic Access group use.
背景：我们的目的是在低收入国家和地区的儿科医院测试一种多方面干预措施的可行性，通过减少抗生素的过度使用和增加窄谱药物的使用来提高抗生素处方的质量，其中包括一系列抗菌药物管理策略。方法我们在两家学术儿科医院的六个科室实施了一项质量改进（QI）计划，用于治疗三类感染：急性下呼吸道感染（ALRI）、尿路感染（UTI）以及皮肤和软组织感染（SSTI）。我们采用了一种非对照前后对比的设计方法，在此之前先进行了一个形成阶段，以确定障碍和促进因素。目标人群是医护人员（HCWs）。该策略包括抗生素审计和反馈、针对病房或路径的治疗指南、基于感染的干预措施（侧重于提高诊断准确性）、根据培养结果调整治疗方法、优化治疗时间（抗生素超时）、基于药房的干预措施以及教育。研究结果我们招募了 617 名患者：基线期（BP）249 人，实施期（IP）588 人。实施后，我们观察到抗生素治疗天数有所增加（1051 对 831；RR：1.23 (1.14;1.33)；p<0.001）。在对年龄和住院地点进行调整后，差异仍然显著。这一增长是以更多使用Access组抗生素（382 vs. 310；RR：1.23 (1.14;1.33)；p<0.001）和更少使用WHO分类的Watch组抗生素（552 vs. 623；RR：0.89 (0.84;0.94)；p<0.001）为代价的。我们观察到，IP 组的抗生素耐药性有所下降（5% 对 13%；p<0.001），但以广谱 β-内酰胺酶为代价：结论：通过一项 QI 计划，证明在儿科医院使用抗生素管理计划是可行的，并可改善抗生素的使用。我们观察到抗生素耐药性有所下降，这可能是由于抗生素Access组使用的增加。
{"title":"IMPROVING ANTIBIOTICS USE IN PEDIATRIC HOSPITALS IN ARGENTINA: FEASIBILITY STUDY","authors":"Facundo Jorro-Baron, Cecilia Echave, Viviana Monica Rodriguez, Maria Jose Aguilar-Fixman, Romina Balboa, Marina Guglielmino, Maria Florencia Garcia-Causarano, Veronica Del Negro, Patricia Dondoglio, Esteban Falcon, Luz Gibbons, Maria Celeste Guerrero, Ximena Juarez, Analia Lopez, Erika Matteucci, Ana Paula Rodriguez, Emilse Vitar, Javier Roberti, Ezequiel Garcia-Elorrio, Andrea Falaschi","doi":"10.1101/2024.02.11.24302598","DOIUrl":"https://doi.org/10.1101/2024.02.11.24302598","url":null,"abstract":"Background: We aimed to test the feasibility of a multifaceted intervention to enhance the quality of antibiotic prescription by reducing its overuse and increasing the use of narrow-spectrum agents, comprising a range of antimicrobial stewardship strategies in LMIC pediatric hospitals. Methods: We implemented a quality improvement (QI) initiative for the treatment of three groups of infections: acute lower respiratory infections (ALRI), urinary tract infections (UTI), and skin and soft tissue infections (SSTI) in six units of two academic pediatric hospitals. We used an uncontrolled before-and-after design, preceded by a formative phase, to identify barriers and facilitators. The target population was Healthcare workers (HCWs). The strategy comprised an antibiotic audit and feedback, ward- or pathway-specific treatment guidelines, infection-based interventions focused on improving diagnostic accuracy, tailoring therapy to culture results, optimizing treatment duration (antibiotic time out), pharmacy-based interventions, and education. Results: We recruited 617 patients: 249 in the baseline period (BP) and 588 in the implementation period (IP). The patients in the IP group were younger, weighed less, had higher critical care requirements, and had higher ALRI.\u0000With implementation, we observed an increase in antibiotic days of therapy (1051 vs. 831; RR: 1.23 (1.14;1.33); p<0.001). After adjusting for age and place of hospitalization, the differences were significant. This increase was at the expense of a higher use of Access group antibiotics (382 vs. 310; RR: 1.23 (1.14;1.33); p<0.001) and lower use of the Watch group according to the WHO classification (552 vs. 623; RR: 0.89 (0.84; 0.94); p<0.001). We observed a decrease in antibiotic resistance in the IP group (5% vs. 13%; p<0.001) at the expense of extended-spectrum β-lactamase.\u0000We found no differences in mortality rates between the two periods.\u0000Conclusion: Through a QI initiative, the use of antibiotic stewardship programs in pediatric hospitals was shown to be feasible and may improve antibiotic use. We observed a decrease in antibiotic resistance, which may be due to an increase in antibiotic Access group use.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-13DOI: 10.1101/2024.02.12.24302736
James R Chang, James R Eubanks, Timothy Jancelewicz, Vijaya M Joshi, Hugo Martinez, Samir H Shah, Elizabeth R Paton, Ranjit R Philip
Background: The severity of pectus excavatum (PEX) as measured by Haller index (HI) does not always correlate with symptoms of aerobic capacity. Transthoracic echocardiograms (TTE) are generally reported as normal which may influence the pediatrician's decision to refer for corrective surgery. The aim of this study was to find a reproducible TTE marker as an indicator of right ventricular compression and compare it to severity of PEX and cardiopulmonary exercise test (CPET) indices. Methods: The study included patients aged 10-19 years with an institution-based protocol for preoperative PEX evaluation with TTE, chest computed tomography (CT) for HI, and CPET from 2015-2021. We divided the patients into two groups, mild/moderate PEX (HI 2-3.5) and severe PEX (HI > 3.5). Tricuspid valve annulus size (TVAS) was compared between the groups as well as with other CPET and TTE indices using Student?s t-test. Spearman?s rank correlation coefficient was used to evaluate correlations between the severity of PEX by HI with the TTE and CPET parameters. Results: Of the 124 patients, 82 (66.1%) had severe PEX and 42 (33.9%) had mild/moderate PEX. The mean TVAS z-scores in the mild/moderate PEX group was -1.98(SD 0.51) and -2.24 (SD 0.71) in the severe PEX group (p 0.046). There was a negative correlation between the TVAS z-score and the severity of PEX but this was not statistically significant (r = -0.154, p = 0.087). There was no significant difference in peak oxygen uptake (peak VO2) or left ventricular ejection fraction between the severity groups. However, the TVAS z-score positively correlated with peak VO2 (median 43 ml/kg/min, r = 0.023, p = 0.01), peak VO2 percent predicted (median 86%, r = 0.19, p = 0.04), and O2 pulse (median 12.7 ml/beat, r = 0.20, p = 0.025), and negatively correlated with VE/VCO2 (median 29, r = -0.23, p = 0.01). Conclusion: The severity of PEX by HI does not factor in the location of cardiac compression and may not always reflect the degree of cardiac limitation. The Tricuspid valve annulus size is a good TTE indicator of cardiopulmonary compromise from PEX. A TVAS z score <-2 is a good predictor of cardiac compromise in pediatric PEX. This may provide additional functional parameters in the decision-making process for corrective surgery.
{"title":"Tricuspid Valve Annulus Size by Echocardiography: Predictor of Cardiac Limitation in Pediatric Pectus Excavatum","authors":"James R Chang, James R Eubanks, Timothy Jancelewicz, Vijaya M Joshi, Hugo Martinez, Samir H Shah, Elizabeth R Paton, Ranjit R Philip","doi":"10.1101/2024.02.12.24302736","DOIUrl":"https://doi.org/10.1101/2024.02.12.24302736","url":null,"abstract":"Background:\u0000The severity of pectus excavatum (PEX) as measured by Haller index (HI) does not always correlate with symptoms of aerobic capacity. Transthoracic echocardiograms (TTE) are generally reported as normal which may influence the pediatrician's decision to refer for corrective surgery. The aim of this study was to find a reproducible TTE marker as an indicator of right ventricular compression and compare it to severity of PEX and cardiopulmonary exercise test (CPET) indices. Methods:\u0000The study included patients aged 10-19 years with an institution-based protocol for preoperative PEX evaluation with TTE, chest computed tomography (CT) for HI, and CPET from 2015-2021. We divided the patients into two groups, mild/moderate PEX (HI 2-3.5) and severe PEX (HI > 3.5). Tricuspid valve annulus size (TVAS) was compared between the groups as well as with other CPET and TTE indices using Student?s t-test. Spearman?s rank correlation coefficient was used to evaluate correlations between the severity of PEX by HI with the TTE and CPET parameters. Results:\u0000Of the 124 patients, 82 (66.1%) had severe PEX and 42 (33.9%) had mild/moderate PEX. The mean TVAS z-scores in the mild/moderate PEX group was -1.98(SD 0.51) and -2.24 (SD 0.71) in the severe PEX group (p 0.046). There was a negative correlation between the TVAS z-score and the severity of PEX but this was not statistically significant (r = -0.154, p = 0.087). There was no significant difference in peak oxygen uptake (peak VO2) or left ventricular ejection fraction between the severity groups. However, the TVAS z-score positively correlated with peak VO2 (median 43 ml/kg/min, r = 0.023, p = 0.01), peak VO2 percent predicted (median 86%, r = 0.19, p = 0.04), and O2 pulse (median 12.7 ml/beat, r = 0.20, p = 0.025), and negatively correlated with VE/VCO2 (median 29, r = -0.23, p = 0.01). Conclusion:\u0000The severity of PEX by HI does not factor in the location of cardiac compression and may not always reflect the degree of cardiac limitation. The Tricuspid valve annulus size is a good TTE indicator of cardiopulmonary compromise from PEX. A TVAS z score <-2 is a good predictor of cardiac compromise in pediatric PEX. This may provide additional functional parameters in the decision-making process for corrective surgery.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-09DOI: 10.1101/2024.02.09.24301930
Elizabeth Ledger, Hans Verhoef, Amadou T Jallow, Nicole Cunningham, Andrew M Prentice, Carla Cerami
Background: Recent work suggests that persistent inflammation, even at low levels, could be more important than low dietary iron intake in the aetiology of iron deficiency and iron deficiency anaemia (IDA) in young children living in poor environments. Methods: We will conduct 2 parallel observational studies in well and unwell rural Gambian children to identify the origins of chronic low-grade inflammation and characterise its relationship to iron handling and iron deficiency anaemia. IDeA Study 1 will enrol 120 well children attending our regular paediatric well-child clinics at 6, 12 and 18 months of age. IDeA Study 2 will enrol 200 sick children suffering from upper-respiratory tract infection, lower respiratory tract infection, gastroenteritis or urinary tract infection and study them on Days 0, 3, 7 and 14 after initial presentation. At each visit, children will be assessed for signs of inflammation. Full blood count and iron-related biomarkers (serum ferritin, serum iron, unsaturated iron-binding capacity, soluble transferrin receptor, transferrin) will be measured before and after an oral dose of ferrous iron to assess status and acute iron absorption. Inflammatory markers (C-reactive protein and α1-acid glycoprotein), hepcidin, erythroferrone and erythropoietin will be measured to characterize the anaemia of inflammation in these children. Conclusion: We will assess the impact of acute and chronic low-grade inflammation on iron absorption and investigate the hypothesis that chronic inflammation, juxtaposed on a poor diet, causes a complex anaemia of inflammation which exacerbates iron deficiency by blocking both non-haem iron absorption and iron utilization by the bone marrow. KEYWORDS: Anaemia, anaemia of inflammation, low-grade inflammation, iron, The Gambia, children, hepcidin, erythroferrone, erythropoietin, C-reactive protein Clinical trial registry: ClinicalTrials.gov NCT04097639 and NCT04095884 Author approval: All authors have read and approved this manuscript.
{"title":"Sources and pathways by which low-grade inflammation contributes to anaemia in rural African children from 6 months to 3 years of age: study protocol for observational studies IDeA 1 and IDeA 2","authors":"Elizabeth Ledger, Hans Verhoef, Amadou T Jallow, Nicole Cunningham, Andrew M Prentice, Carla Cerami","doi":"10.1101/2024.02.09.24301930","DOIUrl":"https://doi.org/10.1101/2024.02.09.24301930","url":null,"abstract":"Background: Recent work suggests that persistent inflammation, even at low levels, could be more important than low dietary iron intake in the aetiology of iron deficiency and iron deficiency anaemia (IDA) in young children living in poor environments. Methods: We will conduct 2 parallel observational studies in well and unwell rural Gambian children to identify the origins of chronic low-grade inflammation and characterise its relationship to iron handling and iron deficiency anaemia. IDeA Study 1 will enrol 120 well children attending our regular paediatric well-child clinics at 6, 12 and 18 months of age. IDeA Study 2 will enrol 200 sick children suffering from upper-respiratory tract infection, lower respiratory tract infection, gastroenteritis or urinary tract infection and study them on Days 0, 3, 7 and 14 after initial presentation. At each visit, children will be assessed for signs of inflammation. Full blood count and iron-related biomarkers (serum ferritin, serum iron, unsaturated iron-binding capacity, soluble transferrin receptor, transferrin) will be measured before and after an oral dose of ferrous iron to assess status and acute iron absorption. Inflammatory markers (C-reactive protein and α1-acid glycoprotein), hepcidin, erythroferrone and erythropoietin will be measured to characterize the anaemia of inflammation in these children. Conclusion: We will assess the impact of acute and chronic low-grade inflammation on iron absorption and investigate the hypothesis that chronic inflammation, juxtaposed on a poor diet, causes a complex anaemia of inflammation which exacerbates iron deficiency by blocking both non-haem iron absorption and iron utilization by the bone marrow. KEYWORDS: Anaemia, anaemia of inflammation, low-grade inflammation, iron, The Gambia, children, hepcidin, erythroferrone, erythropoietin, C-reactive protein\u0000Clinical trial registry: ClinicalTrials.gov NCT04097639 and NCT04095884 Author approval: All authors have read and approved this manuscript.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-09DOI: 10.1101/2024.02.08.24302498
Natoshia R Cunningham, Michelle A Adler, Brittany N Barber Garcia, Taylor Abounader, Alaina K Miller, Mariela Monzalvo, Ismaeel Hashemi, Ryan Cox, Samantha L Ely, Yong Zhou, Mark DeLano, Todd Mulderink, Mathew J Reeves, James L Peugh, Susmita Kashikar-Zuck, Robert C Coghill, Judith E Arnetz, David C Zhu
Background. Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions of childhood and are made worse by co-occurring anxiety. Our research team found that the Aim to Decrease Pain and Anxiety Treatment (ADAPT), a six-session coping skills program using cognitive behavioral therapy strategies, was effective in improving pain-related symptoms and anxiety symptoms compared to standard care. In follow-up, this current randomized clinical trial (RCT) aims to test potential neural mechanisms underlying the effect of ADAPT. Specifically, this two-arm RCT will explore changes in amygdalar functional connectivity (primary outcome) following the ADAPT protocol during the water loading symptom provocation task (WL-SPT). Secondary (e.g., changes in regional cerebral blood flow via pulsed arterial spin labeling MRI) and exploratory (e.g., the association between the changes in functional connectivity and clinical symptoms) outcomes will also be investigated. Methods. We will include patients ages 11 to 16 years presenting to outpatient pediatric gastroenterology care at a midwestern children’s hospital with a diagnosis of FAPD plus evidence of clinical anxiety based on a validated screening tool (the Generalized Anxiety Disorder-7 [GAD-7] measure). Eligible participants will undergo baseline neuroimaging involving the WL-SPT, and assessment of self-reported pain, anxiety, and additional symptoms, prior to being randomized to a six-week remotely delivered ADAPT program plus standard medical care or standard medical care alone (waitlist). Thereafter, subjects will complete a post assessment neuroimaging visit similar in nature to their first visit. Conclusions. This small scale RCT aims to increase understanding of potential neural mechanisms of response to ADAPT. ClinicalTrials.gov registration: NCT03518216
{"title":"Study protocol for a pilot clinical trial to understand neural mechanisms of response to a psychological treatment for pain and anxiety in pediatric functional abdominal pain disorders (FAPD)","authors":"Natoshia R Cunningham, Michelle A Adler, Brittany N Barber Garcia, Taylor Abounader, Alaina K Miller, Mariela Monzalvo, Ismaeel Hashemi, Ryan Cox, Samantha L Ely, Yong Zhou, Mark DeLano, Todd Mulderink, Mathew J Reeves, James L Peugh, Susmita Kashikar-Zuck, Robert C Coghill, Judith E Arnetz, David C Zhu","doi":"10.1101/2024.02.08.24302498","DOIUrl":"https://doi.org/10.1101/2024.02.08.24302498","url":null,"abstract":"Background. Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions of childhood and are made worse by co-occurring anxiety. Our research team found that the Aim to Decrease Pain and Anxiety Treatment (ADAPT), a six-session coping skills program using cognitive behavioral therapy strategies, was effective in improving pain-related symptoms and anxiety symptoms compared to standard care. In follow-up, this current randomized clinical trial (RCT) aims to test potential neural mechanisms underlying the effect of ADAPT. Specifically, this two-arm RCT will explore changes in amygdalar functional connectivity (primary outcome) following the ADAPT protocol during the water loading symptom provocation task (WL-SPT). Secondary (e.g., changes in regional cerebral blood flow via pulsed arterial spin labeling MRI) and exploratory (e.g., the association between the changes in functional connectivity and clinical symptoms) outcomes will also be investigated.\u0000Methods. We will include patients ages 11 to 16 years presenting to outpatient pediatric gastroenterology care at a midwestern children’s hospital with a diagnosis of FAPD plus evidence of clinical anxiety based on a validated screening tool (the Generalized Anxiety Disorder-7 [GAD-7] measure). Eligible participants will undergo baseline neuroimaging involving the WL-SPT, and assessment of self-reported pain, anxiety, and additional symptoms, prior to being randomized to a six-week remotely delivered ADAPT program plus standard medical care or standard medical care alone (waitlist). Thereafter, subjects will complete a post assessment neuroimaging visit similar in nature to their first visit.\u0000Conclusions. This small scale RCT aims to increase understanding of potential neural mechanisms of response to ADAPT. ClinicalTrials.gov registration: NCT03518216","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-03DOI: 10.1101/2024.02.01.24302121
Emma Lott, Darcy Fehlings, Rose Gelineau-Morel, Michael Kruer, Jonathan Mink, Sruthi Thomas, Steve Wisniewski, Bhooma Rajagopalan Aravamuthan, Cerebral Palsy Research Network
Objective: To determine how physicians approach pharmacologic dystonia treatment in people with CP and assess physician readiness to participate in a randomized trial comparing existing pharmacologic dystonia treatments. Methods: We administered a REDCap survey to physician members of the American Academy of Cerebral Palsy and Developmental Medicine and of the Child Neurology Society to assess which pharmacologic agents they use to treat dystonia in CP and their preferred indications and dosing. Results: Of 479 physicians surveyed, 240 (50%) responded. Respondents treated functionally limiting (95%) and generalized (57%) dystonia and most commonly used six medications: baclofen (95%), trihexyphenidyl (79%), gabapentin (67%), carbidopa/levodopa (55%), clonazepam (55%), and diazepam (54%). Baclofen was preferred in people with co-existing spasticity (81%), gabapentin was preferred in people with co-existing pain (49%), and trihexyphenidyl was avoided in people with constipation (34%) or urinary retention (42%). Preferred dosing regimens followed published regimens for dystonia, when available, but otherwise followed published regimens for other CP symptoms (spasticity and seizures). Baclofen was preferred by 64% of respondents as first line treatment, but there was no clear consensus on second or third-line medications. Most respondents (51%) were comfortable randomizing their patients to receive any of the six most commonly used medications used to treat dystonia in CP. Conclusions: This study summarizes current indications and dosing for the six most commonly used medications to treat dystonia in CP as per treating physicians in the US and Canada and also demonstrates physician support for a randomized trial comparing the effectiveness of these treatments.
{"title":"Physician Approaches to the Pharmacologic Treatment of Dystonia in Cerebral Palsy","authors":"Emma Lott, Darcy Fehlings, Rose Gelineau-Morel, Michael Kruer, Jonathan Mink, Sruthi Thomas, Steve Wisniewski, Bhooma Rajagopalan Aravamuthan, Cerebral Palsy Research Network","doi":"10.1101/2024.02.01.24302121","DOIUrl":"https://doi.org/10.1101/2024.02.01.24302121","url":null,"abstract":"Objective: To determine how physicians approach pharmacologic dystonia treatment in people with CP and assess physician readiness to participate in a randomized trial comparing existing pharmacologic dystonia treatments.\u0000Methods: We administered a REDCap survey to physician members of the American Academy of Cerebral Palsy and Developmental Medicine and of the Child Neurology Society to assess which pharmacologic agents they use to treat dystonia in CP and their preferred indications and dosing. Results: Of 479 physicians surveyed, 240 (50%) responded. Respondents treated functionally limiting (95%) and generalized (57%) dystonia and most commonly used six medications: baclofen (95%), trihexyphenidyl (79%), gabapentin (67%), carbidopa/levodopa (55%), clonazepam (55%), and diazepam (54%). Baclofen was preferred in people with co-existing spasticity (81%), gabapentin was preferred in people with co-existing pain (49%), and trihexyphenidyl was avoided in people with constipation (34%) or urinary retention (42%). Preferred dosing regimens followed published regimens for dystonia, when available, but otherwise followed published regimens for other CP symptoms (spasticity and seizures). Baclofen was preferred by 64% of respondents as first line treatment, but there was no clear consensus on second or third-line medications. Most respondents (51%) were comfortable randomizing their patients to receive any of the six most commonly used medications used to treat dystonia in CP.\u0000Conclusions: This study summarizes current indications and dosing for the six most commonly used medications to treat dystonia in CP as per treating physicians in the US and Canada and also demonstrates physician support for a randomized trial comparing the effectiveness of these treatments.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139679113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1101/2024.01.30.24301800
Sadeep Shrestha, Howard William Wiener, Sabrina Chowdhury, Hidemi Kajimoto, Vinodh Srinivasasainagendra, Olga A Mamaeva, Ujval N Brahmbhatt, Dolena R Ledee, Yung Lau, Luz A Padilla, Jake Y. Chen, Nagib Dahdah, Hemant K Tiwari, Michael A. Portman
Background: Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that could result in acute vasculitis. The pathological walls of afflicted coronary arteries show propensity for forming thrombosis and aneurysms. The mechanism of coronary artery aneurysms (CAA) despite intravenous gamma globulin (IVIG) treatment is not known. Methods: We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z>2.5 and large coronary aneurysm (CAA/L) (N = 92) as z>5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. We performed functional mapping and annotation (FUMA) analysis and further assessed the predictive risk score of genomic risk loci using the area under the receiver operating characteristic curve (AUC). Results: The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p<6.32E-08 most significant). Variants in SMAT4, LOC100127, PTPRD, TCAF2 and KLRC2 were the most significant non-intergenic SNPs. FUMA identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of these NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an AUC of 0.86. Conclusions: This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD patients. We have identified multiple novel SNPs associated with CAA/L and related genes with potential functional implications. The study shows that genomics can help define cause of CAA/L to guide management and improve risk stratification of KD patients.
{"title":"Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease","authors":"Sadeep Shrestha, Howard William Wiener, Sabrina Chowdhury, Hidemi Kajimoto, Vinodh Srinivasasainagendra, Olga A Mamaeva, Ujval N Brahmbhatt, Dolena R Ledee, Yung Lau, Luz A Padilla, Jake Y. Chen, Nagib Dahdah, Hemant K Tiwari, Michael A. Portman","doi":"10.1101/2024.01.30.24301800","DOIUrl":"https://doi.org/10.1101/2024.01.30.24301800","url":null,"abstract":"Background: Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that could result in acute vasculitis. The pathological walls of afflicted coronary arteries show propensity for forming thrombosis and aneurysms. The mechanism of coronary artery aneurysms (CAA) despite intravenous gamma globulin (IVIG) treatment is not known. Methods: We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z>2.5 and large coronary aneurysm (CAA/L) (N = 92) as z>5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. We performed functional mapping and annotation (FUMA) analysis and further assessed the predictive risk score of genomic risk loci using the area under the receiver operating characteristic curve (AUC). Results: The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p<6.32E-08 most significant). Variants in SMAT4, LOC100127, PTPRD, TCAF2 and KLRC2 were the most significant non-intergenic SNPs. FUMA identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of these NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an AUC of 0.86. Conclusions: This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD patients. We have identified multiple novel SNPs associated with CAA/L and related genes with potential functional implications. The study shows that genomics can help define cause of CAA/L to guide management and improve risk stratification of KD patients.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"73 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Dilated cardiomyopathy (DCM) is a progressive myocardial disorder characterized by impaired cardiac contraction and ventricular dilation. Some patients with DCM could manifest improvement in these abnormalities called left ventricular reverse remodeling (LVRR). However, the detailed association between genotypes and clinical outcomes, including LVRR, particularly among pediatric patients, remains uncertain. Methods: We prospectively enrolled pediatric patients with DCM from Japanese multi-institutional centers between 2014 and 2023. We identified DCM-related genes and explored the association between gene variants and clinical outcomes, including LVRR, which was defined as any increase in left ventricular ejection fraction during the observation period. Results: A total of 123 pediatric patients (62 males; mean age of 8 months [range, 1?51 months]) were retrospectively enrolled. There were 50 pathogenic variants in 45 patients (35.0%). The most identified gene was MYH7 (14.0%), followed by RYR2 (12.0%), and TPM1 (8.0%). A novel variant in the CASZ1 gene (NM_001079843.2 c.3356G>A, p. Trp1119Ter) was identified. LVRR was achieved in 47.5% of patients. In patients with sarcomere gene variants, the left ventricular ejection fraction remained unchanged (31.4% to 39.8%, P = 0.1913), whereas it significantly increased in patients with non-sarcomere gene variants (33.4% to 47.8%, P = 0.0466) and in patients without gene variants (33.6% to 54.1%, P = 0.003). Conclusions: Pediatric patients with DCM exhibited a marked genetic heterogeneity with a different landscape from adults with DCM. LVRR was not uniform across functional gene groups, opening the door to tailor-made gene-guided prediction in pediatric patients with DCM.
{"title":"Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts","authors":"Keiichi Hirono, Yukiko Hata, Shojiro Ichimata, Naoki Nishida, Teruhiko Imamura, Yoshihiro Asano, Yuki Kuramoto, Kaori Tsuboi, Shinya Takarada, Mako Okabe, Hideyuki Nakaoka, Keijiro Ibuki, Sayaka Ozawa, Jun Muneuch, Kazushi Yasuda, Kotaro Urayama, Hideharu Oka, Tomoyuki Miyamoto, Kenji Baba, Akio Kato, Hirofumi Saiki, Naoki Kuwahara, Masako Harada, Shiro Baba, Mari Morikawa, Hidenori Iwasaki, Yuichiro Hirata, Yuki Ito, Heima Sakaguchi, Susumu Urata, Koichi Toda, Emi Kittaka, Seigo Okada, Yohei Hasebe, shinsuke hoshino, Takanari Fujii, Norie Mitsushita, Masaki Nii, Kayo Ogino, Mitsuhiro Fujino, Yoko Yoshida, Yutaka Fukuda, Satoru Iwashima, Kiyohiro Takigiku, Yasushi Sakata, Ryo Inuzuka, Jun Maeda, Yasunobu Hayabuchi, Tao Fujioka, Hidemasa Namiki, Shuhei Fujita, Koichi Nishida, Ayako Kuraoka, Nobuhiko Kan, Sachiko Kido, Ken Watanabe, Fukiko Ichida","doi":"10.1101/2024.01.24.24301754","DOIUrl":"https://doi.org/10.1101/2024.01.24.24301754","url":null,"abstract":"Background:\u0000Dilated cardiomyopathy (DCM) is a progressive myocardial disorder characterized by impaired cardiac contraction and ventricular dilation. Some patients with DCM could manifest improvement in these abnormalities called left ventricular reverse remodeling (LVRR). However, the detailed association between genotypes and clinical outcomes, including LVRR, particularly among pediatric patients, remains uncertain.\u0000Methods:\u0000We prospectively enrolled pediatric patients with DCM from Japanese multi-institutional centers between 2014 and 2023. We identified DCM-related genes and explored the association between gene variants and clinical outcomes, including LVRR, which was defined as any increase in left ventricular ejection fraction during the observation period.\u0000Results:\u0000A total of 123 pediatric patients (62 males; mean age of 8 months [range, 1?51 months]) were retrospectively enrolled. There were 50 pathogenic variants in 45 patients (35.0%). The most identified gene was MYH7 (14.0%), followed by RYR2 (12.0%), and TPM1 (8.0%). A novel variant in the CASZ1 gene (NM_001079843.2 c.3356G>A, p. Trp1119Ter) was identified. LVRR was achieved in 47.5% of patients. In patients with sarcomere gene variants, the left ventricular ejection fraction remained unchanged (31.4% to 39.8%, P = 0.1913), whereas it significantly increased in patients with non-sarcomere gene variants (33.4% to 47.8%, P = 0.0466) and in patients without gene variants (33.6% to 54.1%, P = 0.003).\u0000Conclusions:\u0000Pediatric patients with DCM exhibited a marked genetic heterogeneity with a different landscape from adults with DCM. LVRR was not uniform across functional gene groups, opening the door to tailor-made gene-guided prediction in pediatric patients with DCM.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139579900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1101/2024.01.26.24301820
Sherry L Kausch, Douglas E Lake, Juliann M Di Fiore, Debra E Weese-Mayer, Nelson Claure, Namasivayam Ambalavanan, Zachary A Vesoulis, Karen D Fairchild, Phyllis A Dennery, Anna Maria Hibbs, Richard J Martin, Premananda Indic, Colm P Travers, Eduardo Bancalari, Aaron Hamvas, James S Kemp, John L Carroll, Randall J Moorman, Brynne A Sullivan
Objectives: Detection of changes in cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, may facilitate earlier detection of sepsis. Our objective was to examine the association of cardiorespiratory events with late-onset sepsis for extremely preterm infants (<29 weeks gestational age (GA)) on versus off invasive mechanical ventilation. Study Design: Retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in five level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean GA 26.4w, SD 1.71). Monitoring data were available and analyzed for 719 infants (47,512 patient-days), of whom 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72h after birth and > or equal to 5d antibiotics). Results: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer IH80 events and more bradycardia events before sepsis. IH events were associated with higher sepsis risk, but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model predicted sepsis with an AUC of 0.783. Conclusion: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.
{"title":"Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Extremely Preterm Infants","authors":"Sherry L Kausch, Douglas E Lake, Juliann M Di Fiore, Debra E Weese-Mayer, Nelson Claure, Namasivayam Ambalavanan, Zachary A Vesoulis, Karen D Fairchild, Phyllis A Dennery, Anna Maria Hibbs, Richard J Martin, Premananda Indic, Colm P Travers, Eduardo Bancalari, Aaron Hamvas, James S Kemp, John L Carroll, Randall J Moorman, Brynne A Sullivan","doi":"10.1101/2024.01.26.24301820","DOIUrl":"https://doi.org/10.1101/2024.01.26.24301820","url":null,"abstract":"Objectives: Detection of changes in cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, may facilitate earlier detection of sepsis. Our objective was to examine the association of cardiorespiratory events with late-onset sepsis for extremely preterm infants (<29 weeks gestational age (GA)) on versus off invasive mechanical ventilation.\u0000Study Design: Retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in five level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean GA 26.4w, SD 1.71). Monitoring data were available and analyzed for 719 infants (47,512 patient-days), of whom 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72h after birth and > or equal to 5d antibiotics).\u0000Results: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer IH80 events and more bradycardia events before sepsis. IH events were associated with higher sepsis risk, but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model predicted sepsis with an AUC of 0.783.\u0000Conclusion: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139580523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-26DOI: 10.1101/2024.01.25.24301051
Victor S. Tumukunde, Joseph Katongole, Stella Namukwaya, Melissa M. Medvedev, Moffat Nyirenda, Cally J. Tann, Janet Seeley, Joy E. Lawn
Kangaroo mother care (KMC) is an evidence-based method to improve newborn survival. However, scale-up even for stable newborns has been slow, with reported barriers to implementation. We examined facilitators and barriers to initiating KMC before stabilisation amongst neonates recruited to the OMWaNA study in Uganda.
{"title":"Kangaroo Mother Care prior to clinical stabilisation: Implementation barriers and facilitators reported by caregivers and health care providers in Uganda","authors":"Victor S. Tumukunde, Joseph Katongole, Stella Namukwaya, Melissa M. Medvedev, Moffat Nyirenda, Cally J. Tann, Janet Seeley, Joy E. Lawn","doi":"10.1101/2024.01.25.24301051","DOIUrl":"https://doi.org/10.1101/2024.01.25.24301051","url":null,"abstract":"Kangaroo mother care (KMC) is an evidence-based method to improve newborn survival. However, scale-up even for stable newborns has been slow, with reported barriers to implementation. We examined facilitators and barriers to initiating KMC before stabilisation amongst neonates recruited to the OMWaNA study in Uganda.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139580041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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