Publications by authors named "Sotirios Fouzas"

67 Publications

Vasopressin but Not Oxytocin Responds to Birth Stress in Infants.

Front Neurosci 2021 27;15:718056. Epub 2021 Aug 27.

Department of Neonatology, University Children's Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany.

Context: Birth triggers a large fetal neuroendocrine response, which is more pronounced in infants born vaginally than in those born by elective cesarean section (ECS). The two related peptides arginine vasopressin (AVP) and oxytocin (OT) play an essential role in peripheral and central stress adaptation and have a shared receptor mediating their function. Elevated cord blood levels of AVP and its surrogate marker copeptin, the C-terminal part of AVP prohormone, have been found after vaginal delivery (VD) as compared to ECS, while release of OT in response to birth is controversial. Moreover, AVP, copeptin and OT have not yet been measured simultaneously at birth.

Objective: To test the hypothesis that AVP but not OT levels are increased in infants arterial umbilical cord blood in response to birth stress and to characterize AVP secretion in direct comparison with plasma copeptin.

Methods: In a prospective single-center cross-sectional study, we recruited healthy women with a singleton pregnancy and more than 36 completed weeks of gestation delivering via VD or ECS (cesarean without prior uterine contractions or rupture of membranes). Arterial umbilical cord blood samples were collected directly after birth, centrifuged immediately and plasma samples were frozen. Concentrations of AVP and OT were determined by radioimmunoassay and that of copeptin by ultrasensitive immunofluorescence assay.

Results: A total of 53 arterial umbilical cord blood samples were collected, = 29 from VD and = 24 from ECS. Ten venous blood samples from pregnant women without stress were collected as controls. AVP and copeptin concentrations were significantly higher in the VD group than in the ECS group (both < 0.001), median (range) AVP 4.78 (2.38-8.66) vs. 2.38 (1.79-3.88) (pmol/L), copeptin 1692 (72.1-4094) vs. 5.78 (3.14-17.97), respectively, (pmol/L). In contrast, there was no difference in OT concentrations (pmol/L) between VD and ECS, 6.00 (2.71-7.69) vs. 6.14 (4.26-9.93), respectively. AVP and copeptin concentrations were closely related (Rs = 0.700, < 0.001) while OT did not show any correlation to either AVP or copeptin. In linear regression models, vaginal delivery and biochemical stress indicators, base deficit and pH, were independent predictors for both AVP and copeptin. OT was not linked to base deficit or pH.

Conclusion: Vaginal birth causes a profound secretion of AVP and copeptin in infants. Whereas AVP indicates acute stress events, copeptin provides information on cumulative stress events over a longer period. In contrast, fetal OT is unaffected by birth stress. Thus, AVP signaling but not OT mediates birth stress response in infants. This unique hormonal activation in early life may impact neurobehavioral development in whole life.
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http://dx.doi.org/10.3389/fnins.2021.718056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430205PMC
August 2021

Parents under siege: the psychological impact of COVID-19 outbreak on children's caregivers.

Swiss Med Wkly 2021 08 13;151(31-32). Epub 2021 Aug 13.

School of Medicine, University of Patras, Greece.

AIMS OF THE STUDY: It is well known that parenting stress is an important but often underestimated psychosocial variable. Data regarding the impact of the corona virus disease 2019 (COVID-19) outbreak on parental psychology are currently lacking. The aim of the present study was to assess parenting stress during the COVID-19 pandemic in Greece. METHODS: An Internet e-survey was conducted adhering to CHERRIES guidelines of the EQUATOR network and released from 16 March to 22 March 2020, using the Perceived Stress Scale (PSS) and Revised Impact of Event Scale (IES-R). A convenience sample of 1105 Greek parents of children with or without chronic or severe underlying disorders was enrolled, identified by a network of collaborating paediatricians across the country, and invited via personal emails. RESULTS: The participation rate was 91.6% and the completion rate was 100%. A total of 178 (16.1%) of the participants had children with underlying disorders (198 affected children in total). Parents of children with underlying disorders had significantly higher stress levels than those of healthy children (PSS 21.22 ± 5.06 vs 19.02 ± 6.85, p <0.001; IES-R 40.71 ± 11.58 v. 35.86 ± 12.69, p <0.001), particularly those caring for children with cardiovascular or respiratory disorders, or immunodeficiencies. The presence of children with underlying disorders was a strong predictor of PSS and IES-R scores, independently of parental sex, age, education and place of residence. CONCLUSIONS: The impact of COVID-19 outbreak on parental stress is substantial, and those caring for children with underlying disorders are more profoundly affected. Pending the global socioeconomic rebooting after the pandemic, the possible short- and long-term consequences of parental stress should not be ignored. As for other vulnerable groups, accurate health information and resources for psychological support should be provided to parents, especially those caring for children with underlying disorders.
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http://dx.doi.org/10.4414/SMW.2021.w30012DOI Listing
August 2021

Anxiety levels in parents of asymptomatic neonates and young infants referred for echocardiography.

J Reprod Infant Psychol 2021 Aug 7:1-8. Epub 2021 Aug 7.

Depatrment of Paediatrics, Neonatal Intensive Care Unit, University of Patras Medical School, Patras, Greece.

Introduction: Previous studies in children with innocent murmurs have shown that parental concern is common.

Methods: We assessed the anxiety levels among parents of asymptomatic neonates or infants up-to 6 weeks referred for cardiologic consultation because of a heart murmur. A six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI) was completed by the parents before and after consultation.

Results: The average STAI score decreased from 14.42 ± 4.54 on arrival to 9.69 ± 4.26 after the consultation (p < 0.001). Overall, the parents felt more calm, less tense, less upset, more relaxed, more content and less worried after the consultation (p < 0.001). Multivariable linear regression analysis showed that the STAI score prior to consultation was related to infants age (coefficient  = - 0.172; P = 0.046) and STAI score post consultation was related to the final diagnosis ( = 0.312; P < 0.001).

Conclusion: In conclusion, parents of asymptomatic neonates and young infants with a murmur exhibit moderate levels of anxiety which can be ameliorated after consultation. Parental education in the field is of paramount importance and the role of both paediatric cardiologists as well as primary care physicians is crucial and decisive.
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http://dx.doi.org/10.1080/02646838.2021.1959023DOI Listing
August 2021

Parental Knowledge, Attitude, and Practices on Antibiotic Use for Childhood Upper Respiratory Tract Infections during COVID-19 Pandemic in Greece.

Antibiotics (Basel) 2021 Jul 1;10(7). Epub 2021 Jul 1.

Department of Paediatrics, Medical School, University of Patras, Rion 26504, Greece.

This cross-sectional study aims to assess parents' knowledge, attitude, and practices on antibiotic use for children with URTIs symptoms in Greece in the era of the COVID-19 pandemic. We distributed a questionnaire to a random sample of parents who visited primary health care centers in Patras, Greece. Out of 412 participants, 86% believed that most infections with common cold or flu symptoms were caused by viruses, although 26.9% believed that antibiotics may prevent complications. Earache was the most common symptom for which antibiotics were needed. Most of them (69%) declare being considerably anxious about their children's health during the COVID-19 pandemic. The majority (85%) knew that COVID-19 was of viral origin, yet half of them declared uncertain whether antibiotics were needed. All demographic characteristics, except for gender, were found to have a significant effect on parents' knowledge, attitude, and practices on antibiotic use for URTIs and COVID-19. Factor analysis revealed six groups of parents with common characteristics associated with misuse of antibiotics. Our findings highlight the need to decrease misconceptions regarding antibiotic use by providing relevant education for parents targeting particular characteristics, especially during the COVID-19 pandemic. Continuous education of healthcare providers in the field is also of paramount importance.
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http://dx.doi.org/10.3390/antibiotics10070802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300644PMC
July 2021

Changing trends in the prevalence of childhood asthma over 40 years in Greece.

Pediatr Pulmonol 2021 Oct 20;56(10):3242-3249. Epub 2021 Jul 20.

Respiratory Unit, Department of Pediatrics, University Hospital of Patras and University of Patras Medical School, Rion, Patras, Greece.

Background: A series of repeated questionnaire surveys among 8- to 9-year-old school children in the city of Patras, Greece, demonstrated a continuous rise in the prevalence of wheeze/asthma from 1978 to 2003, with a plateau between 2003 and 2008. We further investigated wheeze/asthma trends within the same environment over the last decade.

Methods: Two follow-up surveys were conducted in 2013 (N = 2554) and 2018 (N = 2648). Physician-diagnosed wheeze and asthma were analyzed in relation to their occurrence (recent-onset: within the last 2 years; noncurrent: before 2 years; persistent: both prior and within the last 2 years). In 2018, spirometry was also performed in participants reporting symptoms and in a sample of healthy controls.

Results: The prevalence of current wheeze/asthma declined from 6.9% in 2008% to 5.2% in 2013% and 4.3% in 2018. The persistent and noncurrent wheeze/asthma groups followed this overall trend (P-for-trend <0.001), while the prevalence of recent-onset wheeze/asthma remained unchanged (P-for-trend >0.05). Persistent and noncurrent wheezers were also more frequently diagnosed with asthma, in contrast to those with recent-onset wheeze. The FEV z-score was less than -1 in 32.1% of children with recent-onset and in 22.4% of those with persistent wheeze/asthma; both rates were higher than those of the Noncurrent wheeze/asthma group (7.1%; p < .05) and of healthy controls (3.5%; p < .001).

Conclusions: The prevalence of childhood wheeze/asthma has declined significantly during the last decade in Greece. The reversing trend may in part be attributed to changing asthma perceptions among physicians and/or parents, especially in the case of younger children with troublesome respiratory symptoms.
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http://dx.doi.org/10.1002/ppul.25575DOI Listing
October 2021

Attitudes of school teachers toward influenza and COVID-19 vaccine in Greece during the COVID-19 pandemic.

Hum Vaccin Immunother 2021 Oct 9;17(10):3401-3407. Epub 2021 Jul 9.

Department of Paediatrics, Patras Medical School, Patras, Greece.

Our study aims to assess the attitudes, knowledge, and influenza vaccine uptake of school teachers, the intention to uptake influenza vaccine as well as the COVID-19 vaccine and to identify factors associated with vaccine acceptance during the COVID-19 pandemic in Greece. A cross-sectional online survey was conducted among elementary and kindergarten school teachers in the area of Western Greece from June 2020 to August 2020. A self-administered questionnaire was distributed via an internet-based link along with an invitation e-mail. Responses from 399 participants were retrieved. 139 (34.8%) had received the annual influenza vaccine in the season 2019-2020, whereas 215 (53.9%) stated that they would get it in the forthcoming season 2020-2021 ( < .001). 152 (38.1%) intent to get the COVID-19 vaccine when available. For COVID-19 vaccine factors that were independently associated with the intention to uptake included more than 15 years at work ( = .001), prior influenza vaccine uptake ( = .003), believing that COVID-19 vaccine should be mandatory ( = .04) and that school teachers are a high-risk group for COVID-19 ( = .001). In conclusion, COVID-19 pandemic appeared to have an impact on the intention of school teachers to get vaccinated for influenza. The low level of COVID-19 vaccine acceptance intention among the teachers in our cohort warrants further attention. Public health interventions should aim to increase knowledge on both influenza and COVID-19 and prevention of them via immunization in this particular at-risk population.
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http://dx.doi.org/10.1080/21645515.2021.1945903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437491PMC
October 2021

Pediatric Pulmonary Function Testing in COVID-19 Pandemic and Beyond. A Position Statement From the Hellenic Pediatric Respiratory Society.

Front Pediatr 2021 21;9:673322. Epub 2021 May 21.

Pediatric Pulmonology Unit, 3rd Department of Pediatrics, Hippokration Hospital of Thessaloniki, Thessaloniki, Greece.

As the COVID-19 pandemic is still evolving, guidelines on pulmonary function testing that may dynamically adapt to sudden epidemiologic changes are required. This paper presents the recommendations of the Hellenic Pediatric Respiratory Society (HPRS) on pulmonary function testing in children and adolescents during the COVID-19 era. Following an extensive review of the relevant literature, we recommend that pulmonary function tests should be carried out after careful evaluation of the epidemiologic load, structured clinical screening of all candidates, and application of special protective measures to minimize the risk of viral cross infection. These principles have been integrated into a dynamic action plan that may readily adapt to the phase of the pandemic.
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http://dx.doi.org/10.3389/fped.2021.673322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175853PMC
May 2021

Association of lifestyle factors with a high prevalence of overweight and obesity in Greek children aged 10-16 years.

Acta Paediatr 2021 May 29. Epub 2021 May 29.

Department of Pediatrics, University General Hospital of Patras, Patras, Greece.

Aim: To investigate the prevalence of overweight, obesity and central obesity in students of primary and secondary education, and the association with lifestyle parameters.

Methods: A total of 3504 students, aged 10-16 years old, from Western Greece participated in this cross-sectional epidemiological study (participation rate: 90%). Demographic, socioeconomic, dietary, physical activity and screen time data were obtained using a questionnaire. Anthropometric measurements were also obtained. Overweight and obesity were estimated using the Centers for Disease Control and Prevention (CDC) and International Obesity Task Force (IOTF) criteria and central obesity using the WHtR ≥0.5 and IDF criteria.

Results: The prevalence of overweight and obesity was 19.2% and 12.1% with CDC criteria, respectively, and 20.9% and 7.2%, with IOTF criteria respectively. Central obesity was 31.1 and 32.8% using the Waist-to-Height ratio (WHtR) ≥0.5 and International Diabetes Federation (IDF) criteria respectively. Male gender, small number of meals, breakfast skipping, frequent consumption of school food and sweets and the presence of a computer in children's rooms, were identified as the strongest lifestyle factors affecting weight.

Conclusion: Overweight, obesity and central obesity rates remain high among children and adolescents in Greece. The identification of risk factors associated with the manifestation of obesity and central obesity, may contribute to the implementation of targeted prevention and treatment interventions.
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http://dx.doi.org/10.1111/apa.15960DOI Listing
May 2021

Attitudes and beliefs of parents about routine childhood vaccination in Greece.

Hum Vaccin Immunother 2021 Sep 10;17(9):3066-3072. Epub 2021 May 10.

Department of Paediatrics, Medical School, University of Patras, Patras, Greece.

Vaccine hesitancy remains one of the 10 major global threats as per the WHO report in 2019. The aim of the present study is to assess attitudes and perceptions of vaccine hesitant parents in Greece with a view to implementing strategies to increase vaccine uptake. A cross-sectional questionnaire-based prospective survey was conducted between September 2019 and June 2020 on parents of children attending primary education in the city of Patras in Western Greece. Data on parental attitudes and beliefs about vaccinations were collected and analyzed. Multivariable logistic regression was used to investigate factors associated with vaccine uptake. Out of 2154 distributed questionnaires, 1227 were completed and returned (response rate 56.9%). The main vaccine information source for Greek parents was their primary care pediatrician (90.8%). Doubts still exist amongst approximately one-third of them (33.5%) regarding a possible relationship between vaccines and autism. Of note, 44% of the study participants believe that unvaccinated children could attend school. 84.6% of the parents in our cohort admitted that they had fully vaccinated their children. In the multivariable analysis, marital status ( < .002) and Greek nationality ( < .001) were found to be the most significant determinants of vaccine uptake. Overall, we found that the percentage of parents in Greece that are vaccine hesitant is small yet not negligible. Based on our results, targeted public health interventions should particularly focus on single parents and those with non-Greek nationality. Training healthcare professionals to provide adequate information is crucial to clarify misperceptions.
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http://dx.doi.org/10.1080/21645515.2021.1914805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381791PMC
September 2021

SARS-CoV-2 rapid antigen detection tests.

Authors:
Sotirios Fouzas

Lancet Infect Dis 2021 08 4;21(8):1068-1069. Epub 2021 May 4.

Department of Pediatrics, University Hospital of Patras, Rio, Patras 26504, Greece. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(21)00206-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096322PMC
August 2021

Influenza vaccination among caregivers and household contacts of children with asthma.

Vaccine 2021 04 26;39(17):2331-2334. Epub 2021 Mar 26.

Department of Pediatrics, University of Patras Medical School, Patras, 26504 Rio, Patras, Greece.

Data on influenza vaccination status among household contacts of asthmatic children are lacking. Our aim was to assess the influenza vaccination status of parents and caregivers of asthmatic children in the 2018-2019 season as well as to identify reasons for undervaccination. We performed a questionnaire-based survey in parents, caregivers and household contacts of 178 asthmatic children. Only the 50.6% of children were vaccinated, while in 79.8% of cases both parents were unvaccinated. More than 40% of them reported that they were unaware about the necessity of vaccination; approximately 30% stated that they were not properly advised, and the rest were concerned about influenza vaccine side effects and effectiveness. Factor analysis identified three groups: (a) influenza vaccine "believers" who were unaware that vaccination was necessary; (b) "deniers" who were less educated and with older children; (c) older and more educated vaccine "deniers". To improve influenza vaccine coverage among household contacts of asthmatic children, appropriate counseling and targeted interventions should be planned.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.042DOI Listing
April 2021

Preeclampsia Emerging as a Risk Factor of Cardiovascular Disease in Women.

High Blood Press Cardiovasc Prev 2021 Mar 3;28(2):103-114. Epub 2021 Mar 3.

Department of Pediatric, University of Patras Medical School, Rio, Patras, Greece.

The objective of this literature review was to explore the long-term cardiovascular effects of preeclampsia in women. The primary goal was to determine which organs were most commonly affected in this population. Although it was previously believed that preeclampsia is cured after the delivery of the fetus and the placenta current evidence supports an association between preeclampsia and cardiovascular disease later in life, many years after the manifestation of this hypertensive pregnancy related disorder. Therefore preeclampsia may be emerging as a novel cardiovascular risk factor for women, which requires long-term follow up.
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http://dx.doi.org/10.1007/s40292-020-00425-7DOI Listing
March 2021

Childhood chronic cough made easy: a simplified approach for the primary care setting.

Allergol Immunopathol (Madr) 2021 1;49(2):170-177. Epub 2021 Mar 1.

Primary Cilia Dyskinesia Unit, School of Medicine, University of Thessaly, Athens, GreecePediatric Respiratory Unit, School of Medicine, University of Patras, Patras, GreecePediatric Asthma and Cough Centre, Instituti Ospedalieri Bergamaschi, University and Research Hospitals, Bergamo, Italy.

Cough is a defense mechanism, but when it becomes persistent and troublesome, it must be carefully assessed. Chronic cough, that is, cough persisting for more than 4 weeks, has a proven negative impact on a child's quality of life; it interferes with daily activities, sleep, and schooling and may involve frequent health care visits and long-lasting treatments. Currently, there is a plethora of algorithms in the literature aiming to assist in the assessment of chronic cough in children; however, referring to complex flowcharts may be impractical for the usually busy primary care physician. Herein, we provide a simplified tool for the assessment of children with chronic cough in the primary care setting, presenting a basic approach to the most common causes along with hints to avoid common pitfalls in everyday practice. Finally, the most common clinical scenarios are analyzed, aiming to assist primary care physicians in providing the appropriate care to these patients.
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http://dx.doi.org/10.15586/aei.v49i2.38DOI Listing
March 2021

Serum Neurofilament Levels in Children With Febrile Seizures and in Controls.

Front Neurosci 2020 29;14:579958. Epub 2020 Sep 29.

Division of Neonatology and University of Basel Children's Hospital (UKBB), Basel, Switzerland.

Objective: Neuroaxonal damage is reflected by serum neurofilament light chain (sNfL) values in a variety of acute and degenerative diseases of the brain. The aim of this study was to investigate the impact of febrile and epileptic seizures on sNfL, serum copeptin, and prolactin levels in children compared with children with febrile infections without convulsions.

Methods: A prospective cross-sectional study was performed in children aging 6 months to 5 years presenting with fever (controls, = 61), febrile seizures (FS, = 78), or epileptic seizures (ES, = 16) at our emergency department. sNfL, copeptin, and prolactin were measured within a few hours after the event in addition to standard clinical, neurophysiological, and laboratory assessment. All children were followed up for at least 1 year after presentation concerning recurrent seizures.

Results: Serum copeptin values were on average 4.1-fold higher in FS and 3.2-fold higher in ES compared with controls (both < 0.01). Serum prolactin values were on average 1.3-fold higher in FS compared with controls (  < 0.01) and without difference between ES and controls. There was no significant difference of mean sNfL values (95% CI) between all three groups, FS 21.7 pg/ml (19.6-23.9), ES 17.7 pg/ml (13.8-21.6), and controls 23.4 pg/ml (19.2-27.4). In multivariable analysis, age was the most important predictor of sNfL, followed by sex and C reactive protein. Neither the duration of seizures nor the time elapsed from seizure onset to blood sampling had an impact on sNfL. None of the three biomarkers were related to recurrent seizures.

Significance: Serum neurofilament light is not elevated during short recovery time after FS when compared with children presenting febrile infections without seizures. We demonstrate an age-dependent decrease of sNfL from early childhood until school age. In contrast to sNfL levels, copeptin and prolactin serum levels are elevated after FS.
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http://dx.doi.org/10.3389/fnins.2020.579958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550525PMC
September 2020

Aortic intima-media thickness in neonates exposed to early-onset preeclampsia.

Early Hum Dev 2020 12 25;151:105166. Epub 2020 Aug 25.

Neonatal Intensive Care Unit, Department of Pediatrics, University of Patras Medical School, Greece.

Aortic intima-media thickness (aIMT) and its ratio to aortic diameter (aIMT/AoD) were measured on the second and fifth postnatal day in 39 neonates exposed to early-onset preeclampsia and 39 controls. Both aIMT and aIMT/AoD were higher in neonates exposed to preeclampsia (P < 0.001 for all comparisons).
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http://dx.doi.org/10.1016/j.earlhumdev.2020.105166DOI Listing
December 2020

Lung Function Variability in Children and Adolescents With and Without Asthma (LUV Study): Protocol for a Prospective, Nonrandomized, Clinical Trial.

JMIR Res Protoc 2020 Aug 7;9(8):e20350. Epub 2020 Aug 7.

Pediatric Respiratory Unit, University Hospital of Patras, Patras, Greece.

Background: Variability analysis of peak expiratory flow (PEF) and forced expiratory volume at 1 second (FEV1) has been used in research to predict exacerbations in adults with asthma. However, there is a paucity of data regarding PEF and FEV1 variability in healthy children and adolescents and those with asthma.

Objective: The objective of this study is the assessment of PEF and FEV1 variability in (1) healthy children and adolescents, to define the normal daily fluctuation of PEF and FEV1 and the parameters that may influence it, and (2) children and adolescents with asthma, to explore the differences from healthy subjects and reveal any specific variability changes prior to exacerbation.

Methods: The study will include 100 healthy children and adolescents aged 6-18 years (assessment of normal PEF and FEV1 variability) and 100 children and adolescents of the same age with diagnosed asthma (assessment of PEF and FEV1 variability in subjects with asthma). PEF and FEV1 measurements will be performed using an ultraportable spirometer (Spirobank Smart; MIR Medical International Research) capable of smartphone connection. Measurements will be performed twice a day between 7 AM and 9 AM and between 7 PM and 9 PM and will be dispatched via email to a central database for a period of 3 months. PEF and FEV1 variability will be assessed by detrended fluctuation and sample entropy analysis, aiming to define the normal pattern (healthy controls) and to detect and quantify any deviations among individuals with asthma. The anticipated duration of the study is 24 months.

Results: The study is funded by the "C. Caratheodory" Programme of the University of Patras, Greece (PN 47014/24.9.2018). It was approved by the Ethics Committee (decision 218/19-03-2019) and the Scientific Board (decision 329/02-04-2019) of the University Hospital of Patras, Greece. Patient recruitment started in January 2020, and as of June 2020, 100 healthy children have been enrolled (74 of them have completed the measurements). The anticipated duration of the study is 24 months. The first part of the study (assessment of lung function variability in healthy children and adolescents) will be completed in August 2020, and the results will be available for publication by October 2020.

Conclusions: Healthy children and adolescents may present normal short- and long-term fluctuations in lung function; the pattern of this variability may be influenced by age, sex, and environmental conditions. Significant lung function variability may also be present in children and adolescents with asthma, but the patterns may differ from those observed in healthy children and adolescents. Such data would improve our understanding regarding the chronobiology of asthma and permit the development of integrated tools for assessing the level of control and risk of future exacerbations.

Trial Registration: ClinicalTrials.gov NCT04163146; https://clinicaltrials.gov/ct2/show/NCT04163146.

International Registered Report Identifier (irrid): DERR1-10.2196/20350.
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http://dx.doi.org/10.2196/20350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442949PMC
August 2020

Considerations on Medical Education During the Coronavirus Disease 2019 Pandemic and Beyond.

Balkan Med J 2021 01;38(1):61

Department of Pediatrics, University Hospital of Patras, University of Patras School of Medicine, Patras, Greece.

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http://dx.doi.org/10.4274/balkanmedj.galenos.2020.2020.6.183DOI Listing
January 2021

emm Types and clusters and macrolide resistance of pediatric group A streptococcal isolates in Central Greece during 2011-2017.

PLoS One 2020 7;15(5):e0232777. Epub 2020 May 7.

Department of Microbiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece.

Background: The surveillance of emm types and macrolide susceptibility of group A streptococcus (GAS) in various areas and time periods enhances the understanding of the epidemiology of GAS infections and may guide treatment strategies and the formulation of type-specific vaccines. Greece has emerged as a country with high macrolide use. However, studies suggest a gradual reduction in macrolide consumption after 2007.

Methods: During a 7-year period (2011-2017), 604 GAS isolates were recovered from consecutive children presenting with pharyngeal or nonpharyngeal infections in Central Greece; 517 viable isolates underwent molecular analysis, including emm typing.

Results: Isolates belonged to 20 different emm types (in decreasing order of prevalence: 1, 89, 4, 12, 28, 3, 75 and 6, accounting for 88.2% of total isolates). The emm types comprised 10 emm clusters (five most common clusters: E4, A-C3, E1, A-C4 and A-C5). The emm89 isolates were acapsular ('new clade'). Overall macrolide resistance rate was 15.4%, and cMLSB emerged as the predominant resistance phenotype (56.4%). The lowest annual resistance rates occurred in 2014 (13.1%), 2016 (5.5%) and 2017(8.0%) (P for trend = 0.002). Consumption of macrolide/lincosamide/streptogramin B declined by 22.6% during 2011-2017. Macrolide resistance and emm28 and emm77 types were associated (both P<0.001). The most frequently identified genetic lineages of macrolide-resistant GAS included emm28/ST52, emm77/ST63, emm12/ST36, emm89/ST101 and emm4/ST39. We estimated that 98.8% of the isolates belonged to emm types incorporated into a novel 30-valent M protein vaccine.

Conclusions: In Central Greece during 2011-2017, the acapsular emm89 isolates comprised the second most prevalent type. Susceptibility testing and molecular analyses revealed decreasing GAS macrolide resistance rates, which may be attributed to the reduction in the consumption of macrolides and/or the reduced circulation of macrolide-resistant clones in recent years. Such data may provide valuable baseline information in targeting therapeutic intervention and the formulation of type-specific GAS vaccines.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232777PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205280PMC
August 2020

Work of Breathing in Mechanically Ventilated Preterm Neonates.

Pediatr Crit Care Med 2020 05;21(5):430-436

All authors: Neonatal Intensive Care Unit, Department of Pediatrics, University of Patras Medical School, Patras, Greece.

Objectives: To compare the imposed work of breathing by means of pressure-time product of the diaphragm in newborn infants receiving different modes of mechanical ventilation.

Design: Prospective observational crossover study.

Setting: Tertiary care neonatal unit.

Patients: Forty preterm newborns (gestational age ≤ 37 wk) in the phase of weaning from mechanical ventilation.

Interventions: Participants were ventilated in assist control, synchronized intermittent mandatory ventilation, and intermittent mandatory ventilation mode, in a crossover manner. The combination synchronized intermittent mandatory ventilation-pressure support (SIMV-PS) at 50% (SIMV-PS50) and 75% (SIMV-PS75) of the difference between peak inflating and positive end-expiratory pressure, was also applied in a subset of infants (n = 11). Each mode was maintained for 30 minutes. Transdiaphragmatic pressure was obtained by digital subtraction of esophageal from gastric pressure (both measured using a dual pressure-tipped catheter), and pressure-time product of the diaphragm was computed by integration of transdiaphragmatic pressure over inspiratory time.

Measurements And Main Results: The pressure-time product of the diaphragm was 224.2 ± 112.8 in the intermittent mandatory ventilation mode, 165.8 ± 58.8 in the synchronized intermittent mandatory ventilation mode, and 125.5 ± 61.8 cm H2O × s × min in the assist control mode; all values were significantly different to each other (p < 0.0001). The pressure-time product of the diaphragm difference between assist control and intermittent mandatory ventilation, and assist control and synchronized intermittent mandatory ventilation was negatively related to postmenstrual age (regression coefficient, -0.365; p = 0.020 and -0.341; p = 0.031, respectively). In the SIMV-PS subcohort, the pressure-time product of the diaphragm was significantly higher in the intermittent mandatory ventilation mode as compared with assist control (p < 0.0001) or SIMV-PS75 (p = 0.0027), and in the synchronized intermittent mandatory ventilation mode as compared with assist control (p = 0.0301).

Conclusions: In preterm infants, patient-triggered ventilation modalities result in lower work of breathing than intermittent mandatory ventilation, while the assist control mode is also associated with lower pressure-time product of the diaphragm compared with synchronized intermittent mandatory ventilation. The difference in the imposed diaphragmatic workload between these ventilation modalities was inversely related to postmenstrual age, implying that less mature infants benefit more from assist control-based ventilation strategies.
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http://dx.doi.org/10.1097/PCC.0000000000002277DOI Listing
May 2020

Effect of Early-Onset Preeclampsia on Offspring's Blood Pressure during the First Month of Life.

J Pediatr 2020 05 21;220:21-26.e1. Epub 2020 Feb 21.

Neonatal Intensive Care Unit, Department of Pediatrics, University of Patras Medical School, Rion-Patras, Greece.

Objective: To explore the effect of early-onset preeclampsia on the blood pressure of offspring during the first month of life.

Study Design: This prospective case-control study included 106 neonates of mothers with early-onset preeclampsia (developing at <34 weeks of gestation) and 106 infants of normotensive mothers, matched 1-to-1 for sex and gestational age. Serial blood pressure measurements were obtained on admission, daily for the first postnatal week, and then weekly up to the fourth week of life.

Results: There were no differences in blood pressure values on admission and the first day of life between cases and controls. Conversely, infants exposed to preeclampsia had significantly higher systolic (SBP), diastolic (DBP), and mean blood pressure (MBP) on the subsequent days up to the fourth postnatal week (P <.001-.033). Multiple regression analyses with adjustment for sex, gestational age, antenatal corticosteroid use, and maternal antihypertensive medication use confirmed the foregoing findings (P <.001-.048). Repeated-measures ANOVA also identified preeclampsia as a significant determinant of trends in SBP, DBP, and MBP during the first month of life (F = 16.2, P < .001; F = 16.4, P < .001; and F = 17.7, P < .001, respectively).

Conclusions: Infants of mothers with early-onset preeclampsia have elevated blood pressure values throughout the neonatal period compared with infants born to normotensive mothers.
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http://dx.doi.org/10.1016/j.jpeds.2020.01.033DOI Listing
May 2020

Impact of parturition on maternal cardiovascular and neuronal integrity in a high risk cohort - a prospective cohort study.

BMC Pregnancy Childbirth 2019 Nov 5;19(1):403. Epub 2019 Nov 5.

Division of Neonatology, University Children's Hospital Basel (UKBB), Spitalstrasse 33, 4056, Basel, Switzerland.

Background: To better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke.

Methods: The study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data.

Results: Placental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median [interquartile range]) increased significantly post-partum: 49.4 (34.7-77.8) vs 27.7 (16.7-31.4) pg/ml (p < 0.0001). Antepartum NfL was the sole independent predictor of NfL peri-partum change; mode of delivery, duration of labor, clinical characteristics and other biomarkers were all unrelated. Antepartum NfL levels were themselves independently predicted only by maternal age.

Conclusions: Parturition per se increases maternal serum NfL levels, suggesting a possible impact of parturition on maternal neuronal integrity.
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http://dx.doi.org/10.1186/s12884-019-2570-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833198PMC
November 2019

Osteoprotegerin and RANKL serum concentrations in neonates of mothers with early-onset pre-eclampsia: comparison with neonates of normotensive mothers.

Early Hum Dev 2019 08 6;135:1-5. Epub 2019 Jun 6.

Department of Pediatrics, Neonatal Intensive Care Unit, University of Patras Medical School, Greece.

Background: Pre-eclampsia is a known risk factor for long-term cardiovascular complications. Osteoprotegerin (OPG) and the receptor activator of nuclear factor κB ligand (RANKL) have been implicated in the pathogenesis of cardiovascular disease. The OPG-RANKL axis function is also altered in pregnant women with pre-eclampsia, but there is lack of data regarding OPG and RANKL concentrations in their neonates.

Aims: To examine the effects of early-onset pre-eclampsia on OPG and RANKL serum concentrations at birth, taking into account the influence of various perinatal factors.

Study Design: OPG and RANKL serum concentrations were measured in 28 premature newborns of mothers with early onset pre-eclampsia, and in 28 preterm and 28 full-term neonates of normotensive mothers (control groups).

Results: Neonates of pre-eclamptic mothers had higher OPG and lower RANKL levels compared to both control groups (Kruskal-Wallis P < 0.0001 and P = 0.014, respectively). Regression analysis showed that pre-eclampsia (P < 0.0001), birth weight z-score (P = 0.048) and antenatal steroid administration (P = 0.034) were significant determinants of OPG levels. Multivariable regression analysis also showed that pre-eclampsia was an independent predictor of increased diastolic and mean blood pressure in these neonates.

Conclusions: Early-onset pre-eclampsia affects OPG concentrations at birth and is an independent predictor of increased blood pressure in the offspring. Our findings suggest that altered OPG-RANKL axis function may be one of the mechanisms of cardiovascular 'programming' in fetuses exposed to pre-eclampsia.
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http://dx.doi.org/10.1016/j.earlhumdev.2019.06.001DOI Listing
August 2019

Predictive model of heterotopy in Meckel's diverticulum in children.

ANZ J Surg 2019 Jun 8;89(6):E241-E245. Epub 2019 May 8.

Department of Paediatric Surgery, Children's Hospital, Patras, Greece.

Background: The presence of heterotopic tissue in Meckel's diverticulum (MD) increases the incidence of future complications. Based on this concept, this study aimed to detect clinical and morphological parameters able to predict the probability of heterotopy in incidentally discovered uncomplicated MD and to develop a risk-based classification tool.

Methods: The clinical records of 146 patients who underwent MD resection were reviewed. MD complications (bleeding, inflammation, perforation or involvement in pathological processes such as intussusception) and MD dimensions (width, length and the product width × length) were evaluated in association with heterotopy. Regression analysis was used to explore the discrete effect of clinically relevant parameters, which were subsequently combined in a Classification and Regression Tree.

Results: The probability of heterotopy was higher in complicated MDs. The width of the base of the MD and the product width × length were also significant predictors of heterotopy. A stepwise combination (Classification and Regression Tree model) of (i) uncomplicated macroscopic presentation, (ii) width <2.5 cm, (iii) age <10 years and (iv) product width × length <4 cm resulted in a null probability of heterotopy in our study group.

Conclusion: The combination of MD-related clinical and morphological parameters using advanced statistical tools may assist in estimating the probability of heterotopy. This may be applied in incidentally discovered uncomplicated MDs during abdominal surgery for other morbidities. Prospective studies are required to confirm our findings and test the practical usefulness of the classification tool developed here.
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http://dx.doi.org/10.1111/ans.15226DOI Listing
June 2019

Economic Recession and Attendances in the Pediatric Emergency Department.

Biomed Res Int 2019 10;2019:4186486. Epub 2019 Feb 10.

Department of Pediatrics, University of Patras Medical School, Patras, 26504 Rio, Patras, Greece.

The economic recession has been shown to have a negative impact on health services worldwide. The purpose of this study was to examine whether the recent financial crisis in Greece that started in 2009 has affected the attendances in the pediatric emergency department of a University Hospital covering for a large geographical area in Greece. The study was based on a retrospective analysis of the cases presented to the paediatric emergency department and compared the attendances in 2008 (i.e., before the beginning of the economic crisis) with those in 2013 and 2017. Data on demographics and characteristics of emergency department visits, such as timing, reason, and outcome were recorded for each child. There were a total of 35.572 children seeking examination in those three years and data were collected for 5662 (17.36%) of them. Overall, the attendance rate has increased up to 20% without an increase to the hospital admission rates which remained stable throughout the study periods. Between 2008 and 2017, the percentage of febrile children attending the ED increased by 33.8% and of those with respiratory disorders by 63.1%. Our results indicate that the need for pediatric hospital services has changed following the economic crisis which could reflect gaps in the primary care setting and could well also result from financial constraints.
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http://dx.doi.org/10.1155/2019/4186486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387691PMC
July 2019

Variability of Tidal Breathing Parameters in Preterm Infants and Associations with Respiratory Morbidity during Infancy: A Cohort Study.

J Pediatr 2019 02 8;205:61-69.e1. Epub 2018 Nov 8.

University Children's Hospital Basel, Basel, Switzerland.

Objective: To test whether low variability of tidal volume (V) and capnographic indices are predictive of subsequent respiratory morbidity in preterm infants.

Study Design: In a birth cohort of 133 preterm infants, lung function was performed at 44 weeks postmenstrual age. Associations between the coefficient of variation (CV) of V (CV) and of expired CO volume per breath (CV) with rehospitalization, wheeze, and inhalation therapy during infancy were assessed using logistic regression. Area under the curve (AUC) analysis was used to assess whether outcome prediction using bronchopulmonary dysplasia (BPD) classification was enhanced by CV or CV.

Results: For each IQR decrease in CV (range, 4%-35%) and CV, (range, 5%-40%), the OR for rehospitalization increased by 2.25 (95% CI, 1.21-4.20) and 2.31 (95% CI, 1.20-4.45), respectively. The predictive value of BPD for rehospitalization was improved when CV or CV was added to the model, with the AUC increasing from 0.56 to 0.66 in both models. No association was found for the other outcomes.

Conclusions: Compared with BPD classification alone, including near-term variability of tidal breathing parameters improves the prediction of rehospitalization in infancy. These findings may inform parent counseling and monitoring strategies in preterm infants.
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http://dx.doi.org/10.1016/j.jpeds.2018.10.002DOI Listing
February 2019

A ventilated newborn with respiratory distress, abdominal distension and scrotal swelling.

J Paediatr Child Health 2018 Apr;54(4):457

Neonatal Intensive Care Unit, Department of Paediatrics, University General Hospital, Patras, Greece.

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http://dx.doi.org/10.1111/jpc.1_13879DOI Listing
April 2018

Physiological and anatomical dead space in mechanically ventilated newborn infants.

Pediatr Pulmonol 2018 Jan 20;53(1):57-63. Epub 2017 Nov 20.

Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, United Kingdom.

Objectives: To compare the anatomical (V ) and alveolar dead space (V ) in term and prematurely born infants and identify the clinical determinants of those indices.

Working Hypothesis: V and V will be higher in prematurely born compared to term born infants.

Study Design: Retrospective analysis of data collected at King's College Hospital NHS Foundation Trust, London, UK.

Patient Selection: Fifty-six infants (11 term, 45 preterm) were studied at a median age of 8 (IQR 2-33) days.

Methodology: V was determined using Fowler's method of volumetric capnography. V was determined by subtracting V from the physiological dead space which was determined by the Bohr-Enghoff equation. V and V were related to body weight at the time of study.

Results: The median V /kg was higher in prematurely born infants [3.7 (IQR: 3.0-4.5) mL/kg] compared to term infants [2.4 (IQR: 1.9-2.9) mL/kg, adjusted P = 0.001]. The median V /kg was not higher in prematurely born infants [0.3 (IQR: 0.1-0.5)] compared to term infants [0.1 (IQR: 0.0-0.2) mL/kg] after adjusting for differences in respiratory rate and days of ventilation (P = 0.482). V /kg was related to postmenstrual age (r = -0.388, P < 0.001), birth weight (r = -0.397, P < 0.001), and weight at measurement (r = -0.476, P < 0.001). V /kg was related to postmenstrual age (r = -0.254, P < 0.001), birth weight (r = -0.291, P = 0.002), and weight at measurement (r = -0.281, P = 0.003) and related to days of ventilation (r = 0.194, P = 0.044).

Conclusions: V /kg and V /kg increased with decreasing weight and gestation. V was higher in infants that have undergone prolonged mechanical ventilation.
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http://dx.doi.org/10.1002/ppul.23918DOI Listing
January 2018

Asthma and Allergy "Epidemic" and the Role of Vitamin D Deficiency.

Adv Exp Med Biol 2017 ;996:169-183

Cystic Fibrosis Unit, "Aghia Sophia" Children's Hospital, Athens, Greece.

The increase in asthma and allergies prevalence that has been recorded in many countries during the last decades, and the reemergence of vitamin D (VD) deficiency in many populations worldwide, renders fairly plausible the assumption of an underlying association between these two conditions and justifies the research effort invented in this issue. Indeed, there is growing body of evidence from epidemiological, laboratory, and clinical studies, suggesting that such an association does exist. The hypothesis of low levels of VD leading to compromised fetal programming and impairment of various immune functions involved in asthma and allergic disorders, stands as the most credible explanation of this presumed association. However, the evidence is not yet definite and there are some conflicting results among studies. As a consequence, no safe conclusions can be drawn yet, and more research is required in order to fully clarify the involvement of VD deficiency in the pathogenesis of asthma and allergies, and decide if VD has a role to play in the prevention and therapy of these disorders.
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http://dx.doi.org/10.1007/978-3-319-56017-5_14DOI Listing
April 2018

Breath-to-breath variability of exhaled CO as a marker of lung dysmaturity in infancy.

J Appl Physiol (1985) 2017 12 7;123(6):1563-1570. Epub 2017 Sep 7.

Division of Pulmonology and Respiratory Research Group, University Children's Hospital Basel, Basel, Switzerland.

The concept of diffusional screening implies that breath-to-breath variations in CO clearance, when related to the variability of breathing, may contain information on the quality and utilization of the available alveolar surface. We explored the validity of the above hypothesis in a cohort of young infants of comparable postmenstrual age but born at different stages of lung maturity, namely, in term-born infants ( n = 128), preterm-born infants without chronic lung disease of infancy (CLDI; n = 53), and preterm infants with moderate/severe CLDI ( n = 87). Exhaled CO volume (V) and concentration (F) were determined by volumetric capnography, whereas their variance was assessed by linear and nonlinear variability metrics. The relationship between relative breath-to-breath change of V (ΔV) and the corresponding change of tidal volume (ΔV) was also analyzed. Nonlinear F variability was lower in CLDI compared with term and non-CLDI preterm group ( P < 0.001 for both comparisons). In CLDI infants, most of the V variability was attributed to the variability of V ( r = 0.749), whereas in term and healthy preterm infants this relationship was weaker ( r = 0.507 and 0.630, respectively). The ΔV - ΔV slope was less steep in the CLDI group (1.06 ± 0.07) compared with non-CLDI preterm (1.16 ± 0.07; P < 0.001) and term infants (1.20 ± 0.10; P < 0.001), suggesting that the more dysmature the infant lung, the less efficiently it eliminates CO under tidal breathing conditions. We conclude that the temporal variation of CO clearance may be related to the degree of lung dysmaturity in early infancy. NEW & NOTEWORTHY Young infants exhibit appreciable breath-to-breath CO variability that can be quantified by nonlinear variability metrics and may reflect the degree of lung dysmaturity. In infants with moderate/severe chronic lung disease of infancy (CLDI), the variability of the exhaled CO is mainly driven by the variability of breathing, whereas in term-born and healthy preterm infants this relationship is less strong. The slope of the relative CO-to-volume change is less steep in CLDI infants, suggesting that dysmature lungs are less efficient in eliminating CO under tidal breathing conditions.
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http://dx.doi.org/10.1152/japplphysiol.00372.2017DOI Listing
December 2017
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