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Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis.
Gama, B, von Hafe, M, Vieira, R, Soares, H, Azevedo, I, Rocha, G
Archives of disease in childhood. Fetal and neonatal edition. 2024
Abstract
OBJECTIVE Caffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic review and meta-analysis, we aim to summarise the results of trials on the gastrointestinal effects of caffeine in preterm infants. DESIGN We searched MEDLINE, Web of Science, Scopus and ClinicalTrials.gov up to 21 April 2023. We included randomised controlled trials assessing caffeine versus placebo in preterm neonates and reporting gastrointestinal side effects. Risk of bias was assessed using the Cochrane Risk of Bias tool. A Bayesian meta-analysis was performed to estimate the pooled OR of gastrointestinal side effects. RESULTS Nine trials involving 2746 preterm infants were analysed. Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I2=97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I2=84.8%, respectively). Four trials assessed the outcomes spontaneous intestinal perforation, constipation, gastrointestinal disorder (composite outcome: gastro-oesophageal regurgitation or dilated bowel loops), age at oral feeding and cholestasis syndrome and found no differences between groups. One trial assessed the outcomes gastro-oesophageal symptoms and duration of tube feeding and found that caffeine was associated with a reduced burden of gastro-oesophageal reflux symptoms at 2 weeks (p<0.05), but not at term. CONCLUSIONS According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants does not seem to be associated with significant gastrointestinal adverse effects.
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2.
Non-pharmacological management of neonatal pain: a systematic review.
Queirós, I, Moreira, T, Pissarra, R, Soares, H, Guimarães, H
Minerva pediatrics. 2023;(2):282-295
Abstract
INTRODUCTION Shortly after birth, neonates are exposed to several painful medical procedures, such as newborn metabolic screening, vaccination and venipuncture, without proper management of pain. Unpleasant experiences during the neonatal period are proven to be associated with negative long-term consequences. Non-pharmacological interventions have been studied, although rarely administered and seldom documented. The aim of this systematic review was to assess non-pharmacological approaches to neonatal pain during diagnostic and treatment procedures. EVIDENCE ACQUISITION Extensive literature research to access randomized controlled trials on non-pharmacological pain management in neonates was performed in MEDLINE (through PubMed), Scopus and Web of Science from October 2011 to September 2021. First analysis included all article titles and abstracts screening to identify relevant studies, and second analysis included a full-text screening of previously selected studies. Eligibility was assessed independently by two authors, and disagreements were resolved by discussion and consensus. In the end, 19 published studies were included, representing a total of 1930 newborns. Main outcome, neonatal pain, was assessed by different neonatal pain evaluation scales. EVIDENCE SYNTHESIS Non-pharmacological interventions including sucrose/glucose solutions, non-nutritive sucking, breastfeeding, olfactive stimulus, auditory stimulus and sensory stimulus (skin-to-skin care, kangaroo/maternal holding, heat, therapeutic massage, swaddling/facilitated tucking and acupressure) showed decreased behavioral and physiologic pain responses. CONCLUSIONS Evidence suggests non-pharmacological approaches are safe, effective and can be easily applied in daily practice. There is the need for continued research on non-pharmacological interventions on neonatal pain to help healthcare providers build a tailored pain treatment plan for neonates submitted to procedural pain.
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3.
Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework.
Clerbaux, LA, Albertini, MC, Amigó, N, Beronius, A, Bezemer, GFG, Coecke, S, Daskalopoulos, EP, Del Giudice, G, Greco, D, Grenga, L, et al
Journal of clinical medicine. 2022;(15)
Abstract
Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors (age, sex, genetic factors, lipid disorders, heart failure, gut dysbiosis, diet, vitamin D deficiency, air pollution and exposure to chemicals) influence COVID-19 by applying the Adverse Outcome Pathway (AOP), which is well-established in regulatory toxicology. This framework aims to model the sequence of events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how those eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.
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4.
Nephrotoxicity in Neonates.
Soares, H, Moita, R, Maneira, P, Gonçalves, A, Gomes, A, Flor-de-Lima, F, Costa, S, Soares, P, Pissarra, S, Rocha, G, et al
NeoReviews. 2021;(8):e506-e520
Abstract
Acute kidney injury (AKI) is classified based on prerenal, intrinsic, and postrenal causes. In the newborn, AKI can occur after an insult during the prenatal, perinatal, or postnatal period. AKI is usually an underrecognized condition and its true incidence is unknown. AKI may result from the administration of a number of different nephrotoxic medications, which are often used concurrently in critically ill neonates, exponentially increasing the risk of renal injury. Drug toxicity may also compromise the formation and development of nephrons, and this is particularly important in preterm infants, who have incomplete nephrogenesis. Little is known about the pharmacokinetics and pharmacodynamics of different medications used in neonates, especially for the most immature infant, and the use of most medications in this population is off label. Strategies to prevent AKI include the avoidance of hypotension, hypovolemia, fluid imbalances, hypoxia, and sepsis as well as judicious use of nephrotoxic medications. Treatment strategies aim to maintain fluids and electrolytic and acid-base homeostasis, along with an adequate nutritional status. Neonates are especially prone to long-term sequelae of AKI and benefit from long-term follow-up. This review summarizes the most relevant aspects of nephrotoxicity in neonates and describes the prevention, treatment, and follow-up of AKI in neonates.
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5.
COVID-19 mRNA vaccine and antibody response in lactating women: a prospective cohort study.
Charepe, N, Gonçalves, J, Juliano, AM, Lopes, DG, Canhão, H, Soares, H, Serrano, EF
BMC pregnancy and childbirth. 2021;(1):632
Abstract
BACKGROUND Immunological protection via breastfeeding is well known. The immunological profile of human milk changes during lactation. No clinical trials have been conducted in lactating women with the newest mRNA vaccines against SARS- CoV-2. A Few studies have shown the presence of antibodies in breastmilk after vaccination. The aim of this work is to study possible antibodies transfer via breastmilk and also the immunological characteristics of lactating women compared to non-lactating women, after using the BNT162b2 Pfizer vaccine. METHODS This is a prospective cohort study with a convenience homogenous sample of 24 healthcare workers (14 lactating and 10 non-lactating women) enrolled at the time of COVID-19 vaccination. Clinical data was registered in a questionnaire. Titers of SARS-CoV-2 spike IgG, IgA and IgM were quantified in post vaccination blood and human milk. Antibody quantification was performed by an in-house ELISA to SARS-CoV-2 trimeric spike protein. RESULTS All women showed immunity after vaccination with positive antibodies for IgM, IgA and IgG antibodies. The dominant serum antibody response was IgG. Modest levels of antibodies in breastmilk of lactating mothers were observed in this study, especially IgG in 42.9%. There was a moderate association between higher titers of IgG and a longer duration of breastfeeding (R= 0.55, p=0.041). CONCLUSIONS Evidence of antibody transfer in human milk after COVID-19 vaccination is scarce. The presence of antibodies in human milk is reported, but immunization through breastfeeding is still to be established.
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Cholesterol, copper and Abeta in controls, MCI, AD and the AD cholesterol-lowering treatment trial (ADCLT).
Sparks, DL, Petanceska, S, Sabbagh, M, Connor, D, Soares, H, Adler, C, Lopez, J, Ziolkowski, C, Lochhead, J, Browne, P
Current Alzheimer research. 2005;(5):527-39
Abstract
Cholesterol clearly plays an influential role in promoting the production of amyloid beta (Abeta) and possibly the progression of Alzheimer's Disease (AD). The AD Cholesterol-Lowering Treatment trial (ADCLT; 1 year duration) tested atorvastatin and found significant benefit on measures of cognition and depressive symptoms in treated patients (N = 32) compared to placebo (N = 31). We assessed the circulating levels of Abeta(1-40), Abeta(1-42), ceruloplasmin (copper chaperone), apolipoprotein E and HDL-cholesterol in blood collected at each clinical visit during the ADCLT. We also determined the circulating cholesterol, ceruloplasmin, and Abeta levels in AD and MCI (mild cognitive impairment) patients, and controls (two groups stratified by function; high and low) participating in our Brain Bank Program. Each Brain Bank individual was clinically assessed for performance on the Mini-Mental Status Exam (MMSE), Rey auditory verbal learning test (AVLT), Clock draw, and UPSIT (smell identification test). Among individuals of equal age and education, scores on the MMSE were significantly reduced in AD compared to both MCI and controls, as were scores on the UPSIT. Ability on delayed verbal recall was significantly reduced in AD compared to MCI, and in MCI compared to both control groups. Performance on the Clock draw was similar for AD and MCI patients, but was significantly reduced when comparing MCI to control. Both cholesterol and ceruloplasmin levels were significantly increased in low-function controls compared to the high-function control group, but were not different from levels identified in the MCI and AD patients. Significantly increased levels of Abeta(1-40) occurred in low- compared to high-function controls, with a further significant increase in MCI compared to low-function controls. Circulating Abeta(1-40) levels were decreased in AD compared to MCI. Levels of Abeta(1-42) were not significantly different between the groups. The slight gradual increase in circulating Abeta(1-40) and Abeta(1-42) levels produced by atorvastatin treatment in the ADCLT were not significant compared placebo. There was a trend for significant reduction in circulating ceruloplasmin levels after a year of atorvastatin therapy compared to levels observed at screen. The levels of HDL-cholesterol remained stable in the atorvastatin treated AD patients for 9 months and then decreased significantly compared to the placebo group at the 1-year time-point. The combined data support a role for cholesterol in AD and a possible influence of increasing circulating copper levels. The deterioration of function in controls and transition to MCI may be associated with concomitant incremental increases in circulating Abeta(1-40) levels. Increased cholesterol and ceruloplasmin levels may be associated with slight deterioration in function among controls as a precursor to impairment considered MCI. The clinical benefit of atorvastatin therapy is clearly not associated with decreased circulating Abeta or increased HDL-cholesterol, but a positive influence of reduced copper (ceruloplasmin) levels may be a consideration.