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To assess the ideal time for caffeine administration in preterms, identifying its effects and safety. Study Design: Meta-analysis conducted including preterms <32 weeks GA or BW < 1500 g, comparing caffeine administration time: <24 x ≥24HOL, <48 x ≥48HOL, <72 x ≥72HOL. 18 studies included 76.998 patients. The median age of starting caffeine was the first 24 HOL. In the overall comparisons, there was reduction in patent ductus arteriosus (OR 0.71 [0.55, 0. 92]; low evidence), retinopathy of prematurity (OR 0.71 [0.54, 0.93]; moderate evidence), severe brain injury (OR 0.79 [0.70, 0.91]; moderate evidence), bronchopulmonary dysplasia (BPD) (OR 0.69 [0.59, 0.81]; moderate evidence), composite outcome of BPD or death (OR 0.76 [0.66, 0.88]; moderate evidence). Mortality increase was found (OR 1.20 [1.12, 1.29], very low evidence).Caffeine in the first 24 HOL has benefits in reducing morbidities associated with prematurity. Mortality finding is potentially due to survival bias., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Pompe disease (PD) is a glycogen disorder caused by the deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for infantile-onset PD (IOPD)., Methods: We systematically searched the MEDLINE (via PubMed) and Embase databases for prospective clinical studies evaluating ERT for IOPD on pre-specified outcomes. Meta-analysis was also performed., Results: Of 1,722 articles identified, 16 were included, evaluating 316 patients. Studies were heterogeneous and with very low certainty of evidence for most outcomes. A moderate/high risk of bias was present for most included articles. The following outcomes showed improvements associated with alglucosidase alfa, over natural history of PD/placebo, for a mean follow-up of 48.3 months: left ventricular (LV) mass {mean change 131.3 g/m 2 [95% confidence interval (CI) 81.02, 181.59]}, time to start ventilation (TSV) [HR 0.21 (95% CI: 0.12, 0.36)], and survival [HR 0.10 (95% CI: 0.05, 0.19)]. There were no differences between the pre- and post-ERT period for myocardial function and psychomotor development. Adverse events (AEs) after ERT were mild in most cases., Conclusion: Our data suggest that alglucosidase alfa potentially improves LV mass, TSV, and survival in IOPD patients, with no important safety issues., Systematic Review Registration: PROSPERO identifier (CRD42019123700)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Dornelles, Junges, Krug, Gonçalves, de Oliveira Junior and Schwartz.)

Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD)., Methods: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed., Results: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change -2.64 h (95% CI -5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases., Conclusion: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102.

Background: The incidence of myocardial injury (MI) in patients with COVID-19 in Brazil and the prognostic impact of MI have not been elucidated., Objectives: To describe the incidence of MI in patients with COVID-19 in the intensive care unit (ICU) and to identify variables associated with its occurrence. The secondary objective was to assess high-sensitivity troponin I as a predictor of in-hospital mortality., Methods: Retrospective, observational study conducted between March and April 2020 with cases of confirmed COVID-19 admitted to the ICU. Numerical variables were compared by using Student t test or Mann-Whitney U test. The chi-square test was used for categorical variables. Multivariate analysis was performed with variables associated with MI and p<0.2 to determine predictors of MI. The ROC curve was used to determine the troponin value capable of predicting higher in-hospital mortality. Survival functions were estimated by use of the Kaplan-Meier method from the cut-off point indicated in the ROC curve., Results: This study assessed 61 patients (63.9% of the male sex, mean age of 66.1±15.5 years). Myocardial injury was present in 36% of the patients. Systemic arterial hypertension (HAS) [OR 1.198; 95%CI: 2.246-37.665] and body mass index (BMI) [OR 1.143; 95%CI: 1.013-1.289] were independent risk predictors. High-sensitivity troponin I >48.3 ng/mL, which was determined in the ROC curve, predicts higher in-hospital mortality [AUC 0.786; p<0.05]. Survival in the group with high-sensitivity troponin I >48.3 ng/mL was lower than that in the group with values ≤48.3 ng/dL [20.3 x 43.5 days, respectively; p<0.05]., Conclusion: There was a high incidence of MI in severe COVID-19 with impact on higher in-hospital mortality. The independent risk predictors of MI were SAH and BMI. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Background & Aims: Gaucher disease (GD) is a multisystemic disease. Liver involvement in GD is not well characterised and ranges from hepatomegaly to cirrhosis and hepatocellular carcinoma. We aim to describe, and assess the effect of treatment, on the hepatic phenotype of a cohort of patients with GD types I and II., Methods: Retrospective study based on the review of the medical files of the Gaucher Reference Centre of the Hospital de Clínicas de Porto Alegre, Brazil. Data from all GD types I and III patients seen at the centre since 2003 were analysed. Variables were compared as pre- ("baseline") and post-treatment ("follow-up")., Results: Forty-two patients (types I: 39, III: 3; female: 22; median age: 35 y; enzyme replacement therapy: 37; substrate reduction therapy: 2; non-treated: 3; median time on treatment-MTT: 124 months) were included. Liver enzyme abnormalities, hepatomegaly, and steatosis at baseline were seen in 19/28 (68%), 28/42 (67%), and 3/38 patients (8%), respectively; at follow-up, 21/38 (55%), 15/38 (39%) and 15/38 (39%). MRI iron quantification showed overload in 7/8 patients (treated: 7; MTT: 55 months), being severe in 2/7 (treated: 2/2; MTT: 44.5 months). Eight patients had liver biopsy (treated: 6; MTT: 58 months), with fibrosis in 3 (treated: 1; time on treatment: 108 months) and steatohepatitis in 2 (treated: 2; time on treatment: 69 and 185 months). One patient developed hepatocellular carcinoma., Conclusions: GD is a heterogeneous disease that causes different patterns of liver damage even during treatment. Although treatment improves the hepatocellular damage, it is associated with an increased rate of steatosis. This study highlights the importance of a follow-up of liver integrity in these patients., (© 2020 The Authors.)

Context: Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment., Objective: To determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113)., Data Sources: PubMed, Embase, SciELO, LILACS, and Cochrane databases., Study Selection: Prospective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period., Data Extraction: Two independent researchers extracted data using a predesigned data extraction sheet., Statistical Methods: A random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation., Results: Our analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60-7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57-79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93-14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak., Limitations: Major limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals., Conclusions: There was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic., Competing Interests: The authors have declared that no competing interests exist.

Background: Gaucher disease (GD) is caused by deficiency of beta-glucocerebrosidase (GCase) due to biallelic variations in the GBA1 gene. Parkinson's disease (PD) is the second most common neurodegenerative condition. The classic motor symptoms of PD may be preceded by many non-motor symptoms (NMS), which include hyposmia, rapid eye movement (REM) sleep behavior disorder, constipation, cognitive impairment, and depression. Population studies have identified mutations in GBA1 as the main risk factor for idiopathic PD. The present study sought to evaluate the prevalence of NMS in a cohort of patients with GD type 1 from Southern Brazil., Methodology: This is an observational, cross-sectional study, with a convenience sampling strategy. Cognition was evaluated by the Montreal Cognitive assessment (MoCa), daytime sleepiness by the Epworth Scale, depression by the Beck Inventory, constipation by the Unified Multiple System Atrophy Rating Scale, and REM sleep behavior disorder by the Single-Question Screen; hyposmia by the Sniffin' Sticks. Motor symptoms were assessed with part III of the Unified Parkinson's Disease Rating Scale. All patients were also genotyped for the GBA1 3'-UTR SNP (rs708606)., Results: Twenty-three patients (female = 13; on enzyme replacement therapy = 21, substrate reduction therapy = 2) with a mean age of 41.45 ± 15.3 years (range, 22-67) were included. Eight patients were found to be heterozygous for the 3'-UTR SNP (rs708606). Fourteen patients (8 over age 40 years) presented at least one NMS; daytime sleepiness was the most frequent (n = 10). Two patients (aged 63 and 64, respectively) also presented motor symptoms, probably drug-related., Conclusions: NMS were prevalent in this cohort. We highlight the importance of a multidisciplinary follow-up focusing on earlier diagnosis of PD, especially for patients with GD type 1 over the age of 40.

Background: Unlicensed (UL) and Off-label (OL) prescription of medications is common in paediatrics and does not constitute negligent practice since there is often no approved alternative according to FDA bulary., Aim: The study aimed to determine the current frequency of UL and OL prescriptions in children from one month to 12 years of age in a Paediatric Inpatient Unit (PIU)., Methods: This is an observational, prospective study, reviewing the prescriptions of all patients admitted to the PIU in a university hospital in a single week in August 2014 and a single week in January 2015., Results: We included 157 patients of median age 18 months and median length of stay 24 days. There were 1,328 prescription items (average of 8.4 items/patient) and only two patients without UL/OL use. During the winter season (August), 27% of prescriptions were classified as UL and 44.6% as OL, and during summer (January), 29.6% as UL and 45.1% as OL. We identified 188 medications, of which the most prescribed were paracetamol (11%) and dipyrone (9.5%). The most frequent OL classification was regarding drug formulation (15.8%). In the winter week, the most frequent reasons for admission were respiratory (44%), followed by other clinical causes (CC) (17.3%), while in the summer week, they were CC (26.3%), followed by surgical and gastrohepatic (23.7%)., Conclusion: The OL prescription of medicines for children in Brazil is in accordance with the international literature. The higher prevalence of OL due to formulation found in this study is related to the use of formulations other than those used by the FDA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate the efficacy and safety of IV laronidase for MPS I., Methods: A systematic literature review was performed by searching the ClinicalTrials.gov, MEDLINE/PubMed, EMBASE, LILACS, and Cochrane Library databases, limited to clinical trials published until December 31, 2016. The first inclusion criterion was being a randomized controlled trial (RCT). If < five RCTs were identified, open-label and nonrandomized trials, controlled or uncontrolled (quasi-experimental), including ≥ five patients, and evaluating relevant outcomes defined a priori, would also be included. For meta-analysis, primary inferences were based on random-effects models. Assessment of article quality was performed in accordance with the GRADE criteria. The Cochrane Risk of Bias tool was used to examine the risk of bias for RCTs., Results: The selection phase retrieved 632 articles. During the first phase of selection, 158 had the abstract or full text read for assessment of eligibility, of which nine (two RCTs) were included for qualitative synthesis. Four papers were included in the meta-analysis, which was performed for the following outcomes: occurrence of treatment-emergent or infusion-related adverse events (65%; 95%CI 53, 76), mild in most cases; development of IgG antibodies to laronidase (88%; 95%CI 67, 100); apnea-hypopnea index (not significant-NS), urinary glycosaminoglycans (GAGs) [mean change -65.5 μg/mg creatinine (95%CI -68.8, -62.3)], liver size [mean change -31.03% (95%CI -36.1, -25.9)], left ventricular mass index (LVMI) [mean change -1.8 (95%CI -2.32, -0.25)], and distance covered in the 6-minute walk test (NS). Among the outcomes not included in meta-analysis, we found evidence for benefit of laronidase only on shoulder flexion., Conclusions: Our findings suggest that IV laronidase effectively reduces urinary GAGs excretion, hepatomegaly and LVMI, and can improve shoulder flexion in MPS I patients. Laronidase appears to be safe in the studied population.

Background/aims: Hypernatremic dehydration in term neonates is associated with inadequate fluid intake, usually related to insufficient lactation. The use of hypotonic fluids is appropriate to dilute serum sodium (SNa), but cerebral edema may develop when it happens abruptly. Our objective was to clarify how to correct hypernatremic dehydration properly., Methods: The following databases were searched, limited to studies published until January 31st, 2016: Clinical Trials, MEDLINE/PubMed, EMBASE, LILACS, and the Cochrane Library. We included open-label trials, nonrandomized controlled trials, or prospective and retrospective case series evaluating relevant outcomes. Information regarding the way of administering the treatment, type of fluid used, rates of complications and outcomes, as well as the rate of SNa reduction were collected., Results: Searches yielded 771 articles: 64 had the full text reviewed and 9 were included. No randomized clinical trials or systematic reviews focusing on treatment of hypernatremic dehydration and its outcomes were found. We found a scarcity of high quality studies and great methodology heterogeneity., Conclusions: More severe hypernatremia is at greater risk of causing severe adverse effects of treatment. There is no consensus about the optimal rate of SNa drop in this population, but a slower correction appears to be safer. Questions as when parenteral fluids are indicated remain unanswered., (Copyright © 2017 by S. Karger AG, Basel.)

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

Background: The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults., Methods: This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured., Results: Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups., Conclusion: A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults., Trial Registration: NCT01389518.

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.

The scope of this paper is to ascertain the perception of community leadership, health professionals and users regarding citizenship status and the enhancement of the healthcare conditions of families belonging to a vulnerable community. This is an exploratory study of a qualitative nature, guided by theory based on data. Data were collected between July and December 2009, by means of interviews with four community health leaders, a team of eight family health team professionals and twelve health users. The codification of the data resulted in the following categories: Understanding the social conditions, the political conditions, the environmental conditions and the health conditions of families in a vulnerable community. The conclusions reached were, that if on the one hand the social security and health policies made it possible to reduce poverty and local inequalities, on the other hand they do not ensure the requisite enhancement of citizenship or even the improvement of health conditions.