Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 165
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Circulation ; 148(24): e187-e280, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-37942682

RESUMO

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Nascimento Prematuro , Adulto , Feminino , Criança , Recém-Nascido , Humanos , Primeiros Socorros , Consenso , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia
2.
Ann Emerg Med ; 83(4): 327-339, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38142375

RESUMO

STUDY OBJECTIVE: Our primary objectives were to identify clinical practice guideline recommendations for children with acute mild traumatic brain injury (mTBI) presenting to an emergency department (ED), appraise their overall quality, and synthesize the quality of evidence and the strength of included recommendations. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and medical association websites from January 2012 to May 2023 for clinical practice guidelines with at least 1 recommendation targeting pediatric mTBI populations presenting to the ED within 48 hours of injury for any diagnostic or therapeutic intervention in the acute phase of care (ED and inhospital). Pairs of reviewers independently assessed overall clinical practice guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. RESULTS: We included 11 clinical practice guidelines, of which 6 (55%) were rated high quality. These included 101 recommendations, of which 34 (34%) were based on moderate- to high-quality evidence, covering initial assessment, initial diagnostic imaging, monitoring/observation, therapeutic interventions, discharge advice, follow-up, and patient and family support. We did not identify any evidence-based recommendations in high-quality clinical practice guidelines for repeat imaging, neurosurgical consultation, or hospital admission. Lack of strategies and tools to aid implementation and editorial independence were the most common methodological weaknesses. CONCLUSIONS: We identified 34 recommendations based on moderate- to high-quality evidence that may be considered for implementation in clinical settings. Our review highlights important areas for future research. This review also underlines the importance of providing strategies to facilitate the implementation of clinical practice guideline recommendations for pediatric mTBI.


Assuntos
Concussão Encefálica , Humanos , Criança , Concussão Encefálica/diagnóstico , Concussão Encefálica/terapia , Serviço Hospitalar de Emergência
3.
Cochrane Database Syst Rev ; 6: CD015229, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842054

RESUMO

BACKGROUND: Persistent visceral pain is an unpleasant sensation coming from one or more organs within the body. Visceral pain is a common symptom in those with advanced cancer. Interventional procedures, such as neurolytic sympathetic nerve blocks, have been suggested as additional treatments that may play a part in optimising pain management for individuals with this condition. OBJECTIVES: To evaluate the benefits and harms of neurolytic sympathetic nerve blocks for persistent visceral pain in adults with inoperable abdominopelvic cancer compared to standard care or placebo and comparing single blocks to combination blocks. SEARCH METHODS: We searched the following databases without language restrictions on 19 October 2022 and ran a top-up search on 31 October 2023: CENTRAL; MEDLINE via Ovid; Embase via Ovid; LILACS. We searched trial registers without language restrictions on 2 November 2022: ClinicalTrials.gov; WHO International Clinical Trials Registry Platform (ICTRP). We searched grey literature, checked reference lists of reviews and retrieved articles for additional studies, and performed citation searches on key articles. We also contacted experts in the field for unpublished and ongoing trials. Our trial protocol was preregistered in the Cochrane Database of Systematic Reviews on 21 October 2022. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) comparing any sympathetic nerve block targeting sites commonly used to treat abdominal pelvic pain from inoperable malignancies in adults to standard care or placebo. DATA COLLECTION AND ANALYSIS: We independently selected trials based on predefined inclusion criteria, resolving any differences via adjudication with a third review author. We used a random-effects model as some heterogeneity was expected between the studies due to differences in the interventions being assessed and malignancy types included in the study population. We chose three primary outcomes and four secondary outcomes of interest. We sought consumer input to refine our review outcomes and assessed extracted data using Cochrane's risk of bias 2 tool (RoB 2). We assessed the certainty of evidence using the GRADE system. MAIN RESULTS: We included 17 studies with 1025 participants in this review. Fifteen studies with a total of 951 participants contributed to the quantitative analysis. Single block versus standard care Primary outcomes No included studies reported our primary outcome, 'Proportion of participants reporting no worse than mild pain after treatment at 14 days'. The evidence is very uncertain about the effect of sympathetic nerve blocks on reducing pain to no worse than mild pain at 14 days when compared to standard care due to insufficient data (very low-certainty evidence). Sympathetic nerve blocks may provide small to 'little to no' improvement in quality of life (QOL) scores at 14 days after treatment when compared to standard care, but the evidence is very uncertain (standardised mean difference (SMD) -0.73, 95% confidence interval (CI) -1.70 to 0.25; I² = 87%; 4 studies, 150 participants; very low-certainty evidence). The evidence is very uncertain about the risk of serious adverse events as defined in our review as only one study contributed data to this outcome. Sympathetic nerve blocks may have an 'increased risk' to 'no additional risk' of harm compared with standard care (very low-certainty evidence). Secondary outcomes Sympathetic nerve blocks showed a small to 'little to no' effect on participant-reported pain scores at 14 days using a 0 to 10 visual analogue scale (VAS) for pain compared with standard care, but the evidence is very uncertain (mean difference (MD) -0.44, 95% CI -0.98 to 0.11; I² = 56%; 5 studies, 214 participants; very low-certainty evidence). There may be a 'moderate to large' to 'little to no' reduction in daily consumption of opioids postprocedure at 14 days with sympathetic nerve blocks compared with standard care, but the evidence is very uncertain (change in daily consumption of opioids at 14 days as oral milligrams morphine equivalent (MME): MD -41.63 mg, 95% CI -78.54 mg to -4.72 mg; I² = 90%; 4 studies, 130 participants; very low-certainty evidence). The evidence is very uncertain about the effect of sympathetic nerve blocks on participant satisfaction with procedure at 0 to 7 days and time to need for retreatment or treatment effect failure (or both) due to insufficient data. Combination block versus single block Primary outcomes There is no evidence about the effect of combination sympathetic nerve blocks compared with single sympathetic nerve blocks on the proportion of participants reporting no worse than mild pain after treatment at 14 days because no studies reported this outcome. There may be a small to 'little to no' effect on QOL score at 14 days after treatment, but the evidence is very uncertain (very low-certainty evidence). The evidence is very uncertain about the risk of serious adverse events with combination sympathetic nerve blocks compared with single sympathetic nerve blocks due to limited reporting in the included studies (very low-certainty evidence). Secondary outcomes The evidence is very uncertain about the effect of combination sympathetic nerve blocks compared with single sympathetic nerve blocks on participant-reported pain score and change in daily consumption of opioids postprocedure, at 14 days. There may be a small to 'little to no' effect, but the evidence is very uncertain (very low-certainty evidence). There is no evidence about the effect on participant satisfaction with procedure at 0 to 7 days and time to need for retreatment or treatment effect failure (or both) due to these outcomes not being measured by the studies. Risk of bias The risk of bias was predominately high for most outcomes in most studies due to significant concerns regarding adequate blinding. Very few studies were deemed as low risk across all domains for any outcome. AUTHORS' CONCLUSIONS: There is limited evidence to support or refute the use of sympathetic nerve blocks for persistent abdominopelvic pain due to inoperable malignancy. We are very uncertain about the effect of combination sympathetic nerve blocks compared with single sympathetic nerve blocks. The certainty of the evidence is very low and these findings should be interpreted with caution.


Assuntos
Neoplasias Abdominais , Bloqueio Nervoso Autônomo , Viés , Neoplasias Pélvicas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Bloqueio Nervoso Autônomo/métodos , Adulto , Neoplasias Pélvicas/complicações , Neoplasias Abdominais/complicações , Dor do Câncer/terapia , Dor do Câncer/etiologia , Dor Abdominal/etiologia , Dor Abdominal/terapia , Manejo da Dor/métodos , Bloqueio Nervoso/métodos , Qualidade de Vida
4.
Pediatr Emerg Care ; 40(4): 261-264, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37205877

RESUMO

OBJECTIVES: Providing emergency care to acutely ill or injured children is stressful and requires a high level of training. Paramedics who provide prehospital care are typically not involved in the circle of care and do not receive patient outcome information. The aim of this quality improvement project was to assess paramedics' perceptions of standardized outcome letters pertaining to acute pediatric patients that they had treated and transported to an emergency department. METHODS: Between December 2019 and December 2020, 888 outcome letters were distributed to paramedics who provided care for 370 acute pediatric patients transported to the Children's Hospital of Eastern Ontario in Ottawa, Canada. All paramedics who received a letter (n = 470) were invited to participate in a survey that collected their perceptions and feedback about the letters, as well as their demographic information. RESULTS: The response rate was 37% (172/470). Approximately half of the respondents were Primary Care Paramedics and half Advanced Care Paramedics. The respondents' median age was 36 years, median years of service was 12 years, and 64% identified as male. Most agreed that the outcome letters contained information pertinent to their practice (91%), allowed them to reflect on care they had provided (87%), and confirmed clinical suspicions (93%). Respondents indicated that they found the letters useful for 3 reasons: 1) increases capacity to link differential diagnoses, prehospital care, or patient outcomes; 2) contributes to a culture of continuous learning and improvement; and 3) gives closure, reduces stress, or provides answers for difficult cases. Suggestions for improvement included providing more information, provision of letters on all patients transported, faster turnaround time between call and receipt of letter and inclusion of recommendations or interventions/assessments. CONCLUSIONS: Paramedics appreciated receiving hospital-based patient outcome information after their provision of care and reported that the letters offered opportunities for closure, reflection, and learning.


Assuntos
Serviços Médicos de Emergência , Humanos , Masculino , Criança , Adulto , Inquéritos e Questionários , Serviço Hospitalar de Emergência , Ontário , Hospitais Pediátricos
5.
Biophys J ; 121(16): 3049-3060, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35841142

RESUMO

Intrinsically disordered proteins (IDPs) play critical roles in regulatory protein interactions, but detailed structural/dynamic characterization of their ensembles remain challenging, both in isolation and when they form dynamic "fuzzy" complexes. Such is the case for mRNA cap-dependent translation initiation, which is regulated by the interaction of the predominantly folded eukaryotic initiation factor 4E (eIF4E) with the intrinsically disordered eIF4E binding proteins (4E-BPs) in a phosphorylation-dependent manner. Single-molecule Förster resonance energy transfer showed that the conformational changes of 4E-BP2 induced by binding to eIF4E are non-uniform along the sequence; while a central region containing both motifs that bind to eIF4E expands and becomes stiffer, the C-terminal region is less affected. Fluorescence anisotropy decay revealed a non-uniform segmental flexibility around six different labeling sites along the chain. Dynamic quenching of these fluorescent probes by intrinsic aromatic residues measured via fluorescence correlation spectroscopy report on transient intra- and inter-molecular contacts on nanosecond-to-microsecond timescales. Upon hyperphosphorylation, which induces folding of ∼40 residues in 4E-BP2, the quenching rates decreased at most labeling sites. The chain dynamics around sites in the C-terminal region far away from the two binding motifs significantly increased upon binding to eIF4E, suggesting that this region is also involved in the highly dynamic 4E-BP2:eIF4E complex. Our time-resolved fluorescence data paint a sequence-level rigidity map of three states of 4E-BP2 differing in phosphorylation or binding status and distinguish regions that form contacts with eIF4E. This study adds complementary structural and dynamics information to recent studies of 4E-BP2, and it constitutes an important step toward a mechanistic understanding of this important IDP via integrative modeling.


Assuntos
Fator de Iniciação 4E em Eucariotos , Proteínas Intrinsicamente Desordenadas , Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Fatores de Iniciação em Eucariotos/química , Fatores de Iniciação em Eucariotos/genética , Fatores de Iniciação em Eucariotos/metabolismo , Proteínas Intrinsicamente Desordenadas/química , Fosforilação , Ligação Proteica
6.
J Chem Inf Model ; 62(17): 4175-4190, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36001481

RESUMO

The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene encodes a tightly regulated dual-specificity phosphatase that serves as the master regulator of PI3K/AKT/mTOR signaling. The carboxy-terminal tail (CTT) is key to regulation and harbors multiple phosphorylation sites (Ser/Thr residues 380-385). CTT phosphorylation suppresses the phosphatase activity by inducing a stable, closed conformation. However, little is known about the mechanisms of phosphorylation-induced CTT-deactivation dynamics. Using explicit solvent microsecond molecular dynamics simulations, we show that CTT phosphorylation leads to a partially collapsed conformation, which alters the secondary structure of PTEN and induces long-range conformational rearrangements that encompass the active site. The active site rearrangements prevent localization of PTEN to the membrane, precluding lipid phosphatase activity. Notably, we have identified phosphorylation-induced allosteric coupling between the interdomain region and a hydrophobic site neighboring the active site in the phosphatase domain. Collectively, the results provide a mechanistic understanding of CTT phosphorylation dynamics and reveal potential druggable allosteric sites in a previously believed clinically undruggable protein.


Assuntos
PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases , Simulação de Dinâmica Molecular , PTEN Fosfo-Hidrolase/química , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Estrutura Secundária de Proteína , Transdução de Sinais
7.
Cochrane Database Syst Rev ; 8: CD005249, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34346056

RESUMO

BACKGROUND: Many small, sick, and preterm infants are unable to co-ordinate sucking, swallowing, and breathing, and therefore require gavage feeding. In gavage feeding, milk feeds are delivered through a tube passed via the nose or the mouth into the stomach. Intermittent bolus milk feeds may be administered by a syringe to gently push milk into the infant's stomach (push feed). Alternatively, milk can be poured into a syringe attached to the tube and allowed to drip in by gravity (gravity feed). OBJECTIVES: To determine whether use of push feeding compared with gravity feeding results in more rapid establishment of full gavage feeds without increasing adverse events among preterm or low birth weight infants, or both, who require intermittent bolus tube feeding. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 30 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing push versus gravity intermittent gavage tube feeding in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 grams) infants, or both. DATA COLLECTION AND ANALYSIS: We assessed the methods of trials regarding blinding of randomisation and outcome measurement. We evaluated treatment effects with a fixed-effect model using risk ratio (RR), relative risk reduction, risk difference (RD), and number needed to treat for an additional beneficial outcome (NNTB) for categorical data; and using mean, standard deviation, and mean difference (MD) for continuous data. We analysed outcomes measured as count data, for example, frequency of apnoea, bradycardia, and episodes of pulse oximeter oxygen (SpO2) desaturation, by comparing rates of events and the rate ratio. We evaluated heterogeneity to help determine the suitability of pooling results. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: One small cross-over trial (31 infants) met the criteria for inclusion in this review. The certainty of evidence for all outcomes was very low due to imprecision of estimates, wide confidence intervals, and unclear risk of bias. The primary outcome - time taken to establish full gavage feeding (days) and feeding intolerance (number of episodes per day) - was not reported in the included study. The evidence is very uncertain about the effects of push versus gravity intermittent gavage tube feeding on all other outcomes. Investigators reported respiratory rate (breaths per minute) at completion of feeding (MD 0.58, 95% confidence interval (CI) -5.97 to 7.13; 1 study, 31 participants; very low-certainty evidence); respiratory rate (breaths per minute) 10 to 30 minutes after completion of feeding (MD 3.1, 95% CI -3.43 to 9.63; 1 study, 31 participants; very low-certainty evidence); heart rate (beats per minute) at completion of feeding (MD 2.6, 95% CI -9.71 to 4.51; 1 study, 31 participants; very low-certainty evidence); and heart rate (beats per minute) 10 to 30 minutes after completion of feeding (MD 2.4, 95% CI -9.16 to 4.36; 1 study, 31 participants; very low-certainty evidence). We are very uncertain of the effects of push versus gravity intermittent gavage feeding on respiratory rate during and after feeding. AUTHORS' CONCLUSIONS: We do not have sufficient evidence to determine the effects of intermittent bolus gavage feeding for preterm and low birth weight infants. The single small study of 31 infants comparing effects of push versus gravity bolus gavage feeding did not report the primary outcome identified in this review. Thus, evidence is insufficient to show whether use of push compared with gravity gavage feeding results in more rapid establishment of full gavage feeds without increasing adverse events in preterm or low birth weight infants who receive intermittent bolus gavage feeding. In addition, the included study was too small to measure potential adverse events that can occur during gavage tube feeding, for example, episodes of oxygen desaturation, apnoea, or bradycardia.


Assuntos
Nutrição Enteral , Recém-Nascido de Baixo Peso , Animais , Estudos Cross-Over , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Leite
8.
J Clin Monit Comput ; 35(4): 689-710, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32458169

RESUMO

OBJECTIVE: To gain a deeper understanding of the information requirements of clinicians conducting neonatal resuscitation in the first 10 min after birth. BACKGROUND: During the resuscitation of a newborn infant in the first minutes after birth, clinicians must monitor crucial physiological adjustments that are relatively unobservable, unpredictable, and highly variable. Clinicians' access to information regarding the physiological status of the infant is also crucial to determining which interventions are most appropriate. To design displays to support clinicians during newborn resuscitation, we must first carefully consider the information requirements. METHODS: We conducted a work domain analysis (WDA) for the neonatal transition in the first 10 min after birth. We split the work domain into two 'subdomains'; the physiology of the neonatal transition, and the clinical resources supporting the neonatal transition. A WDA can reveal information requirements that are not yet supported by resources. RESULTS: The physiological WDA acted as a conceptual tool to model the exact processes and functions that clinicians must monitor and potentially support during the neonatal transition. Importantly, the clinical resources WDA revealed several capabilities and limitations of the physical objects in the work domain-ultimately revealing which physiological functions currently have no existing sensor to provide clinicians with information regarding their status. CONCLUSION: We propose two potential approaches to improving the clinician's information environment: (1) developing new sensors for the information we lack, and (2) employing principles of ecological interface design to present currently available information to the clinician in a more effective way.


Assuntos
Ressuscitação , Humanos , Lactente , Recém-Nascido , Monitorização Fisiológica
9.
Paediatr Child Health ; 26(7): 402-407, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34777657

RESUMO

Concussion in children and adolescents is an important health concern. Most paediatric patients fully recover in 1 month or less following an acute concussion. However, some experience prolonged or persistent concussion symptoms for months. Those with prolonged post-concussion-related symptoms may have impaired quality of life, and limited involvement in social, academic, and physical activities with associated mental health implications. In this review, we share key updated clinical recommendations from the Living Guideline for Diagnosing and Managing Pediatric Concussion that will improve the way general paediatricians and family doctors diagnose and manage paediatric patients with suspected concussion.

10.
Circulation ; 140(24): e826-e880, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31722543

RESUMO

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.


Assuntos
Reanimação Cardiopulmonar/normas , Serviços Médicos de Emergência/normas , Tratamento de Emergência , Hipotermia Induzida/normas , Criança , Serviço Hospitalar de Emergência/normas , Tratamento de Emergência/normas , Humanos , Parada Cardíaca Extra-Hospitalar/terapia
12.
Pediatr Blood Cancer ; 66(9): e27832, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31131962

RESUMO

Hypodysfibrinogenemia, the least frequently reported congenital fibrinogen disorder is characterized by low circulating levels of a dysfunctional protein, and is associated with phenotypic features of both hypo- and dysfibrinogenemia. Herein, we report an adolescent male with unprovoked venous thromboembolism and hypodysfibrinogenemia. Patient had recurrent, progressive thrombosis despite therapeutic anticoagulation with both low molecular weight heparin and warfarin. He had clinical and radiological improvement after transition to a direct thrombin inhibitor. Sequencing of the FGG gene identified a novel heterozygous mutation, c.1075G>T. Structural visualization of the identified variant was pursued and suggested that the mutation likely destabilizes the Ca2+ -binding site of fibrinogen resulting in pathogenicity.


Assuntos
Afibrinogenemia , Fibrinogênios Anormais , Heterozigoto , Mutação Puntual , Trombose Venosa , Adolescente , Afibrinogenemia/genética , Afibrinogenemia/metabolismo , Sítios de Ligação , Cálcio/química , Cálcio/metabolismo , Fibrinogênios Anormais/química , Fibrinogênios Anormais/genética , Fibrinogênios Anormais/metabolismo , Humanos , Masculino , Trombose Venosa/genética , Trombose Venosa/metabolismo , Trombose Venosa/patologia
13.
J Biol Chem ; 292(34): 14147-14164, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28655774

RESUMO

Characterization of the second nucleotide-binding domain (NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, in part because NBD1 contains the F508del mutation, which is the dominant cause of cystic fibrosis. Research on NBD2 has also been hampered by the overall instability of the domain and the difficulty of producing reagents. Nonetheless, multiple disease-causing mutations reside in NBD2, and the domain is critical for CFTR function, because channel gating involves NBD1/NBD2 dimerization, and NBD2 contains the catalytically active ATPase site in CFTR. Recognizing the paucity of structural and biophysical data on NBD2, here we have defined a bioinformatics-based method for manually identifying stabilizing substitutions in NBD2, and we used an iterative process of screening single substitutions against thermal melting points to both produce minimally mutated stable constructs and individually characterize mutations. We present a range of stable constructs with minimal mutations to help inform further research on NBD2. We have used this stabilized background to study the effects of NBD2 mutations identified in cystic fibrosis (CF) patients, demonstrating that mutants such as N1303K and G1349D are characterized by lower stability, as shown previously for some NBD1 mutations, suggesting a potential role for NBD2 instability in the pathology of CF.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação Puntual , Adenosina Trifosfatases/química , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Substituição de Aminoácidos , Sítios de Ligação , Domínio Catalítico , Catatonia , Biologia Computacional , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/química , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Estabilidade Enzimática , Deleção de Genes , Células HEK293 , Humanos , Fusão de Membrana , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Domínios e Motivos de Interação entre Proteínas , Estabilidade Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Temperatura de Transição
14.
Thorax ; 73(8): 776-778, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29054885

RESUMO

Oxygen saturation, measured by pulse oximetry (SpO2), is a vital clinical measure. Our descriptive, cross-sectional study describes SpO2 measurements from 6289 healthy subjects from age 1 to 80 years at 15 locations from sea level up to the highest permanent human habitation. Oxygen saturation measurements are illustrated as percentiles. As altitude increased, SpO2 decreased, especially at altitudes above 2500 m. The increase in altitude had a significant impact on SpO2 measurements for all age groups. Our data provide a reference range for expected SpO2 measurements in people from 1 to 80 years from sea level to the highest city in the world.


Assuntos
Altitude , Oxigênio/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Oximetria , Peru , Valores de Referência
15.
J Pediatr ; 201: 34-39.e3, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30251638

RESUMO

OBJECTIVE: To determine whether the use of a hydrocolloid nasal barrier dressing during binasal continuous positive airway pressure (CPAP) therapy, compared with no barrier dressing, reduces the rate of nasal injury in very preterm and/or very low birth weight infants. STUDY DESIGN: A single-center randomized controlled trial conducted in the neonatal intensive care unit at The Royal Women's Hospital, Melbourne. Eligible infants were born <30 weeks of gestation and/or with birth weight <1250 g, and had received ≥4 hours, but <48 hours, of CPAP. Infants were randomly allocated to receive either a hydrocolloid nasal barrier dressing during CPAP (barrier group), or no barrier dressing (no barrier group). The primary outcome was the incidence of any nasal injury during CPAP support, until the infant was both >30 weeks of postmenstrual age and >1250 g, unless CPAP therapy was stopped earlier. Nasal injury was regularly assessed by bedside nurses using a standardized form. RESULTS: A total of 108 preterm infants were enrolled: 53 infants in the barrier group and 55 infants in the no barrier group. Infants in the barrier group had a significantly lower rate of nasal injury compared with the no barrier group: 18 of 53 (34%) vs 31 of 55 (56%), respectively (P = .02), number needed to treat; 5 infants. No significant differences were detected in any secondary respiratory outcomes, or in the rate of common neonatal morbidities. CONCLUSIONS: Prophylactic use of a nasal barrier dressing within 48 hours of commencing treatment with binasal CPAP in very preterm or very low birth weight infants reduces nasal injury. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register ACTRN12616000438459.


Assuntos
Curativos Hidrocoloides , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Ventilação com Pressão Positiva Intermitente/efeitos adversos , Nariz/lesões , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Austrália , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva Neonatal , Ventilação com Pressão Positiva Intermitente/instrumentação , Masculino
16.
J Pediatr ; 193: 47-53, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29106924

RESUMO

OBJECTIVE: To determine whether the use of heated-humidified gases for respiratory support during the stabilization of infants <30 weeks of gestational age (GA) in the delivery room reduces rates of hypothermia on admission to the neonatal intensive care unit (NICU). STUDY DESIGN: A multicenter, unblinded, randomized trial was conducted in Melbourne, Australia, between February 2013 and June 2015. Infants <30 weeks of GA were randomly assigned to receive either heated-humidified gases or unconditioned gases during stabilization in the delivery room and during transport to NICU. Infants born to mothers with pyrexia >38°C were excluded. Primary outcome was rate of hypothermia on NICU admission (rectal temperature <36.5°C). RESULTS: A total of 273 infants were enrolled. Fewer infants in the heated-humidified group were hypothermic on admission to NICU (36/132 [27%]) compared with controls (61/141 [43%], P < .01). There was no difference in rates of hyperthermia (>37.5°C); 20% (27/132) in the heated-humidified group compared with 16% (22/141) in the controls (P = .30). There were no differences in mortality or respiratory outcomes. CONCLUSIONS: The use of heated-humidified gases in the delivery room significantly reduces hypothermia on admission to NICU in preterm infants, without increased risk of hyperthermia. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register (www.anzctr.org.au) ACTRN12613000093785.


Assuntos
Gases/administração & dosagem , Hipotermia/prevenção & controle , Terapia Respiratória/métodos , Austrália , Salas de Parto , Feminino , Febre/epidemiologia , Gases/efeitos adversos , Humanos , Umidificadores , Hipotermia/epidemiologia , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Terapia Respiratória/efeitos adversos
17.
J Pediatr ; 198: 181-186.e2, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29705115

RESUMO

OBJECTIVE: To compare the suction mask, a new facemask that uses suction to create a seal between the mask and the infant's face, with a conventional soft, round silicone mask during positive pressure ventilation (PPV) in the delivery room in newborn infants >34 weeks of gestation. STUDY DESIGN: Single-center randomized controlled trial in the delivery room. The primary outcome was mask leak. RESULTS: Forty-five infants were studied at a median gestational age of 38.1 weeks (IQR, 36.4-39.0 weeks); 22 were randomized to the suction mask and 23 to the conventional mask. The suction mask did not reduce mask leak (49.9%; IQR, 11.0%-92.7%) compared with the conventional mask (30.5%; IQR, 10.6%-48.8%; P = .51). The suction mask delivered lower peak inspiratory pressure (27.2 cm H2O [IQR, 25.0-28.7 cm H2O] vs 30.4 cm H2O [IQR, 29.4-32.5 cm H2O]; P < .05) and lower positive end expiratory pressure (3.7 cm H2O [IQR, 3.1-4.5 cm H2O] vs 5.1 cm H2O [IQR, 4.2-5.7 cm H2O ]; P < .05). There was no difference in the duration of PPV or rates of intubation or admission to the neonatal intensive care unit. In 5 infants (23%), the clinician switched from the suction to the conventional mask, 2 owing to intermittently low peak inspiratory pressure, 2 owing to failure to respond to PPV, and 1 owing to marked facial bruising after 6 minutes of PPV. CONCLUSIONS: The use of the suction mask to provide PPV in newborn infants did not reduce facemask leak. Adverse effects such as the inability to achieve the set pressures and transient skin discoloration are concerning. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12616000768493.


Assuntos
Máscaras , Respiração com Pressão Positiva/instrumentação , Sucção , Salas de Parto , Desenho de Equipamento , Falha de Equipamento , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino
19.
Aust N Z J Obstet Gynaecol ; 58(2): 197-203, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28856670

RESUMO

BACKGROUND: Our aim was to report perinatal characteristics of very preterm births before arrival (BBAs) at a hospital, and perinatal and infant mortality rates up to one year, comparing BBAs with births in a hospital. MATERIALS AND METHODS: A population-based cohort study of 22-31 weeks' gestation births in the state of Victoria, Australia from 1990-2009. BBAs were defined as unintentional births at home or on route to hospital. Perinatal data were obtained from the Department of Health and Human Services, Victoria. Perinatal and infant mortality data comparing BBAs with births in hospitals were analysed by logistic regression, adjusted for gestational age, birthweight and sex. RESULTS: One hundred and thirty-three BBAs were recorded: 51 (38%) stillbirths and 82 (62%) livebirths. Compared with births in a hospital, BBAs were less mature (26.3 weeks (SD 2.9) vs 27.7 weeks (SD 2.8), P < 0.001) and a higher proportion were born to teenagers: 13% versus 5% (adjusted odds ratio (aOR) 2.86, P < 0.001). BBAs were significantly more likely to be stillborn (aOR 2.13, 95% confidence interval (CI) 1.41, 3.23, P < 0.001) die within 28 days of livebirth (aOR 2.97, 95% CI 1.54, 5.73, P = 0.001) or die within a year of livebirth (aOR 2.87, 95% CI 1.51, 5.46, P = 0.001) compared with hospital births. Overall, 54 BBAs survived to one year (41% all BBAs, 67% liveborn BBAs), compared with 69% of hospital births (87% of livebirths). CONCLUSIONS: Very preterm birth before arrival is more common in teenagers and is associated with significantly increased risks of perinatal and infant mortality compared with birth in a hospital.


Assuntos
Recém-Nascido Prematuro , Nascimento Prematuro/epidemiologia , Adolescente , Adulto , Peso ao Nascer , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Masculino , Gravidez , Transtornos Puerperais/epidemiologia , Fatores Sexuais , Vitória/epidemiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA