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Carnitine is required to transport fatty acid across the mitochondrial membrane to undergo beta oxidation. In addition to disorders of fatty acid metabolism, a relative carnitine deficiency has been reported in pulmonary arterial hypertension (PAH). Here we performed an observational study in which food and supplement consumption were collected in an observation period followed by open label administration of a carnitine supplement to determine feasibility of increasing plasma carnitine levels in humans PAH. We confirmed that relative carnitine deficiency in PAH is not due to reduced dietary consumption and that plasma levels of carnitine can be increased in PAH patients with supplementation that is well tolerated.
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OBJECTIVES: To conduct a finite element analysis of the impact of different variables on tooth sectioning efficiency and trauma to surrounding tissues when utilizing high-speed surgical handpieces and elevators. METHODS: CBCT data from the horizontally impacted third mandibular molar (M3M) of a patient were utilized to establish digital models of the M3M, adjacent M2M, and surrounding bone. To simulate tooth sectioning, a 3D finite element model was established with the following variables: remaining tooth tissue thickness (1-5 mm), tooth section fissure width (1-3 mm), elevator depth in fissure (2-6 mm), elevator position (buccal, lingual, central), elevator width (2-5 mm), and application of force (rotating, levering). Using this model, the distribution of stress on the M3M and the surrounding tissue was assessed while measuring tooth sectioning efficiency and trauma to the surrounding tissue. RESULTS: Factors associated with uniform stress at the site of sectioning included thin (≤ 3 mm) remaining tooth tissue, appropriate fissure width (~ 2 mm), a wide (≥ 4 mm) elevator, and central elevator positioning. Levering the elevator yielded greater stress on the M3M than rotating force. Greater sectioning efficiency was associated with increased stress placed on the distobuccal side of M2M. CONCLUSIONS: Tooth sectioning efficiency can be improved by adjusting the high-speed surgical handpiece and elevator. However, it is important to remain attentive to the trauma to which adjacent teeth are exposed during this process. CLINICAL SIGNIFICANCE: These results offer guidance for approaches to improving operator efficiency and reducing trauma to surrounding tissues during tooth sectioning.
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Tomografia Computadorizada de Feixe Cônico , Análise de Elementos Finitos , Mandíbula , Dente Serotino , Dente Impactado , Humanos , Dente Serotino/cirurgia , Dente Impactado/cirurgia , Dente Impactado/diagnóstico por imagem , Mandíbula/cirurgia , Imageamento Tridimensional , Equipamentos Odontológicos de Alta Rotação , Análise do Estresse DentárioRESUMO
OBJECTIVE: To investigate the impact of mineralized dentin matrix (MDM) on the prognosis on bone regeneration and migration of retained roots after coronectomy. MATERIALS AND METHODS: Patients were divided into three groups based on the type of bone graft after coronectomy: Group C (n = 20, collagen), Group T (n = 20, tricalcium phosphate (TCP) + collagen), and Group D (n = 20, MDM + collagen). CBCT scans, conducted immediately and 6 months after surgery, were analyzed using digital software. Primary outcomes, including changes in bone defect depth and retained root migration distance, were evaluated 6 months after surgery. RESULTS: After 6 months, both Groups D and T exhibited greater reduction of the bone defect and lesser retained root migration than Group C (p < 0.001). Group D had greater regenerated bone volume in the distal 2 mm (73 mm3 vs. 57 mm3, p = 0.011) and lesser root migration (2.18 mm vs. 2.96 mm, p < 0.001) than Group T. The proportion of completely bone embedded retained roots was also greater in Group D than in Group C (70.0% vs. 42.1%, p = 0.003). CONCLUSIONS: MDM is an appropriate graft material for improving bone defect healing and reducing retained root migration after coronectomy. CLINICAL RELEVANCE: MDM is an autogenous material prepared chairside, which can significantly improve bone healing and reduce the risk of retained root re-eruption. MDM holds promise as a routine bone substitute material after M3M coronectomy.
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Regeneração Óssea , Fosfatos de Cálcio , Colágeno , Tomografia Computadorizada de Feixe Cônico , Dentina , Humanos , Masculino , Feminino , Fosfatos de Cálcio/uso terapêutico , Prognóstico , Pessoa de Meia-Idade , Colágeno/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/cirurgia , Adulto , Coroa do Dente/cirurgia , Resultado do Tratamento , Transplante Ósseo/métodos , Substitutos Ósseos/uso terapêuticoRESUMO
PURPOSE: There is variability in clinical outcomes with vertebral body tethering (VBT) partly due to a limited understanding of the growth modulation (GM) response. We used the largest sample of patients with 3D spine reconstructions to characterize the vertebra and disc morphologic changes that accompany growth modulation during the first two years following VBT. METHODS: A multicenter registry was used to identify idiopathic scoliosis patients who underwent VBT with 2 years of follow-up. Calibrated biplanar X-rays obtained at longitudinal timepoints underwent 3D reconstruction to obtain precision morphological measurements. GM was defined as change in instrumented coronal angulation from post-op to 2-years. RESULTS: Fifty patients (mean age: 12.5 ± 1.3yrs) were analyzed over a mean of 27.7 months. GM was positively correlated with concave vertebra height growth (r = 0.57, p < 0.001), 3D spine length growth (r = 0.36, p = 0.008), and decreased convex disc height (r = - 0.42, p = 0.002). High modulators (patients experiencing GM > 10°) experienced an additional 1.6 mm (229% increase) of mean concave vertebra growth during study period compared to the Poor Modulators (GM < - 10°) group, (2.3 vs. 0.7 mm, p = 0.039), while convex vertebra height growth was similar (1.3 vs. 1.4 mm, p = 0.91). CONCLUSION: When successful, VBT enables asymmetric vertebra body growth, leading to continued postoperative coronal angulation correction (GM). A strong GM response is correlated with concave vertebral body height growth and overall instrumented spine growth. A poor GM response is associated with an increase in convex disc height (suspected tether rupture). Future studies will investigate the patient and technique-specific factors that influence increased growth remodeling.
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BACKGROUND: Hospitalization rates for childhood pneumonia vary widely. Risk-based clinical decision support (CDS) interventions may reduce unwarranted variation. METHODS: We conducted a pragmatic randomized trial in two US pediatric emergency departments (EDs) comparing electronic health record (EHR)-integrated prognostic CDS versus usual care for promoting appropriate ED disposition in children (<18 years) with pneumonia. Encounters were randomized 1:1 to usual care versus custom CDS featuring a validated pneumonia severity score predicting risk for severe in-hospital outcomes. Clinicians retained full decision-making authority. The primary outcome was inappropriate ED disposition, defined as early transition to lower- or higher-level care. Safety and implementation outcomes were also evaluated. RESULTS: The study enrolled 536 encounters (269 usual care and 267 CDS). Baseline characteristics were similar across arms. Inappropriate disposition occurred in 3% of usual care encounters and 2% of CDS encounters (adjusted odds ratio: 0.99, 95% confidence interval: [0.32, 2.95]) Length of stay was also similar and adverse safety outcomes were uncommon in both arms. The tool's custom user interface and content were viewed as strengths by surveyed clinicians (>70% satisfied). Implementation barriers include intrinsic (e.g., reaching the right person at the right time) and extrinsic factors (i.e., global pandemic). CONCLUSIONS: EHR-based prognostic CDS did not improve ED disposition decisions for children with pneumonia. Although the intervention's content was favorably received, low subject accrual and workflow integration problems likely limited effectiveness. Clinical Trials Registration: NCT06033079.
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[This corrects the article DOI: 10.1371/journal.pone.0246393.].
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INTRODUCTION: Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (a) characteristics of smokers who begin using ECs during pregnancy, (b) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (c) risk for neonatal health complications among smokers who initiate ECs during pregnancy. METHODS: Pregnant women using CCs exclusively pre-pregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified as dual users (used both ECs and CCs) or EC replacers (used ECs exclusively). RESULTS: Of 29,505 pregnant smokers, 1.5% reported using ECs during the last 3 pregnancy months. Among them, 29.7% became EC-exclusive users. EC initiators were disproportionately non-Hispanic White. Relative to quitters, EC initiators had lower income, were less likely to be married, have intended pregnancies, receive first-trimester prenatal care, and participate in a federal assistance program. Compared to CC-exclusive users, EC initiators overall, and dual users specifically, were more likely to reduce pre- and post-natal CC usage relative to pre-pregnancy levels. EC initiators' risk for neonatal health complications fell between quitters and CC-exclusive users, though differences were not statistically significant. CONCLUSIONS: Although EC initiators reduced CC use more than CC-exclusive users, only 29.7% reported complete CC cessation, and there was insufficient evidence of reduction in neonatal health complications relative to CC-exclusive users. Currently, ECs should not be considered a viable gestational smoking cessation strategy. IMPLICATIONS: Health agencies have identified a critical need for research evaluating the use of e-cigarettes in supporting prenatal smoking cessation. Using the US Pregnancy Risk Assessment Monitoring System surveillance study data, we provide real-world evidence that prenatal e-cigarette initiation as a smoking cessation tool is used infrequently among pregnant combustible cigarettes smokers. Most using e-cigarettes in the last three months of pregnancy also used combustible cigarettes.
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OBJECTIVES: To support a pragmatic, electronic health record (EHR)-based randomized controlled trial, we applied user-centered design (UCD) principles, evidence-based risk communication strategies, and interoperable software architecture to design, test, and deploy a prognostic tool for children in emergency departments (EDs) with pneumonia. METHODS: Risk for severe in-hospital outcomes was estimated using a validated ordinal logistic regression model to classify pneumonia severity. To render the results usable for ED clinicians, we created an integrated SMART on Fast Healthcare Interoperability Resources (FHIR) web application built for interoperable use in two pediatric EDs using different EHR vendors: Epic and Cerner. We followed a UCD framework, including problem analysis and user research, conceptual design and early prototyping, user interface development, formative evaluation, and postdeployment summative evaluation. RESULTS: Problem analysis and user research from 39 clinicians and nurses revealed user preferences for risk aversion, accessibility, and timing of risk communication. Early prototyping and iterative design incorporated evidence-based design principles, including numeracy, risk framing, and best-practice visualization techniques. After rigorous unit and end-to-end testing, the application was successfully deployed in both EDs, which facilitated enrollment, randomization, model visualization, data capture, and reporting for trial purposes. CONCLUSION: The successful implementation of a custom application for pneumonia prognosis and clinical trial support in two health systems on different EHRs demonstrates the importance of UCD, adherence to modern clinical data standards, and rigorous testing. Key lessons included the need for understanding users' real-world needs, regular knowledge management, application maintenance, and the recognition that FHIR applications require careful configuration for interoperability.
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Registros Eletrônicos de Saúde , Pneumonia , Humanos , Prognóstico , Pneumonia/terapia , Criança , Interface Usuário-Computador , Software , Interoperabilidade da Informação em SaúdeRESUMO
OBJECTIVES: To study bone healing of two-wall bone defects after alveolar ridge preservation using mineralized dentin matrix. MATERIALS AND METHODS: After distal roots extraction of second and fourth premolars (P2, P4) on one lateral mandible in 12 beagles, two-wall bone defects (5 × 5 × 5 mm) were surgically created distally to the remaining mesial roots of P2 and P4. A total of 24 sites were randomly allocated to three groups (implant material- time of execution): mineralized dentin matrix (MDM)-3 m (MDM + collagen membrane; 3 months), MDM-6 m (MDM particles + collagen membrane; 6 months), and C-6 m (collagen membrane only; 6 months). Clinical, radiographic, digital, and histological examinations were performed 3 and 6 months after surgery. RESULTS: The bone healing in MDM groups were better compared to Control group (volume of bone regenerated in total: 25.12 mm3 vs. 13.30 mm3, p = .046; trabecular volume/total volume: 58.84% vs. 39.18%, p = .001; new bone formation rate: 44.13% vs. 31.88%, p = .047). Vertically, the radiological bone level of bone defect in MDM-6 m group was higher than that in C-6 m group (vertical height of bone defect: 1.55 mm vs. 2.74 mm, p = .018). Horizontally, no significant differences in buccolingual bone width were found between MDM and C groups at any time or at any level below the alveolar ridge. The percentages of remaining MDM were <1% in both MDM-3 m and MDM-6 m groups. CONCLUSIONS: MDM improved bone healing of two-wall bone defects and might be considered as a socket fill material used following tooth extraction.
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Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Cães , Animais , Alvéolo Dental/cirurgia , Alvéolo Dental/patologia , Processo Alveolar/cirurgia , Processo Alveolar/patologia , Colágeno , Extração Dentária , Dentina , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/cirurgia , Perda do Osso Alveolar/patologiaRESUMO
Metabolic effects of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and not fully recapitulated by increasing endogenous GLP-1. We tested the hypothesis that GLP-1 receptor (GLP-1R) agonists exert weight loss-independent, GLP-1R-dependent effects that differ from effects of increasing endogenous GLP-1. Individuals with obesity and prediabetes were randomized to receive for 14 weeks the GLP-1R agonist liraglutide, a hypocaloric diet, or the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin. The GLP-1R antagonist exendin(9-39) and placebo were administered in a two-by-two crossover study during mixed-meal tests. Liraglutide and diet, but not sitagliptin, caused weight loss. Liraglutide improved insulin sensitivity measured by HOMA for insulin resistance (HOMA-IR), the updated HOMA model (HOMA2), and the Matsuda index after 2 weeks, prior to weight loss. Liraglutide decreased fasting and postprandial glucose levels, and decreased insulin, C-peptide, and fasting glucagon levels. In contrast, diet-induced weight loss improved insulin sensitivity by HOMA-IR and HOMA2, but not the Matsuda index, and did not decrease glucose levels. Sitagliptin increased endogenous GLP-1 and GIP values without altering insulin sensitivity or fasting glucose levels, but decreased postprandial glucose and glucagon levels. Notably, sitagliptin increased GIP without altering weight. Acute GLP-1R antagonism increased glucose levels in all groups, increased the Matsuda index and fasting glucagon level during liraglutide treatment, and increased endogenous GLP-1 values during liraglutide and sitagliptin treatments. Thus, liraglutide exerts rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity that are not achieved by increasing endogenous GLP-1. ARTICLE HIGHLIGHTS: Metabolic benefits of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and are not fully achieved by increasing endogenous GLP-1 through dipeptidyl peptidase 4 (DPP-4) inhibition. We investigated weight loss-independent, GLP-1 receptor (GLP-1R)-dependent metabolic effects of liraglutide versus a hypocaloric diet or the DPP-4 inhibitor sitagliptin. GLP-1R antagonism with exendin(9-39) was used to assess GLP-1R-dependent effects during mixed meals. Liraglutide improved insulin sensitivity and decreased fasting and postprandial glucose prior to weight loss, and these benefits were reversed by exendin(9-39). GLP-1R agonists exert rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity not achieved by increasing endogenous GLP-1.
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Inibidores da Dipeptidil Peptidase IV , Resistência à Insulina , Estado Pré-Diabético , Humanos , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Dipeptidil Peptidase 4/metabolismo , Glucagon/metabolismo , Estado Pré-Diabético/tratamento farmacológico , Dieta Redutora , Estudos Cross-Over , Obesidade/tratamento farmacológico , Glicemia/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Fosfato de Sitagliptina/farmacologia , Fosfato de Sitagliptina/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Redução de PesoRESUMO
BACKGROUND CONTEXT: With an increasing number of web-based calculators designed to provide the probabilities of an individual achieving improvement after lumbar spine surgery, there is a need to determine the accuracy of these models. PURPOSE: To perform an internal and external validation study of the reduced Quality Outcomes Database web-based Calculator (QOD-Calc). STUDY DESIGN: Observational longitudinal cohort. PATIENT SAMPLE: Patients enrolled study-wide in Quality Outcomes Database (QOD) and patients enrolled in DaneSpine at a single institution who had elective lumbar spine surgery with baseline data to complete QOD-Calc and 12-month postoperative data. OUTCOME MEASURES: Oswestry Disability Index (ODI), Numeric Rating Scales (NRS) for back and leg pain, EuroQOL-5D (EQ-5D). METHODS: Baseline data elements were entered into QOD-Calc to determine the probability for each patient having Any Improvement and 30% Improvement in NRS leg pain, back pain, EQ-5D and ODI. These probabilities were compared with the actual 12-month postop data for each of the QOD and DaneSpine cases. Receiver-operating characteristics analyses were performed and calibration plots created to assess model performance. RESULTS: 24,755 QOD cases and 8,105 DaneSpine lumbar cases were included in the analysis. QOD-Calc had acceptable to outstanding ability (AUC: 0.694-0.874) to predict Any Improvement in the QOD cohort and moderate to acceptable ability (AUC: 0.658-0.747) to predict 30% Improvement. QOD-Calc had acceptable to exceptional ability (AUC: 0.669-0.734) to predict Any improvement and moderate to exceptional ability (AUC: 0.619-0.862) to predict 30% Improvement in the DaneSpine cohort. AUCs for the DaneSpine cohort was consistently lower that the AUCs for the QOD validation cohort. CONCLUSION: QOD-Calc performs well in predicting outcomes in a patient population that is similar to the patients that was used to develop it. Although still acceptable, model performance was slightly worse in a distinct population, despite the fact that the sample was more homogenous. Model performance may also be attributed to the low discrimination threshold, with close to 90% of cases reporting Any Improvement in outcome. Prediction models may need to be developed that are highly specific to the characteristics of the population.
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Dor nas Costas , Vértebras Lombares , Humanos , Dor nas Costas/tratamento farmacológico , Dor nas Costas/cirurgia , Dor nas Costas/epidemiologia , Internet , Vértebras Lombares/cirurgia , Procedimentos Neurocirúrgicos , Resultado do Tratamento , Estudos LongitudinaisRESUMO
Newborn metabolite perturbations may identify potential biomarkers or mechanisms underlying adverse, smoking-related childhood health outcomes. We assessed associations between third-trimester smoking and newborn metabolite concentrations using the Tennessee Pregnancy Risk Assessment Monitoring System (PRAMS, 2009-2019) as the discovery cohort and INSPIRE (2012-2014) as the replication cohort. Children were linked to newborn screening metabolic data (33 metabolites). Third-trimester smoking was ascertained from birth certificates (PRAMS) and questionnaires (INSPIRE). Among 8600 and 1918 mother-child dyads in PRAMS and INSPIRE cohorts, 14% and 13% of women reported third-trimester smoking, respectively. Third-trimester smoking was associated with higher median concentrations of free carnitine (C0), glycine (GLY), and leucine (LEU) at birth (PRAMS: C0: adjusted fold change 1.11 [95% confidence interval (CI) 1.08, 1.14], GLY: 1.03 [95% CI 1.01, 1.04], LEU: 1.04 [95% CI 1.03, 1.06]; INSPIRE: C0: 1.08 [95% CI 1.02, 1.14], GLY: 1.05 [95% CI 1.01, 1.09], LEU: 1.05 [95% CI 1.01, 1.09]). Smoking cessation (vs. continued smoking) during pregnancy was associated with lower median metabolite concentrations, approaching levels observed in infants of non-smoking women. Findings suggest potential pathways underlying fetal metabolic programming due to in utero smoke exposure and a potential reversible relationship of cessation.
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OBJECTIVES: The study represents a preliminary evaluation of the accuracy of the dynamic navigation system (DNS) in coronectomy of the mandibular third molar (M3M). METHODS: The study included participants with an impacted M3M near the inferior alveolar canal. The coronectomy planes were designed before the surgery using cone-beam computed tomography (CBCT) imaging data and then loaded into the DNS program. Intraoperatively, the navigation system was used to guide the complete removal of the target crown. Postoperative CBCT imaging was used to assess any three-dimensional deviations of the actual postoperative from the planned preoperative section planes for each patient. RESULTS: A total of 12 patients (13 teeth) were included. The root mean square (RMS) deviation of the preoperatively designed plane from the actual postoperative surface was 0.69 ± 0.21 mm, with a maximum of 1.45 ± 0.83/-1.87 ± 0.63 mm deviation. The areas with distance deviations < 1 mm, 1-2 mm, and 2-3 mm were 71.97 ± 5.72 %, 22.96 ± 6.57 %, and 4.52 ± 2.28 %, respectively. Most patients showed extremely high convexity of the surface area located in the mesial region adjacent to the base of the extraction socket. There was no observable evidence of scratching of the buccolingual bone plate at the base of the extraction socket by the handpiece drill. CONCLUSIONS: These results provide preliminary support for the use of DNS-based techniques when extracting M3M using a buccal approach. This would improve the accuracy of coronectomy and reduce the potiential damage to the surrounding tissue. CLINICAL SIGNIFICANCE: DNS is effective for guiding coronectomy.
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Dente Serotino , Traumatismos do Nervo Trigêmeo , Humanos , Dente Serotino/diagnóstico por imagem , Dente Serotino/cirurgia , Projetos Piloto , Extração Dentária , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Tomografia Computadorizada de Feixe Cônico , Computadores , Nervo Mandibular/diagnóstico por imagemRESUMO
BACKGROUND: Research on health effects and potential harms of electronic cigarette (EC) use during pregnancy is limited. We sought to determine the risks of pregnancy EC use on pregnancy-related adverse birth outcomes and assess whether quitting ECs reduces the risks. METHODS: Women with singleton live births who participated in the US Pregnancy Risk Assessment Monitoring System (PRAMS) survey study 2016-2020 were classified into four mutually exclusive groups, by their use of ECs and combustible cigarettes (CCs) during pregnancy: non-use, EC only use, CC only use, and dual use. We determined the risk of preterm birth, low birth weight, and small-for-gestational-age (SGA) by comparing cigarette users to non-users with a modified Poisson regression model adjusting for covariates. In a subset of women who all used ECs prior to pregnancy, we determined whether quitting EC use reduces the risk of preterm birth, low birth weight, and SGA by comparing to those who continued its use. All analyses were weighted to account for the PRAMS survey design and non-response rate. RESULTS: Of the 190,707 women (weighted N = 10,202,413) included, 92.1% reported cigarette non-use, 0.5% EC only use, 6.7% CC only use, and 0.7% dual use during pregnancy. Compared with non-use, EC only use was associated with a significantly increased risk of preterm birth (adjusted risk ratio [aRR]: 1.29, 95% confidence interval [CI]: 1.00, 1.65) and low birth weight (aRR: 1.38, 95%CI: 1.09, 1.75), but not SGA (aRR: 1.04, 95%CI: 0.76, 1.44). Among 7,877 (weighted N = 422,533) women EC users, quitting use was associated with a significantly reduced risk of low birth weight (aRR: 0.76, 95%CI: 0.62, 0.94) and SGA (aRR: 0.77, 95%CI: 0.62, 0.94) compared to those who continued to use ECs during pregnancy. CONCLUSIONS: Pregnancy EC use, by itself or dual use with CC, is associated with preterm birth and low birth weight. Quitting use reduces that risk. ECs should not be considered as a safe alternative nor a viable gestational smoking cessation strategy.
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Sistemas Eletrônicos de Liberação de Nicotina , Nascimento Prematuro , Vaping , Gravidez , Recém-Nascido , Humanos , Feminino , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Vaping/efeitos adversos , Estudos Transversais , Medição de Risco , Arritmias Cardíacas/complicações , Retardo do Crescimento FetalRESUMO
BACKGROUND: Unwarranted variation in disposition decisions exist among children with pneumonia. We validated three prognostic models for predicting pneumonia severity among children in the emergency department (ED) and hospital. METHODS: We performed a two-center, prospective study of children 6 months to <18 years presenting to the ED with pneumonia from January 2014 to May 2019. We evaluated three previously developed disease-specific prognostic models which use demographic, clinical, and diagnostic predictor variables, with each model estimating risk for Very Severe (mechanical ventilation or shock), Severe (ICU without very severe features), and Moderate/Mild (Hospitalization without severe features or ED discharge) pneumonia. Predictive accuracy was measured using discrimination (concordance or c-statistic) and re-calibration. RESULTS: There were 1088 children included in one or more of the three models. Median age was 3.6 years and the majority of children were male (53.7%) and identified as non-Hispanic White (63.7%). The distribution for the ordinal severity outcome was mild or moderate (79.1%), severe (15.9%), and very severe (4.9%). The three models each demonstrated excellent discrimination (C-statistic range across models [0.786-0.803]) with no appreciable degradation in predictive accuracy from the derivation cohort. CONCLUSIONS: All three prognostic models accurately identified risk for three clinically meaningful levels of pneumonia severity and demonstrated very good predictive performance. Physiologic variables contributed the most to model prediction. Application of these objective tools may help standardize and improve disposition and other management decisions for children with pneumonia.
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Serviços Médicos de Emergência , Pneumonia , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Prognóstico , Estudos Prospectivos , Hospitalização , Pneumonia/diagnósticoRESUMO
OBJECTIVES: This study investigated the application of an intraoral banana peel suturing model in helping students to acquire intraoral surgical techniques. METHODS: This is a self-control study conducted from January 2021 to March 2021. An intraoral banana peel suturing model was implemented to provide oral suture experience for undergraduates majoring in stomatology. The sutures students placed in the model were photographed and evaluated blindly by a professional team using an established scoring system. Training scores were recorded before (training 1) and after 2 months of training (training 2). Linear regression was used to examine factors related to the scores. Suturing training was conducted in the School and Hospital of Stomatology at Peking University. A total of eighty-two students in Peking University School and Hospital of Stomatology were in their fourth pre-clinical year and followed a workshop on surgical sutures according to the curriculum. All students who should take this course were included, and the response rate was 100%. RESULTS: The mean training 2 score (23.04 ± 3.83) was higher than the mean training 1 score (13.94 ± 3.15). The training 1 score was not significantly correlated with any of the students' general characteristics. The training 2 score was correlated with the training 1 score and the cumulative duration of practice outside of class. CONCLUSION: The intraoral banana peel suturing model can be used for suture training, and dental students' suture ability was improved after using the banana peel for suture practice.
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Musa , Estudantes de Medicina , Humanos , Estudantes de Odontologia , Competência Clínica , Avaliação Educacional/métodos , Suturas , Técnicas de Sutura/educaçãoRESUMO
BACKGROUND: Severe COVID-19 is associated with innate immunopathology, and CD14, a proximal activator of innate immunity, has been suggested as a potential therapeutic target. METHODS: We conducted the COVID-19 anti-CD14 Treatment Trial (CaTT), a Phase II randomized, double-blind, placebo-controlled trial at 5 US-sites between April 12, 2021 and November 30, 2021 (NCT04391309). Hospitalized adults with COVID-19 requiring supplemental oxygen (<30 LPM) were randomized 1:1 to receive 4 daily doses of intravenous IC14, an anti-CD14 monoclonal antibody, or placebo. All participants received remdesivir. The primary outcome was time-to-resolution of illness, defined as improvement on the 8-point NIH-Ordinal COVID-19 Scale to category ≤3. Secondary endpoints were safety and exploratory endpoints were pro-inflammatory and antiviral mediators in serum on days 0-5 & 7. The trial was stopped after 40 patients were randomized and treated due to slow enrollment. FINDINGS: 40 participants were randomized and treated with IC14 (n = 20) or placebo (n = 20). The median time-to-recovery was 6 days (95% CI, 5-11) in the IC14 group vs. 5 days (95% CI, 4-10) in the Placebo group (recovery rate ratio: 0.77 (95% CI, 0.40, 1.48) (log-rank p = 0.435). The number of adverse events was similar in each group, and no IC14-attributable secondary infections occurred. In repeated-measures mixed-effects analyses, IC14 treatment increased serum sCD14 concentrations, an expected pharmacodynamic effect. Pre-planned, exploratory analyses suggested that IC14 treatment decreased the trajectories of circulating MIP-1ß and TNF-α. INTERPRETATION: IC14 treatment did not improve time-to-resolution of illness in hypoxemic patients with COVID-19 in this small trial. Results of exploratory analyses suggested IC14 had biologic effects that warrant future clinical investigation. FUNDING: National Institute of Allergy and Infectious Diseases.
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COVID-19 , Adulto , Humanos , SARS-CoV-2 , Administração Intravenosa , Método Duplo-Cego , Resultado do TratamentoRESUMO
AIMS: To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the proportion of fat to lean tissue mass when compared to caloric restriction (CR) alone, as well as when compared to treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, that also enhances GLP-1 activity - to determine the independent effects of each treatment. METHODS: A total of 88 adults with obesity and prediabetes were randomized to 14 weeks of intervention with CR (-390 kcal/d), liraglutide (1.8 mg/d), or the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg/d) as a weight-neutral comparator. Changes between groups in appetite and hunger ratings measured via visual analogue scales, dietary intakes, body weight, body composition via dual energy x-ray absorptiometry, and resting energy expenditure via indirect calorimetry were assessed using the Kruskal-Wallis test or Pearson's chi-squared test. RESULTS: Weight loss ≥5% of baseline body weight occurred in 44% of participants in the CR group, 22% of the liraglutide group and 5% of the sitagliptin group (p = 0.02). The ratio of fat to lean mass decreased by 6.5% in the CR group, 2.2% in the liraglutide group, and 0% in the sitagliptin group (p = 0.02). Visceral fat reduced by 9.5% in the CR group, 4.8% in the liraglutide group, and 0% in the sitagliptin group (p = 0.04). A spontaneous reduction in dietary simple carbohydrates in the CR group was associated with improved homeostatic model assessment of insulin resistance score (HOMA-IR). CONCLUSIONS: Although both liraglutide and CR are valuable strategies for cardiometabolic risk reduction, CR was associated with greater weight loss and more favourable improvements in body composition than treatment with liraglutide alone. Differences in the response to each of these interventions enables patients to be stratified to the most optimal intervention for their personal risk factors.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Estado Pré-Diabético , Humanos , Adulto , Liraglutida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/complicações , Restrição Calórica , Apetite , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/induzido quimicamente , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Peso Corporal , Ingestão de Alimentos , Distribuição da Gordura Corporal , Redução de Peso , Dipeptidil Peptidases e Tripeptidil Peptidases , Doenças Cardiovasculares/complicaçõesRESUMO
INTRODUCTION: Intradialytic hypotension (IDH) is a common clinical complication and is associated with increased morbidity and mortality in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of IDH has been attributed to the rapid reduction of plasma volume during hemodialysis and the inadequate compensatory mechanisms in response to hypovolemia, such as the lack of vasoconstriction. This may be due to the increased production of vasodilators, such as bradykinin. In this study we test the hypothesis that bradykinin B2 receptor blockade prevents intradialytic hypotension. METHODS: We performed a post-hoc analysis of a double-blind, placebo-controlled, randomized, 2 × 2 crossover clinical trial comparing the continuous infusion of icatibant, a bradykinin B2 receptor blocker, and placebo during hemodialysis. Icatibant or placebo was infused for 30 min before and during hemodialysis in 11 patients on MHD. RESULTS: Seven of the patients had IDH, defined as a reduction of systolic blood pressure equal to or greater than 20 mmHg during hemodialysis. Stratified analysis, based on the presence of IDH, revealed that icatibant prevented the decrease in blood pressure compared to placebo in patients with IDH [blood pressure at average nadir (2.5 h after hemodialysis): Placebo,114.3 ± 8.9 vs. icatibant, 125.6 ± 9.1 mmHg, mean ± S.E.M]. Icatibant did not affect blood pressure in the group of patients without IDH. CONCLUSION: Bradykinin B2 receptor blocker may prevent the occurrence of IDH. Further studies should evaluate the hemodynamic effects of icatibant during hemodialysis and the symptomatology associated with IDH.