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AIMS: We describe the varied clinical presentations, barriers in diagnosis and outcomes of anti-HMGCR myopathy in a large national cohort. METHODS: Adults found positive for serum anti-HMGCR autoantibodies via line blot or enzyme-immunoassay followed by immunoprecipitation were included in the study. RESULTS: Of 75 patients identified, the records of 72 (96 %) described weakness as the presenting symptom. The records of 65 gave a reliable description of proximal weakness. In 22/65 (33.8 %) the weakness was described as predominantly or solely lower limb weakness. Forty-five of 75 (60 %) presented with a subacute onset (duration of symptoms >4 weeks -≤6 months), whilst 22/75 (29.3 %) presented with a more indolent chronic onset (duration of symptoms >6 months). Eighteen of 75 (24 %) suffered falls and 2/75 (2.7 %) had "general decline". In three patients no weakness was described: two presented with myalgia and one with a skin rash characterized as Jessner lymphocytic skin rash. Median creatine kinase at presentation was 7337 U/L (range 1050-25,500). Muscle biopsy was performed in 38 (50.7 %). Associated malignancy was infrequent. Four patients recovered without immunosuppression. Five-year and 10-year survival was 92.7 % (95 % CI 80.6-97.4 %), and 82.5 % (95 % CI 61.2-92.8 %) respectively. CONCLUSION: Recurrent falls, a long prodrome and dominant lower limb proximal weakness were common in this anti-HMGCR myopathy cohort. These features overlap with frailty syndrome and sporadic inclusion body myositis emphasizing the importance of considering anti-HMGCR myopathy in that clinical context. A minority of patients recover after statin withdrawal alone.
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Gastroenterologists encounter many nutrition-related disorders in their practice, yet the nutritional needs of patients with chronic gastrointestinal (GI) and liver disease are largely unaddressed by treating physicians, due to suboptimal nutrition education. To address this gap, we developed and piloted a culinary medicine course for a GI fellowship training program. The objective of this study is to describe the development, implementation, and acceptability of the course. A registered dietitian, a chef instructor, and a gastroenterology clinical professor trained in culinary medicine developed the four-class tailored curriculum and delivered the classes remotely. Each class had a theme related to commonly encountered GI disorders and included hands-on meal preparation, a nutrition lecture, and a patient case study discussion. Post-course feedback surveys were disseminated. Twenty-three GI physicians enrolled in the course and the attendance rates in classes 1-4 were 83%, 65%, 61%, and 48%, respectively. Among 15 completed feedback surveys, 80% reported that the class contents were either moderately or extremely useful and all endorsed the curriculum for other gastroenterologists. Future studies of culinary medicine programs tailored to medical specialties should identify strategies to maintain engagement and assess the impact on nutrition knowledge, competencies, and translation of these new skills to clinical practice.
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Gastroenterologia , Distúrbios Nutricionais , Ciências da Nutrição , Humanos , Ciências da Nutrição/educação , Currículo , Educação em Saúde , DocentesRESUMO
Primary immunodeficiency Disorders (PIDS) are rare, mostly monogenetic conditions which can present to a number of specialties. Although infections predominate in most PIDs, some individuals can manifest autoimmune or inflammatory sequelae as their initial clinical presentation. Identifying patients with PIDs can be challenging, as some can present later in life. This is often seen in patients with Common Variable Immunodeficiency Disorders (CVID), where symptoms can begin in the sixth or even seventh decades of life. Some patients with PIDs including CVID can initially present to rheumatologists with autoimmune musculoskeletal manifestations. It is imperative for these patients to be identified promptly as immunosuppression could lead to life-threatening opportunistic infections in these immunocompromised individuals. These risks could be mitigated by prior treatment with subcutaneous or intravenous (SCIG/IVIG) immunoglobulin replacement or prophylactic antibiotics. Importantly, many of these disorders have an underlying genetic defect. Individualized treatments may be available for the specific mutation, which may obviate or mitigate the need for hazardous broad-spectrum immunosuppression. Identification of the genetic defect has profound implications not only for the patient but also for affected family members, who may be at risk of symptomatic disease following an environmental trigger such as a viral infection. Finally, there may be clinical clues to the underlying PID, such as recurrent infections, the early presentation of severe or multiple autoimmune disorders, as well as a relevant family history. Early referral to a clinical immunologist will facilitate appropriate diagnostic evaluation and institution of treatment such as SCIG/IVIG immunoglobulin replacement. This review comprises three sections; an overview of PIDs, focusing on CVID, secondly genetic testing of PIDs and finally the clinical presentation of these disorders to rheumatologists.
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Doenças Autoimunes , Imunodeficiência de Variável Comum , Doenças Reumáticas , Humanos , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/genética , Imunoglobulinas Intravenosas/uso terapêutico , Doenças Autoimunes/complicações , Testes Genéticos , Doenças Reumáticas/tratamento farmacológicoRESUMO
BACKGROUND: Hereditary angioedema is a rare genetic disease that leads to severe and unpredictable swelling attacks. NTLA-2002 is an in vivo gene-editing therapy based on clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9. NTLA-2002 targets the gene encoding kallikrein B1 (KLKB1), with the goal of lifelong control of angioedema attacks after a single dose. METHODS: In this phase 1 dose-escalation portion of a combined phase 1-2 trial of NTLA-2002 in adults with hereditary angioedema, we administered NTLA-2002 at a single dose of 25 mg, 50 mg, or 75 mg. The primary end points were the safety and side-effect profile of NTLA-2002 therapy. Secondary and exploratory end points included pharmacokinetics, pharmacodynamics, and clinical efficacy determined on the basis of investigator-confirmed angioedema attacks. RESULTS: Three patients received 25 mg of NTLA-2002, four received 50 mg, and three received 75 mg. At all dose levels, the most common adverse events were infusion-related reactions and fatigue. No dose-limiting toxic effects, serious adverse events, grade 3 or higher adverse events, or clinically important laboratory findings were observed after the administration of NTLA-2002. Dose-dependent reductions in the total plasma kallikrein protein level were observed between baseline and the latest assessment, with a mean percentage change of -67% in the 25-mg group, -84% in the 50-mg group, and -95% in the 75-mg group. The mean percentage change in the number of angioedema attacks per month between baseline and weeks 1 through 16 (primary observation period) was -91% in the 25-mg group, -97% in the 50-mg group, and -80% in the 75-mg group. Among all the patients, the mean percentage change in the number of angioedema attacks per month from baseline through the latest assessment was -95%. CONCLUSIONS: In this small study, a single dose of NTLA-2002 led to robust, dose-dependent, and durable reductions in total plasma kallikrein levels, and no severe adverse events were observed. In exploratory analyses, reductions in the number of angioedema attacks per month were observed at all dose levels. (Funded by Intellia Therapeutics; ClinicalTrials.gov number, NCT05120830.).
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Angioedemas Hereditários , Sistemas CRISPR-Cas , Edição de Genes , Adulto , Humanos , Angioedema , Angioedemas Hereditários/sangue , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/genética , Proteína Inibidora do Complemento C1/uso terapêutico , Relação Dose-Resposta a Droga , Edição de Genes/métodos , Calicreína Plasmática/genética , Resultado do TratamentoRESUMO
INTRODUCTION: Despite major advances in the field of neuroscience over the last three decades, the quality of assessments available to patients with memory problems in later life has barely changed. At the same time, a large proportion of dementia biomarker research is conducted in selected research samples that often poorly reflect the demographics of the population of patients who present to memory clinics. The Oxford Brain Health Clinic (BHC) is a newly developed clinical assessment service with embedded research in which all patients are offered high-quality clinical and research assessments, including MRI, as standard. METHODS AND ANALYSIS: Here we describe the BHC protocol, including aligning our MRI scans with those collected in the UK Biobank. We evaluate rates of research consent for the first 108 patients (data collection ongoing) and the ability of typical psychiatry-led NHS memory-clinic patients to tolerate both clinical and research assessments. ETHICS AND DISSEMINATION: Our ethics and consenting process enables patients to choose the level of research participation that suits them. This generates high rates of consent, enabling us to populate a research database with high-quality data that will be disseminated through a national platform (the Dementias Platform UK data portal).
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Encéfalo , Pesquisa , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Transtornos da Memória , Protocolos ClínicosRESUMO
BACKGROUND: A poor diet can result from adverse social determinants of health and increases the risk of adverse pregnancy outcomes. OBJECTIVE: We aimed to assess, using data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be prospective cohort, whether nulliparous pregnant individuals who lived in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert. METHODS: The exposure was living in a food desert based on a spatial overview of food access indicators by income and supermarket access per the Food Access Research Atlas. The outcome was periconceptional diet quality per the Healthy Eating Index (HEI)-2010, analyzed by quartile (Q) from the highest or best (Q4, reference) to the lowest or worst dietary quality (Q1); and secondarily, nonadherence (yes or no) to 12 key aspects of dietary quality. RESULTS: Among 7,956 assessed individuals, 24.9% lived in a food desert. The mean HEI-2010 score was 61.1 of 100 (SD: 12.5). Poorer periconceptional dietary quality was more common among those who lived in a food desert compared with those who did not live in a food desert (Q4: 19.8%, Q3: 23.6%, Q2: 26.5%, and Q1: 30.0% vs. Q4: 26.8%, Q3: 25.8%, Q2: 24.5%, and Q1: 22.9%; overall P < 0.001). Individuals living in a food desert were more likely to report a diet in lower quartiles of the HEI-2010 (i.e., poorer dietary quality) (aOR: 1.34 per quartile; 95% CI: 1.21, 1.49). They were more likely to be nonadherent to recommended standards for 5 adequacy components of the HEI-2010, including fruit, total vegetables, greens and beans, seafood and plant proteins, and fatty acids, and less likely to report excess intake of empty calories. CONCLUSIONS: Nulliparous pregnant individuals living in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert.
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Dieta , Desertos Alimentares , Gravidez , Feminino , Humanos , Estudos Prospectivos , Resultado da Gravidez , VerdurasRESUMO
Prenatal depression is prevalent and adversely impacts maternal and infant health. This study addresses a critical literature gap and investigates the association between maternal diet quality and prenatal depressive symptoms, as well as the moderating effect of economic well-being on this link. A cross-sectional design was used, including 43 healthy pregnant women in the second trimester aggregated from two research projects. Prenatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Dietary quality was evaluated using two non-consecutive 24 h dietary recalls, from which the Adapted Dietary Inflammatory Index (ADII) and the Healthy Eating Index (HEI)-2015 were derived. Economic well-being was indicated by the income-to-poverty ratio. A higher HEI-2015 (adherence to dietary guidelines; ß = -0.53, p = 0.01) and negative ADII (anti-inflammatory diet; ß = 0.40, p = 0.06) were associated with fewer prenatal depressive symp-toms. Among pregnant women with worse economic well-being, a pro-inflammatory diet was as-sociated with more prenatal depressive symptoms (b = 1.69, p = 0.004), but among those with better economic well-being, the association was not significant (b = 0.51, p = 0.09). Dietary interventions aimed at reducing dietary inflammation might hold some promise for improving mental health among pregnant women who are economically vulnerable.
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Depressão , Dieta , Feminino , Gravidez , Humanos , Depressão/epidemiologia , Estudos Transversais , Dieta/psicologia , Gestantes , Pobreza , VitaminasRESUMO
INTRODUCTION: Improving the diet quality of young adults may support chronic disease prevention. The approaches used and efficacy of promoting small dietary behavior changes through easy-to-learn (ETL) interventions (requiring no more than 1 hour to teach the behavior) among young adults have not yet been systematically reviewed. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 2 independent electronic searches across 6 databases were conducted to identify any articles describing ETL interventions among young adults (aged 18-35 years) and reporting dietary intake outcomes. RESULTS: Among 9,538 articles identified, 9 studies met eligibility criteria. Five studies reported significant improvement in the selected dietary outcome. Of these, 3 studies used an implementation intentions approach, in which participants were given or asked to write out a simple dietary behavior directive and carry it on their person. Less than half of included studies were rated as positive for overall quality. DISCUSSION: The available evidence suggests that ETL interventions targeting the dietary behaviors of young adults may be effective in improving dietary intake. Limitations of included studies were lack of follow-up after the intervention period and low generalizability. IMPLICATIONS FOR RESEARCH AND PRACTICE: Further dietary intervention studies targeting young adults should systematically evaluate the efficacy of ETL intervention approaches among diverse samples.
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Dieta , Ingestão de Alimentos , Humanos , Adulto Jovem , Terapia Comportamental , AprendizagemRESUMO
Maternal obesity is associated with an increased risk for prenatal depressive symptoms. Mindfulness-based interventions (MBIs) have been shown to reduce the risk of prenatal depression. This pilot study assesses the feasibility and acceptability of a smartphone-based MBI among pregnant women with obesity, and its potential for improving maternal mental and behavioral health outcomes. Five second-trimester pregnant women with a prepregnancy body mass index > 30 kg/m2 participated in a 30-day audio-guided mindfulness practice using the Headspace app. All participants engaged in the pregnancy module, while three concurrently engaged in the mindful eating module. Daily engagement with the app was tracked and a post-trial survey assessed maternal acceptability. Validated pre- and post-trial questionnaires explored changes in perceived stress, anxiety, depression, and eating habits. All participants completed the study with varying levels of adherence to the prescribed daily practice; the average number of days of engagement was 23/30 (77%) for the pregnancy module and 20/30 (67%) for the mindful eating module. All subjects reported some degree of perceived benefit, and none reported negative experiences. Trends were observed for improvements in maternal mental wellbeing and eating behaviors. This pilot study shows that a smartphone-based MBI is feasible, acceptable, and perceived to provide benefit among pregnant women with obesity.
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Atenção Plena , Aplicativos Móveis , Feminino , Humanos , Gravidez , Gestantes , Projetos Piloto , Estudos de Viabilidade , Depressão/terapia , Obesidade/terapia , SmartphoneRESUMO
The Oxford Brain Health Clinic (BHC) is a joint clinical-research service that provides memory clinic patients and clinicians access to high-quality assessments not routinely available, including brain MRI aligned with the UK Biobank imaging study (UKB). In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) explored the alignment of measures from BHC patients to the largest brain MRI study in the world (ultimately 100,000 participants). Adaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences (i.e., additional imaging modalities) to improve patients' tolerance for the MRI assessment. We adapted the UKB structural MRI analysis pipeline to take into account the characteristics of a memory clinic population (e.g., high amount of white matter hyperintensities and hippocampal atrophy). We then compared the imaging derived phenotypes (IDPs) extracted from the structural scans to visual ratings from radiology reports, non-imaging factors (age, cognition) and to reference distributions derived from UKB data. Of the first 108 BHC attendees (August 2020-November 2021), 92.5 % completed the clinical scans, 88.0 % consented to use of data for research, and 43.5 % completed the additional research sequences, demonstrating that the protocol is well tolerated. The high rates of consent to research makes this a valuable real-world quality research dataset routinely captured in a clinical service. Modified tissue-type segmentation with lesion masking greatly improved grey matter volume estimation. CSF-masking marginally improved hippocampal segmentation. The IDPs were in line with radiology reports and showed significant associations with age and cognitive performance, in line with the literature. Due to the age difference between memory clinic patients of the BHC (age range 65-101 years, average 78.3 years) and UKB participants (44-82 years, average 64 years), additional scans on elderly healthy controls are needed to improve reference distributions. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.
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Bancos de Espécimes Biológicos , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética , Atrofia/patologia , Reino UnidoRESUMO
Exposure to, perception of, and response to stress have all been shown to influence appetite and dietary behaviors in non-pregnancy human and animal studies, mediated in part by the appetite stimulating hormone ghrelin. Yet, the impact of prenatal stress on biological pathways associated with appetite in the context of pregnancy is not well understood. The objective of this study was to assess the relationship between these layered dimensions of stress with fasting and postprandial plasma ghrelin concentrations among Hispanic pregnant women with overweight or obesity, a population known to experience heightened levels of stress. Thirty-three non-diabetic Hispanic women with pre-pregnancy body mass index of 25.0-34.9 kg/m2 participated in a crossover study at 28-32 weeks' gestation. At each visit, participants provided fasting blood and saliva samples, consumed a standardized mixed-meal, and completed a 15-minute task: friendly conversation (control) or the Trier Social Stress Test (experimental stress exposure). Six timed blood and saliva samples were collected up to 2 h from baseline and assayed for ghrelin and cortisol, respectively, and area-under-the-curve (AUC) values were computed. Day-to-day stress levels were assessed by the Perceived Stress Scale. Physiological and psychological stress reactivity was determined by cortisol AUC and change in self-reported affect state, respectively, during the experimental stress visit. Maternal perceived stress was positively associated with ghrelin concentrations in the fasted (ß = 0.06, p = 0.02) and postprandial state (ß = 0.05, p = 0.02). Mean ghrelin AUC was not significantly different following acute stress versus control. Measures of acute stress reactivity were not associated with ghrelin AUC. Contrary to our hypothesis, among Hispanic pregnant women with overweight and obesity, exposure to an acute stress induction task did not alter postprandial ghrelin concentrations, and changes in individual psychological and physiological stress reactivity did not associate with postprandial ghrelin. However, our findings suggest that maternal report of general perceived stress over the last month is associated with higher fasting and postprandial ghrelin concentrations. Differences in the effects of short-term stress exposure versus day-to-day perception of stress on appetite and food intake in pregnancy deserves further investigation.
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Grelina , Sobrepeso , Humanos , Feminino , Gravidez , Sobrepeso/metabolismo , Gestantes , Hidrocortisona , Estudos Cross-Over , Obesidade/metabolismo , Apetite , Estresse Psicológico , Período Pós-PrandialRESUMO
OBJECTIVE: To develop a machine learning algorithm utilizing heart rate variability (HRV) and salivary cortisol to detect the presence of acute stress among pregnant women that may be applied to future clinical research. METHODS: ECG signals and salivary cortisol were analyzed from 29 pregnant women as part of a crossover study involving a standardized acute psychological stress exposure and a control non-stress condition. A filter-based features selection method was used to identify the importance of different features [heart rate (HR), time- and frequency-domain HRV parameters and salivary cortisol] for stress assessment and reduce the computational complexity. Five machine learning algorithms were implemented to assess the presence of stress with and without salivary cortisol values. RESULTS: On graphical visualization, an obvious difference in heart rate (HR), HRV parameters and cortisol were evident among 17 participants between the two visits, which helped the stress assessment model to distinguish between stress and non-stress exposures with greater accuracy. Eight participants did not display a clear difference in HR and HRV parameters but displayed a large increase in cortisol following stress compared to the non-stress conditions. The remaining four participants did not demonstrate an obvious difference in any feature. Six out of nine features emerged from the feature selection method: cortisol, three time-domain HRV parameters, and two frequency-domain parameters. Cortisol was the strongest contributing feature, increasing the assessment accuracy by 10.3% on average across all five classifiers. The highest assessment accuracy achieved was 92.3%, and the highest average assessment accuracy was 76.5%. CONCLUSION: Salivary cortisol contributed a significant increase in accuracy of the assessment model compared to using a range of HRV parameters alone. Our machine learning model demonstrates acceptable accuracy in detection of acute stress among pregnant women when combining salivary cortisol with HR and HRV parameters.
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Hidrocortisona , Estresse Psicológico , Estudos Cross-Over , Feminino , Frequência Cardíaca/fisiologia , Humanos , Aprendizado de Máquina , Gravidez , Estresse Psicológico/diagnósticoRESUMO
Background: Gestational diabetes mellitus (GDM) and elevated glucose concentrations below the threshold for GDM diagnosis have been associated with adverse pregnancy and offspring outcomes. Dietary interventions initiated during pregnancy have demonstrated inconsistent beneficial effects. Limited data exist regarding the effects of periconceptional diet on gestational glycemia. Objective: To evaluate independent associations between periconceptional diet quality with GDM frequency and glucose concentrations from GDM screening and diagnostic tests among nulliparous gravidas. Design: This is a secondary analysis of N=7997 participants from the NuMoM2b multicenter, prospective, observational cohort study of first pregnancies. The Alternative Healthy Eating Index (AHEI)-2010 was computed from food frequency questionnaires completed in early pregnancy (6-13 weeks), reporting usual dietary intake over the preceding 3 months. GDM screening was performed either by non-fasting 1-hour 50g glucose load (N=6845), followed by 3-hour 100g glucose tolerance test (GTT) for those with raised glucose concentrations (N=1116; at risk for GDM), or by a single 2-hour 75g GTT (N=569; all GDM risk levels). Logistic and linear regression were used to estimate the associations between the AHEI-2010 score with odds of GDM, having raised blood glucose on the 1-hour screening test, and continuous glucose concentrations on screening and diagnostic tests. All models were adjusted for a priori covariates: maternal age, race/ethnicity, early-pregnancy body mass index, smoking habits, rate of gestational weight gain, energy intake, nausea and vomiting in early pregnancy, study site. Results: Poorer periconceptional diet quality was observed among participants who were younger, with higher BMI, lower income levels, and of non-Hispanic Black or Hispanic ethnicity. The GDM rate was 4%. Each 1-point increase in AHEI-2010 score was associated with a 1% decrease in the odds of being diagnosed with GDM (beta=-0.015, p=0.022, OR=0.986, 95% CI 0.973 to 0.998). Diet quality was inversely associated with each post glucose load concentration on the non-fasting screening test and the 2-hour and 3-hour GTT. Conclusion: Poor periconceptional diet quality is independently associated with an increased risk of GDM and with minor elevations in serum glucose concentrations on GDM screening and diagnostic tests, in a diverse cohort of nulliparas. Periconception intervention studies targeting diet quality are warranted.
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Diabetes Gestacional , Ganho de Peso na Gestação , Glicemia/análise , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/etiologia , Dieta , Feminino , Humanos , Gravidez , Estudos ProspectivosRESUMO
Cortisol is a steroid hormone that regulates a wide range of vital signs throughout the body. However, current cortisol monitoring methods are inconvenient for everyday settings. Heart Rate (HR) and Heart Rate Variability (HRV) are easily collected biological parameters whose fluctuations highly correlate with cortisol, however, there does not exist a work attempting to estimate cortisol levels using these signals. In this paper, to the best of our knowledge, for the first time, we propose a machine learning-based salivary cortisol level estimation method using HR and HRV collected from pregnant women wearing an ECG chest strap. We first extract HR and HRV parameters from inter-beat-interval data derived from electrocardiogram signals. Then, we apply a feature selection algorithm to select the most contributing features and introduce a machine learning-based weak supervision method to address the unbalanced number of labels collected in real settings. Five machine learning algorithms are implemented to perform binary classification of baseline cortisol level (BL) versus two distinct cortisol levels (CL1 and CL2). One deep neural network is used to perform the classification across all three levels. As a pioneer study, we obtain prediction accuracy of up to 69% (BL VS. CL1), 71% (BL VS. CL2), and 60% (BL VS. CL1 VS. CL2).
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Eletrocardiografia , Hidrocortisona , Eletrocardiografia/métodos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Redes Neurais de Computação , Gravidez , Aprendizado de Máquina SupervisionadoRESUMO
OBJECTIVE: To investigate the effect of an antenatal diet and exercise intervention during pregnancy on sleep duration. As a secondary objective, associations between sleep duration and gestational weight gain (GWG), maternal metabolic parameters and pregnancy outcomes were assessed. DESIGN: Secondary analysis. SETTING: Large tertiary Maternity Hospital in Dublin, Ireland. POPULATION: 326 women with overweight or obesity who participated in the Pregnancy Exercise And Nutrition Research Study (PEARS) randomised controlled trial between March 2013 and August 2016. METHODS: Secondary analysis of a randomised trial. MAIN OUTCOME MEASURES: Impact of the PEARS intervention on sleep duration, and association of sleep duration and maternal metabolic parameters, and pregnancy outcomes. RESULTS: Participants had a mean age of 32.5 ± 4.5 years and median (interquartile range [IQR]) body mass index of 28.3 (26.6-31.2) kg/m2 . The intervention group had a longer sleep duration in late pregnancy (mean difference 17.1 minutes (95% confidence interval [CI] 0.5-33.7) and a higher proportion achieving optimum sleep duration of 7-9 h (54.3 vs. 42.9%, relative risk [RR] 1.28 (95% CI 1.01-1.62). In late pregnancy, sleep duration of <6 h was associated with lower breastfeeding rates on discharge (RR 0.74, 95% CI 0.57-0.95) and higher triglyceride levels (mean difference 0.24, 95% CI 0.10-0.38). There were no significant associations between sleep and incidence of gestational diabetes mellitus or pre-eclampsia/toxaemia, or other metabolic parameters assessed (insulin, fasting glucose, HOMA-IR). CONCLUSION: A diet and exercise intervention from early pregnancy may promote longer and optimal sleep duration, with maternal benefits such as lower triglyceride levels and higher breastfeeding rates.
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Complicações na Gravidez , Pyrus , Telemedicina , Adulto , Feminino , Humanos , Gravidez , Estilo de Vida , Complicações na Gravidez/prevenção & controle , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Sono , TriglicerídeosRESUMO
OBJECTIVE: This study tested the hypothesis, in a prospective cohort study design, that maternal saturated free fatty acid (sFFA) concentration during pregnancy is prospectively associated with offspring (newborn) hypothalamic (HTH) microstructure and to explore the functional relevance of this association with respect to early-childhood body fat percentage (BF%). METHODS: In N = 94 healthy newborns (born mean 39.3 [SD 1.5] weeks gestation), diffusion-weighted magnetic resonance imaging was performed shortly after birth (25.3 [12.5] postnatal days), and a subgroup (n = 37) underwent a dual-energy x-ray absorptiometry scan in early childhood (4.7 [SD 0.7] years). Maternal sFFA concentration during pregnancy was quantified in fasting blood samples via liquid chromatography-mass spectrometry. Infant HTH microstructural integrity was characterized using mean diffusivity (MD). Multiple linear regression was used to test the association between maternal sFFA and HTH MD, accounting for newborn sex, age at scan, mean white matter MD, and image quality. Multiple linear regression models also tested the association between HTH MD and early-childhood BF%, accounting for breastfeeding status. RESULTS: Maternal sFFA during pregnancy accounted for 8.3% of the variation in newborn HTH MD (ß-std = 0.25; p = 0.006). Furthermore, newborn HTH MD prospectively accounted for 15% of the variation in early-childhood BF% (ß-std = 0.32; p = 0.019). CONCLUSIONS: These findings suggest that maternal overnutrition during pregnancy may influence the development of the fetal hypothalamus, which, in turn, may have clinical relevance for childhood obesity risk.
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Obesidade Infantil , Infecções Sexualmente Transmissíveis , Criança , Pré-Escolar , Ácidos Graxos não Esterificados , Feminino , Humanos , Hipotálamo/diagnóstico por imagem , Lactente , Recém-Nascido , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Hereditary angioedema (HAE) leads to significant morbidity and mortality from unpredictable intermittent peripheral, abdominal and laryngeal swelling. Access to appropriate healthcare and effective therapies, which can prevent and treat attacks, reduce the suffering and greatly improve quality of life. Although treatments such as C1 inhibitor (Berinert), and Icatibant are available in New Zealand (Aotearoa), there are no published data available on their use. AIM: To present a national audit of HAE and acquired angioedema (AAE) in 2019. METHODS: Patients were identfied and demographical and clinical data on HAE were collected retrospectively by interview and notes review. RESULTS: The total number of known adult (48) and children (3) HAE and AAE (3) patients is 54. Of these, 41/54 (75%) of HAE and AAE patients were recruited to the audit. Icatibant has been available for the treatment of acute HAE attacks since 2016, and is now used in 73% of HAE patients. Icatibant is also used by patients for laryngeal attacks in the community, who may not then present to hospital. Androgens are used in half of the patients as prophylaxis, but 33% of the latter were identified as not having regular liver ultrasound screening. Tranexamic acid is used as prophylaxis in one-fifth of patients. Participants have had 40 children, half of whom may be affected. Three have been diagnosed with HAE, suggesting that the majority have not yet been tested. CONCLUSIONS: Corrective actions arising from this audit will improve our capacity to provide long-term care for HAE patients and their families.
Assuntos
Angioedema , Angioedemas Hereditários , Adulto , Criança , Humanos , Qualidade de Vida , Nova Zelândia/epidemiologia , Estudos Retrospectivos , Angioedema/diagnóstico , Angioedema/tratamento farmacológico , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/epidemiologia , Proteína Inibidora do Complemento C1/uso terapêuticoRESUMO
OBJECTIVES: Elevated circulating levels of complement component 3 (C3) and C-reactive protein (CRP) have been linked with adverse pregnancy outcomes. Lifestyle interventions may hold potential to ameliorate these effects. We investigated the effect of an antenatal healthy lifestyle intervention on maternal C3 and CRP concentrations and assessed their relationship with maternal and fetal metabolic markers and outcomes. STUDY DESIGN: Secondary analysis of data from the Pregnancy Exercise And Nutrition Research Study (PEARS) randomized controlled trial. METHODS: Women (n = 406) with C3 and CRP concentrations determined in early pregnancy (14-16 weeks) and/or late pregnancy (28-weeks) with corresponding fasting glucose, insulin, c-peptide, and lipid profiles were included in the analysis. Pregnancy outcomes included: diagnoses of gestational diabetes (GDM), pre-eclampsia (PET) or pregnancy induced hypertension (PIH), pre-term birth (delivery < 37 weeks), low birth weight (<2500 g), small-for-gestational age (SGA) defined using < 5th or 10th centile for birthweight and cord blood measures of glucose and lipid metabolism. T-tests investigated changes in C3 and CRP over time. Chi-square, Pearson's' correlations and multiple regression investigated relationships with outcomes. RESULTS: The PEARS intervention did not influence maternal C3 or CRP concentrations in pregnancy. There was no relationship between CRP concentrations and any maternal or infant outcome. Women who developed GDM had higher C3 concentrations in early (p = 0.01) and late pregnancy (p = 0.02). Women who developed PIH/PET had lower C3 concentrations in early (p = 0.02), but not late (p = 0.10) pregnancy. Maternal C3 concentrations in early pregnancy were a small but significant predictor of maternal insulin concentrations in early (ß = 0.40, 95% CI 0.27, 0.53; p < 0.001) and late (ß = 0.30, 95% CI 0.17, 0.43p < 0.001) pregnancy, early total cholesterol (TC), and both early and late triglycerides, LDL and HDL Cholesterol concentrations (all p < 0.001). Women who delivered SGA babies (<10th centile) had lower C3 concentrations than women who did not in both early (p < 0.001) and late pregnancy (p = 0.01). No relationship between maternal C3 or CRP and fetal glucose concentrations or lipid profiles was observed. CONCLUSION: Maternal C3 may play a role in multiple adverse pregnancy outcomes including cardiometabolic ill-health. Further research on this, and strategies to reduce C3 in a pregnant population, are warranted.
Assuntos
Proteína C-Reativa/metabolismo , Complemento C3/metabolismo , Obesidade/metabolismo , Adulto , Índice de Massa Corporal , Diabetes Gestacional/metabolismo , Exercício Físico/fisiologia , Feminino , Humanos , Estilo de Vida , Sobrepeso/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Resultado da Gravidez , Gestantes , Cuidado Pré-Natal/métodos , Telemedicina/métodosRESUMO
CONTEXT: Hispanic women are at elevated risk of gestational glucose intolerance and postpartum type 2 diabetes compared with non-Hispanic White women. Identification of potentially modifiable factors contributing to this trajectory of beta-cell dysfunction is warranted. OBJECTIVE: We aimed to determine the association between rate of gestational weight gain (rGWG) and glucose-insulin metabolism in Hispanic pregnant women with overweight and obesity. METHODS: This cross-sectional, observational study, conducted from 2018-2020 at the clinical research center at University of California, Irvine, included 33 nondiabetic Hispanic pregnant women at 28 to 30 weeks' gestation with pre-pregnancy body mass index (BMI) 25.0 to 34.9 kg/m2. Participants consumed a standardized liquid mixed meal after an overnight fast. Serial blood samples were collected at fasting and up to 2 hours postprandial. The glucose and insulin area under the curve (AUC), insulin sensitivity index (ISI) and insulin secretion sensitivity index (ISSI)-2 were computed. RESULTS: Average rGWG (0.36â ±â 0.22 kg/week) was classified as excessive in 60% of women. While rGWG was not associated with the glucose or insulin AUC or ISI, it accounted for 13.4% of the variance in ISSI-2 after controlling for covariates (maternal age, parity, and pre-pregnancy BMI); for each 1 unit increase in rGWG, ISSI-2 decreased 2.1 units (Pâ =â 0.015). CONCLUSION: Even in the absence of gestational diabetes, rGWG was inversely associated with beta-cell function in a high-risk population of Hispanic pregnant women with overweight and obesity. Beta-cell decline is an established risk factor for transition to type 2 diabetes, and these cross-sectional findings highlight rGWG as a potentially modifiable contributor to this process.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Gestacional/diagnóstico , Ganho de Peso na Gestação , Obesidade Materna/metabolismo , Sobrepeso/metabolismo , Adulto , Glicemia/análise , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Feminino , Teste de Tolerância a Glucose , Hispânico ou Latino , Humanos , Insulina/metabolismo , Resistência à Insulina , Idade Materna , Obesidade Materna/sangue , Sobrepeso/sangue , Período Pós-Prandial , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long-term safety study of berotralstat in patients with HAE. METHODS: APeX-S is an ongoing, phase 2, open-label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE-C1-INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long-term safety and the secondary objective was to evaluate effectiveness. RESULTS: Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11-540) and 307 (14-429) days for the 150-mg and 110-mg groups, respectively. Treatment-emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug-related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug-related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline. CONCLUSIONS: In this analysis, both berotralstat doses, 150 and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT03472040).