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1.
Obesity (Silver Spring) ; 30(11): 2122-2133, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36321276

RESUMO

OBJECTIVE: Monoacylglycerol O-acyltransferase 1 (Mogat1), a lipogenic enzyme that converts monoacylglycerol to diacylglycerol, is highly expressed in adipocytes and may regulate lipolysis by re-esterifying fatty acids released during times when lipolytic rates are low. However, the role of Mogat1 in regulating adipocyte fat storage during differentiation and diet-induced obesity is relatively understudied. METHODS: Here, adipocyte-specific Mogat1 knockout mice were generated and subjected to a high-fat diet to determine the effects of Mogat1 deficiency on diet-induced obesity. Mogat1 floxed mice were also used to develop preadipocyte cell lines wherein Mogat1 could be conditionally knocked out to study adipocyte differentiation in vitro. RESULTS: In preadipocytes, it was found that Mogat1 knockout at the onset of preadipocyte differentiation prevented the accumulation of glycerolipids and reduced the differentiation capacity of preadipocytes. However, the loss of adipocyte Mogat1 did not affect weight gain or fat mass induced by a high-fat diet in mice. Furthermore, loss of Mogat1 in adipocytes did not affect plasma lipid or glucose concentrations or insulin tolerance. CONCLUSIONS: These data suggest Mogat1 may play a role in adipocyte differentiation in vitro but not adipose tissue expansion in response to nutrient overload in mice.


Assuntos
Adiposidade , Monoglicerídeos , Camundongos , Animais , Monoglicerídeos/metabolismo , Obesidade/metabolismo , Adipócitos/metabolismo , Dieta Hiperlipídica , Diferenciação Celular , Camundongos Knockout , Aciltransferases/metabolismo , Camundongos Endogâmicos C57BL
2.
Br J Cardiol ; 29(1): 8, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747310

RESUMO

Prevalence of atrial fibrillation (AF) and diabetes is increasing worldwide. Diabetes is a risk factor for AF and both increase stroke risk. Previous AF screening studies have recruited highrisk patient groups, but not with diabetes as the target group. This study aims to determine whether people with diabetes have a higher prevalence of AF than the general population and investigate whether determinants, such as diabetes duration or diabetes control, add to AF risk. In a cross-sectional screening study, patients with diabetes were recruited via their GP surgeries or a diabetes centre. A 30-second single-lead electrocardiogram (ECG) was recorded using the Kardia® device, along with physiological measurements and details relating to risk factor variables. There were 300 participants recruited and 16 patients identified with AF (5.3% prevalence). This demonstrated a significantly greater likelihood of AF than the background population (p=0.043). People with diabetes and AF were significantly older than those who only had diabetes. More people with type 2 diabetes had AF than people with type 1. Prediction of AF diagnosis by age, sex, diabetes type, diabetes duration and level of control revealed only age as a significant predictor. In conclusion, these findings add to existing data around the association of these chronic conditions, supporting AF screening in this high-risk group, particularly in those of older age. This can contribute to appropriate management of both conditions in combination, not least with regards to stroke prevention.

3.
Pharmacoecon Open ; 6(4): 605-617, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35733076

RESUMO

BACKGROUND: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse. OBJECTIVE: The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo. METHODS: A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses. RESULTS: The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (£176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses. CONCLUSION: A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo.

4.
Health Technol Assess ; 26(3): 1-94, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35060851

RESUMO

BACKGROUND: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5-7 days during an upper respiratory tract infection reduces the risk of relapse. OBJECTIVES: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. DESIGN: A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. SETTING: A total of 122 UK paediatric departments, of which 91 recruited patients. PARTICIPANTS: A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m2) or an equivalent dose of placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. RESULTS: There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference -0.024, 95% confidence interval -0.14 to 0.09; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. LIMITATIONS: A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. CONCLUSIONS: The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. FUTURE WORK: Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 3. See the NIHR Journals Library website for further project information.


Steroid-sensitive nephrotic syndrome is a kidney condition in which protein leaks into the urine, causing generalised swelling. In most children, the condition recurs or relapses. Relapses often occur following an upper respiratory tract infection (i.e. a cough, cold or sore throat). Research in tropical countries suggests that if children have a small dose of daily steroids for a week at the time of an upper respiratory tract infection then they are less likely to relapse. The selection of children for these studies and the different patterns of infection mean that we are not certain if this treatment would work in the UK. A total of 365 children with relapsing nephrotic syndrome took part. Half of the children took a steroid and the other half took dummy tablets (placebo) for 6 days at the start of an upper respiratory tract infection. We followed up the children for 12 months and collected information on relapses and other treatments and information from questionnaires about behaviour and quality of life. We also investigated whether or not there were cost savings with this treatment. There were 271 children who had an upper respiratory tract infection in the 12 months of the study and so only these children were included in the analyses. Giving 6 days of a low-dose steroid at the time of an upper respiratory tract infection did not reduce the risk of a relapse. There was also no effect on the overall number of relapses, the number of children needing to start extra preventative treatments or side effects of steroids. Although there was no clinical effect, the economic evaluation found that giving prednisolone led to lower treatment costs overall and higher quality of life and might, therefore, offer better value for money, but this has to be interpreted against the clinical evidence of no significant effect. Our conclusion is that there is no clinical benefit to giving children low-dose prednisolone at the time of an upper respiratory tract infection.


Assuntos
Síndrome Nefrótica , Infecções Respiratórias , Criança , Pré-Escolar , Análise Custo-Benefício , Humanos , Recidiva Local de Neoplasia , Síndrome Nefrótica/tratamento farmacológico , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Qualidade de Vida , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia
5.
Br J Cardiol ; 29(4): 38, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37332266

RESUMO

Atrial fibrillation (AF) and diabetes are increasingly prevalent worldwide, both increasing stroke risk. AF can be detected by patient-led electrocardiogram (ECG) screening applications. Understanding patients' views around AF screening is important when considering recommendations, and this study explores these views where there is an existing diagnosis of diabetes. Nine semi-structured qualitative interviews were conducted with participants from a previous screening study (using a mobile ECG device), who were identified with AF. Thematic analysis was completed using NVivo 12 Plus software and themes were identified within each research question for clarity. Themes were identified in four groups: 1. patients' understanding of AF - the 'concept of irregularity' and 'consideration of consequence'; 2. views on screening - 'screening as a resource-intensive initiative', 'fear of outcomes from screening' and 'expectations of screening reliability'; 3. views on incorporating screening into routine care - 'importance of screening convenience'; and 4. views on the screening tool - 'technology as a barrier' and 'feasibility of the mobile ECG recording device for screening'. In conclusion, eliciting patients' views has demonstrated the need for clear and concise information around the delivery of an AF diagnosis. Screening initiatives should factor in location, convenience, personnel, and cost, all of which were important for promoting screening inclusion.

6.
JAMA Pediatr ; 176(3): 236-243, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34928294

RESUMO

IMPORTANCE: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. OBJECTIVE: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. RESULTS: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). CONCLUSIONS AND RELEVANCE: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39.


Assuntos
Síndrome Nefrótica , Infecções Respiratórias , Corticosteroides/uso terapêutico , Criança , Humanos , Masculino , Síndrome Nefrótica/complicações , Síndrome Nefrótica/tratamento farmacológico , Prednisolona/uso terapêutico , Qualidade de Vida , Recidiva , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/prevenção & controle
7.
Asia Pac Allergy ; 11(4): e37, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34786367

RESUMO

Rituximab is a chimeric monoclonal antibody, which is mainly used in the treatment of lymphoma and autoimmune disorders, but also has been recently approved for the treatment of nephrotic syndrome. The treatment dose is between 375 mg/m2 and 750 mg/m2. Rituximab has been associated with hypersensitivity reactions, which can be classified either into early and late infusion-associated adverse reactions. Different desensitization protocols have been described in adult patients who require rituximab, however, there is a limited experience in children and in patients with nephrotic syndrome. Additionally, all the published protocols for adults and children are based on the low-dose rituximab desensitization. We report the first case in the literature of desensitization to high-dose rituximab in a child with nephrotic syndrome, suggesting a well-tolerated protocol adjusted on the high dose and the clinical reaction to the drug. This protocol can be used for children with nephrotic syndrome and severe reaction that require 750 mg/m2 of rituximab.

8.
Mol Metab ; 49: 101204, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33676028

RESUMO

OBJECTIVE: Monoacylglycerol acyltransferase (MGAT) enzymes catalyze the synthesis of diacylglycerol from monoacylglycerol. Previous work has suggested the importance of MGAT activity in the development of obesity-related hepatic insulin resistance. Indeed, antisense oligonucleotide (ASO)-mediated knockdown of Mogat1 mRNA, which encodes MGAT1, reduced hepatic MGAT activity and improved glucose tolerance and insulin resistance in high-fat diet (HFD)-fed mice. However, recent work has suggested that some ASOs may have off-target effects on body weight and metabolic parameters via activation of the interferon alpha/beta receptor 1 (IFNAR-1) pathway. METHODS: Mice with whole-body Mogat1 knockout or a floxed allele for Mogat1 to allow for liver-specific Mogat1-knockout (by either a liver-specific transgenic or adeno-associated virus-driven Cre recombinase) were generated. These mice were placed on an HFD, and glucose metabolism and insulin sensitivity were assessed after 16 weeks on diet. In some experiments, mice were treated with control scramble or Mogat1 ASOs in the presence or absence of IFNAR-1 neutralizing antibody. RESULTS: Genetic deletion of hepatic Mogat1, either acutely or chronically, did not improve hepatic steatosis, glucose tolerance, or insulin sensitivity in HFD-fed mice. Furthermore, constitutive Mogat1 knockout in all tissues actually exacerbated HFD-induced obesity, insulin sensitivity, and glucose intolerance on an HFD. Despite markedly reduced Mogat1 expression, liver MGAT activity was unaffected in all knockout mouse models. Mogat1 overexpression in hepatocytes increased liver MGAT activity and TAG content in low-fat-fed mice but did not cause insulin resistance. Multiple Mogat1 ASO sequences improved glucose tolerance in both wild-type and Mogat1 null mice, suggesting an off-target effect. Hepatic IFNAR-1 signaling was activated by multiple Mogat1 ASOs, but its blockade did not prevent the effects of either Mogat1 ASO on glucose homeostasis. CONCLUSION: These results indicate that genetic loss of Mogat1 does not affect hepatic MGAT activity or metabolic homeostasis on HFD and show that multiple Mogat1 ASOs improve glucose metabolism through effects independent of targeting Mogat1 or activation of IFNAR-1 signaling.


Assuntos
Aciltransferases/genética , Aciltransferases/metabolismo , Metabolismo dos Carboidratos , Oligonucleotídeos Antissenso/metabolismo , Animais , Dieta Hiperlipídica , Diglicerídeos/metabolismo , Fígado Gorduroso/metabolismo , Feminino , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Resistência à Insulina , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Oligonucleotídeos Antissenso/genética , Fenótipo , Receptor de Interferon alfa e beta/metabolismo , Transcriptoma
9.
IEEE Trans Biomed Circuits Syst ; 15(1): 2-28, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33606635

RESUMO

A person's behavior significantly influences their health and well-being. It also contributes to the social environment in which humans interact, with cascading impacts to the health and behaviors of others. During social interactions, our understanding and awareness of vital nonverbal messages expressing beliefs, emotions, and intentions can be obstructed by a variety of factors including greatly flawed self-awareness. For these reasons, human behavior is a very important topic to study using the most advanced technology. Moreover, technology offers a breakthrough opportunity to improve people's social awareness and self-awareness through machine-enhanced recognition and interpretation of human behaviors. This paper reviews (1) the social psychology theories that have established the framework to study human behaviors and their manifestations during social interactions and (2) the technologies that have contributed to the monitoring of human behaviors. State-of-the-art in sensors, signal features, and computational models are categorized, summarized, and evaluated from a comprehensive transdisciplinary perspective. This review focuses on assessing technologies most suitable for real-time monitoring while highlighting their challenges and opportunities in near-future applications. Although social behavior monitoring has been highly reported in psychology and engineering literature, this paper uniquely aims to serve as a disciplinary convergence bridge and a guide for engineers capable of bringing new technologies to bear against the current challenges in real-time human behavior monitoring.


Assuntos
Tecnologia , Emoções , Humanos , Intenção , Monitorização Fisiológica
10.
Br J Cardiol ; 28(4): 42, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35747069

RESUMO

Quality of life (QoL) is an essential consideration when managing the wellbeing of patients and assists in interpretation of symptoms, functional status and perceptions. Atrial fibrillation (AF) and diabetes demand significant healthcare resources. Existing data demonstrate a negative impact on QoL as individual conditions, but there is less evidence relating to the impact of these disease groups in combination. This study therefore explores QoL in patients with AF and diabetes. This cross-sectional, observational study required participants to complete the short form (SF)-36 survey via an online platform and was offered to people affected by AF alone and people with AF and diabetes in combination. The SF-36 provides a prevalidated tool with eight domains relating to physical and psychological health. A total of 306 surveys were completed (231 AF group, 75 AF and diabetes group).The mean and standard deviation (SD)were calculated for each QoL domain,after re-coding in accordance with SF-36 guidance. Multi-variate analysis of variance (MANOVA) demonstrated an overall significant difference between the groups when considered jointly across all domains.There were significant differences between AF and AF with diabetes QoL responses in physical functioning, energy fatigue,emotional wellbeing, social functioning and pain. In these domains, the mean was highest in the AF group. There were no significant differences in the role physical,role emotional and general health domains. In conclusion, this study demonstrates that diabetes and AF has a more detrimental effect on QoL than AF alone, in the majority of domains. Further research into the general AF population and where chronic conditions co-exist is important to comprehend the true impact this disease combination has on QoL.

11.
Liver Transpl ; 27(1): 116-133, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916011

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common indication for liver transplantation. The growing prevalence of NAFLD not only increases the demand for liver transplantation, but it also limits the supply of available organs because steatosis predisposes grafts to ischemia/reperfusion injury (IRI) and many steatotic grafts are discarded. We have shown that monoacylglycerol acyltransferase (MGAT) 1, an enzyme that converts monoacylglycerol to diacylglycerol, is highly induced in animal models and patients with NAFLD and is an important mediator in NAFLD-related insulin resistance. Herein, we sought to determine whether Mogat1 (the gene encoding MGAT1) knockdown in mice with hepatic steatosis would reduce liver injury and improve liver regeneration following experimental IRI. Antisense oligonucleotides (ASO) were used to knockdown the expression of Mogat1 in a mouse model of NAFLD. Mice then underwent surgery to induce IRI. We found that Mogat1 knockdown reduced hepatic triacylglycerol accumulation, but it unexpectedly exacerbated liver injury and mortality following experimental ischemia/reperfusion surgery in mice on a high-fat diet. The increased liver injury was associated with robust effects on the hepatic transcriptome following IRI including enhanced expression of proinflammatory cytokines and chemokines and suppression of enzymes involved in intermediary metabolism. These transcriptional changes were accompanied by increased signs of oxidative stress and an impaired regenerative response. We have shown that Mogat1 knockdown in a mouse model of NAFLD exacerbates IRI and inflammation and prolongs injury resolution, suggesting that Mogat1 may be necessary for liver regeneration following IRI and that targeting this metabolic enzyme will not be an effective treatment to reduce steatosis-associated graft dysfunction or failure.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Aciltransferases , Animais , Humanos , Fígado , Camundongos , Camundongos Endogâmicos C57BL
12.
Medicine (Baltimore) ; 99(30): e21388, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791751

RESUMO

BACKGROUND: Increasing prevalence of atrial fibrillation has a significant impact on health, society, and healthcare resource utilization, due to increased morbidity, mortality, risk of stroke, and reduction in quality of life. Early diagnosis allows for treatment initiation, a reduction in complications and associated costs, and so innovation to improve screening and enable easy access are needed Developments in digital technology have significantly contributed to the availability of screening tools. The single-lead electrocardiogram AliveCor (Mountainview, CA) device offers the opportunity to provide heart rhythm screening and has been used extensively in clinical practice and research studies. METHODS: This review investigates the feasibility, validity, and utility of the AliveCor device as a tool for atrial fibrillation detection in clinical practice and in wider research. Databases searched included PUBMED, CINAHL, MEDLINE, and World of Science, plus grey literature search. Search terms related to atrial fibrillation, screening, and AliveCor with adults >18 years. Feasibility metrics were applied including process, resource, management, and scientific outcomes. Studies not written in the English language were excluded. Validity of AliveCor was explored by extracting sensitivity and specificity data from eligible studies and overall effectiveness analyzed by incorporating the above, with wider issues surrounding screening approaches, cost effectiveness and appropriateness of AliveCor as a screening tool. RESULTS: The AliveCor device screening was reviewed in 11 studies matching inclusion criteria. Atrial fibrillation detection rates ranged from 0.8% to 36% and this largely correlated to the study population, where wider age inclusion and mass/population screening represented lower atrial fibrillation detection. Recruitment from higher-risk groups (older age, targeted localities, chronic disease) identified higher numbers with atrial fibrillation. Feasibility metrics demonstrated AliveCor as an effective tool of choice in terms of process, resources, and management. Duration of screening time had an impact on rates of atrial fibrillation detection. There was however significant heterogeneity between studies reviewed. CONCLUSION: The AliveCor device offers a convenient, valid, and feasible means of monitoring for atrial fibrillation. Further analysis of electrocardiograms produced by AliveCor may be necessary in some circumstances. The AliveCor electrocardiogram device can be successfully implemented into both opportunistic and systematic screening strategies for atrial fibrillation.


Assuntos
Fibrilação Atrial/diagnóstico , Eletrocardiografia/instrumentação , Humanos
13.
Front Pediatr ; 8: 29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117834

RESUMO

Objective: Acute kidney injury (AKI) is a significant cause of morbidity and mortality among hospitalised patients. The objectives in this study were (i) to investigate the incidence of AKI using the National Health Services (NHS) AKI e-alert algorithm as a means of identifying AKI; and (ii) in a randomly selected sub-group of children with AKI identified using the algorithm, to evaluate the recognition and management of AKI. Patients and Methods: Retrospective cross-sectional study with initial electronic retrieval of creatinine measurements at six hospitals in England over a six-month period. Results were evaluated using the NHS AKI e-alert algorithm with recognition and management of AKI stages 1, 2 and 3 reviewed in a sub-set of randomly selected patient case notes. Patients aged 29 to 17 years were included. AKI stage 1 was defined as a rise of 1.5 - ≤2x baseline creatinine level; AKI stage 2 a rise of ≤ 2.0 and < 3.0; AKI stage 3 a rise of ≥ 3.0. Urine output was not considered for AKI staging. Results: 57,278 creatinine measurements were analysed. 5,325 (10.8%) AKI alerts were noted in 1,112 patients with AKI 1 (62%), AKI 2 (16%) and AKI 3 (22%). There were 222 (20%) <1y, 432 (39%) 1 ≤ 6y, 192 (17%) 6 ≤ 11y, 207 (19%) 11 ≤ 16y, and 59 (5%) 16-17y. Case notes of 123 of 1,112 [11.1%] children with AKI alerts were reviewed. Confirmed AKI was recognised with a documented management plan following its identification in n = 32 [26%] patients only. Conclusions: In this first multicentre study of the incidence of AKI in children admitted to selected hospitals across England, the incidence of AKI was 10.8% with most patients under the age of 6 years and with AKI stage 1. Recognition and management of AKI was seen in just over 25% children. These data highlight the need to improve recognition of AKI in hospitalised children in the UK.

14.
Arrhythm Electrophysiol Rev ; 8(3): 161-165, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31463053

RESUMO

The British Heart Rhythm Society's Clinical Practice Guidelines on the Management of Patients Developing QT Prolongation on Antipsychotic Medication are written for heart rhythm consultants, primary care physicians, specialist registrars, nurses and physiologists who may be requested to review ECGs or advise on cases where antipsychotic-induced QT prolongation is suspected or proven. The guidance is adapted from the latest Maudsley Prescribing Guidelines in Psychiatry, published in 2018.

15.
Arrhythm Electrophysiol Rev ; 8(1): 70-74, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30918671

RESUMO

Vernakalant is an antiarrhythmic drug licensed for the pharmacological cardioversion of recent onset AF. Randomised clinical trials, backed up by real-world experience, have confirmed its efficacy at restoring sinus rhythm. Vernakalant can be administered simply with a short time to action, facilitating early discharge from hospital in selected patients in place of electrical cardioversion. The authors explore the data behind vernakalant and discuss how it can be introduced into clinical practice.

16.
J Lipid Res ; 60(3): 528-538, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30610082

RESUMO

During prolonged fasting, the liver plays a central role in maintaining systemic energy homeostasis by producing glucose and ketones in processes fueled by oxidation of fatty acids liberated from adipose tissue. In mice, this is accompanied by transient hepatic accumulation of glycerolipids. We found that the hepatic expression of monoacylglycerol acyltransferase 1 (Mogat1), an enzyme with monoacylglycerol acyltransferase (MGAT) activity that produces diacyl-glycerol from monoacylglycerol, was significantly increased in the liver of fasted mice compared with mice given ad libitum access to food. Basal and fasting-induced expression of Mogat1 was markedly diminished in the liver of mice lacking the transcription factor PPARα. Suppressing Mogat1 expression in liver and adipose tissue with antisense oligonucleotides (ASOs) reduced hepatic MGAT activity and triglyceride content compared with fasted controls. Surprisingly, the expression of many other PPARα target genes and PPARα activity was also decreased in mice given Mogat1 ASOs. When mice treated with control or Mogat1 ASOs were gavaged with the PPARα ligand, WY-14643, and then fasted for 18 h, WY-14643 administration reversed the effects of Mogat1 ASOs on PPARα target gene expression and liver triglyceride content. In conclusion, Mogat1 is a fasting-induced PPARα target gene that may feed forward to regulate liver PPARα activity during food deprivation.


Assuntos
Jejum , Privação de Alimentos , Fígado/enzimologia , N-Acetilglucosaminiltransferases/metabolismo , Tecido Adiposo/metabolismo , Animais , Regulação Enzimológica da Expressão Gênica , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , N-Acetilglucosaminiltransferases/deficiência , N-Acetilglucosaminiltransferases/genética , PPAR alfa/genética , Fatores de Tempo , Triglicerídeos/metabolismo
17.
Emerg Nurse ; 27(1): 14-20, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30550052

RESUMO

Atrial fibrillation (AF) is the most common arrhythmia, and there is a one in four lifetime risk of developing the condition for people who are over the age of 40. Vernakalant, a new addition to intravenous antiarrhythmic drugs for cardioversion of AF, is the first atrial-specific antiarrhythmic drug for pharmacological cardioversion of recent onset AF and is more effective than placebo and amiodarone. The drug offers patients an alternative to other pharmacological agents for chemical cardioversion and avoids the risks associated with electrical cardioversion. Its main advantage is rapid conversion of AF, which potentially reduces atrial remodelling and it can be used in patients with little or no underlying cardiovascular disease and in those with moderate disease such as stable coronary and hypertensive heart disease. Post-marketing and clinical trials suggest a favourable rate of conversion to sinus rhythm. Jersey General Hospital was the first in the UK to obtain and introduce the drug in practice. This article describes the evidence and guidelines for its use and the local implementation process.


Assuntos
Anisóis/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Pirrolidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido
18.
Vaccine ; 36(30): 4404-4424, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-29907482

RESUMO

BACKGROUND: Vibrio cholera is a major contributor of diarrheal illness that causes significant morbidity and mortality globally. While there is literature on the health economics of diarrheal illnesses more generally, few studies have quantified the cost-of-illness and cost-effectiveness of cholera-specific prevention and control interventions. The present systematic review provides a comprehensive overview of the literature specific to cholera as it pertains to key health economic measures. METHODS: A systematic review was performed with no date restrictions up through February 2017 in PubMed, Econlit, Embase, Web of Science, and Cochrane Review to identify relevant health economics of cholera literature. After removing duplicates, a total of 1993 studies were screened and coded independently by two reviewers, resulting in 22 relevant studies. Data on population, methods, and results (cost-of-illness and cost-effectiveness of vaccination) were compared by country/region. All costs were adjusted to 2017 USD for comparability. RESULTS: Costs per cholera case were found to be rather low: <$100 per case in most settings, even when costs incurred by patients/families and lost productivity are considered. When wider socioeconomic costs are included, estimated costs are >$1000/case. There is adequate evidence to support the economic value of vaccination for the prevention and control of cholera when vaccination is targeted at high-incidence populations and/or areas with high case fatality rates due to cholera. When herd immunity is considered, vaccination also becomes a cost-effective option for the general population and is comparable in cost-effectiveness to other routine immunizations. CONCLUSIONS: Cholera vaccination is a viable short-to-medium term option, especially as the upfront costs of building water, sanitation, and hygiene (WASH) infrastructure are considerably higher for countries that face a significant burden of cholera. While WASH may be the more cost-effective solution in the long-term when implemented properly, cholera vaccination can still be a feasible, cost-effective strategy.


Assuntos
Cólera/prevenção & controle , Cólera/economia , Análise Custo-Benefício , Humanos , Vacinação/economia
19.
J Lipid Res ; 59(9): 1630-1639, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29853530

RESUMO

Adipocyte triglyceride storage provides a reservoir of energy that allows the organism to survive times of nutrient scarcity, but excessive adiposity has emerged as a health problem in many areas of the world. Monoacylglycerol acyltransferase (MGAT) acylates monoacylglycerol to produce diacylglycerol; the penultimate step in triglyceride synthesis. However, little is known about MGAT activity in adipocytes, which are believed to rely primarily on another pathway for triglyceride synthesis. We show that expression of the gene that encodes MGAT1 is robustly induced during adipocyte differentiation and that its expression is suppressed in fat of genetically-obese mice and metabolically-abnormal obese human subjects. Interestingly, MGAT1 expression is also reduced in physiologic contexts where lipolysis is high. Moreover, knockdown or knockout of MGAT1 in adipocytes leads to higher rates of basal adipocyte lipolysis. Collectively, these data suggest that MGAT1 activity may play a role in regulating basal adipocyte FFA retention.


Assuntos
Aciltransferases/metabolismo , Tecido Adiposo/enzimologia , N-Acetilglucosaminiltransferases/metabolismo , Aciltransferases/deficiência , Aciltransferases/genética , Adipócitos/citologia , Tecido Adiposo/metabolismo , Animais , Diferenciação Celular , Ácidos Graxos não Esterificados/metabolismo , Regulação Enzimológica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , N-Acetilglucosaminiltransferases/deficiência , N-Acetilglucosaminiltransferases/genética , Obesidade/metabolismo , Obesidade/patologia , RNA Interferente Pequeno/genética
20.
Liver Transpl ; 24(7): 908-921, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29729104

RESUMO

The prevalence of obesity-associated nonalcoholic fatty liver disease has significantly increased over the past decade, and end-stage liver disease secondary to nonalcoholic steatohepatitis has become 1 of the most common indications for liver transplantation. This both increases the demand for organs and decreases the availability of donor livers deemed suitable for transplantation. Although in the past many steatotic livers were discarded due to concerns over enhanced susceptibility to ischemia/reperfusion injury (IRI) and organ failure, the discrepancy between supply and demand has resulted in increasing use of expanded criteria donor organs including steatotic livers. However, it remains controversial whether steatotic livers can be safely used for transplantation and how best to improve the performance of steatotic grafts. We aimed to evaluate the impact of diet-induced hepatic steatosis in a murine model of IRI. Using a diet of high trans-fat, fructose, and cholesterol (HTF-C) and a diet high in saturated fats, sucrose, and cholesterol (Western diet), we were able to establish models of mixed macrovesicular and microvesicular steatosis (HTF-C) and microvesicular steatosis (Western). We found that the presence of hepatic steatosis, whether it is predominantly macrovesicular or microvesicular, significantly worsens IRI as measured by plasma alanine aminotransferase levels and inflammatory cytokine concentration, and histological evaluation for necrosis. Additionally, we report on a novel finding in which hepatic IRI in the setting of steatosis results in the induction of the necroptosis factors, receptor interacting protein kinase (RIPK) 3, RIPK1, and mixed-lineage kinase domain-like. These data lay the groundwork for additional experimentation to test potential therapeutic approaches to limit IRI in steatotic livers by using a genetically tractable system. Liver Transplantation 24 908-921 2018 AASLD.


Assuntos
Transplante de Fígado/efeitos adversos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/patologia , Traumatismo por Reperfusão/patologia , Animais , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Testes de Função Hepática , Transplante de Fígado/normas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologia , Traumatismo por Reperfusão/etiologia , Coleta de Tecidos e Órgãos/normas
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