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1.
Sci Rep ; 12(1): 8630, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606393

RESUMO

We expanded a published mathematical model of SARS-CoV-2 transmission with complex, age-structured transmission and with laboratory-derived source and wearer protection efficacy estimates for a variety of face masks to estimate their impact on COVID-19 incidence and related mortality in the United States. The model was also improved to allow realistic age-structured transmission with a pre-specified R0 of transmission, and to include more compartments and parameters, e.g. for groups such as detected and undetected asymptomatic infectious cases who mask up at different rates. When masks are used at typically-observed population rates of 80% for those ≥ 65 years and 60% for those < 65 years, face masks are associated with 69% (cloth) to 78% (medical procedure mask) reductions in cumulative COVID-19 infections and 82% (cloth) to 87% (medical procedure mask) reductions in related deaths over a 6-month timeline in the model, assuming a basic reproductive number of 2.5. If cloth or medical procedure masks' source control and wearer protection efficacies are boosted about 30% each to 84% and 60% by cloth over medical procedure masking, fitters, or braces, the COVID-19 basic reproductive number of 2.5 could be reduced to an effective reproductive number ≤ 1.0, and from 6.0 to 2.3 for a variant of concern similar to delta (B.1.617.2). For variants of concern similar to omicron (B.1.1.529) or the sub-lineage BA.2, modeled reductions in effective reproduction number due to similar high quality, high prevalence mask wearing is more modest (to 3.9 and 5.0 from an R0 = 10.0 and 13.0, respectively). None-the-less, the ratio of incident risk for masked vs. non-masked populations still shows a benefit of wearing masks even with the higher R0 variants.

2.
ANZ J Surg ; 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429226

RESUMO

INTRODUCTION: Patient initiated follow up (PIFU) allows patients to initiate a hospital follow up appointment on an 'as required' basis in contrast to the traditional physician-initiated model. We present a clinical pathway for patients referred with rectal bleeding at a large tertiary public hospital in South Auckland, New Zealand and demonstrate the utility of PIFU and its impact on reducing follow up appointments. METHOD: The purpose of the pathway was to allow standardized care by the clinicians and allow for PIFU. Two separate protocols were developed - 'Painful PR bleeding' and 'Painless PR bleeding'. A new clinic (NC) was started following these protocols, and this was compared to historical controls (HC). The primary outcome was the rate of follow up appointments. RESULTS: There were 133 patients in the NC and 135 in the HC, with significantly less follow ups in the NC (6% versus 45%, p < 0.0001). A small percentage of patients in the NC group were directly discharged (10%) whilst 70% of patients were discharged with a PIFU card. Thirty phone calls were made using PIFU, with 10 patients returning to clinic and 20 requiring advice and reassurance only. At 5 year follow up, there was a single colorectal malignancy found in both groups. CONCLUSION: Initiating a protocol that includes patient initiated follow up vastly reduces the need for routine return to clinic for the majority of patients, without sacrificing patient care. A protocolised approach to clinic for other areas in general surgery should be considered.

3.
J Cyst Fibros ; 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35440408

RESUMO

BACKGROUND: While the clinical benefits of CFTR modulators are clear, their high prices render them inaccessible outside of the world's richest countries. Despite this, there is currently limited evidence regarding global access to these transformative therapies. Therefore, this study aims to estimate the minimum costs of production of CFTR modulators, assuming robust generic competition, and to compare them with current list prices to evaluate the feasibility of increased global access to treatment. METHODS: Minimum costs of production for CFTR modulators were estimated via an algorithm validated in previous literature and identification of cost-limiting key starting materials from published routes of chemical synthesis. This algorithm utilised per kilogram active pharmaceutical ingredient costs obtained from global import/export data. Estimated production costs were compared with published list prices in a range of countries. RESULTS: Costs of production for elexacaftor/tezacaftor/ivacaftor are estimated at $5,676 [$4,628-6,723] per year, over 90% lower than the US list price. Analysis of chemical structure and published synthetic pathways for elexacaftor/tezacaftor/ivacaftor revealed relatively straightforward routes of synthesis related to currently available products. Total cost of triple therapy for all eligible diagnosed CF patients worldwide would be $489 million per year. Comparatively, the annual cost at US list price would be $31.2 billion. CONCLUSIONS: Elexacaftor/tezacaftor/ivacaftor could be produced via generic companies for a fraction of the list price. The current pricing model restricts access to the best available therapy, thereby exacerbating existing inequalities in CF care. Urgent action is needed to increase the availability of triple combination treatment worldwide. One strategy based on previous success is originator-issued voluntary licenses.

4.
Sci Rep ; 12(1): 6780, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474076

RESUMO

Mycobacterium tuberculosis transmission dynamics in high-burden settings are poorly understood. Growing evidence suggests transmission may be characterized by extensive individual heterogeneity in secondary cases (i.e., superspreading), yet the degree and influence of such heterogeneity is largely unknown and unmeasured in high burden-settings. We conducted a prospective, population-based molecular epidemiology study of TB transmission in both an urban and rural setting of Botswana, one of the highest TB burden countries in the world. We used these empirical data to fit two mathematical models (urban and rural) that jointly quantified both the effective reproductive number, [Formula: see text], and the propensity for superspreading in each population. We found both urban and rural populations were characterized by a high degree of individual heterogeneity, however such heterogeneity disproportionately impacted the rural population: 99% of secondary transmission was attributed to only 19% of infectious cases in the rural population compared to 60% in the urban population and the median number of incident cases until the first outbreak of 30 cases was only 32 for the rural model compared to 791 in the urban model. These findings suggest individual heterogeneity plays a critical role shaping local TB epidemiology within subpopulations.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Estudos Prospectivos , População Rural , Tuberculose/epidemiologia , População Urbana
5.
Adv Ther ; 39(6): 3019-3030, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35451741

RESUMO

INTRODUCTION: Obesity significantly increases the risk of developing (or worsening) more than 200 chronic diseases, and it is also a risk factor for severe COVID-19. With the rising prevalence of obesity in the UK, there is a need to develop obesity care competencies that apply to healthcare professionals (HCPs) at all levels of the health service, to increase the capacity for contemporary, evidence-based treatment that is effective, compassionate, and avoids stigmatising patients. METHODS: A UK Obesity Care Competencies Working Group consisting of experts by profession and experts by experience was created to provide a framework of obesity care competencies for HCPs involved in specialist obesity care (tiers 2-4 in the UK). The framework was adapted from a set of competencies recently published by the USA-based Obesity Medicine Education Collaborative (OMEC) and was intended to be adaptable to nurses and allied health professionals, as well as physicians, owing to the multidisciplinary team approach used in healthcare in the UK. RESULTS: The UK Obesity Care Competencies Working Group developed a set of 29 competencies, divided into five focal areas, namely obesity knowledge, patient care and procedural skills, practice-based learning and improvement, professionalism and interpersonal communication skills, and systems-based practice. The working group recommends that the obesity care competencies are targeted at HCPs training as specialists. The competencies could be imported into existing training programmes to help standardise obesity-related medical education and could also be used to direct a new General Practitioner with Extended Role (GPwER) qualification. CONCLUSION: This list of obesity care competencies aims to provide an initial framework to improve education for HCPs and therefore to improve patient care in obesity. The acceptance and integration of these competencies into the healthcare system should provide a stepping stone toward addressing trends in health inequality.


Assuntos
COVID-19 , Competência Clínica , Atenção à Saúde , Disparidades nos Níveis de Saúde , Humanos , Obesidade/terapia , Reino Unido
6.
BMJ Open ; 12(4): e058103, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440459

RESUMO

INTRODUCTION: The cost-effectiveness and long-term health impact of behavioural weight management programmes depends on post-treatment weight-loss maintenance. Growing evidence suggests that interventions using acceptance and commitment therapy (ACT) could improve long-term weight management. We developed an ACT-based, guided self-help intervention to support adults who have recently completed a behavioural weight loss programme. This study will assess the feasibility and acceptability of this type of intervention and findings will inform the development of a full-scale trial. METHODS AND ANALYSIS: This is a pragmatic, randomised, single-blind, parallel group, two-arm, feasibility study with an embedded process evaluation. We will recruit and randomise 60 adults who have recently completed a behavioural weight loss programme to the ACT-based intervention or standard care, using a computer-generated sequence with 2:1 allocation stratified by diabetes status and sex. Baseline and 6-month measurements will be completed using online questionnaires. Qualitative interviews will be conducted with a subsample of participants and coaches about their experiences at 3 (mid-intervention) and 6 (postintervention) months. Feasibility and acceptability of the intervention, and a full-scale trial will be assessed using a number of outcomes, including adherence to, and engagement with the intervention, recruitment and retention rates, proportion of missing data for each outcome measure, participants' experiences of the intervention and study, and coaches' experiences of delivering intervention support. Quantitative and qualitative findings will be integrated and summarised to contribute to the interpretation of the main feasibility evaluation findings. Value of information methods will be used to estimate the decision uncertainty associated with the intervention's cost-effectiveness and determine the value of a definitive trial. ETHICS AND DISSEMINATION: Ethical approval was received from Cambridge South Research Ethics Committee on 15/03/2021 (21/EE/0024). This protocol (V.2) was approved on 19 April 2021. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. TRIAL REGISTRATION NUMBER: ISRCTN12685964.


Assuntos
Terapia de Aceitação e Compromisso , Programas de Redução de Peso , Adulto , Estudos de Viabilidade , Humanos , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Perda de Peso
8.
Front Immunol ; 13: 858423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422813

RESUMO

The identification of practical early diagnostic biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumor disease (DFTD), a highly lethal transmissible cancer afflicting virtually an entire species, the Tasmanian devil (Sarcophilus harrisii). Despite a latent period that can exceed one year, to date DFTD diagnosis requires visual identification of tumor lesions. To enable earlier diagnosis, which is essential for the implementation of effective conservation strategies, we analyzed the extracellular vesicle (EV) proteome of 87 Tasmanian devil serum samples using data-independent acquisition mass spectrometry approaches. The antimicrobial peptide cathelicidin-3 (CATH3), released by innate immune cells, was enriched in serum EV samples of both devils with clinical DFTD (87.9% sensitivity and 94.1% specificity) and devils with latent infection (i.e., collected while overtly healthy, but 3-6 months before subsequent DFTD diagnosis; 93.8% sensitivity and 94.1% specificity). Although high expression of antimicrobial peptides has been mostly related to inflammatory diseases, our results suggest that they can be also used as accurate cancer biomarkers, suggesting a mechanistic role in tumorous processes. This EV-based approach to biomarker discovery is directly applicable to improving understanding and diagnosis of a broad range of diseases in other species, and these findings directly enhance the capacity of conservation strategies to ensure the viability of the imperiled Tasmanian devil population.


Assuntos
Vesículas Extracelulares , Neoplasias Faciais , Marsupiais , Animais , Peptídeos Catiônicos Antimicrobianos , Detecção Precoce de Câncer , Vesículas Extracelulares/patologia , Neoplasias Faciais/diagnóstico , Neoplasias Faciais/veterinária
9.
Artigo em Inglês | MEDLINE | ID: mdl-35457323

RESUMO

This study investigated the relationship between fear of COVID-19, previous exposure to COVID-19, perceived vulnerability to disease, sleep quality, and psychological distress among healthcare workers (HCWs) in Taif city in Saudi Arabia, which has a population of 702,000 people. A cross-sectional study design was adopted. HCWs (n = 202) completed a survey containing the Fear of COVID-19 Scale (FCV-19S), Perceived Vulnerability to Disease (PVD), Pittsburgh Sleep Quality Index (PSQI), and Depression, Anxiety, and Stress Scale (DASS-21). FCV-19S and sleep quality were significant predictors for psychological distress. Female gender was a significant predictor for depression and stress. Single, divorced, and widowed marital status were predictive for anxiety. FCV-19S was weakly correlated with PVD but moderately with depression, anxiety, and stress. Of the two PVD subscales, perceived infectability was weakly correlated with psychological distress. PVD and previous experience with COVID-19 were not significant predictors. Sleep quality and FCV-19S were major predictors of psychological distress. Findings indicated that poor sleep quality was strongly associated with psychological distress, while fear of COVID-19 had a moderate association. Such results support the need to design and implement psychological programs to assist HCWs in dealing with the psychological impact of this ongoing pandemic.


Assuntos
COVID-19 , Angústia Psicológica , COVID-19/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Feminino , Pessoal de Saúde , Humanos , SARS-CoV-2 , Arábia Saudita/epidemiologia
10.
Obes Facts ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35417910

RESUMO

INTRODUCTION: Adults with overweight and obesity are vulnerable to weight gain and mental health deterioration during the COVID-19 pandemic. We developed a web-based, guided self-help intervention based on Acceptance and Commitment Therapy (ACT) that aims to support adults with overweight and obesity to prevent weight gain by helping them to manage their eating behaviours, be more physically active and protect their emotional wellbeing ("SWiM-C"). SWiM-C is a guided self-help programme using non-specialist guides to enhance scalability and population reach while minimising cost. This study evaluated the effect of SWiM-C on bodyweight, eating behaviour, physical activity and mental wellbeing in adults with overweight and obesity over 4 months during the COVID-19 pandemic in the UK. METHODS: We randomised adults (BMI≥25kg/m2) to SWiM-C or to a wait-list standard advice group. Participants completed outcome assessments online at baseline and 4 months. The primary outcome was self-measured weight; secondary outcomes were eating behaviour, physical activity, experiential avoidance/psychological flexibility, depression, anxiety, stress, and wellbeing. We estimated differences between study groups in change in outcomes from baseline to 4 months using linear regression, adjusted for outcome at baseline and the randomisation stratifiers (BMI, sex). The trial was pre-registered (ISRCTN12107048). RESULTS: 486 participants were assessed for eligibility; 388 participants were randomised (196 standard advice, 192 SWiM-C) and 324 were analysed. The adjusted difference in weight between SWiM-C and standard advice was -0.60kg (-1.67 to 0.47, p=0.27). SWiM-C led to improvements in uncontrolled eating (-3.61 [-5.94 to -1.28]), cognitive restraint (5.28 [2.81 to 7.75]), experiential avoidance (-3.39 [-5.55 to -1.23]), and wellbeing (0.13 [0.07 to 0.18]). CONCLUSIONS: SWiM-C improved several psychological determinants of successful weight management and had a protective effect on wellbeing during the pandemic. However, differences in weight and some other outcomes were compatible with no effect of the intervention, suggesting further refinement of the intervention is needed.

11.
Cell Tissue Res ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35394216

RESUMO

Prion diseases (PrD) or transmissible spongiform encephalopathies (TSE) are invariably fatal and pathogenic neurodegenerative disorders caused by the self-propagated misfolding of cellular prion protein (PrPC) to the neurotoxic pathogenic form (PrPTSE) via a yet undefined but profoundly complex mechanism. Despite several decades of research on PrD, the basic understanding of where and how PrPC is transformed to the misfolded, aggregation-prone and pathogenic PrPTSE remains elusive. The primary clinical hallmarks of PrD include vacuolation-associated spongiform changes and PrPTSE accumulation in neural tissue together with astrogliosis. The difficulty in unravelling the disease mechanisms has been related to the rare occurrence and long incubation period (over decades) followed by a very short clinical phase (few months). Additional challenge in unravelling the disease is implicated to the unique nature of the agent, its complexity and strain diversity, resulting in the heterogeneity of the clinical manifestations and potentially diverse disease mechanisms. Recent advances in tissue isolation and processing techniques have identified novel means of intercellular communication through extracellular vesicles (EVs) that contribute to PrPTSE transmission in PrD. This review will comprehensively discuss PrPTSE transmission and neurotoxicity, focusing on the role of EVs in disease progression, biomarker discovery and potential therapeutic agents for the treatment of PrD.

12.
BMC Genomics ; 23(1): 257, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379185

RESUMO

BACKGROUND: Polyandrous social insects such as the honey bee are prime candidates for parental manipulation of gene expression in offspring. Although there is good evidence for parent-of-origin effects in honey bees the epigenetic mechanisms that underlie these effects remain a mystery. Small RNA molecules such as miRNAs, piRNAs and siRNAs play important roles in transgenerational epigenetic inheritance and in the regulation of gene expression during development. RESULTS: Here we present the first characterisation of small RNAs present in honey bee reproductive tissues: ovaries, spermatheca, semen, fertilised and unfertilised eggs, and testes. We show that semen contains fewer piRNAs relative to eggs and ovaries, and that piRNAs and miRNAs which map antisense to genes involved in DNA regulation and developmental processes are differentially expressed between tissues. tRNA fragments are highly abundant in semen and have a similar profile to those seen in the semen of other animals. Intriguingly we also find abundant piRNAs that target the sex determination locus, suggesting that piRNAs may play a role in honey bee sex determination. CONCLUSIONS: We conclude that small RNAs may play a fundamental role in honey bee gametogenesis and reproduction and provide a plausible mechanism for parent-of-origin effects on gene expression and reproductive physiology.


Assuntos
MicroRNAs , Animais , Abelhas/genética , Epigênese Genética , MicroRNAs/genética , Reprodução/genética
13.
ANZ J Surg ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35482412

RESUMO

BACKGROUND: Attenuation of the inflammatory response in patients undergoing colectomy with modern perioperative care and laparoscopic surgery has been a focus of research in recent years. Despite reported benefits, significant heterogeneity remains with studies including patients undergoing both rectal and colon surgery and including surgery with postoperative complications. Therefore, the aim of the study was to evaluate the inflammatory response in patients undergoing elective colectomy without complications, specifically comparing open and laparoscopic approaches. METHODS: A multicenter prospective study was conducted across four public hospitals in Auckland and Christchurch, New Zealand. Consecutive adults undergoing elective colectomy were included over a 3-year period. Perioperative blood samples were collected and analysed for the following inflammatory markers: IL-6, IL-1ß, TNFα, IL-10, CRP, leucocyte and neutrophil count. Statistical analysis was performed using SPSS statistical software. RESULTS: A total of 168 colectomy patients without complications were included in the analysis. Patients that underwent laparoscopy had significantly reduced IL-6, neutrophils and CRP on postoperative day (POD) 1 (p < 0.05) compared to an open approach. IL-10 and TNFα were significantly reduced on POD 2 (p < 0.05) in laparoscopic patients. Patients with a Body Mass Index (BMI) greater than 30 kg/m2 had significantly higher levels of CRP regardless of operative approach. Statins altered both preoperative and postoperative inflammatory markers. CONCLUSION: The postoperative inflammatory response is influenced by surgical approach, perioperative medications, and patient factors. These findings have important implications in the utility of biomarkers in the diagnosis of postoperative surgical complications, in particular in the early diagnosis of anastomotic leak.

14.
Nat Commun ; 13(1): 1934, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35411049

RESUMO

The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3-deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells. UBL3 also regulates MHC II and CD86 in human dendritic cells (DCs) and macrophages. UBL3 impacts ubiquitination of MARCH1 substrates, a mechanism that requires UBL3 plasma membrane anchoring via prenylation. Loss of UBL3 alters adaptive immunity with impaired development of thymic regulatory T cells, loss of conventional type 1 DCs, increased number of trogocytic marginal zone B cells, and defective in vivo MHC II and MHC I antigen presentation. In summary, we identify UBL3 as a conserved, critical factor in MARCH1-mediated ubiquitination with important roles in immune responses.


Assuntos
Antígenos de Histocompatibilidade Classe II , Ubiquitinas , Animais , Antígeno B7-2/metabolismo , Células Dendríticas , Antígenos de Histocompatibilidade Classe II/metabolismo , Complexo Principal de Histocompatibilidade , Camundongos , Camundongos Endogâmicos C57BL , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Ubiquitinas/metabolismo
15.
Eur J Pharm Biopharm ; 174: 35-46, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35364255

RESUMO

Suboptimal control of postoperative pain following knee arthroplasty can slow recovery and reduce patient satisfaction. Intraarticular (IA) administration of bupivacaine and ketorolac offers efficient pain control and minimizes opioid consumption. However, the clinical benefits of this approach are short lived due to rapid clearance of drugs from the joint cavity. Here, we describe a poloxamer based thermoresponsive in situ gelling system for the sustained IA delivery of bupivacaine hydrochloride (BH) and ketorolac tromethamine (KT) following knee surgery in an ovine model. Drug loaded formulations were prepared using poloxamer 407, poloxamer 188 and sodium chloride. In vitro characterization was conducted, followed by in vivo evaluation of sustained drug release and safety in an ovine model of knee joint surgery. Rheological studies revealed a Newtonian-like flow of the developed formulation at room temperature, confirming its injectability, followed by a transition to a viscous gel as temperature approached body temperature. The developed formulation successfully sustained the in vivo release of BH for 72 h and KT for 48 h, as determined by circulating drug levels, compared to 24 and 8 h for marketed drug solutions. The concentrations of BH and KT in the synovial fluids at 72 h were 11.5 and 1.8 times that of marketed products, suggesting a significant increase in the IA residence time. The developed formulation induced a comparable inflammatory response compared to the marketed drug solutions, however a significantly higher chondrotoxicity was observed following administration of the gel formulations. Poloxamers based in situ gelling systems are promising delivery platforms for the sustained and localised IA delivery of BH and KT, with potential clinical benefits in managing the postoperative pain following knee arthroplasty.


Assuntos
Bupivacaína , Cetorolaco , Animais , Géis , Cetorolaco de Trometamina , Dor Pós-Operatória/tratamento farmacológico , Poloxâmero , Ovinos
16.
Surgery ; 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35379520

RESUMO

BACKGROUND: Sarcopenia refers to the progressive age and pathology-associated loss of skeletal muscle, which has been shown to independently predict mortality in patients undergoing major elective surgery. Emergency laparotomy is commonly performed for a range of procedures and is associated with high rates of mortality. However, the prognostic utility of sarcopenia after emergency laparotomy remains unknown. The aim of this study was to compare short and long-term survival between patients with and without sarcopenia undergoing emergency laparotomy. METHODS: MEDLINE, EMBASE, and Scopus databases were systematically searched for articles comparing survival outcomes between adults with and without radiologically defined sarcopenia after emergency gastrointestinal surgery regardless of indication and approach (open/laparoscopic). The primary outcome was postoperative mortality. Sensitivity analysis of adjusted multivariate analyses was performed. RESULTS: Twenty articles comprising 6,737 patients were included. Sarcopenia was most commonly assessed using axial abdominal computerized tomography at L3, although cut-off thresholds were heterogeneous and rarely sex-specific. Postoperative mortality was higher among patients with sarcopenia than without in the in-hospital setting, and at 30- and 90-day follow-up on univariate but not on multivariate meta-analysis. However, mortality was significantly higher among sarcopenic cohorts in the 1-year (odds ratio 2.8, 95% confidence interval: 1.5-5.6; P = .002) follow-up period, despite adjusting for confounding preoperative and patient factors. CONCLUSION: The meta-analysis has shown sarcopenia to provide useful long-term prognostic information following emergency laparotomy. This may aid with preoperative risk assessment, patient counseling, and in perioperative decision-making for patients undergoing emergency laparotomy.

17.
PLoS One ; 17(3): e0263856, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35324908

RESUMO

INTRODUCTION: Depression is a leading mental health problem worldwide. People with long-term conditions are at increased risk of experiencing depression. The COVID-19 pandemic led to strict social restrictions being imposed across the UK population. Social isolation can have negative consequences on the physical and mental wellbeing of older adults. In the Behavioural Activation in Social IsoLation (BASIL+) trial we will test whether a brief psychological intervention (based on Behavioural Activation), delivered remotely, can mitigate depression and loneliness in older adults with long-term conditions during isolation. METHODS: We will conduct a two-arm, parallel-group, randomised controlled trial across several research sites, to evaluate the clinical and cost-effectiveness of the BASIL+ intervention. Participants will be recruited via participating general practices across England and Wales. Participants must be aged ≥65 with two or more long-term conditions, or a condition that may indicate they are within a 'clinically extremely vulnerable' group in relation to COVID-19, and have scored ≥5 on the Patient Health Questionnaire (PHQ9), to be eligible for inclusion. Randomisation will be 1:1, stratified by research site. Intervention participants will receive up to eight intervention sessions delivered remotely by trained BASIL+ Support Workers and supported by a self-help booklet. Control participants will receive usual care, with additional signposting to reputable sources of self-help and information, including advice on keeping mentally and physically well. A qualitative process evaluation will also be undertaken to explore the acceptability of the BASIL+ intervention, as well as barriers and enablers to integrating the intervention into participants' existing health and care support, and the impact of the intervention on participants' mood and general wellbeing in the context of the COVID-19 restrictions. Semi-structured interviews will be conducted with intervention participants, participant's caregivers/supportive others and BASIL+ Support Workers. Outcome data will be collected at one, three, and 12 months post-randomisation. Clinical and cost-effectiveness will be evaluated. The primary outcome is depressive symptoms at the three-month follow up, measured by the PHQ9. Secondary outcomes include loneliness, social isolation, anxiety, quality of life, and a bespoke health services use questionnaire. DISCUSSION: This study is the first large-scale trial evaluating a brief Behavioural Activation intervention in this population, and builds upon the results of a successful external pilot trial. TRIAL REGISTRATION: ClinicalTrials.Gov identifier ISRCTN63034289, registered on 5th February 2021.


Assuntos
COVID-19 , Ocimum basilicum , Idoso , Análise Custo-Benefício , Depressão/prevenção & controle , Humanos , Solidão , Pandemias , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Isolamento Social
18.
Nat Rev Drug Discov ; 21(5): 379-399, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35236964

RESUMO

The field of extracellular vesicle (EV) research has developed rapidly over the last decade from the study of fundamental biology to a subject of significant clinical relevance. The potential of harnessing EVs in the diagnosis and treatment of diseases - including cancer and neurological and cardiovascular disorders - is now being recognized. Accordingly, the applications of EVs as therapeutic targets, biomarkers, novel drug delivery agents and standalone therapeutics are being actively explored. This Review provides a brief overview of the characteristics and physiological functions of the various classes of EV, focusing on their association with disease and emerging strategies for their therapeutic exploitation.


Assuntos
Doenças Cardiovasculares , Vesículas Extracelulares , Neoplasias , Biomarcadores , Humanos , Neoplasias/tratamento farmacológico
19.
Commun Biol ; 5(1): 222, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35273325

RESUMO

Label-free multiphoton microscopy is a powerful platform for biomedical imaging. Recent advancements have demonstrated the capabilities of transient absorption microscopy (TAM) for label-free quantification of hemoglobin and stimulated Raman scattering (SRS) microscopy for pathological assessment of label-free virtual histochemical staining. We propose the combination of TAM and SRS with two-photon excited fluorescence (TPEF) to characterize, quantify, and compare hemodynamics, vessel structure, cell density, and cell identity in vivo between age groups. In this study, we construct a simultaneous nonlinear absorption, Raman, and fluorescence (SNARF) microscope with the highest reported in vivo imaging depth for SRS and TAM at 250-280 µm to enable these multimodal measurements. Using machine learning, we predict capillary-lining cell identities with 90% accuracy based on nuclear morphology and capillary relationship. The microscope and methodology outlined herein provides an exciting route to study several research topics, including neurovascular coupling, blood-brain barrier, and neurodegenerative diseases.


Assuntos
Microscopia , Análise Espectral Raman , Animais , Encéfalo/diagnóstico por imagem , Camundongos , Análise Espectral Raman/métodos
20.
Br J Anaesth ; 128(5): 796-805, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35256150

RESUMO

BACKGROUND: Preoperative anaemia is a risk factor for adverse postoperative outcomes after cardiac surgery. Iron deficiency is a frequent cause of low preoperative haemoglobin. An effective treatment for preoperative anaemia associated with iron deficiency has not been determined. METHODS: We conducted a single-centre, open-label, pragmatic randomised trial, enrolling 156 elective cardiac surgery patients who had low preoperative haemoglobin (100-130 g L-1) with iron deficiency (serum ferritin <100 µg L-1 or transferrin saturation <30%) to compare intravenous ferric derisomaltose 1000 mg and darbepoetin 200 µg subcutaneously (intervention group) with oral ferrous sulphate 600 mg daily (control group). The primary outcome was transfusion of at least one unit of allogeneic red cells during surgery and within the following 5 days. Secondary outcomes included the change in haemoglobin concentration between randomisation and surgery, red cell transfusion volume, postoperative blood loss, pre-specified postoperative complications, length of hospital stay, and in-hospital death. RESULTS: The odds of red cell transfusion were lower in the intervention group compared with the control group (adjusted odds ratio=0.33; 95% confidence interval [CI], 0.15-0.75; P=0.008). Of the secondary outcomes, the only significant difference was the increase in haemoglobin between randomisation and surgery, intervention vs control 9.5 g L-1 (95% CI, 6.8-12.2; P<0.001). CONCLUSIONS: In patients with a low preoperative haemoglobin and iron deficiency, preoperative treatment with a single dose of ferric derisomaltose and darbepoetin decreased the proportion of participants who received a perioperative blood transfusion as a consequence of a greater increase in haemoglobin compared with treatment with oral ferrous sulphate. CLINICAL TRIAL REGISTRATION: ISRCTN Number: 41421863; EUDRACT number: 2011-003695-36.


Assuntos
Anemia Ferropriva , Anemia , Procedimentos Cirúrgicos Cardíacos , Hematínicos , Anemia/tratamento farmacológico , Anemia/etiologia , Anemia Ferropriva/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dissacarídeos , Eritropoese , Compostos Férricos , Hematínicos/uso terapêutico , Hemoglobinas , Mortalidade Hospitalar , Humanos , Ferro/uso terapêutico
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