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1.
Clin Exp Dermatol ; 45(3): 318-322, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31419323

RESUMO

Psoriasis is commonly treated with topical corticosteroids, oral cytotoxic drugs and biologic agents, which can be associated with significant adverse effects (AEs), high cost and response attenuation. Additionally, patients often use alternative therapies ad hoc, which can be challenging to integrate into a treatment regimen, owing to a lack of adequately powered controlled trials assessing efficacy and safety. We developed a novel topical botanical complex, herbal anti-inflammatory treatment (HAT1), through extensive preclinical in vitro and in vivo modelling to define key mechanisms of action and clinical potential. To assess the efficacy and safety of HAT1 in psoriasis, we performed a 10-week, open-label, pilot clinical trial comparing topical treatment of HAT1 with calcipotriol 0.005% in adult patients with mild to moderate psoriasis. Primary and secondary endpoints included the percentage of patients obtaining improvement of ≥ 75% in Psoriasis Area and Severity Index (PASI 75), Physician's Global Assessment (PGA) response, and evaluation of tolerability and safety of HAT1. In the HAT1 arm, 85.7% of study patients reached PASI 75 compared with 21.4% in the calcipotriol comparator group. Additionally, 78.6% of patients in the HAT1 arm achieved a 'clear' or 'minimal' PGA response. HAT1 was well tolerated, with no AEs observed throughout the trial. These results suggest that HAT1 reduces psoriasis disease activity in a clinically relevant manner. Ongoing studies, including well-powered, double-blind, randomized controlled trials will be required to assess the potential of HAT1 in psoriasis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Anti-Inflamatórios/efeitos adversos , Calcitriol/efeitos adversos , Calcitriol/uso terapêutico , Criança , Doença Crônica , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Extratos Vegetais/efeitos adversos , Adulto Jovem
2.
J Sci Food Agric ; 99(10): 4842-4848, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30980531

RESUMO

BACKGROUND: Changes in the metabolite composition of potato tubers during low-temperature storage can affect their nutritional value, susceptibility to bruising, and processing qualities. Here, we measured changes in the amounts of folate, vitamin B6 , and vitamin C, and the blackspot pigment precursors chlorogenic acid and tyrosine, as well as phenylalanine, in five potato varieties stored at 7.8 °C for 8 months in 2015 and 2016. RESULTS: Folate content increased in all varieties in both years during low-temperature storage, with statistically significant changes occurring in six out of eight conditions. Increase rates ranged from 11% to 141%. Vitamin B6 content increased in all varieties during the storage period, but changes were statistically significant in only two out of eight conditions. Increase rates ranged from 5% to 24%. Ascorbic acid content decreased in all varieties in both years during the storage period. Decrease rates ranged from 16% to 78%, and were statistically significant in seven out of eight conditions. For chlorogenic acid, no consistent trend was observed. Changes varied between -14% and +14%, but none was statistically significant. Tyrosine content increased in all varieties in both years, except in Sage Russet in 2015. Increase rates ranged from 19% to 238% and were statistically significant in three out of seven conditions. Changes in phenylalanine content were very similar to those observed for tyrosine, with increases up to 272% in Teton Russet. CONCLUSIONS: These results show that storage at low temperature substantially affects tuber nutritional quality and biochemical bruising potential. © 2019 Society of Chemical Industry.


Assuntos
Ácido Ascórbico/análise , Ácido Clorogênico/análise , Ácido Fólico/análise , Armazenamento de Alimentos/métodos , Fenilalanina/análise , Solanum tuberosum/química , Tirosina/análise , Vitamina B 6/análise , Temperatura Baixa , Valor Nutritivo , Tubérculos/química
3.
Eur J Appl Physiol ; 118(3): 647-656, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29353321

RESUMO

Criterion data for total energy expenditure (TEE) in elite rugby are lacking, which prediction equations may not reflect accurately. This study quantified TEE of 27 elite male rugby league (RL) and rugby union (RU) players (U16, U20, U24 age groups) during a 14-day in-season period using doubly labelled water (DLW). Measured TEE was also compared to estimated, using prediction equations. Resting metabolic rate (RMR) was measured using indirect calorimetry, and physical activity level (PAL) estimated (TEE:RMR). Differences in measured TEE were unclear by code and age (RL 4369 ± 979; RU 4365 ± 1122; U16, 4010 ± 744; U20, 4414 ± 688; U24, 4761 ± 1523 Kcal day- 1). Differences in PAL (overall mean 2.0 ± 0.4) were unclear. Very likely differences were observed in RMR by code (RL 2366 ± 296; RU 2123 ± 269 Kcal day- 1). Differences in relative RMR between U20 and U24 were very likely (U16, 27 ± 4; U20, 23 ± 3; U24, 26 ± 5 Kcal kg- 1 day- 1). Differences were observed between measured and estimated TEE, using Schofield, Cunningham and Harris-Benedict equations for U16 (187 ± 614, unclear; - 489 ± 564, likely and - 90 ± 579, unclear Kcal day- 1), U20 (- 449 ± 698, likely; - 785 ± 650, very likely and - 452 ± 684, likely Kcal day- 1) and U24 players (- 428 ± 1292; - 605 ± 1493 and - 461 ± 1314 Kcal day- 1, all unclear). Rugby players have high TEE, which should be acknowledged. Large inter-player variability in TEE was observed demonstrating heterogeneity within groups, thus published equations may not appropriately estimate TEE.


Assuntos
Calorimetria/métodos , Metabolismo Energético , Futebol Americano/fisiologia , Adolescente , Calorimetria/normas , Óxido de Deutério/farmacocinética , Humanos , Masculino , Isótopos de Oxigênio/farmacocinética , Adulto Jovem
4.
Eur Arch Otorhinolaryngol ; 275(5): 1103-1110, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29605865

RESUMO

AIMS: The frequency of the use of intratympanic steroids (ITS) as a treatment for idiopathic sudden sensorineural hearing loss (ISSNHL) in Europe is still unknown and remains a contentious issue amongst otolaryngologists. We undertook a survey of otolaryngologists in Germany and Austria to establish if there is any professional consensus with which to form a protocol for its use. METHODS: A survey of 21 questions was distributed electronically to otolaryngologists in Germany and Austria and data on demographics, indications for intratympanic treatment, procedure, follow-up, and outcomes were analysed. RESULTS: We received 908 responses. 49.1% of otolaryngologists used ITS for ISSNHL. Of those otolaryngologists who use ITS, 73.7% do not use it as primary treatment. 20.6% use ITS in conjunction with oral steroids for primary treatment and only 5.8% use ITS as monotherapy for primary treatment. 90.5% use ITS as salvage therapy. 81.1% do not consider the use of ITS after 2 weeks from the onset of symptoms. 8.3% used a tympanostomy tube and while the most commonly used steroid was dexamethasone at a concentration of 4 mg/ml (61%), a wide variety or other steroids and concentrations were used. CONCLUSIONS: This survey illustrates wide variation of current practice of intratympanic corticosteroid injection for ISSHL in Germany and Austria. In the absence of high-level evidence, knowing what current practice is allows clinicians to assess what they do against what their colleagues are doing, and if they do something very different, make them question their practice. Moreover, the obtained data will help to direct future clinical trials with the aim to compare the outcomes of more commonly used protocols.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Áustria , Esquema de Medicação , Alemanha , Humanos , Injeção Intratimpânica , Otolaringologia , Inquéritos e Questionários , Resultado do Tratamento
5.
J Wound Care ; 26(12): 762-764, 2017 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-29244964

RESUMO

Pretibial lacerations are a common cause of presentation to accident and emergency departments. The management of these wounds is contentious with a variation in practise between individual institutions. We present the case of a 49-year-old female with a background of pulmonary atresia and associated pulmonary hypertension, who underwent successful outpatient negative pressure wound therapy (NPWT) for three pretibial lacerations. We would propose that this therapy is an effective option for the management of these wounds in independently mobile patients who are at high-risk when under anaesthetic.


Assuntos
Lacerações/terapia , Traumatismos da Perna/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Assistência Ambulatorial , Feminino , Humanos , Hipertensão Pulmonar/complicações , Lacerações/complicações , Traumatismos da Perna/complicações , Pessoa de Meia-Idade , Atresia Pulmonar/complicações , Risco
7.
Planta ; 240(1): 137-46, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24748553

RESUMO

MAIN CONCLUSION: PDX1.2 is expressed in the basal part of the globular-stage embryo, and plays critical roles in development, hypocotyl elongation, and stress response. The Arabidopsis thaliana PDX1.2 protein belongs to a small family of three members. While PDX1.1 and PDX1.3 have been extensively described and are well established to function in vitamin B6 biosynthesis, the biological role of PDX1.2 still remains elusive. Here, we show that PDX1.2 is expressed early in embryo development, and that heat shock treatment causes a strong up-regulation of the gene. Using a combined genetic approach of T-DNA insertion lines and expression of artificial micro RNAs, we can show that PDX1.2 is critically required for embryo development, and for normal hypocotyl elongation. Plants with reduced PDX1.2 expression also display reduced primary root growth after heat shock treatments. The work overall provides a set of important new findings that give greater insights into the developmental role of PDX1.2 in plants.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico , Arabidopsis/embriologia , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Temperatura Alta , Hipocótilo/embriologia , Hipocótilo/genética , Hipocótilo/fisiologia , MicroRNAs/genética , Mutagênese Insercional , Especificidade de Órgãos , Raízes de Plantas/embriologia , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Sementes/embriologia , Sementes/genética , Sementes/fisiologia , Regulação para Cima
8.
Pharmacogenomics J ; 14(6): 542-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25001883

RESUMO

Warfarin is used in paediatric populations, but dosing algorithms incorporating pharmacogenetic data have not been developed for children. Previous studies have produced estimates of the effect of polymorphisms in Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) on stable warfarin dosing, but data on time in therapeutic range, initial dosing and adverse effects are limited. Participants (n=97) were recruited, and routine clinical data and salivary DNA samples were collected from all participants and analysed for CYP2C9*2, *3 and VKORC1-1639 polymorphisms.VKORC1 -1639 was associated with a greater proportion of the first 6 months' treatment time spent within the target International Normalised Ratio (INR) range, accounting for an additional 9.5% of the variance in the proportion of time. CYP2C9*2 was associated with a greater likelihood of INR values exceeding the target range during the initiation of treatment (odds ratio (OR; per additional copy) 4.18, 95% confidence interval (CI) 1.42, 12.34). CYP2C9*2 and VKORC1-1639 were associated with a lower dose requirement, and accounted for almost 12% of the variance in stable dose. VKORC1-1639 was associated with an increased likelihood of mild bleeding complications (OR (heterozygotes vs homozygotes) 4.53, 95% CI 1.59, 12.93). These data show novel associations between VKORC1-1639 and CYP2C9*2 and INR values in children taking warfarin, as well as replicating previous findings with regard to stable dose requirements. The development of pharmacogenomic dosing algorithms for children using warfarin has the potential to improve clinical care in this population.


Assuntos
Citocromo P-450 CYP2C9/genética , Polimorfismo de Nucleotídeo Único/genética , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Citocromo P-450 CYP2C9/metabolismo , Relação Dose-Resposta a Droga , Humanos , Lactente , Estudos Retrospectivos , Vitamina K Epóxido Redutases/metabolismo , Varfarina/farmacologia , Varfarina/uso terapêutico
9.
Phys Rev Lett ; 112(4): 045505, 2014 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-24580469

RESUMO

We present an x-ray pair distribution function (XPDF) analysis and extended x-ray absorption fine structure (EXAFS) data for ZrW2O8 (10-500 K) with a focus on the stiffness of the Zr-O-W linkage. The XPDF is highly sensitive to W-Zr and W-W correlations, but much less so to O-O or W-O correlations. The Zr-W peak in the XPDF data has a weak temperature dependence and, hence, this linkage is relatively stiff and does not permit bending of the Zr-O-W link. We propose that the low energy vibrational modes that lead to negative thermal expansion involve correlated rotations of ZrO6 octahedra that produce large <111> translations of the WO4 tetrahedra, rather than a transverse motion of O atoms that imply a flexible Zr-O-W linkage.

10.
Child Care Health Dev ; 40(4): 553-61, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23551299

RESUMO

BACKGROUND: Children living with complex heart defects (CHD) are likely to have ongoing social, emotional, physical, and health concerns, and are in need of additional psychosocial support. Summer camps can provide therapeutic benefits. Little research exists regarding the value of shorter camping experiences from the perspectives of children with CHD. The aim of our study was to explore what children and adolescents with CHD considered meaningful when attending a therapeutic camping weekend in the company of peers with similar medical diagnoses. METHODS: Engaging a phenomenological approach we used participant generated photography and reflective semi-structured interviews to explore participants' lived experience and value derived from their weekend camping experiences. The study was completed with thirteen participants ranging in age from 9 to 16 years. Interviews were recorded and transcribed verbatim. Data were analysed using Van Manen's guidelines. RESULTS: Three themes reflecting the camp experiences were generated from the data. Meaningful experiences spanned three outcomes which had some overlapping influences: (i) Developing relationships and feeling accepted by peers and counsellors at camp; (ii) Enjoying and learning during the weekend; and (iii) Experiencing the natural and human-built therapeutic environmental features of camp. The camping programme features, inputs, and processes as identified by the participants in contributing to these outcomes are described. CONCLUSION: This qualitative study showed that children living with complex CHD valued the opportunity for participating in weekend camping experiences in the company of peers with similar heart defects. Findings contribute to a better understanding of what programme features and processes were considered meaningful. Given the scarcity of resources to devote to such social support activities, the findings may help professionals to plan effective interventions to maximize benefits during a shorter camping experience.


Assuntos
Comportamento do Adolescente , Acampamento , Comportamento Infantil , Cardiopatias Congênitas/psicologia , Relações Interpessoais , Apoio Social , Adolescente , Comportamento do Adolescente/psicologia , Atitude Frente a Saúde , Acampamento/psicologia , Criança , Comportamento Infantil/psicologia , Feminino , Cardiopatias Congênitas/epidemiologia , Humanos , Masculino , Grupo Associado , Pesquisa Qualitativa , Autoimagem , Inquéritos e Questionários , Estados Unidos
11.
J Hosp Infect ; 147: 197-205, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521417

RESUMO

BACKGROUND: In recent years, hand drying has been highlighted as a key step in appropriate hand hygiene, as moisture on hands can increase the transfer of micro-organisms from hands to surfaces and vice versa. AIM: To understand bacterial and viral aerosolization following hand drying, and study the transfer of micro-organisms from hands to surfaces after drying using different methods. METHODS: Groups of five volunteers had their hands pre-washed with soap, rinsed and dried, then inoculated with a concentrated mixture of Pseudomonas fluorescens and MS2 bacteriophage. Volunteers entered an empty washroom, one at a time, and rinsed their hands with water or washed their hands with soap prior to drying with a jet dryer or paper towels. Each volunteer applied one hand successively to various surfaces, while their other hand was sampled using the glove juice method. Both residual bacteria and viruses were quantified from the washroom air, surface swabs and hand samples. FINDINGS: P. fluorescens and MS2 bacteriophages were rarely aerosolized while drying hands for any of the drying methods studied. Results also showed limited, and similar, transfer of both micro-organisms studied on to surfaces for all drying methods. CONCLUSION: The use of jet dryers or paper towels produces low levels of aerosolization when drying hands in a washroom. Similarly, all drying methods result in low transfer to surfaces. While the coronavirus disease 2019 pandemic raised concerns regarding public washrooms, this study shows that all methods tested are hygienic solutions for dry washed hands.


Assuntos
Aerossóis , Mãos , Levivirus , Pseudomonas fluorescens , Humanos , Mãos/microbiologia , Mãos/virologia , Pseudomonas fluorescens/virologia , Desinfecção das Mãos/métodos , Bactérias/isolamento & purificação , Dessecação/métodos , Higiene das Mãos/métodos , COVID-19 , Vírus/isolamento & purificação , Microbiologia Ambiental
12.
Psychol Med ; 43(7): 1415-22, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23113986

RESUMO

BACKGROUND: Official suicide statistics for England are based on deaths given suicide verdicts and most cases given an open verdict following a coroner's inquest. Previous research indicates that some deaths given accidental verdicts are considered to be suicides by clinicians. Changes in coroners' use of different verdicts may bias suicide trend estimates. We investigated whether suicide trends may be over- or underestimated when they are based on deaths given suicide and open verdicts. Method Possible suicides assessed by 12 English coroners in 1990/91, 1998 and 2005 and assigned open, accident/misadventure or narrative verdicts were rated by three experienced suicide researchers according to the likelihood that they were suicides. Details of all suicide verdicts given by these coroners were also recorded. RESULTS: In 1990/91, 72.0% of researcher-defined suicides received a suicide verdict from the coroner, this decreased to 65.4% in 2005 (p trend < 0.01); equivalent figures for combined suicide and open verdicts were 95.4% (1990/91) and 86.7% (2005). Researcher-defined suicides with a verdict of accident/misadventure doubled over that period, from 4.6% to 9.1% (p < 0.01). Narrative verdict cases rose from zero in 1990/91 to 25 in 2005 (4.2% of researcher-defined suicides that year). In 1998 and 2005, 50.0% of the medicine poisoning deaths given accidental/misadventure verdicts were rated as suicide by the researchers. CONCLUSIONS: Between 1990/91 and 2005, the proportion of researcher-defined suicides given a suicide verdict by coroners decreased, largely due to an increased use of accident/misadventure verdicts, particularly for deaths involving poisoning. Consideration should be given to the inclusion of 'accidental' deaths by poisoning with medicines in the statistics available for monitoring suicides rates.


Assuntos
Acidentes/tendências , Causas de Morte/tendências , Médicos Legistas , Suicídio/tendências , Acidentes/classificação , Inglaterra , Humanos , Suicídio/classificação
14.
Ann Oncol ; 23(6): 1555-61, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22012966

RESUMO

BACKGROUND: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/administração & dosagem , Bortezomib , Clorambucila/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma de Célula do Manto/mortalidade , Masculino , Pirazinas/administração & dosagem , Rituximab , Resultado do Tratamento
15.
J Laryngol Otol ; 136(11): 1044-1050, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34674777

RESUMO

OBJECTIVE: Granular myringitis is a chronic and difficult-to-treat condition of the tympanic membrane. This paper presents a minimally invasive treatment technique using the potassium titanyl phosphate laser. DESIGN: A retrospective case review of patients who underwent potassium titanyl phosphate laser treatment between 2015 and 2020 was performed. All patients underwent final telephone follow up in 2020 to ascertain whether they had any ongoing myringitis symptoms, and all were offered further face-to-face follow up. RESULTS: Fourteen patients with myringitis were identified, with one patient having both ears affected. Of the 15 affected ears, 2 required a second treatment, resulting in a total of 17 laser treatment cases. At the first post-operative review, the appearance of the drum had improved in 10 out of 17 treatments (59 per cent). CONCLUSION: Potassium titanyl phosphate laser surface tympanoplasty may provide safe, quick and effective resolution of myringitis.


Assuntos
Lasers de Estado Sólido , Otite Média , Timpanoplastia , Humanos , Doença Crônica , Lasers de Estado Sólido/uso terapêutico , Otite Média/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Membrana Timpânica , Timpanoplastia/métodos
16.
Comput Biol Med ; 151(Pt A): 106024, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36327887

RESUMO

BACKGROUND: COVID-19 infected millions of people and increased mortality worldwide. Patients with suspected COVID-19 utilised emergency medical services (EMS) and attended emergency departments, resulting in increased pressures and waiting times. Rapid and accurate decision-making is required to identify patients at high-risk of clinical deterioration following COVID-19 infection, whilst also avoiding unnecessary hospital admissions. Our study aimed to develop artificial intelligence models to predict adverse outcomes in suspected COVID-19 patients attended by EMS clinicians. METHOD: Linked ambulance service data were obtained for 7,549 adult patients with suspected COVID-19 infection attended by EMS clinicians in the Yorkshire and Humber region (England) from 18-03-2020 to 29-06-2020. We used support vector machines (SVM), extreme gradient boosting, artificial neural network (ANN) models, ensemble learning methods and logistic regression to predict the primary outcome (death or need for organ support within 30 days). Models were compared with two baselines: the decision made by EMS clinicians to convey patients to hospital, and the PRIEST clinical severity score. RESULTS: Of the 7,549 patients attended by EMS clinicians, 1,330 (17.6%) experienced the primary outcome. Machine Learning methods showed slight improvements in sensitivity over baseline results. Further improvements were obtained using stacking ensemble methods, the best geometric mean (GM) results were obtained using SVM and ANN as base learners when maximising sensitivity and specificity. CONCLUSIONS: These methods could potentially reduce the numbers of patients conveyed to hospital without a concomitant increase in adverse outcomes. Further work is required to test the models externally and develop an automated system for use in clinical settings.


Assuntos
COVID-19 , Aprendizado Profundo , Adulto , Humanos , Inteligência Artificial , COVID-19/diagnóstico , Aprendizado de Máquina , Hospitais
17.
Osteoarthr Cartil Open ; 4(2): 100269, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36475292

RESUMO

Objective: To investigate the feasibility of 'parkrun' for people with knee osteoarthritis (OA) and examine its potential to improve symptoms and increase physical activity. Design: This uncontrolled mixed methods pilot study enrolled people with knee OA not meeting physical activity guidelines. Participants were asked to walk in four consecutive parkrun events supervised by an exercise physiologist/physiotherapist. Feasibility was assessed by recruitment data (numbers screened and time to enrol 15 participants), adherence to the protocol, acceptability (measured by confidence, enjoyment, difficulty ratings and qualitative interviews), and safety (adverse events). Secondary measures were changes in knee pain, function, stiffness, and physical activity levels. Results: Participants (n â€‹= â€‹17) were enrolled over 11 months and recruitment was slower than anticipated. Fourteen participants attended all four parkruns and three of these participants shortened the 5 â€‹km course to ∼3 â€‹km. Across all four parkruns, 75% of participants reported high confidence that they could complete the upcoming parkrun and the majority (87%) enjoyed participating. Most participants rated parkrun either "slightly difficult" (38.5%) or "moderately difficult" (35%) and two mild adverse events were reported. Participants showed improvements in knee pain, function, stiffness, and physical activity levels. Conclusions: This pilot study demonstrates parkrun's feasibility, acceptability, safety and, its potential to improve knee OA symptoms and physical activity levels. Participating in parkrun was acceptable and enjoyable for some, but not all participants. The scalability, accessibility and wide appeal of parkrun supports the development of larger programs of research to evaluate the use of parkrun for people with knee OA.

18.
Diabetologia ; 54(10): 2724-35, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21755314

RESUMO

AIM/HYPOTHESIS: We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy. METHODS: Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55 mg/kg), diabetic + aliskiren (10 mg kg(-1) day(-1), pump), or diabetic + lisinopril (10 mg kg(-1) day(-1), drinking water) rats were evaluated over 16 weeks. For oxygen-induced retinopathy studies, rats were exposed to 80% oxygen (22 h/day) from postnatal days 0 to 11, and then room air from postnatal days 12 to 18. Aliskiren (10 or 30 mg kg(-1) day(-1), pump) or lisinopril (10 mg kg(-1) day(-1), drinking water) was administered during retinopathy development between postnatal days 12 and 18. RESULTS: Systolic BP in diabetic (mRen-2)27 rats was reduced with 10 mg kg(-1) day(-1) aliskiren, but only lisinopril normalised systolic blood pressure. In diabetic (mRen-2)27 rats, 10 mg kg(-1) day(-1) aliskiren and lisinopril reduced retinal acellular capillaries and leucostasis to non-diabetic levels. In oxygen-induced retinopathy, neoangiogenesis and retinal inflammation (leucostasis, ED-1 immunolabelling) were partially reduced by 10 mg kg(-1) day(-1) aliskiren and normalised by 30 mg kg(-1) day(-1) aliskiren, whereas lisinopril normalised neoangiogenesis and reduced leucostasis and ED-1 immunolabelling. Aliskiren and lisinopril normalised retinal vascular endothelial growth factor expression; however, only aliskiren reduced intercellular adhesion molecule-1 to control levels. CONCLUSIONS/INTERPRETATION: Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.


Assuntos
Amidas/uso terapêutico , Retinopatia Diabética/induzido quimicamente , Retinopatia Diabética/tratamento farmacológico , Fumaratos/uso terapêutico , Oxigênio/toxicidade , Renina/metabolismo , Animais , Animais Geneticamente Modificados , Retinopatia Diabética/metabolismo , Feminino , Lisinopril/uso terapêutico , Camundongos , Neovascularização Patológica/tratamento farmacológico , Ratos , Renina/antagonistas & inibidores , Renina/genética
19.
Reprod Biomed Online ; 20(6): 843-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20385510

RESUMO

Epigenetic alterations at several maternal loci have been associated with imprinting disorders in children conceived using assisted reproductive technologies. To date, epimutations at paternal loci have been observed in the spermatozoa of infertile men, but there is little evidence of paternal epimutations in babies conceived using assisted reproductive treatment. This is a report of a female infant with classic Russell-Silver Syndrome (RSS) who was conceived using intracytoplasmic injection of spermatozoa obtained from testicular aspiration. Methylation studies revealed hypomethylation of the paternally derived H19/IGF2 locus. As far as is known, this is the second assisted reproduction treatment-conceived patient with classic RSS and this epigenotype. This case provides further evidence that epimutations affecting paternal alleles might be associated with assisted reproductive treatment.


Assuntos
Metilação de DNA , Fator de Crescimento Insulin-Like II/metabolismo , RNA não Traduzido/genética , Síndrome de Silver-Russell/genética , Injeções de Esperma Intracitoplásmicas , Feminino , Humanos , Fator de Crescimento Insulin-Like II/genética , Masculino , RNA Longo não Codificante
20.
Eur J Appl Physiol ; 110(1): 171-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20440622

RESUMO

Flow-mediated dilation (FMD) assesses the health of the vascular endothelium. Despite widespread adoption of scaling practices in cardiac research, scaling for body size or composition has not been used for FMD. The present study investigated the relationships between brachial FMD and body composition in 129 children aged 9-10 (75 female symbol, 54 male symbol), and 50 men aged 16-49. Body composition variables (total, lean, fat mass in the whole body, arm, forearm) were assessed by dual-energy X-ray absorptiometry, FMD was measured in the brachial artery using high-resolution ultrasound. FMD was scaled using simple ratios (y/x) and allometric approaches (y/x ( b )) after log-log least squares linear regression produced allometric exponents (b). Size independence was confirmed via bivariate correlations (x:y/x; x:y/x ( b )). No relationships were evident between FMD and body composition variables in adults. Small correlations existed between FMD and measures of segmental fat mass in children (r = -0.18 to -0.19, p < 0.05), there were no significant relationships between FMD and measures of lean or total mass in children. For all significant relationships, b-exponents were different from 1 (CIs -0.36 to 0.07), suggesting ratio scaling approaches were flawed. This was confirmed when ratio scaling produced negative residual size correlations, whereas allometric scaling produced size-independent indices. Correlations between FMD and body composition were weak in children and insignificant in adults. As the results of this study are limited to the populations examined, our findings do not support the adoption of scaling procedures to correct FMD.


Assuntos
Antropometria , Composição Corporal , Artéria Braquial/fisiologia , Vasodilatação , Absorciometria de Fóton , Adiposidade , Adolescente , Adulto , Fatores Etários , Artéria Braquial/diagnóstico por imagem , Criança , Feminino , Humanos , Análise dos Mínimos Quadrados , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fluxo Sanguíneo Regional , Ultrassonografia , Adulto Jovem
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