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1.
Ann Oncol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729567

RESUMO

BACKGROUND: SERENA-1 (NCT03616587) is a phase I, multi-part, open-label study of camizestrant in pre- and post-menopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Parts A and B aim to determine the safety and tolerability of camizestrant monotherapy and define doses for clinical evaluation. PATIENTS AND METHODS: Women aged ≥18 years with metastatic or recurrent ER+, HER2- breast cancer, refractory (or intolerant) to therapy, were assigned 25 mg up to 450 mg once daily (QD; escalation) or 75, 150, or 300 mg QD (expansion). Safety and tolerability, antitumor efficacy, pharmacokinetics, and impact on mutations in the estrogen receptor gene (ESR1m) circulating tumor (ct)DNA levels were assessed. RESULTS: By 9 March 2021, 108 patients received camizestrant monotherapy at 25-450 mg doses. Of these, 93 (86.1%) experienced treatment-related adverse events (TRAEs), 82.4% of which were grade 1 or 2. The most common TRAEs were visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), and nausea (15%). There were no TRAEs grade 3 or higher, or treatment-related serious adverse events at doses ≤150 mg. Median tmax was achieved ∼2-4 h post-dose at all doses investigated, with an estimated half-life of 20-23 h. Efficacy was observed at all doses investigated, including in patients with prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and/or fulvestrant treatment, with and without baseline ESR1 mutations, and with visceral disease, including liver metastases. CONCLUSIONS: Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile. The pharmacokinetics profile supports once-daily dosing, with evidence of pharmacodynamic and clinical efficacy in heavily pre-treated patients, regardless of ESR1m. This study established 75-, 150-, and 300-mg QD doses for phase II testing (SERENA-2, NCT04214288 and SERENA-3, NCT04588298).

2.
J Hosp Infect ; 134: 71-79, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36716796

RESUMO

BACKGROUND: The UK High-Consequence Infectious Diseases (HCID) Network of high-level isolation units provides care for patients with contact- or airborne-transmissible highly infectious and highly dangerous diseases. In most HCID units, the healthcare workers (HCWs) wear personal protective equipment (PPE) ensembles incorporating a powered air-purifying respirator (PAPR) for head and respiratory protection. Some PAPRs have components worn outside/over other PPE, necessitating decontamination of re-usable elements. Two alternative PAPRs, with all re-usable elements worn under PPE, were trialled in this study. AIM: To undertake scenario-based testing of PAPRs and PPE to determine usability, comfort and ability to remove contaminated PPE without personal cross-contamination. METHODS: Trained healthcare volunteers (N=20) wearing PAPR/PPE ensembles were sprayed with ultraviolet fluorescent markers. They undertook exercises to mimic patient care, and subsequently, after doffing the contaminated PPE following an established protocol, any personal cross-contamination was visualized under ultraviolet light. Participants also completed a questionnaire to gauge how comfortable they found the PPE. FINDINGS AND CONCLUSIONS: The ensembles were tested under extreme 'worst case scenario' conditions, augmented by physical and manual dexterity tests. Participating volunteers considered the exercise to be beneficial in terms of training and PPE evaluation. Data obtained, including feedback from questionnaires and doffing buddy observations, supported evidence-based decisions on the PAPR/PPE ensemble to be adopted by the HCID Network. One cross-contamination event was recorded in the ensemble chosen; this could be attributed to doffing error, and could therefore be eliminated with further practice.


Assuntos
Doenças Transmissíveis , Dispositivos de Proteção Respiratória , Humanos , Equipamento de Proteção Individual , Pessoal de Saúde , Corantes
3.
Sleep Breath ; 27(4): 1269-1277, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36173506

RESUMO

PURPOSE: Cardiac rehabilitation (CR) improves clinical outcomes in patients with cardiovascular disease (CDV). Patients with CVD often have multiple comorbidities, including obstructive sleep apnea (OSA), potentially affecting their ability to participate and achieve functional improvement during CR. We aimed to test the hypothesis that OSA reduces peak exercise capacity (EC) in patients undergoing CR and to explore if OSA treatment modifies this relationship. METHODS: Data from a retrospective cohort of CR patients was analyzed. OSA was defined as a respiratory event index > 5/h or physician diagnosis. Patients with OSA were considered "treated" if using continuous positive airway pressure regularly during the CR period. Change in METs was the primary study outcome. RESULTS: Among 312 CR patients, median age of 67 years, 103 (33%) had known OSA (30 treated, 73 untreated). Patients with OSA vs. those with no OSA were more likely to be obese and male; otherwise, groups were similar. Compared with the no OSA group, patients with OSA had lower pre-CR METs (3.3 [2.9-4.5] vs. 3.9 [3.1-5], P = .01) and lower post-CR METs (5.3 [4-7] vs. 6 [4.6-7.6], P = .04), but achieved a similar increase in METs post-CR (1.8 [0.6-2.6] vs. 2.0 [0.9-3], P = .22). Furthermore, compared to no OSA, pre-CR and post-CR METs tended to be similar in patients with treated OSA, but lower in untreated patients, with similar increases in METs across all groups, even when adjusting for covariates via multivariable regression. CONCLUSION: OSA is prevalent in patients with CVD undergoing CR. CR substantially improves exercise capacity independent of OSA status, but screening for-and treatment of-OSA may improve the absolute exercise capacity achieved through CR.


Assuntos
Reabilitação Cardíaca , Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Humanos , Masculino , Idoso , Apneia Obstrutiva do Sono/terapia , Estudos Retrospectivos , Tolerância ao Exercício
5.
Clin Oncol (R Coll Radiol) ; 33(10): e433-e441, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34090753

RESUMO

AIMS: Careful management of a patient's nutritional status during and after treatment for head and neck squamous cell cancers (HNSCC) is crucial for optimal outcomes. The aim of this study was to develop a model for stratifying a patient's risk of requiring reactive enteral feeding through a nasogastric tube during radiotherapy for HNSCC, based on clinical and treatment-related factors. MATERIALS AND METHODS: A cohort of consecutive patients treated with definitive (chemo)radiotherapy for HNSCC between January 2016 and January 2018 was identified in the institutional electronic database for retrospective analysis. Patients requiring enteral feeding pretreatment were excluded. Clinical and treatment data were obtained from prospectively recorded electronic clinical notes and planning software. RESULTS: Baseline patient characteristics and tumour-related parameters were captured for 225 patients. Based on the results of the univariate analysis and using a stepwise backwards selection process, clinical and dosimetric variables were selected to optimise a clinically predictive multivariate model, fitted using logistic regression. The parameters found to affect the probability, P, of requiring a nasogastric feeding tube for >4 weeks in our clinical multivariate model were: tumour site, tumour stage (early T0/1/2 stage versus advanced T3/T4 stage), chemotherapy drug (none versus any drug) and mean dose to the contralateral parotid gland. A scoring model using the regression coefficients of the selected variables in the clinical multivariate model achieved an area under the curve (AUC) of 0.745 (95% confidence interval 0.678-0.812), indicating good discriminative performance. Internal validation of the model involved splitting the dataset 80:20 into training and test datasets 10 times and assessing differences in AUC of the model fitted to these. CONCLUSIONS: We developed an easy-to-use prediction model based on both clinical and dosimetric parameters, which, once externally validated, can lead to more personalised treatment planning and inform clinical decision-making on the appropriateness of prophylactic versus reactive enteral feeding.


Assuntos
Nutrição Enteral , Neoplasias de Cabeça e Pescoço , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Intubação Gastrointestinal , Estudos Retrospectivos
6.
Anaesthesia ; 76(12): 1616-1624, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33932033

RESUMO

The absolute number of Never Events is used by UK regulators to help assess hospital safety performance, without account of hospital workload. We applied funnel plots, as an established means of taking workload into account, to published Never Event data for 151 acute Trusts in NHS England, matched to finished consultant episodes for 3 years, 2017-2020. Trusts with excess event rates should have the most Never Events if absolute number is a valid way to judge performance. The absolute number of Never Events was correlated with workload (r2 = 0.51, p < 0.001), but the five Trusts above the upper 95% confidence limit did not have the highest number of Never Events. However, a limitation to interpretation was that the data were skewed; 12 out of 151 Trusts lay below the lower 95% limit. This skew probably arises because funnel plots pool all Never Events and workload data; whereas, ideally, different Never Events should use as denominator only the relevant workload actions that could cause them. We conclude that the manner in which Never Event data are currently used by regulators, in part to judge or rate hospitals, is mathematically invalid. The focus should shift from identifying 'outlier' hospitals to reducing the overall national mean Never Event rate through shared learning and an integrated system-wide approach.


Assuntos
Erros Médicos/estatística & dados numéricos , Segurança do Paciente/legislação & jurisprudência , Bases de Dados Factuais , Hospitais , Humanos , Carga de Trabalho/estatística & dados numéricos
7.
Oral Oncol ; 115: 105140, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548862

RESUMO

PURPOSE: For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction. MATERIAL AND METHODS: All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model. RESULTS: Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE] ±â€¯SE = 0.72 ±â€¯0.02 vs 0.53 ±â€¯0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPE = 0.79 vs 0.79, p = 0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76 ±â€¯0.02). CONCLUSIONS: TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease.


Assuntos
Neoplasias Orofaríngeas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Prognóstico
9.
Clin Oncol (R Coll Radiol) ; 31(11): e1-e9, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31543301

RESUMO

Although surgery and radiotherapy remain the most commonly used treatments for non-melanoma skin cancer, there are a variety of alternatives. Here we discuss the use of electrochemotherapy and ablative treatments and examine the evidence for their effectiveness against a number of non-melanoma skin cancers.


Assuntos
Eletroquimioterapia/métodos , Estradiol/análogos & derivados , Noretindrona/uso terapêutico , Neoplasias Cutâneas/terapia , Testosterona/análogos & derivados , Combinação de Medicamentos , Estradiol/farmacologia , Estradiol/uso terapêutico , Humanos , Noretindrona/farmacologia , Testosterona/farmacologia , Testosterona/uso terapêutico
10.
Bone Marrow Transplant ; 53(1): 84-90, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29131155

RESUMO

Adolescent and young adult (AYA) oncology patients experience many physical and psychological symptoms at the end of life (EOL); however, data on these experiences for AYA patients who have undergone hematopoietic cell transplantation (HCT) remains sparse. We sought to investigate the characteristics of AYA patients aged 15-25 years who received allogeneic HCT and subsequently died while inpatient at our institution between the years 2008 and 2014. A standardized data extraction tool was used to collect information about patient demographics, treatment and symptoms. We found that during this time frame, 34 AYA patients had received HCT and died while inpatient at our institution, 23 (68%) of whom died because of treatment-related complications. Compared with non-HCT AYA oncology patients (n=35), patients who received HCT (n=34) were more likely to have died in the intensive care unit (71% vs 23%, P<0 .0001) and to have received mechanical ventilation (68% vs 17%, P<0.0001) or hemodialysis (53% vs 0%, P<0.0001) in the last 30 days of life. These findings demonstrate that AYA patients who receive allogeneic HCT receive intensive EOL treatment, suggesting that these patients may benefit from early integration of expert interdisciplinary services to prospectively assess and manage distressing symptoms.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Assistência Terminal/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Adulto Jovem
11.
Clin Oncol (R Coll Radiol) ; 29(12): 835-840, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28918176

RESUMO

AIMS: Treatment for head and neck cancers using definitive radiotherapy, with or without chemotherapy, is associated with significant acute toxicity. Our aim was to assess 90 day mortality after radical radiotherapy. A further aim was to identify patient, tumour or treatment factors associated with early death after treatment and whether these could be used to predict outcomes. MATERIALS AND METHODS: In total, 1116 patients with squamous cell pharyngeal and larynx cancer between January 2011 and December 2015 were included. Patients with T1 larynx cancer were excluded. Patients were treated using radical radiotherapy, with or without chemotherapy. Ninety day mortality was calculated using survival of less than 135 days from the planned start date for radical radiotherapy, to include early deaths during and up to 90 days after treatment. RESULTS: Overall, 90 day mortality was 4.7%. Among the subgroup of patients treated with concurrent platinum chemotherapy, the 90 day mortality rate was 0.4%. Overall survival at 1, 3 and 5 years was 84%, 62% and 53%, respectively. Factors associated with a higher risk of early death included performance status > 1, haemoglobin <100 g/l, weight < 60 kg, age > 80 years and presence of multiple comorbidities. CONCLUSION: We report excellent crude overall survival rates among our radically treated cohort of head and neck cancer patients. Several factors were associated with an increased risk of death within 90 days of completion of radical head and neck radiotherapy. Given the potential severe acute effects and the impact on patient quality of life associated with radical head and neck radiotherapy, this information is helpful to inform treatment-related discussions with patients.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Morte , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Análise de Sobrevida
12.
AJNR Am J Neuroradiol ; 38(6): 1235-1241, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28428205

RESUMO

BACKGROUND AND PURPOSE: Assessing the response to treatment in infiltrative brain tumors by using lesion volume-based response criteria is challenging. We hypothesized that in such tumors, volume measurements alone may not accurately capture changes in actual tumor burden during treatment. We longitudinally evaluated volume changes in both normal-appearing supratentorial white matter and the brain stem lesions in patients treated for diffuse intrinsic pontine glioma to determine to what extent adjuvant systemic therapies may skew the accuracy of tumor response assessments based on volumetric analysis. MATERIALS AND METHODS: The anatomic MR imaging and diffusion tensor imaging data of 26 patients with diffuse intrinsic pontine glioma were retrospectively analyzed. Treatment included conformal radiation therapy in conjunction with vandetanib and dexamethasone. Volumetric and diffusion data were analyzed with time, and differences between time points were evaluated statistically. RESULTS: Normalized brain stem lesion volume decreased during combined treatment (slope = -0.222, P < .001) and increased shortly after completion of radiation therapy (slope = 0.422, P < .001). Supratentorial white matter volume steadily and significantly decreased with time (slope = -0.057, P < .001). CONCLUSIONS: Longitudinal changes in brain stem lesion volume are robust; less pronounced but measurable changes occur in the supratentorial white matter. Volume changes in nonirradiated supratentorial white matter during the disease course reflect the effects of systemic medication on the water homeostasis of normal parenchyma. Our data suggest that adjuvant nontumor-targeted therapies may have a more substantial effect on lesion volume changes than previously thought; hence, an apparent volume decrease in infiltrative tumors receiving combined therapies may lead to overestimation of the actual response and tumor control.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/terapia , Glioma/diagnóstico por imagem , Esteroides/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Substância Branca/diagnóstico por imagem , Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/tratamento farmacológico , Criança , Pré-Escolar , Terapia Combinada , Dexametasona/uso terapêutico , Imagem de Tensor de Difusão , Progressão da Doença , Intervalo Livre de Doença , Feminino , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Piperidinas/uso terapêutico , Estudos Prospectivos , Quinazolinas/uso terapêutico , Substância Branca/patologia
13.
Br J Dermatol ; 176(6): 1475-1485, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28118487

RESUMO

BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. METHODS: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. RESULTS: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated. CONCLUSIONS: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments.


Assuntos
Eletroquimioterapia/métodos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anestesia/métodos , Progressão da Doença , Eletroquimioterapia/efeitos adversos , Eletroquimioterapia/instrumentação , Eletrodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Metástase Neoplásica , Dor/etiologia , Medição da Dor , Estudos Prospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Carga Tumoral
14.
Phys Rev Lett ; 117(15): 155301, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27768342

RESUMO

We report on the anisotropic expansion of ultracold bosonic dysprosium gases at temperatures above quantum degeneracy and develop a quantitative theory to describe this behavior. The theory expresses the postexpansion aspect ratio in terms of temperature and microscopic collisional properties by incorporating Hartree-Fock mean-field interactions, hydrodynamic effects, and Bose-enhancement factors. Our results extend the utility of expansion imaging by providing accurate thermometry for dipolar thermal Bose gases. Furthermore, we present a simple method to determine scattering lengths in dipolar gases, including near a Feshbach resonance, through observation of thermal gas expansion.

15.
Bone Joint Res ; 5(5): 178-84, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27179004

RESUMO

OBJECTIVES: The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment. METHODS: A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants. RESULTS: A majority of the patients were female (66%, 73 of 110). The mean patient age was 62 years (range 18 to 89). A majority of patients met the inclusion criteria for the PROFHER trial (75%, 83 of 110). Plate fixation was the most common mode of surgery (68%, 75 patients), followed by intramedullary fixation (12%, 13 patients), reverse shoulder arthroplasty (10%, 11 patients) and hemiarthroplasty (7%, eight patients). The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases (91%, 100 patients). Implant costs for plate fixation were significantly less than both hemiarthroplasty (p < 0.05) and reverse shoulder arthroplasty (p < 0.0001). Implant costs for intramedullary fixation were significantly less than plate fixation (p < 0.01), hemiarthroplasty (p < 0.0001) and reverse shoulder arthroplasty (p < 0.0001). CONCLUSIONS: Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may, therefore, have been effectively managed non-operatively.Cite this article: Mr B. J. F. Dean. A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178-184. DOI: 10.1302/2046-3758.55.2000596.

16.
J Comp Physiol B ; 186(2): 215-27, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26644087

RESUMO

Taurine is the most abundant amino acid in the blood of the cuttlefish, Sepia officinalis, where levels can exceed 200 mmol L(-1). In mammals, intracellular taurine modulates cardiac Ca(2+) handling and carbohydrate metabolism at much lower concentrations but it is not clear if it exerts similar actions in cephalopods. Blood Ca(2+) levels are high in cephalopods and we hypothesized that taurine would depress cardiac Ca(2+) flux and modulate contractility in systemic and branchial hearts of cuttlefish. Heart performance was assessed with an in situ perfused systemic heart preparation and contractility was evaluated using isometrically contracting systemic and branchial heart muscle rings. Stroke volume, cardiac output, and Ca(2+) sensitivity were significantly lower in systemic hearts perfused with supplemental taurine (100 mmol L(-1)) than in controls. In muscle ring preparations, taurine impaired relaxation at high contraction frequencies, an effect abolished by supra-physiological Ca(2+) levels. Taurine did not affect oxygen consumption in non-contracting systemic heart muscle, but extracellular glucose utilization was twice that of control preparations. Collectively, our results suggest that extracellular taurine depresses cardiac Ca(2+) flux and potentiates glucose utilization in cuttlefish. Variations in taurine levels may represent an important mechanism for regulating cardiovascular function and metabolism in cephalopods.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Sepia/metabolismo , Taurina/farmacologia , Animais , Sinalização do Cálcio/efeitos dos fármacos , Feminino , Coração/fisiologia , Preparação de Coração Isolado , Consumo de Oxigênio/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo
17.
Diabetes Obes Metab ; 17(1): 98-101, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25238025

RESUMO

The sodium-dependent glucose transporter 2 (SGLT2) inhibitor remogliflozin etabonate (RE) was evaluated in a 12-week, double-blind, randomized, placebo- and active-controlled, parallel-group study. A total of 252 newly diagnosed and drug-naïve people with type 2 diabetes and glycated haemoglobin (HbA1c) concentrations of 7.0-≤9.5% (53-80 mmol/mol) were recruited. Participants were randomized to RE (100, 250, 500 or 1000 mg once daily or 250 mg twice daily), placebo or 30 mg pioglitazone once daily. The primary endpoint was change in HbA1c concentration from baseline. Secondary endpoints included changes in fasting plasma glucose, body weight and lipid profiles, safety and tolerability. We observed a statistically significant trend in the RE dose-response relationship for change from baseline in HbA1c at week 12 (p < 0.047). RE was generally well tolerated and no effects on LDL cholesterol were observed.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/administração & dosagem , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Moduladores de Transporte de Membrana/administração & dosagem , Pró-Fármacos/administração & dosagem , Pirazóis/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Seguimentos , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Análise de Intenção de Tratamento , Moduladores de Transporte de Membrana/efeitos adversos , Moduladores de Transporte de Membrana/uso terapêutico , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Pioglitazona , Pró-Fármacos/efeitos adversos , Pró-Fármacos/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Redução de Peso/efeitos dos fármacos
18.
Diabetes Obes Metab ; 17(1): 94-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25223369

RESUMO

We compared the efficacy of twice-daily doses of remogliflozin etabonate (RE) and once-daily pioglitazone with placebo for reduction in glycated haemoglobin (HbA1c) concentration. In this 12-week, double-blind, randomized, active- and placebo-controlled trial, 336 treatment-naïve subjects with type 2 diabetes and an HbA1c of 7.0-9.5% (53-80 mmol/mol) were randomized to RE (50, 100, 250, 500 or 1000 mg twice daily), matching placebo or 30 mg pioglitazone once daily. The primary endpoint was change in HbA1c from baseline. Other endpoints included changes in body weight, lipid levels, safety and tolerability. RE produced a decreasing dose response in HbA1c at week 12 (p < 0.001), with reductions in HbA1c versus placebo ranging from 0.64 to 1.07% (p < 0.001). Statistically significant reductions in body weight for RE compared with placebo were also observed. Twice-daily RE resulted in a dose-ordered improvement in glycaemic control and was generally well tolerated.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/administração & dosagem , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Moduladores de Transporte de Membrana/administração & dosagem , Pró-Fármacos/administração & dosagem , Pirazóis/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Seguimentos , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Hemoglobinas Glicadas/análise , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Análise de Intenção de Tratamento , Moduladores de Transporte de Membrana/efeitos adversos , Moduladores de Transporte de Membrana/uso terapêutico , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Pioglitazona , Pró-Fármacos/efeitos adversos , Pró-Fármacos/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Redução de Peso/efeitos dos fármacos
19.
West Indian Med J ; 63(1): 54-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25303195

RESUMO

OBJECTIVE: Many neurosurgical cases are done without the need for blood transfusion, yet blood is unnecessarily cross-matched, resulting in wasted resources. This study was undertaken to document and compare the number of units of blood components requested, cross-matched and transfused in neurosurgical cases at the University Hospital of the West Indies (UHWI). METHODS: A prospective, observational study was undertaken over one year. Data collected for each patient included demographic information, relevant perioperative data, and blood banking data including blood components requested, cross-matched and transfused. Data were analysed using SPSS version 16. RESULTS: Data were analysed on 152 patients, 71 females (46.7%) and 81 males (53.3%). The mean age was 48.7 ± 19.6 years and 100 of the procedures were done electively (65.8%). Blood components were ordered in 114 (75%) cases, red cells more commonly in 113 (74.3%) patients, and plasma in 19 (12.5%) patients. Overall, 20 patients (13.2%) were transfused. Most patients (90.9%) needed one to two units of blood. Of the 236 units of blood components that were cross-matched or prepared, only 62 were transfused. The cross-match/preparation to transfusion ratio (CTR/PTR) was 6.00 for red cells and 1.31 for plasma. Preoperative haemoglobin ≤ 10.0 g/dL (p = 0.001), estimated blood loss of ≥ 1 litre (p < 0.001), higher American Society of Anesthesiologists (ASA) physical status score (p < 0.03) and a resident as lead surgeon (p < 0.05), were significant predictors of blood transfusion. CONCLUSION: The transfusion rate was low with a high cross-match to transfusion ratio, suggesting that less cross-matching is needed. A new approach to blood ordering for neurosurgical cases is recommended.

20.
Br J Radiol ; 87(1043): 20140501, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25189280

RESUMO

OBJECTIVE: In the ongoing absence of available trial data, a national survey was carried out to provide details on radiotherapy treatment strategy for non-melanoma skin cancer (NMSC). METHODS: A survey of clinical oncologists treating NMSC was performed. The respondents were asked for basic information on workload as well as a proposed treatment strategy for various clinical scenarios for patients of varying fitness. RESULTS: A total of 43 completed and 20 partially completed surveys were received. There was a wide variation in the workload and additional disease sites that respondents had responsibility for. Kilovoltage radiotherapy was available to 81% of responders. The respondents' approach was affected by the fitness of patients, with longer fractionation regimes proposed for younger, fitter patients and shorter or non-standard fractionations more likely for the infirm elderly. Four daily fractionation regimes (18-20 Gy in 1 fraction, 35 Gy in 5 fractions, 45 Gy in 10 fractions and 55 Gy in 20 fractions) were most commonly suggested. There was a large degree of variation in non-standard fractions proposed with significant potential differences in radiobiological effect. Concern over the use of kilovoltage photons on skin over cartilage was apparent, as was a reluctance to use radiotherapy in areas of increased risk of poor wound healing. CONCLUSION: The survey results largely showed practice to be in line with available published evidence. The variation seen in some areas, such as non-standard fractionation, would benefit from the publication of local outcomes to achieve a more consistent approach. ADVANCES IN KNOWLEDGE: This study provides information on national practices and identifies variations, particularly within widespread use of non-standard fractionation.


Assuntos
Vigilância da População , Neoplasias Cutâneas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Incidência , Masculino , Melanoma , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Resultado do Tratamento , Reino Unido/epidemiologia
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