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 â¼2-4 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).
Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Idoso , Adulto , Receptores de Estrogênio/metabolismo , Administração Oral , Receptor alfa de Estrogênio/genética , Idoso de 80 Anos ou mais , Dose Máxima Tolerável , Relação Dose-Resposta a Droga , Azetidinas , IsoquinolinasRESUMO
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 ExercícioRESUMO
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 numéricosRESUMO
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 TumoralRESUMO
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.
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 fármacosRESUMO
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 fármacosRESUMO
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.
RESUMO
PURPOSE: Cisplatin/5-fluorouracil (5-FU) is an accepted palliative chemotherapy treatment for head and neck squamous cell carcinoma, improving quality of life but not overall survival. Capecitabine in place of 5-FU removes the morbidity of an infusional regime with potential benefit in patient well-being. This study looks at outcomes for cisplatin plus capecitabine (PX) outside of a trial setting. METHODS: Consecutive patients receiving this treatment in a single centre were retrospectively analysed. Cisplatin (mean dose 75 mg/m²) was given on day 1 of a 3-week cycle and capecitabine (mean dose 808 mg/m² twice daily) on days 1-14, for up to 6 cycles. RESULTS: Sixty-five patients (median age 58.6 years) received a median of 4 cycles of chemotherapy. The overall response rate was 30.7%, with a median overall survival of 7.3 months. Treatment was well tolerated with a 10.7% grade 3 and a 1.5% grade 4 neutropenia rate, with no other grade 4 toxicities. One patient died of neutropenic sepsis whilst on treatment. Twenty-seven percent of patients stopped treatment early due to chemotherapy-related side effects. CONCLUSION: PX is well tolerated outside the trial setting with outcomes similar to historical published literature. Ease of administration and benefit to patient convenience make it an attractive alternative to standard palliative treatment.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Capecitabina , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Quimioterapia Combinada , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Recidiva , Estudos RetrospectivosRESUMO
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 , CorantesRESUMO
The development of anaesthetic services in Jamaica arose out of the recognition that dedicated physicians offered a better morbidity/mortality profile to patients. From untrained personnel offering anaesthesia at the turn of the 20th century, much progress has been made, such that specialized anaesthetists have been trained for the various surgical subspecialties.
Assuntos
Anestesiologia/história , Anestesiologia/educação , História do Século XIX , História do Século XX , Humanos , JamaicaRESUMO
The one-year Diploma in Anaesthetics (DA) was the first postgraduate programme offered by the then Faculty of Medicine of The University of the West Indies (UWI). It was instituted in 1966, when the need for trained physician anaesthetists became paramount. Over 200 physicians have been awarded the DA which was discontinued in 1994. The four-year Doctor of Medicine in Anaesthetics [DM (Anaesthetics)] was commenced in 1974 and continues to train most of the region's physician anaesthetists. The majority of the 119 graduates (as of December 2011) are providing invaluable services to the people of the Caribbean. The time has come for the establishment of a regional certifying body, the Caribbean College of Anaesthetists. This college would determine the standards for the training and clinical practice of anaesthetists as perioperative physicians including: the conduct of anaesthesia, critical care, acute and chronic pain management. It would also facilitate continuing medical education and recertification of all practising anaesthetists within the region.
Assuntos
Anestesiologia/educação , Faculdades de Medicina , Certificação , Cuidados Críticos , Humanos , Jamaica , Enfermeiros Anestesistas/educação , UniversidadesRESUMO
We present a theoretical treatment of coherent light scattering from an interacting 1D Bose gas at finite temperatures. We show how this can provide a nondestructive measurement of the atomic system states. The equilibrium states are determined by the temperature and interaction strength, and are characterized by the spatial density-density correlation function. We show how this correlation function is encoded in the angular distribution of the fluctuations of the scattered light intensity, thus providing a sensitive, quantitative probe of the density-density correlation function and therefore the quantum state of the gas.
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 RetrospectivosRESUMO
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¯SEâ¯=â¯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 (CPEâ¯=â¯0.79 vs 0.79, pâ¯=â¯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 , PrognósticoRESUMO
Degeneration of basal forebrain cholinergic neurons is a common feature of Alzheimer's disease and is proposed to be an early and key event in the condition's etiology. This review discusses recent findings that strongly link the p75 neurotrophin receptor (p75(NTR)) to both cholinergic neuron degeneration and the production of toxic forms of amyloid-beta (Abeta), which is found deposited as amyloid plaques in the brains of Alzheimer's disease patients. Although elucidating the underlying molecular mechanisms and the clinical significance of these findings will require further experimentation, a number of possible scenarios and future research directions are presented.
Assuntos
Acetilcolina/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Fibras Colinérgicas/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Núcleo Basal de Meynert/metabolismo , Núcleo Basal de Meynert/fisiopatologia , Encéfalo/fisiopatologia , Humanos , Degeneração Neural/genética , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Fatores de Crescimento Neural/deficiência , Receptor de Fator de Crescimento Neural/genéticaRESUMO
OBJECTIVE: There is little information on adverse anaesthetic outcomes from the Caribbean. The aim of this study was to investigate the occurrence of anaesthetic morbidity and mortality at the University Hospital of the West Indies (UHWI) and to identify possible risk factors. METHODS: All anaesthetic procedures at the UHWI were monitored for adverse events and patient outcomes for the 12-month period from March 2004 to February 2005. Possible risk factors for these adverse events were assessed using logistic regression. RESULTS: Of 3185 anaesthetic procedures, the incidence of intra-operative events was 201 per 1000 (95% CI 187, 215); 151 per 1000 being cardiovascular and 26 per 1000 respiratory. Others included excess blood loss and equipment failure, hyperglycaemia, nausea and vomiting. Patients with intraoperative complications were three times more likely to have complications during recovery (OR = 3.35; 95% CI 2.59, 4.33, p < 0.001). The incidence of complications among paediatric patients was 139 per 1000 (95% CI 104, 174) intra-operatively and 58 per 1000 (95% CI 34, 81) during recovery. Risk factors for developing complications (p < 0.05) included age > 50 years, ASA status > or = II, prolonged anaesthesia, high surgical risk, general or combined anaesthetic techniques, senior anaesthetist, intubated patients and co-morbidities. There were 14 operative mortalities, none of which was anaesthesia-related CONCLUSION: Anaesthetic complication rates at the UHWI are comparable to those in developed countries, except for higher paediatric complication rates and ICU admissions and lower rates of postoperative nausea and vomiting.
Assuntos
Anestesia/efeitos adversos , Hospitais Universitários/estatística & dados numéricos , Complicações Intraoperatórias/epidemiologia , Morbidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Anestesia/mortalidade , Período de Recuperação da Anestesia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Índias Ocidentais/epidemiologia , Adulto JovemRESUMO
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 terapêuticoRESUMO
This study tested the hypothesis that milk has a direct effect on the establishment of infection with Teladorsagia circumcincta, and provides information on the effects of suckling on resilience to infection in young lambs. Of 46 six-week-old twin-born lambs, one from each twin was allowed to continue suckling (S-) and its twin-weaned (W-) while both were concurrently infected with an average of either 0 (-0; n=7/group), 250 (-250; n=8/group) or 1000 (-1000; n=8/group) third stage infective larvae (L3) of T. circumcincta per day, providing six treatment groups. All groups grazed minimally contaminated pasture, and after 42 days were slaughtered for necropsy. Low pasture larval contamination was confirmed in W0 and S0 lambs by faecal egg counts (FEC) of less than 30 eggs per gram (EPG) and burdens of less than 140 worms. There was no difference in FEC between weaned and suckled lambs. Within infection regime, total worm burdens were 55-60% greater in the weaned compared with their suckled counterparts (P=0.05), and represented 27 and 17%, respectively, net establishment of larvae. The greater worm burdens of both groups of weaned animals, which compared with their suckled counterparts, and of those infected with 1000 compared with 250 larvae per day, were associated with shorter female adults that had fewer eggs in utero, perhaps indicating intra-worm population regulation, but highlighting the limitation of FEC in assessing nematode burdens of such young lambs. There was no effect of infection on live weight gain of either weaned or suckled groups and the possibility was raised that, in such young lambs, immune unresponsiveness may be responsible. The major benefit of continued milk consumption appears to lie more in providing nutrients for enhanced growth rather than in improving resilience of the lambs to infection.