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1.
Proc Natl Acad Sci U S A ; 120(47): e2206235120, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37956276

RESUMO

The paper explores three periods in the UK electricity consumption-production system since World War II. The first two involved the development of an increasingly centralized, integrated system that provided electricity to meet growing post-war demand. It saw two major changes in governance, first to nationalization, then to privatization and liberalization. The third period started at the turn of the Century, driven by increasing evidence of the impact of fossil fuels on the Earth's climate. The paper focuses on the drivers of change, within the UK and externally, and how they affected governance, technology deployment, and industry structure. It draws on the multi-level perspective and the concepts of governance and technological branching points to inform the analysis of each period. It shows that there is a considerable distance to travel toward a truly sustainable electricity system.

2.
Global Spine J ; 13(7): 1856-1864, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34732096

RESUMO

OBJECTIVES: To compare the effect of delaying surgery on clinical outcome in patients with chronic sciatica secondary to lumbar disc herniation. METHODS: Patients with sciatica lasting 4-12 months and lumbar disc herniation at the L4-L5 or L5-S1 level were randomized to undergo microdiscectomy (early surgery) or to receive 6 months of nonoperative treatment followed by surgery if needed (delayed surgery). Outcomes were leg pain, Oswestry Disability Index score (ODI), back pain, SF-36 physical component (PCS) and mental component (MCS) summary scores, employment, and satisfaction measured preoperatively and at 6 weeks, 3 months, 6 months, and 1 year after surgery. RESULTS: Of the 64 patients in the early surgery group, 56 underwent microdiscectomy an average of 3 ± 2 weeks after enrollment. Of the 64 patients randomized to nonoperative care, 22 patients underwent delayed surgery an average of 53 ± 24 weeks after enrollment. The early surgery group experienced less leg pain than the delayed surgery group, which was the primary outcome, at 6 months after surgery (early surgery 2.8 ± .4 vs delayed surgery 4.8 ± .7; difference, 2.0; 95% confidence interval, .5-3.5). The overall estimated mean difference between groups significantly favored early surgery for leg pain, ODI, SF36-PCS, and back pain. The adverse event rate was similar between groups. CONCLUSIONS: Patients presenting with chronic sciatica treated with delayed surgery after prolonging standardized non-operative care have inferior outcomes compared to those that undergo expedited surgery.

3.
Clin Orthop Relat Res ; 480(3): 574-584, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597280

RESUMO

BACKGROUND: A recent randomized controlled trial (RCT), performed by the authors, comparing early surgical microdiscectomy with 6 months of nonoperative care for chronic lumbar radiculopathy showed that early surgery resulted in improved outcomes. However, estimates of the incremental cost-utility ratio (ICUR), which is often expressed as the cost of gaining one quality-adjusted life year (QALY), of microdiscectomy versus nonsurgical management have varied. Radiculopathy lasting more than 4 months is less likely to improve without surgical intervention and may have a more favorable ICUR than previously reported for acute radiculopathy. QUESTION/PURPOSE: In the setting of chronic radiculopathy caused by lumbar disc herniation, defined as symptoms and/or signs of 4 to 12 months duration, is surgical management more cost-effective than 6 months of nonoperative care from the third-party payer perspective based on a willingness to pay of less than CAD 50,000/QALY? METHODS: A decision analysis model served as the vehicle for the cost-utility analysis. A decision tree was parameterized using data from our single-center RCT that was augmented with institutional microcost data from the Ontario Case Costing Initiative. Bottom-up case costing methodology generates more accurate cost estimates, although institutional costs are known to vary. There were no major surgical cost drivers such as implants or bone graft substitutes, and therefore, the jurisdictional variance would be minimal for tertiary care centers. QALYs derived from the EuroQoL-5D were the health outcome and were derived exclusively from the RCT data, given the paucity of studies evaluating the surgical treatment of lumbar radiculopathy lasting 4 to 12 months. Cost-effectiveness was assessed using the ICUR and a threshold of willingness to pay CAD 50,000 (USD 41,220) per QALY in the base case. Sensitivity analyses were performed to account for the uncertainties within the estimate of cost utility, using both a probabilistic sensitivity analysis and two one-way sensitivity analyses with varying crossover rates after the 6-month nonsurgical treatment had concluded. RESULTS: Early surgical treatment of patients with chronic lumbar radiculopathy (defined as symptoms of 4 to 12 months duration) was cost-effective, in that the cost of one QALY was lower than the CAD 50,000 threshold (note: the purchasing power parity conversion factor between the Canadian dollar (CAD) and the US dollar (USD) for 2019 was 1 USD = 1.213 CAD; therefore, our threshold was USD 41,220). Patients in the early surgical treatment group had higher expected costs (CAD 4118 [95% CI 3429 to 4867]) than those with nonsurgical treatment (CAD 2377 [95% CI 1622 to 3518]), but they had better expected health outcomes (1.48 QALYs [95% CI 1.39 to 1.57] versus 1.30 [95% CI 1.22 to 1.37]). The ICUR was CAD 5822 per QALY gained (95% CI 3029 to 30,461). The 2-year probabilistic sensitivity analysis demonstrated that the likelihood that early surgical treatment was cost-effective was 0.99 at the willingness-to-pay threshold, as did the one-way sensitivity analyses. CONCLUSION: Early surgery is cost-effective compared with nonoperative care in patients who have had chronic sciatica for 4 to 12 months. Decision-makers should ensure adequate funding to allow timely access to surgical care given that it is highly likely that early surgical intervention is potentially cost-effective in single-payer systems. Future work should focus on both the clinical effectiveness of the treatment of chronic radiculopathy and the costs of these treatments from a societal perspective to account for occupational absences and lost patient productivity. Parallel cost-utility analyses are critical so that appropriate decisions about resource allocation can be made. LEVEL OF EVIDENCE: Level III, economic and decision analysis.


Assuntos
Discotomia/economia , Deslocamento do Disco Intervertebral/economia , Deslocamento do Disco Intervertebral/terapia , Microcirurgia/economia , Modalidades de Fisioterapia/economia , Radiculopatia/economia , Radiculopatia/terapia , Adulto , Análise Custo-Benefício , Discotomia/métodos , Feminino , Humanos , Vértebras Lombares , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida
4.
J Agric Food Chem ; 69(51): 15681-15690, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34928147

RESUMO

By using a high-resolution mass spectrometer, four vitamin A palmitate (VAP) degradants were identified from microencapsulated VAP degradation samples. Based on the degradants, VAP first breaks down into anhydroretinol (ANHR) and palmitic acid (PA) through ester thermal elimination (ETE). Sequentially, the formed ANHR reacts with remaining VAP to ANHR-VAP and with a second ANHR to ANHR-ANHR. The migration of H+ in the transition state predicts that the H+ concentration in media will affect the ETE. Based on the degradation mechanism discovered from this study, a new product was developed and its media pH changed from 4.2 to 6.2. The new microencapsulated VAP degraded from 22.3% to 4.8% on an annualized basis. In the VAP degradation, no oxidized apo-carotenoids were found. The oxidized apo-carotenoids were detected in the degradation of ß-carotene, a pro-vitamin A, through natural oxidation by oxygen in air. This indicated that, in ambient and dry conditions on its own, VAP decay was unlike that of ß-carotene through natural oxidation.


Assuntos
Diterpenos , beta Caroteno , Carotenoides , Ésteres de Retinil , Vitamina A
5.
J Bone Joint Surg Am ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637408

RESUMO

BACKGROUND: Randomized controlled trials evaluating acute sciatica have not demonstrated prolonged improvements in terms of patient-reported pain and function. For chronic sciatica, however, microdiscectomy has been found to be superior at 1 year. Whether this effect persists during the second year is not known. The purpose of the present study was to report the 2-year outcomes following lumbar microdiscectomy as compared with standardized nonoperative care for the treatment of chronic sciatica resulting from a lumbar disc herniation. METHODS: The present study is a secondary analysis of a previously reported randomized controlled trial with extension to 2 years of follow-up. Patients with radiculopathy for 4 to 12 months resulting from an L4-L5 or L5-S1 disc herniation were randomized to microdiscectomy or 6 months of nonoperative care followed by surgery if needed. Intention-to-treat analysis was performed at 2 years for the primary outcome (the intensity of leg pain) (range of possible scores, 0 [no pain] to 10 [worst pain]) as well as for secondary outcomes (including the Oswestry Disability Index score, the intensity of back pain, and quality of life). RESULTS: One hundred and twenty-eight patients were randomized in the present study. Twenty-four (38%) of the 64 patients who had been randomized to nonoperative care crossed over to surgical treatment by 2 years following enrollment. At the 2-year time point, the follow-up rate was approximately 70%. At 2 years, the operative group had less leg pain than the nonoperative group (mean, 2.8 ± 0.4 compared with 4.2 ± 0.4; treatment effect, 1.3 [95% confidence interval, 0.3 to 2.4]). The treatment effect favored surgery for all secondary outcome measures at 6 months and 1 year and for back pain intensity and physical function at 2 years. CONCLUSIONS: At 2 years, the present study showed that microdiscectomy was superior to nonoperative care for the treatment of chronic sciatica resulting from an L4-L5 or L5-S1 disc herniation. However, the difference between the groups did not surpass the minimal clinically important difference at 2 years as was reached at earlier follow-up points, likely as the result of patients crossing over from nonoperative to operative treatment. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

6.
N Engl J Med ; 382(12): 1093-1102, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32187469

RESUMO

BACKGROUND: The treatment of chronic sciatica caused by herniation of a lumbar disk has not been well studied in comparison with acute disk herniation. Data are needed on whether diskectomy or a conservative approach is better for sciatica that has persisted for several months. METHODS: In a single-center trial, we randomly assigned patients with sciatica that had lasted for 4 to 12 months and lumbar disk herniation at the L4-L5 or L5-S1 level in a 1:1 ratio to undergo microdiskectomy or to receive 6 months of standardized nonoperative care followed by surgery if needed. Surgery was performed by spine surgeons who used conventional microdiskectomy techniques. The primary outcome was the intensity of leg pain on a visual analogue scale (ranging from 0 to 10, with higher scores indicating more severe pain) at 6 months after enrollment. Secondary outcomes were the score on the Oswestry Disability Index, back and leg pain, and quality-of-life scores at 6 weeks, 3 months, 6 months, and 1 year. RESULTS: From 2010 through 2016, a total of 790 patients were screened; of those patients, 128 were enrolled, with 64 in each group. Among the patients assigned to undergo surgery, the median time from randomization to surgery was 3.1 weeks; of the 64 patients in the nonsurgical group, 22 (34%) crossed over to undergo surgery at a median of 11 months after enrollment. At baseline, the mean score for leg-pain intensity was 7.7 in the surgical group and 8.0 in the nonsurgical group. The primary outcome of the leg-pain intensity score at 6 months was 2.8 in the surgical group and 5.2 in the nonsurgical group (adjusted mean difference, 2.4; 95% confidence interval, 1.4 to 3.4; P<0.001). Secondary outcomes including the score on the Owestry Disability Index and pain at 12 months were in the same direction as the primary outcome. Nine patients had adverse events associated with surgery, and one patient underwent repeat surgery for recurrent disk herniation. CONCLUSIONS: In this single-center trial involving patients with sciatica lasting more than 4 months and caused by lumbar disk herniation, microdiskectomy was superior to nonsurgical care with respect to pain intensity at 6 months of follow-up. (Funded by Physicians' Services Incorporated Foundation; ClinicalTrials.gov number, NCT01335646.).


Assuntos
Tratamento Conservador , Discotomia , Glucocorticoides/administração & dosagem , Deslocamento do Disco Intervertebral/cirurgia , Modalidades de Fisioterapia , Ciática/terapia , Adulto , Tratamento Conservador/métodos , Estudos Cross-Over , Discotomia/efeitos adversos , Feminino , Seguimentos , Humanos , Injeções Epidurais , Análise de Intenção de Tratamento , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/tratamento farmacológico , Masculino , Dor/etiologia , Medição da Dor , Satisfação do Paciente , Complicações Pós-Operatórias , Qualidade de Vida , Ciática/etiologia , Ciática/cirurgia , Resultado do Tratamento
7.
Br J Hosp Med (Lond) ; 77(10): 569-571, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27723389

RESUMO

The 1960s was a period of reform and innovation in the provision of care for people with mental health problems. The most important development was the move away from residential institutions and the development of community services based on district general hospitals.


Assuntos
Serviços Comunitários de Saúde Mental/história , Institucionalização/história , Psiquiatria/história , Atenção à Saúde/história , Política de Saúde/história , História do Século XX , Humanos , Psiquiatria/educação , Especialização/história , Suicídio/história , Suicídio/legislação & jurisprudência , Reino Unido
8.
Gene ; 576(2 Pt 1): 591, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26519997
10.
Open Biol ; 3(1): 120144, 2013 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-23303309

RESUMO

The vast majority of all agents used to directly kill cancer cells (ionizing radiation, most chemotherapeutic agents and some targeted therapies) work through either directly or indirectly generating reactive oxygen species that block key steps in the cell cycle. As mesenchymal cancers evolve from their epithelial cell progenitors, they almost inevitably possess much-heightened amounts of antioxidants that effectively block otherwise highly effective oxidant therapies. Also key to better understanding is why and how the anti-diabetic drug metformin (the world's most prescribed pharmaceutical product) preferentially kills oxidant-deficient mesenchymal p53(- -) cells. A much faster timetable should be adopted towards developing more new drugs effective against p53(- -) cancers.


Assuntos
Antioxidantes/metabolismo , Metástase Neoplásica/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Oxidantes/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Espécies Reativas de Oxigênio/metabolismo
11.
Avian Dis ; 56(3): 521-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23050469

RESUMO

We analyzed factors involved in the introduction of infectious laryngotracheitis (ILT) virus (ILTV) onto broiler farms during a localized outbreak in an immunologically naive broiler population. The outbreak occurred in the state of Mississippi, United States in 2002-2003. From the responses to a retrospective survey questionnaire administered via personal interviews, 181 farm-level risk factors were defined and analyzed for their association with ILTV introduction using logistic regression. There were 27 case farms (93% of all the infected broiler farms) and two sets of controls: farms matched to the cases by location and those randomly selected among the broiler farms in Mississippi. We found that farm suppliers such as gas company representatives, who are likely to visit other farms, and farm-workers who visit other chicken farms, are likely vehicles of ILTV introduction onto broiler farms. These risks can be greatly reduced by following biosecurity procedures, in particular if farm workers bathe and change footwear prior to entering broiler houses on their own farm. Footbaths for farm visitors can provide a false sense of security during an ILT outbreak when, indeed, other practices such as plastic boots or changing boots are more effective in preventing ILTV transmission. Sharing of equipment used for removal of caked broiler litter between subsequent flocks may also serve as an important vehicle of ILTV transmission. During the 2002-2003 outbreak, shared litter removal equipment was associated with ILTV transmission despite a requirement being put in place for litter decontamination. We also found that tunnel-ventilated broiler houses with inlets toward a neighboring poultry farm are more likely to get infected with ILTV. In addition to this analysis, the data collected provide a good overview of the actual practices and deficiencies of biosecurity undertaken on broiler farms in this part of the United States.


Assuntos
Galinhas , Surtos de Doenças/veterinária , Infecções por Herpesviridae/veterinária , Herpesvirus Galináceo 1 , Doenças das Aves Domésticas/virologia , Animais , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/transmissão , Infecções por Herpesviridae/virologia , Abrigo para Animais , Mississippi/epidemiologia , Modelos Biológicos , Razão de Chances , Doenças das Aves Domésticas/epidemiologia , Fatores de Risco
12.
Per Med ; 6(6): 607, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29783359
13.
Am J Surg ; 186(1): 17-9, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12842741

RESUMO

BACKGROUND: Ischemia distal to a functioning arteriovenous dialysis access is an infrequent but potentially serious complication that can be difficult to manage while maintaining access patency. METHODS: Retrospective review was made of all patients requiring operative intervention for dialysis access-induced distal ischemia from 1998 to 2002 in a tertiary vascular surgery referral practice. RESULTS: Twelve patients had 13 hands with ischemic changes requiring intervention after placement of hemodialysis access. Ischemia was successfully treated in all cases by distal revascularization-interval ligation. Dialysis access patency was better than expected. CONCLUSIONS: Distal revascularization-interval ligation is the optimal management for dialysis access-induced ischemia and should be attempted whenever possible.


Assuntos
Braço/irrigação sanguínea , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Isquemia/cirurgia , Diálise Renal , Adulto , Idoso , Feminino , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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