264 resultados para Long-Term Potentiation
Resumo:
Purpose
The increasing impact and costs of long term sickness absence have been well documented. However, the diversity and complexity of interventions and of the contexts in which these take place makes a traditional review problematic. Therefore, we undertook a systematic realist review to identify the dominant programme theories underlying best practice, to assess the evidence for these theories, and to throw light on important enabling or disabling contextual factors.
Method
A search of the scholarly literature from 1950 to 2011 identified 5,576 articles, of which 269 formed the basis of the review.
Results
We found that the dominant programme theories in relation to effective management related to: early intervention or referral by employers; having proactive organisational procedures; good communication and cooperation between stakeholders; and workplace-based occupational rehabilitation. Significant contextual factors were identified as the level of support for interventions from top management, the size and structure of the organisation, the level of financial and organisational investment in the management of long-term sickness absence, and the quality of relationships between managers and staff.
Conclusions
Consequently, those with responsibility for managing absence should bear in mind the contextual factors that are likely to have an impact on interventions, and do what they can to ensure stakeholders have at least a mutual understanding (if not a common purpose) in relation to their perceptions of interventions, goals, culture and practice in the management of long term sickness absence.
Resumo:
Reliable prediction of long-term medical device performance using computer simulation requires consideration of variability in surgical procedure, as well as patient-specific factors. However, even deterministic simulation of long-term failure processes for such devices is time and resource consuming so that including variability can lead to excessive time to achieve useful predictions. This study investigates the use of an accelerated probabilistic framework for predicting the likely performance envelope of a device and applies it to femoral prosthesis loosening in cemented hip arthroplasty.
A creep and fatigue damage failure model for bone cement, in conjunction with an interfacial fatigue model for the implant–cement interface, was used to simulate loosening of a prosthesis within a cement mantle. A deterministic set of trial simulations was used to account for variability of a set of surgical and patient factors, and a response surface method was used to perform and accelerate a Monte Carlo simulation to achieve an estimate of the likely range of prosthesis loosening. The proposed framework was used to conceptually investigate the influence of prosthesis selection and surgical placement on prosthesis migration.
Results demonstrate that the response surface method is capable of dramatically reducing the time to achieve convergence in mean and variance of predicted response variables. A critical requirement for realistic predictions is the size and quality of the initial training dataset used to generate the response surface and further work is required to determine the recommendations for a minimum number of initial trials. Results of this conceptual application predicted that loosening was sensitive to the implant size and femoral width. Furthermore, different rankings of implant performance were predicted when only individual simulations (e.g. an average condition) were used to rank implants, compared with when stochastic simulations were used. In conclusion, the proposed framework provides a viable approach to predicting realistic ranges of loosening behaviour for orthopaedic implants in reduced timeframes compared with conventional Monte Carlo simulations.
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Background Moderate di?erences in e?cacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could a? ect treatment choices. We sought any such di?erences.
Methods We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plusanthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44 000); one anthracyclinebased regimen versus another (n=7000) or versus cyclo phosphamide, methotrexate, and ?uorouracil (CMF; n=18 000); and polychemotherapy versus no chemotherapy (n=32 000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to de? ne standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported.
Findings In trials adding four separate cycles of a taxane to a ?xed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided signi?cance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no signi?cant di?erence (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or
standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little a? ected by age, nodal status, tumour diameter or di?erentiation (moderate or poor; few were well di?erentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality di?erences paralleled breast cancer mortality di?erences, despite taxane, anthracycline, and other toxicities.
Interpretation 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute bene?t, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both.
Resumo:
The human fetus learns about its chemosensory environment and this influences its behavior at birth and during the nursing period. This study examined whether prenatal experience could influence behavior much later in life. The dietary preference of two groups of children (8- to 9-years old) was examined. Mothers of one group had consumed garlic during pregnancy, mothers of the control group had not. Children received two tests, 1 month apart, of a meal containing two portions of potato gratin, one flavored with garlic. The total amount of potato, and the percentage of garlic flavored potato, eaten was calculated and examined separately by ANOVA for factors of prenatal exposure, the child's sex, and trial. Children prenatally exposed to garlic ate significantly more garlic flavored potato and a significantly greater overall amount of potato on trial 2, compared to controls. The results demonstrate prenatal experience may affect behavior well into childhood. © 2012 Wiley Periodicals, Inc.
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Background: There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine.
Study design: Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices.
Results: A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm.
Conclusions: The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. © 2013 Elsevier Inc. All rights reserved.
Resumo:
Objectives: To evaluate the effectiveness of (1) dissemination strategies to improve clinical practice behaviors (eg, frequency and documentation of pain assessments, use of pain medication) among health care team members, and (2) the implementation of the pain protocol in reducing pain in long term care (LTC) residents. Design: A controlled before-after design was used to evaluate the effectiveness of the pain protocol, whereas qualitative interviews and focus groups were used to obtain additional context-driven data. Setting: Four LTC facilities in southern Ontario, Canada; 2 for the intervention group and 2 for the control group. Participants: Data were collected from 200 LTC residents; 99 for the intervention and 101 for the control group. Intervention: Implementation of a pain protocol using a multifaceted approach, including a site working group or Pain Team, pain education and skills training, and other quality improvement activities. Measurements: Resident pain was measured using 3 assessment tools: the Pain Assessment Checklist for Seniors with Limited Ability to Communicate, the Pain Assessment in the Communicatively Impaired Elderly, and the Present Pain Intensity Scale. Clinical practice behaviors were measured using a number of process indicators; for example, use of pain assessment tools, documentation about pain management, and use of pain medications. A semistructured interview guide was used to collect qualitative data via focus groups and interviews. Results: Pain increased significantly more for the control group than the intervention group over the 1-year intervention period. There were significantly more positive changes over the intervention period in the intervention group compared with the control group for the following indicators: the use of a standardized pain assessment tool and completed admission/initial pain assessment. Qualitative findings highlight the importance of reminding staff to think about pain as a priority in caring for residents and to be mindful of it during daily activities. Using onsite champions, in this case advanced practice nurses and a Pain Team, were key to successfully implementing the pain protocol. Conclusions: These study findings indicate that the implementation of a pain protocol intervention improved the way pain was managed and provided pain relief for LTC residents.
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To compare long-term neurodevelopmental and functional outcomes of neonatal intensive care unit (NICU) survivors with neonatal intraparenchymal echodensities (IPE) with porencephaly on cranial ultrasonography with matched controls. To compare the developmental trajectories of these infants over the childhood years with those of matched controls.
Resumo:
The low tactile threshold in preterm infants when they are in the neonatal intensive care unit (NICU), while their physiological systems are unstable and immature, potentially renders them more vulnerable to the effects of repeated invasive procedures. There is a small but growing literature on pain and tactile responsivity following procedural pain in the NICU, or early surgery. Long-term effects of repeated pain in the neonatal period on neurodevelopment await further research. However, there are multiple sources of stress in the NICU, which contribute to inducing high overall 'allostatic load', therefore determining specific effects of neonatal pain in human infants is challenging.
Resumo:
There are multiple lines of evidence suggesting that in vulnerable prematurely born infants, repeated and prolonged pain exposure may affect the subsequent development of pain systems, as well as potentially contribute to alterations in long-term development and behavior. Multiple factors cumulatively contribute to altered developmental trajectories in such infants. These include characteristics of the developing organism (low tactile threshold, sensitization, rapid brain development), characteristics intrinsic to the infant (gestation, illness severity), characteristics of the experience in the neonatal intensive care unit (pain exposure and cumulative stress), and characteristics of the caregivers within their family and social context. This article provides a model for examining long-term effects of pain in the newborn period embedded in a developmental context framework.