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991.
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Peter S. Grimison BSc MBBS MPH FRACP R. John Simes BSc MBBS MD SM FRACP H. Malcolm Hudson BSc PhD Martin R. Stockler MBBS MSc FRACP 《Value in health》2009,12(6):967-976
ObjectivesTo optimize, apply, and validate a scoring algorithm that provides a utility index from a cancer-specific quality of life questionnaire called the Utility-Based Questionnaire-Cancer (UBQ-C) using data sets from randomized trials in breast cancer. The index is designed to reflect the perspective of cancer patients in a specific clinical context so as to best inform clinical decisions.MethodsWe applied the UBQ-C scoring algorithm to trials of chemotherapy for advanced (n = 325) and early (n = 126) breast cancer. The algorithm converts UBQ-C subscales into a subset index, and combines it with a global health status item into an overall HRQL index, which is then converted to a utility index using a power transformation. The optimal subscale weights were determined by their correlations with the global scale in the relevant data set. The validity of the utility index was tested against other patient characteristics.ResultsOptimal weights (range 0–1) for the subset index in advanced (early) breast cancer were: physical function 0.20 (0.09); social/usual activities 0.23 (0.25); self-care 0.04 (0.01); and distresses 0.53 (0.64). Weights for the overall HRQL index were health status 0.66 (0.63) and subset index 0.34 (0.37). The utility index discriminated between breast cancer that was advanced rather than early (means 0.88 vs. 0.94, P < 0.0001) and was responsive to the toxic effects of chemotherapy in early breast cancer (mean change 0.07, P < 0.0001).ConclusionsThe scoring algorithm for the UBQ-C utility index can be optimized in different clinical contexts to reflect the relative importance of different aspects of quality of life to the patients in a trial. It can be used to generate sensitive and responsive utility scores, and quality-adjusted life-years that can be used within a trial to compare the net benefit of treatments and inform clinical decision-making. 相似文献
993.
Ushtana Antia Malcolm D. Tingle Bruce R. Russell 《The Journal of pharmacy and pharmacology》2009,61(7):877-882
Objectives ‘Party pills’ have found use worldwide as a substitute for amphetamine‐derived designer drugs. Whilst some information exists about the metabolism of these drugs, there is little information about their ability to inhibit the metabolism of co‐administered drugs. This study aimed to determine whether predictions can be made about global interactions between ‘party pills’ constituents and other drugs metabolised by the same cytochrome P450 (CYP) isoenzymes. Methods The inhibitory effects of seven benzyl and phenyl piperazines were measured in microsomal incubation assays of probe substrates for five major CYP isoenzymes. In addition, the metabolism of benzylpiperazine and trifluoromethylphenylpiperazine, the two most commonly used constituents of ‘party pills’, was investigated using human liver microsomes assays and known inhibitors of CYP isoenzymes. Key findings All piperazine analogues tested showed significant inhibitory activity against most, if not all, isoenzymes tested. The metabolism of benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) involved CYP2D6, CYP1A2 and CYP3A4. Furthermore, BZP and TFMPP inhibited each other's metabolism. Conclusions Fluorophenylpiperazine, methoxyphenylpiperazine, chlorophenylpiperazine, methylbenzylpiperazine and methylenedioxybenzylpiperazine had significant inhibitory effects on CYP2D6, CYP1A2, CYP3A4, CYP2C19 and CYP2C9 isoenzymes but each piperazine had a different inhibitory profile. The metabolic interaction between BZP and TFMPP may have clinical implications, as these agents are often combined in ‘party pills’. 相似文献
994.
Malcolm C Bateson 《British medical journal》1999,318(7200):1745-1748
995.
Elizabeth N Williams DipPhysio Lecturer in Paediatrics Nigel S Broughton FRCS FRCS Ed FRACS Malcolm B Menelaus MD FRCS FRACS Senior Orthopaedic Surgeon; 《Developmental medicine and child neurology》1999,41(7):446-449
The aim of this study was to examine children with myelomeningocele (spina bifida) who were investigated according to the level of neurosegmental lesion and to determine the number who walked and their average age at commencement/cessation of walking. The data have been collected since 1978 at the Royal Children's Hospital, Melbourne during annual evaluations of patients with spina bifida and high-level paralysis. After screening for established criteria and assigning to a neurosegmental lesion level, 173 children were examined for their ability to walk, with or without aids, in a community setting. Thirty-five children had lesions at the thoracic level, and seven walked at a mean age of 4 years 6 months. Three children with a lesion at the thoracic level ceased walking at a mean age of 7 years 6 months. Ten children had lesions at the high-lumbar level (L1/2), and five walked at a mean age of 5 years 2 months. Three children who had lesions at the high-lumbar level ceased walking at a mean age of 6 years 11 months. Fifteen children had lesions at the mid-lumbar level (L3) and nine walked at a mean age of 5 years. Three ceased walking at a mean age of 7 years. Forty-five children had lesions at the low-lumbar level (L4/5) and 38 walked at a mean age of 3 years 10 months. Five ceased walking at a mean age of 9 years 1 month. Sixty-eight children had lesions at the sacral level; all of whom walked at an average age of 2 years 2 months. None had ceased walking by the end of the study period. Delay in achieving ambulation can be expected in all children with spina bifida, including those with low neurosegmental level lesions. Furthermore, some children with high lesion level, given the opportunity, might be expected to ambulate effectively in the community but may cease walking after 3 to 4 years of this activity, which is earlier than previously recorded. 相似文献
996.
997.
The clinical manifestation of most diseases of the central nervous system results from neuronal dysfunction or loss. Diseases such as stroke, epilepsy and neurodegeneration (e.g. Alzheimer's disease and Parkinson's disease) share common cellular and molecular mechanisms (e.g. oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction) that contribute to the loss of neuronal function. Neurotrophic factors (NTFs) are secreted proteins that regulate multiple aspects of neuronal development including neuronal maintenance, survival, axonal growth and synaptic plasticity. These properties of NTFs make them likely candidates for preventing neurodegeneration and promoting neuroregeneration. One approach to delivering NTFs to diseased cells is through viral vector-mediated gene delivery. Viral vectors are now routinely used as tools for studying gene function as well as developing gene-based therapies for a variety of diseases. Currently, many clinical trials using viral vectors in the nervous system are underway or completed, and seven of these trials involve NTFs for neurodegeneration. In this review, we discuss viral vector-mediated gene transfer of NTFs to treat neurodegenerative diseases of the central nervous system. 相似文献
998.
999.
Cognitive Behavior Therapies for Psychotic Disorders: Current Empirical Status and Future Directions 总被引:3,自引:0,他引:3
Brandon A. Gaudiano 《Clinical psychology》2005,12(1):33-50
Although cognitive behavior therapy (CBT) has strong empirical support for treating a diverse array of psychological conditions, only recently has research begun to examine its efficacy in treating the symptoms associated with schizophrenia and other psychotic disorders. Several randomized controlled trials have been conducted on CBT for psychosis with some positive results, but trials comparing CBT to other nonspecific interventions have yielded less impressive findings. No well-controlled trial to date has attempted to dismantle the components of CBT for psychosis, to compare it to another empirically supported psychosocial intervention for this population, or to identify the specific mechanisms responsible for treatment effectiveness. In this paper, a review of the empirical status of CBT for psychosis is presented. In addition, promising but preliminary new research in this area is reviewed, including prevention and early intervention approaches and acceptance/mindfulness-based strategies. Within this context, limitations in the current literature are reviewed, and recommendations for future research are discussed. 相似文献
1000.