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941.
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943.
《Clinical oncology (Royal College of Radiologists (Great Britain))》2014,26(7):419-430
Medical treatments for glioblastoma face several challenges. Lipophilic alkylators remain the mainstay of treatment, emphasising the primacy of good blood–brain barrier penetration. Temozolomide has emerged as a major contributor to improved patient survival. The roles of procarbazine and vincristine in the procarbazine, lomustine and vincristine (PCV) schedule have attracted scrutiny and several lines of evidence now support the use of lomustine as effective single-agent therapy. Bevacizumab has had a convoluted development history, but clearly now has no major role in first-line treatment, and may even be detrimental to quality of life in this setting. In later disease, clinically meaningful benefits are achievable in some patients, but more impressively the combination of bevacizumab and lomustine shows early promise. Over the last decade, investigational strategies in glioblastoma have largely subscribed to the targeted kinase inhibitor paradigm and have mostly failed. Low prevalence dominant driver lesions such as the FGFR-TACC fusion may represent a niche role for this agent class. Immunological, metabolic and radiosensitising approaches are being pursued and offer more generalised efficacy. Finally, trial design is a crucial consideration. Progress in clinical glioblastoma research would be greatly facilitated by improved methodologies incorporating: (i) routine pharmacokinetic and pharmacodynamic assessments by preoperative dosing; and (ii) multi-stage, multi-arm protocols incorporating new therapy approaches and high-resolution biology in order to guide necessary improvements in science. 相似文献
944.
PurposeThis systematic review aims to better define the limitations and patterns with which patients with MBC and CNS metastasis are enrolled into early phase developmental therapeutics trials.MethodsIn June 2016, PubMed search was conducted using the following keywords: “Breast cancer”. Drug-development phase 1, phase 2 or phase 1/2 trials for patients with MBC were included. Multiple-histology trials and trials without an efficacy endpoint were excluded.ResultsIn total, 1474 studies were included; Inclusion criteria for 423 (29%) allowed for CNS metastasis, 770 (52%) either excluded or did not document eligibility of patients with CNS disease. Trials accruing patients with HER2-positive MBC and including targeted therapies had higher odds of allowing for patients with CNS disease (adjusted OR 1.56, 95% CI 1.08–2.2.6; p = 0.019 and 1.49, 95% 1.08–2.06; p = 0.014, respectively). There were also higher odds of accrual of patients with CNS involvement into clinical trials over time (odds ratio = 1.10, 95% CI 1.07–1.12; p < 0.0001).ConclusionMost published early phase clinical trials either did not clearly document or did not allow for accrual of patients with CNS disease. Early phase trials with targeted agents or enrolling HER2+ MBC had higher odds of permitting CNS metastases. 相似文献
945.
Jeffrey S. Berns 《Clinical journal of the American Society of Nephrology》2014,9(11):1988-1992
CKD is an important public health problem associated with substantial morbidity, impaired quality of life, shortened life expectancy, and excessive health care costs. Given its long preclinical latency, screening of asymptomatic individuals for CKD has been considered as a potentially useful means of early detection, with a goal of reducing CKD progression and its complications. A recent clinical practice guideline from the American College of Physicians that recommended against screening for CKD in asymptomatic adults without risk factors has reignited debate regarding CKD screening. Despite the lack of randomized controlled trial evidence showing benefits of CKD screening, even among individuals at increased risk for CKD, such as those with diabetes or hypertension or who are of certain high-risk racial or ethnic groups, a thoughtful and selective approach to CKD screening seems to be cost-effective and clinically valuable. CKD screening is recommended by several nephrology professional societies and appropriate in at-risk asymptomatic individuals with the intent of identifying and managing CKD, diagnosing the etiology of CKD, limiting or preventing CKD progression and its associated cardiovascular disease risk, and minimizing risk of AKI, inappropriate drug dosing, and nephrotoxic injury. 相似文献
946.
《Journal of acupuncture and meridian studies》2014,7(3):105-114
This paper presents some previously proposed neurobiological mechanisms on how acupuncture may work in some clinical applications from a clinician's perspective. For the treatment of musculoskeletal conditions, the proposed mechanisms included microinjury, increased local blood flow, facilitated healing, and analgesia. Acupuncture may trigger a somatic autonomic reflex, thereby affecting the gastric and cardiovascular functions. Acupuncture may also change the levels of neurotransmitters such as serotonin and dopamine, thereby affecting the emotional state and craving. This mechanism may form the basis for the treatment of smoking cessation. By affecting other pain-modulating neurotransmitters such as met-enkephalin and substance P along the nociceptive pathway, acupuncture may relieve headache. Acupuncture may affect the hypothalamus pituitary axis and reduce the release of the luteinizing hormone in the treatment of polycystic ovary syndrome. In addition, two other approaches to the acupuncture mechanism, the fascia connective tissue network and the primo vascular system, are briefly reviewed. Finally, the idea of true versus sham acupuncture points, which are commonly used in clinical trials, is examined because the difference between true and sham points does not exist in the neurobiological model. 相似文献
947.
HIV stigma remains a significant challenge for individuals living with HIV disease that can adversely affect overall well-being and patterns of HIV health service engagement. Finding ways to effectively address stigma concerns is, therefore, an important consideration in the clinical management of HIV disease. This study examined changes in perceived stigma in a sample of 48 adults living with HIV disease as an outcome of their participation in a mental health services program integrated with community-based HIV primary care. Participants completed a self-report instrument that provided a multidimensional measure of perceived HIV stigma, including distancing, blaming, and discrimination dimensions. This scale was administered at the baseline mental health service visit and then re-administered at the three-month follow-up point. Study results showed reductions in self-reported perceived HIV stigma over time for the distancing (t = 4.01, p = 0.000, d = 0.43), blaming (t = 2.79, p = 0.008, d = 0.35), and discrimination (t = 2.90, p = 0.006, d = 0.42) dimensions of stigma. These findings suggest that participation in HIV mental health services may have a favorable impact on perceived HIV stigma. Implications of these findings are discussed, including possible mechanisms that might explain the observed results as well as suggested directions for future research in this area. Randomized controlled trials would represent an important next step to investigate the extent to which HIV mental health services can reduce levels of perceived HIV stigma. 相似文献
948.
赵小丹 《中国继续医学教育》2021,(4)
目的对骨科临床教学中应用3D打印技术联合CBL教学法的临床实际应用价值进行研究分析。方法择取2018年4月—2019年4月间在我院骨科的实习生共80例作为研究对象,采用随机数字表法,将所有实习生分为观察组(40人)、对照组(40人);对照组应用常规教具联合CBL教学法,观察组应用3D打印技术联合CBL教学法,对比两组实习生的教学效果以及对教学活动的满意度。结果在理论知识以及临床操作方面,观察组实习同学成绩高于对照组(P<0.05);在对教学满意度方面,观察组实习同学高于对照组(P<0.05)。结论在骨科临床教学中,应用3D打印技术联合CBL教学法具有显著临床教学效果,学生的理论知识以及临床操作成绩更为优异,对教学满意度更高。 相似文献
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950.