Do we want more cancer patients on clinical trials If so, what are the barriers to greater accrual

It is often stated that only a small proportion of adult cancer patients participate in clinical trials. This is said to be a bad thing, with calls for more trials to include more patients. Here I argue that whether or not greater accrual to clinical trials would be a good thing depends on the trials we conduct. The vast majority of clinical trials in cancer are currently early phase trials, and most do not lead to further studies even if they have encouraging results. The key metric is thus not the number of patients on clinical trials, but the number on the sort of large, randomized, Phase III trials that can be used as a basis for clinical decisions. I also address two important barriers to greater clinical trial participation. The first barrier is financial: clinical research has long been the poor cousin of basic research, with perhaps no more than a nickel in the cancer research dollar going to clinical research. The second barrier is regulatory: clinical research has become so overburdened by regulation that it takes years to initiate a trial, and dedicated staff just to deal with the paperwork once the trial starts. This not only adds significantly to the costs of clinical research, but scares many young investigators away. It has been estimated that nearly half of all US-sponsored trials are being conducted abroad, and it is plausible that excessive regulation is at least partly responsible. That statistic should serve as a wake-up call to the US clinical research community to implement the recommendations of the now decade-old report of National Cancer Institute Clinical Trials Program Review Group, which largely center around simplifying trials and streamlining trial procedures.     

Les essais cliniques en médecine nucléaire

The EU clinical trials directive (2001/20/EC) was published on the 4th April 2001 and was transposed into French law in 2004. This new clinical trial regulation has modified considerably the research area including clinical trials conducted with radiopharmaceutical medicinal products. This new regulation aims at ensuring the protection of the health and safety of clinical trial participants, the ethical soundness and the reliability and robustness of data generated in clinical trials. In practice, the sponsor has to submit a clinical trial application to the Afssaps for authorization and to the concerned Ethics Committee for a positive opinion. The content of the clinical trial application regarding the investigational medicinal product is very detailed and a heavy technical dossier could be required in order to justify the quality of the medicinal product used in the clinical trial. Furthermore, pharmacy and radiopharmacy required specific authorizations for preparing these medicinal products. This new regulation could refrain nuclear medicine from conducting clinical trials.     

神经内科硕士研究生临床和科研能力的培养

临床医学硕士研究生阶段是培养临床和科研思维能力的重要阶段,从某种意义上说是人生和医疗生涯的关键时期。神经内科硕士研究生不仅应该具有一定的临床工作能力,还应具有一定的科研能力。临床工作能力培养包括临床基本功的培训,基本理论的加强和基本技能的培养,临床思维能力的培养及医患沟通能力的培养等多个方面。科研能力包括文献阅读能力、科研思维能力和论文写作能力等。这样,硕士研究生毕业后不仅能够诊治神经内科常见病和多发病,会思考临床工作中的问题,更重要的是能想办法探索和解决这些问题。这也是硕士研究生和本科生的本质区别。因此,研究生阶段是医学生涯一个重要的里程碑,临床和科研能力的培养对个人未来的发展具有十分重要的意义。     

Laboratory technicians; the Clinical Laboratory Law and its meaning to private physicians

The present laws and regulations relating to clinical laboratories in California are the outcome of over a quarter century of cooperative development. The medical profession, public health department, laboratory workers, and the legislature have worked together in this development.At first the system of certifying technicians and laboratories was on a voluntary basis. The clinical laboratory law in effect legalized and made generally applicable a system which had already been accepted voluntarily. The application of the clinical laboratory law provides physicians a reasonable assurance that competence and reliability will prevail in clinical laboratory operation. Of great importance is the conduct of proper training programs by approved laboratories. Since modern medical practice is so dependent on accurate clinical laboratory work it is essential that special effort be directed by physicians toward influencing young people to enter the profession of medical technology.     

高等医学院校临床实践教学管理存在的问题与对策

临床实践教学在高等医学教育教学活动中占有特殊地位,临床实践教学管理对临床实践教学过程顺利进行至关重要。文章阐述了临床实践教学管理的内涵,分析了当前高等医学院校在临床实践教学管理中存在的问题,并针对临床实践教学管理工作中存在的薄弱环节提出了解决的对策。     

Information retrieval for patient care.

Doctors need clinical information during most consultations with patients, and much of this need could be satisfied by material from online sources. Advances in data communication technologies mean that multimedia information can be transported rapidly to various clinical care locations. However, selecting the few items of information likely to be useful in a particular clinical situation from the mass of information available is a major problem. Current information retrieval systems are designed primarily for use in research rather than clinical care. The design, implementation, and critical evaluation of new information retrieval systems for clinical care should be guided by knowledgeable clinical users.     

医患视角下的临床路径实施情况调查

目的:调查分析实施过程中各种可能的影响因素。方法:就临床路径实施情况对患者及医务人员进行问卷调查,并分析其影响因素。结果:试点临床路径后患者住院时间及住院费用有显著下降,受试者对临床路径认知程度、自身文化水平、不同疾病差异等导致问卷结果差异和变异情况的发生。结论:临床路径的实施有着多方面的积极作用,进一步推广应用需改进临床路径的宣传教育、制定和落实情况,并加强有关影响因素的深入研究。     

Application of predictive biosimulation within pharmaceutical clinical development: examples of significance for translational medicine and clinical trial design

The challenge of accurately predicting human clinical outcome based on preclinical data has led to a high failure rate of compounds in human clinical trials. A series of methods are described by which biosimulation can address these challenges and guide the design and evaluation of experimental and clinical protocols. Early compound development often proceeds on the basis of preclinical data from animal models. The systematic evaluation possible in a simulation can assist in the critical step of translating the preclinical outcomes to human physiology. Later in the process, clinical trials definitively establish a therapy's beneficial effects, as well as any adverse side effects. Biosimulation allows for the optimal design of clinical trials to ensure that key issues are addressed effectively and efficiently, and in doing so, improves the success rate of the trials.     

Molecular characterization of clinical Saccharomyces cerevisiae isolates and their association with non-clinical strains

We assessed the molecular characterization of 96 clinical isolates of S. cerevisiae from a Spanish medical institution and we compared them with 6 non-clinical strains isolated from wine, beer and bread and 1 S. boulardii strain collected from a commercial preparation. The strains were subjected to HinfI mtDNA restriction analysis and PCR amplification of delta sequences. Although both techniques are appropriate for routine clinical analysis, that based on PCR turned out to be the most discriminating. This study, apart from providing tools for clinical application, deals with the relationships between clinical and non-clinical strains. The two baker's yeasts analysed shared mtDNA and PCR patterns with a group of 31 clinical isolates. An exogenous entry of a strain was also reflected in the case of 19 clinical isolates and the therapeutic strain S. boulardii. Both baker's yeasts and S. boulardii were identified respectively among 32.3% and 19.8% of the clinical isolates and there seemed to be a connection between their ability to colonize humans and their ability to cause vaginal infection. The rest of food isolates were not grouped with clinical strains.     

医患视角下的临床路径实施情况调查

目的：调查分析实施过程中各种可能的影响因素。方法：就临床路径实施情况对患者及医务人员进行问卷调查,并分析其影响因素。结果：试点临床路径后患者住院时间及住院费用有显著下降,受试者对临床路径认知程度、自身文化水平、不同疾病差异等导致问卷结果差异和变异情况的发生。结论：临床路径的实施有着多方面的积极作用,进一步推广应用需改进临床路径的宣传教育、制定和落实情况,并加强有关影响因素的深入研究。     

Clinical trials in systemic sclerosis: lessons learned and outcomes

The pathogenesis of systemic sclerosis (SSc) is complex and largely unclear. The clinical heterogeneity of the disease and its progression over a number of years makes the choice of endpoints in the design of clinical trials difficult. The overwhelming need in this disease is to diagnose it early and identify those patients who will benefit most from early, aggressive treatment that potentially can alter the clinical disease course. To achieve this, innumerable challenges must be overcome. This article reviews data from recent clinical trials and the lessons derived from retrospective observational studies, databases, and patient registries. Taken together, these observations will help to improve our understanding of the diverse clinical course of SSc and permit refinement of existing outcome measures for the design of future clinical trials, in which the likelihood of observing a positive treatment effect with the drugs at our disposal will be maximized.     

On clinical efficacy: why biofeedback does--and does not--work

Questions of clinical efficacy are becoming more prominent in this era of diminishing funds for research and clinical care, and new treatment procedures, in particular, are being rigorously scrutinized. This presents a challenge for the relatively recent field of biofeedback and applied psychophysiology. This field has a strong scientific orientation and a rapidly expanding research base, which includes many well-controlled clinical outcome studies. The point is raised, and illustrated with data from current clinical outcome studies, that it is time for a shift in emphasis away from simply piling study upon study and toward more thoughtful interpretation of experimental and clinical findings and the development of a clearer conceptual framework for biofeedback therapy and research.     

Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers

Neoplastic growth and dissemination involve increased proteolytic activity that is able to escape the regulative elements. Matrix metalloproteinases (MMPs), particularly gelatinases A and B (MMP-2 and -9), play a role in tumor invasion and angiogenesis, and they participate in cancer progression in several neoplasias. The expression of tissue inhibitors of gelatinases, TIMPs-1 and -2, has also been shown to be associated with the clinical course in some cancers. The prognostic value of these markers, however, seems to vary a great deal in different neoplastic diseases. In this review, the impact of the gelatinases and their inhibitors on the clinical course in several solid cancers is evaluated based on the growing data from recent clinical studies. The clinical data most often explore the overexpression of mRNA or immunoreactive protein in tumor tissue, or measure the concentration of the circulating proteinase or its inhibitor in pretreatment or follow-up serum samples. The growing amount of recent clinical data suggests that the impact of gelatinases on treatment decisions should be tested in clinical trials.     

Pruritus is a common feature in sheep infected with the BSE agent

Background

The variability in the clinical or pathological presentation of transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie and bovine spongiform encephalopathy (BSE), has been attributed to prion protein genotype, strain, breed, clinical duration, dose, route and type of inoculum and the age at infection. The study aimed to describe the clinical signs in sheep infected with the BSE agent throughout its clinical course to determine whether the clinical signs were as variable as described for classical scrapie in sheep. The clinical signs were compared to BSE-negative sheep to assess if disease-specific clinical markers exist.

Results

Forty-seven (34%) of 139 sheep, which comprised 123 challenged sheep and 16 undosed controls, were positive for BSE. Affected sheep belonged to five different breeds and three different genotypes (ARQ/ARQ, VRQ/VRQ and AHQ/AHQ). None of the controls or BSE exposed sheep with ARR alleles were positive. Pruritus was present in 41 (87%) BSE positive sheep; the remaining six were judged to be pre-clinically infected. Testing of the response to scratching along the dorsum of a sheep proved to be a good indicator of clinical disease with a test sensitivity of 85% and specificity of 98% and usually coincided with weight loss. Clinical signs that were displayed significantly earlier in BSE positive cases compared to negative cases were behavioural changes, pruritic behaviour, a positive scratch test, alopecia, skin lesions, teeth grinding, tremor, ataxia, loss of weight and loss of body condition. The frequency and severity of each specific clinical sign usually increased with the progression of disease over a period of 16–20 weeks.

Conclusion

Our results suggest that BSE in sheep presents with relatively uniform clinical signs, with pruritus of increased severity and abnormalities in behaviour or movement as the disease progressed. Based on the studied sheep, these clinical features appear to be independent of breed, affected genotype, dose, route of inoculation and whether BSE was passed into sheep from cattle or from other sheep, suggesting that the clinical phenotype of BSE is influenced by the TSE strain more than by other factors. The clinical phenotype of BSE in the genotypes and breed studied was indistinguishable from that described for classical scrapie cases.     

Evaluation of the effectiveness of antibacterial therapy

It is recommended to estimate the clinical effect of antibacterial therapy in patients with different purulent inflammatory complications with an account of the data on both the clinical and bacteriological examinations. The full affect consisted in disappearance of the clinical signs and complete bacteriological sanation of the purulent inflammatory foci. The partial effect was shown by a marked decrease in the clinical manifestations without complete bacteriological sanation of the foci. The ill effect was evidenced by clinical picture having no time course and no favourable time course in bacteriological tests. No effect was indicated by deterioration of the clinical picture and no favourable time course in the bacteriological tests.     

Comparison between videotape and personal teaching as methods of communicating clinical skills to medical students.

The efficacy of video recording in transmitting clinical knowledge and skills to medical students was tested by recording on videotape demonstrations of physical examinations given by five clinicians to a randomly selected group of 12 students (personal group) from the first clinical year and then showing these recordings, under identical conditions, to 13 students from the same year (video group). The efficacy of both the personal and video mediums in terms of whether content was retained was tested by a questionnaire completed by all students at the end of the sessions and by a structured clinical assessment in which students were asked to demonstrate some of the same clinical tasks three weeks after the demonstration. In answering the questionnaire the video group obtained a mean (SD) score of 20.8 (7.0) (maximum possible score 40), which was not significantly different from the score achieved by the personal group (17.4 (7.7)). The video group was able to reproduce 44 (10)% of the total clinical steps demonstrated and the personal group 45 (14)%. Videotaped demonstrations can be as effective as personal teaching of clinical methods, and video should be developed as a medium for first line clinical teaching.     

Clinical penetrance of C282Y homozygous HFE haemochromatosis

The prevalence of the C282Y homozygous HFE genotype is high, approximately 1 in 200 in populations of Anglo-Celtic descent, and most authorities assumed this mutation would have a high clinical penetrance. Recent studies report the clinical penetrance of C282Y homozygous hereditary haemochromatosis is much lower than its prevalence, with possibly less than 5% developing clinical disease, although there is lack of consensus on a precise estimate. This review discusses reasons for this paradigm shift, including controversy on various definitions of clinical penetrance.It is inescapable that there are pronounced variations in clinical penetrance, and that certain C282Y homozygous individuals will not develop the clinical phenotype. This has prompted a search for modifier gene mutations amongst iron-metabolism genes, especially the known non- HFE haemochromatosis genes, and for possible environmental factors which might explain the observed variation in clinical penetrance.     

"There are too many, but never enough": qualitative case study investigating routine coding of clinical information in depression

Background

We sought to understand how clinical information relating to the management of depression is routinely coded in different clinical settings and the perspectives of and implications for different stakeholders with a view to understanding how these may be aligned.

Materials and Methods

Qualitative investigation exploring the views of a purposefully selected range of healthcare professionals, managers, and clinical coders spanning primary and secondary care.

Results

Our dataset comprised 28 semi-structured interviews, a focus group, documents relating to clinical coding standards and participant observation of clinical coding activities. We identified a range of approaches to coding clinical information including templates and order entry systems. The challenges inherent in clearly establishing a diagnosis, identifying appropriate clinical codes and possible implications of diagnoses for patients were particularly prominent in primary care. Although a range of managerial and research benefits were identified, there were no direct benefits from coded clinical data for patients or professionals. Secondary care staff emphasized the role of clinical coders in ensuring data quality, which was at odds with the policy drive to increase real-time clinical coding.

Conclusions

There was overall no evidence of clear-cut direct patient care benefits to inform immediate care decisions, even in primary care where data on patients with depression were more extensively coded. A number of important secondary uses were recognized by healthcare staff, but the coding of clinical data to serve these ends was often poorly aligned with clinical practice and patient-centered considerations. The current international drive to encourage clinical coding by healthcare professionals during the clinical encounter may need to be critically examined.     

Clinical examination,xeromammography, and fine-needle aspiration cytology in diagnosis of breast tumours.

The diagnostic accuracy of clinical examination, xeromammography, and fine-needle aspiration cytology was compared with definitive histological findings in 255 breast lumps excised during one year. When suitable aspirates were obtained for cytological examination the diagnostic accuracy of aspiration cytology was higher than clinical examination or xeromammography. A diagnostic accuracy of 99% was achieved when all three screening tests were in agreement. As well as confirming a clinical diagnosis of malignancy, cytology is useful in identifying malignancy when clinical findings suggest that the tumour is benign. The availability of accurate cytology has affected patient management in many ways. Xeromammography did not enhance the diagnostic accuracy of clinical examination and aspiration cytology in patients presenting with a breast lump and, as a procedure with potential hazard, the benefit of routine xeromammography is questionable when an efficient cytological service is available.