Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group.
PURPOSE: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. RESULT: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. CONCLUSION: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point. (+info)
Prevention of recurrent nephrolithiasis.
The first episode of nephrolithiasis provides an opportunity to advise patients about measures for preventing future stones. Low fluid intake and excessive intake of protein, salt and oxalate are important modifiable risk factors for kidney stones. Calcium restriction is not useful and may potentiate osteoporosis. Diseases such as hyperparathyroidism, sarcoidosis and renal tubular acidosis should be considered in patients with nephrolithiasis. A 24-hour urine collection with measurement of the important analytes is usually reserved for use in patients with recurrent stone formation. In these patients, the major urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Effective preventive and treatment measures include thiazide therapy to lower the urinary calcium level, citrate supplementation to increase the urinary citrate level and, sometimes, allopurinol therapy to lower uric acid excretion. Uric acid stones are most often treated with citrate supplementation. Data now support the cost-effectiveness of evaluation and treatment of patients with recurrent stones. (+info)
US-Japan workshops in medical mycology: past, present and future.
The Extramural Mycology Program of the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) has organized and implemented a five workshop series in medical mycology during a critical period in the evolution of contemporary medical mycology (1992 to 2000; http://www.niaid.nih.gov/research/dmid.htm). The goals of the workshop series were to: initiate interactions; build collaborations; identify research needs; turn needs into opportunities; stimulate molecular research in medical mycology; and summarize recommendations emerging from the workshop proceedings. A recurring recommendation in the series was to foster communications within and beyond the field of medical mycology. US-Japan interactions were noted as one specific example of potential information exchange for mutual benefit. The first formal action directed at this recommendation was the workshop Emergence and Recognition of Fungal Diseases convened under the auspices of the US-Japan Cooperative Medical Science Program (USJCMSP; http://www.niaid. nih.gov/dmid/us%5Fjapan/default.htm) in Bethesda, Maryland USA on 30 June 1999 (D.M. Dixon & T. Matsumoto, co-chairs). A major goal of the workshop was to present contemporary medical mycology to the Joint Committee of the USJCMSP through representative research presentations in order to make the Committee aware of current status in the field, and the potential for scientific interactions. The second formal action is the workshop, under the auspices of the Japanese Society for Medical Mycology Medical Perspectives of Fungal Genome Studies scheduled for 28 November 2000 in Tokyo, Japan (T. Matsumoto & D.M. Dixon, co-chairs). The NIAID Mycology Workshop series recommended interactions between the following groups: academic and pharmaceutical; medical and molecular (model systems); medical and plant pathogens; basic and clinical; mycologists and immunologists. The first two US-Japan workshops can be viewed as consistent with these recommendations, and serve as a Western/Eastern gateway for exchange. The focus of the second US-Japan workshop on genome projects for the medically important fungi provides an excellent model for international communications. Given the tsunami of information that is flowing from genomics and bioinformatics, it is clear that global interactions will be essential in managing and interpreting the data. (+info)
Guidelines and algorithms: perceptions of why and when they are successful and how to improve them.
Medicine is increasingly complex, a reality created by the explosion of knowledge during the last 50 years. The cost of applying this knowledge creates a daunting economic challenge. As a result, there has been a profusion of guidelines intended to influence medical practice. This report explores the interrelated issues and concepts that impact the value and success of guidelines. These include medical quality and error, compliance, and the impact on outcomes in an evidence-based medicine context. Lessons learned from previous guidelines must be understood in relation to human behavior. Legal implications of the guidelines must be considered because both an increase and a decrease in liability can be anticipated. Many products have been labeled "advocacy guidelines" with a negative context. They are believed to express motivation rather than optimizing care. The ideal of professionalism is challenged, and there is potential for the growing use of guidelines in enforcing punitive actions. Constructive experience has emphasized the appropriate required elements for practice guidelines: a systematic review of the literature, an assessment of the volume and level of the evidence, and development of a review process by an appropriate multidisciplinary group for consistency, clinical impact, and resource implications leading to clearly stated and reasonable recommendations. The dissemination of guidelines, beyond conventional publication in a journal, will impact the success of the intended outcomes. The exploitation of electronic avenues, including the Internet and the evolving interactive electronic medical record, seems to be essential for future success in these endeavors. (+info)
Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).
Since the 1990 NIH-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include: menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events. (+info)
The NIH criteria for parathyroidectomy in asymptomatic primary hyperparathyroidism: are they too limited?
OBJECTIVE: To determine whether preoperative and postoperative symptoms and outcome differ in patients who meet or fail to meet the NIH criteria for parathyroidectomy. SUMMARY BACKGROUND DATA: The NIH Consensus Conference on primary hyperparathyroidism in 1990 defined criteria for surgical intervention suggesting that some patients can be safely managed without surgery. METHODS: Over a 3-year period, 202 consecutive patients undergoing parathyroidectomy for primary hyperparathyroidism at a tertiary referral center were prospectively given a questionnaire regarding their symptoms and associated conditions during their initial and follow-up office visits as were 63 thyroid control patients. The 178 patients who completed the follow-up questionnaire were assigned to 2 groups according to the NIH criteria for parathyroidectomy. The frequency of preoperative symptoms and conditions associated with primary hyperparathyroidism as well as postoperative improvement in symptoms and surgical outcome were compared. RESULTS: Of the 178 parathyroid patients, 103 met the NIH criteria for parathyroidectomy whereas 75 did not. Patient profiles were similar in each group except mean ages, 55 versus 65, and preoperative serum calcium levels, 11.5 mg/dL versus 11.0 mg/dL (NIH and non-NIH groups, respectively; P < 0.001). The incidence of preoperative nonspecific somatic and neuropsychiatric symptoms and associated conditions was equivalent in both groups and more common than in the 63 thyroid control patients. After parathyroidectomy, symptomatic improvement was dramatic and equal between the 2 parathyroid groups. Postoperative mean serum calcium levels were similar (8.78 mg/dL, NIH group, versus 8.75 mg/dL, non-NIH group). CONCLUSION: Symptoms were more common in patients with primary hyperparathyroidism versus thyroid controls, but were not different between those patients who met the NIH criteria for parathyroidectomy and those who did not. Patients in both parathyroid groups benefited symptomatically after successful parathyroidectomy. (+info)
The pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part IV: the 1984 coronary primary prevention trial ends it--almost.
As of the early 1980s, despite the wealth of evidence from experimental animal models, the extensive epidemiologic evidence, the powerful genetic evidence, and the strongly suggestive clinical intervention trial results, most clinicians still remained unpersuaded regarding the relevance of the lipid hypothesis. What was needed was a well-designed, large-scale, long-term, double-blind study demonstrating a statistically significant impact of treatment on coronary heart disease events. The National Institutes of Health (NIH) had laid the groundwork for such a study as early as 1970, but the study was not completed and the results published until 1984. This study, the Coronary Primary Prevention Trial, showed that treatment with a bile acid binding resin reduced major coronary events in hypercholesterolemic men by 19%, with a P value of 0.05. The NIH followed this up with a national Consensus Development Conference on Lowering Blood Cholesterol to Prevent Heart Disease. For the first time, the NIH now went on record advocating screening for hypercholesterolemia and urging aggressive treatment for those at high risk. The Institute initiated a national cooperative program to that end, the National Cholesterol Education Program. For the first time, preventing coronary heart disease became a national public health goal. (+info)
Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement.
The National Institutes of Health Consensus Development Conference on Gastrointestinal Surgery for Severe Obesity brought together surgeons, gastroenterologists, endocrinologists, psychiatrists, nutritionists, and other health care professionals as well as the public to address: the nonsurgical treatment options for severe obesity, the surgical treatments for severe obesity and the criteria for selection, the efficacy and risks of surgical treatments for severe obesity, and the need for future research on and epidemiological evaluation of these therapies. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel recommended that (1) patients seeking therapy for severe obesity for the first time should be considered for treatment in a non-surgical program with integrated components of a dietary regimen, appropriate exercise, and behavioral modification and support, (2) gastric restrictive or bypass procedures could be considered for well-informed and motivated patients with acceptable operative risks, (3) patients who are candidates for surgical procedures should be selected carefully after evaluation by a multidisciplinary team with medical, surgical, psychiatric, and nutritional expertise, (4) the operation be performed by a surgeon substantially experienced with the appropriate procedures and working in a clinical setting with adequate support for all aspects of management and assessment, and (5) lifelong medical surveillance after surgical therapy is a necessity. The full text of the consensus panel's statement follows. (+info)