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Methods for voluntary weight loss and control. NIH Technology Assessment Conference Panel.

One quarter to one third of Americans are overweight; as many as 40% of women and 24% of men are trying to lose weight at any given time; many have tried a variety of methods, such as diets, exercise, behavior modification, and drugs. In controlled settings, participants who remain in weight loss programs usually lose approximately 10% of their weight. However, one third to two thirds of the weight is regained within 1 year, and almost all is regained within 5 years. For many overweight persons, achieving and maintaining a healthy weight is a lifelong challenge. Successful weight loss improves several cardiovascular risk factors and diabetic control; effects on mortality are not clear. Several epidemiologic studies have found that weight loss is associated with increased mortality but the reasons for weight loss were not known. Survey data also confirm that many Americans who are not overweight, particularly young women, are trying to lose weight, which may have adverse physical and psychological consequences. Because of the importance of these issues, research on weight and on weight loss and control should assume a high priority on the nation's health agenda.

Adult↗

Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration.

The US Food and Drug Administration (FDA) approved marketing of diethylstilbestrol in 1941 and conjugated equine estrogens (CEE) in 1942 for treatment of menopausal symptoms. Estrogen sales doubled and tripled in the mid-1960s to mid-1970s, until 1975, when reports of increased endometrial cancer in estrogen users resulted in a dramatic decline. Estrogen use increased again, with evidence of protective effects of progestins on estrogen-induced endometrial changes, combined with a 1982 report that Premarin (conjugated estrogen tablets; Wyeth Pharmaceuticals, Philadelphia, PA) retained bone mass and a 1984 National Institutes of Health (NIH) Consensus Conference on Osteoporosis statement that estrogens were the most effective means for preventing bone loss. Despite conflicting reports in 1985 regarding the relation between estrogens and coronary heart disease (CHD), many published observations of reduced CHD risk in estrogen users--reinforced by clinical trial findings in 1995 of favorable lipoprotein changes in women assigned to CEE with or without a progestin--promoted increased use through the 1990s. By 2001, approximately 15 million US women were using estrogen therapy, with or without progestins. The 2002 Women's Health Initiative (WHI) report of greater harm than benefit of combined CEE plus a progestin resulted in a precipitous decrease in estrogen and progestin use and a serious reevaluation of menopausal hormone therapy, as well as increased interest in alternative approaches to managing menopausal symptoms, including use of "bioidentical" hormones. FDA guidelines regarding treatment indications for vasomotor symptoms, vaginal atrophy, and osteoporosis prevention have resulted in approval of several estrogen (and progestin) formulations, doses, and routes of administration, thereby providing many options for women who seek conventional therapy.

Drug Approval↗

NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the use of endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy. PARTICIPANTS: A non-Federal, non-advocate, 13-member panel representing the fields of gastroenterology, hepatology, clinical epidemiology, oncology, biostatistics, surgery, health services research, radiology, internal medicine, and the public. In addition, experts in these same fields presented data to the panel and to a conference audience of approximately 300. EVIDENCE: Presentations by experts; a systematic review of the medical literature provided by the Agency for Healthcare Research and Quality; and an extensive bibliography of ERCP research papers, prepared by the National Library of Medicine. Scientific evidence was given precedence over clinical anecdotal experience. CONFERENCE PROCESS: Answering predefined questions, the panel drafted a statement based on the scientific evidence presented in open forum and the scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the experts and the audience for comment. The panel then met in executive session to consider these comments and released a revised statement at the end of the conference. The statement was made available on the World Wide Web at http://consensus.nih.gov immediately after the conference. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: In the diagnosis of choledocholithiasis, magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and ERCP have comparable sensitivity and specificity. Patients undergoing cholecystectomy do not require ERCP preoperatively if there is low probability of having choledocholithiasis. Laparoscopic common bile duct exploration and postoperative ERCP are both safe and reliable in clearing common bile duct stones. ERCP with endoscopic sphincterotomy (ES) and stone removal is a valuable therapeutic modality in choledocholithiasis with jaundice, dilated common bile duct, acute pancreatitis, or cholangitis. In patients with pancreatic or biliary cancer, the principal advantage of ERCP is palliation of biliary obstruction when surgery is not elected. In patients who have pancreatic or biliary cancer and who are surgical candidates, there is no established role for preoperative biliary drainage by ERCP. Tissue sampling for patients with pancreatic or biliary cancer not undergoing surgery may be achieved by ERCP, but this is not always diagnostic. ERCP is the best means to diagnose ampullary cancers. ERCP has no role in the diagnosis of acute pancreatitis except when biliary pancreatitis is suspected. In patients with severe biliary pancreatitis, early intervention with ERCP reduces morbidity and mortality compared with delayed ERCP. ERCP with appropriate therapy is beneficial in selected patients who have either recurrent pancreatitis or pancreatic pseudocysts. Patients with type I sphincter of Oddi dysfunction (SOD) respond to endoscopic sphincterotomy (ES). Patients with type II SOD should not undergo diagnostic ERCP alone. If sphincter of Oddi manometer pressures are >40 mmHg, ES is beneficial in some patients. Avoidance of unnecessary ERCP is the best way to reduce the number of complications. ERCP should be avoided if there is a low likelihood of biliary stone or stricture, especially in women with recurrent pain, a normal bilirubin, and no other objective sign of biliary disease. Endoscopists performing ERCP should have appropriate training and expertise before performing advanced procedures. With newer diagnostic imaging technologies emerging, ERCP is evolving into a predominantly therapeutic procedure.

Acute Disease↗

News media coverage of screening mammography for women in their 40s and tamoxifen for primary prevention of breast cancer.

CONTEXT: In the late 1990s, 3 events pertaining to breast cancer prevention received considerable attention in the US news media: a National Institutes of Health (NIH) consensus panel recommended against routine screening mammography for women in their 40s (January 1997), the National Cancer Institute (NCI) subsequently reversed the recommendation (March 1997), and an NCI-sponsored study demonstrated the efficacy of tamoxifen in the primary prevention of breast cancer (April 1998). OBJECTIVE: To examine how the major US news media covered the potential benefits and harms of 2 breast cancer preventive strategies. DESIGN AND SETTING: Content analysis of US news stories reporting on the breast cancer prevention events. We used Lexis-Nexis to search for print news stories in the 10 highest-circulation US newspapers and requested transcripts from 3 major television networks to obtain all relevant news coverage in the 2 weeks following each event. MAIN OUTCOME MEASURES: Attitude toward preventive strategy (encourage, neutral, discourage); level of uncertainty about benefit and how benefits and harms were presented. RESULTS: Twenty-seven stories about the NIH consensus panel, 24 about the NCI reversal, and 34 about tamoxifen appeared in high-profile news media within 2 weeks of each event. Sixty-seven percent of NIH consensus panel stories left the impression that there was a lot of uncertainty about whether women aged 40 to 49 years should undergo screening, but 59% suggested that women should probably or definitely be screened. Only 4 stories suggested that women faced a genuine decision about what to do. The level of uncertainty reported was substantially lower following the NCI reversal (21% suggested a lot of uncertainty), and most stories (96%) suggested that women should be screened. In contrast, tamoxifen stories highlighted uncertainty about what women at high risk should do (62% suggested there was a lot of uncertainty), and none left the impression that women should definitely take the drug (24% suggested they probably should). Sixty-five percent of these stories suggested that women faced a genuine choice and would have to weigh the risks and benefits themselves. CONCLUSIONS: Most news stories favored routine use of screening mammography and urged caution about using tamoxifen. Almost all noted the potential harms of each preventive strategy; however, the negative aspects of tamoxifen received greater emphasis. Whereas taking tamoxifen was presented as a difficult decision, having a mammogram was presented as something women ought to do.

Adult↗

NIH conference. Airway inflammation.

Diseases characterized by airway inflammation, excessive airway secretion, and airway obstruction affect a substantial proportion of the population. These diseases include asthma, chronic bronchitis, bronchiectasis, and cystic fibrosis. Asthma and chronic bronchitis may affect 25 million persons in the United States. Much progress has been made in the last decade toward an understanding of the mechanisms underlying chronic airway inflammation; recent work has resulted in several new concepts of the initiation and maintenance of airway inflammation. Airway production of chemokines, cytokines, and growth factors in response to irritants, infectious agents, and inflammatory mediators may play an important role in the modulation of acute and chronic airway inflammation. Lipid mediators may be produced by resident airway cells and by inflammatory cells; production of these mediators may also be altered by inflammatory cytokines. Increased airway obstruction may be related to intercurrent viral respiratory infection and to the induction of airway inflammation and airway hyperreactivity that results from such infection. Furthermore, several models exist to explain the processes by which airway inflammation is perpetuated in diseases such as asthma and chronic bronchitis. These include neurogenic inflammation, the perpetuation of the acute inflammatory response, and cycles of airway epithelial cell-mediated and inflammatory cell-mediated recruitment and activation of inflammatory cells. An understanding of these mechanisms of airway inflammation may provide the clinician with new therapeutic approaches to the treatment of these common and chronic diseases.

Bronchi↗

NIH conference. Antiretroviral therapy in AIDS.

OBJECTIVE: To review recent developments of antiretroviral therapy for the acquired immunodeficiency syndrome (AIDS) and related disorders. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: An edited and updated summary of a Clinical Staff Conference held 26 October 1988 at the National Institutes of Health. The speakers discussed their own work as well as related work from other groups. DATA SYNTHESIS: The discovery that human immunodeficiency virus (HIV) causes AIDS has permitted the development of rational antiviral therapy for this disease. Various steps in the replicative cycle of HIV can be targeted for intervention. More basic research into the life cycle of HIV is therefore likely to yield new therapeutic approaches. In 1985, nucleoside analogues called dideoxynucleosides were discovered to be potent inhibitors of HIV replication in vitro. Dideoxynucleosides selectively inhibit HIV reverse transcriptase after they are phosphorylated intracellularly to 5'-triphosphates. One dideoxynucleoside, 3'-azido-2',3'-dideoxythymidine (AZT or zidovudine) has been found to prolong the life of patients with AIDS. This drug can partially reverse HIV dementia and decrease short-term progression to AIDS; it has been approved for treating HIV-infected patients with fewer than 500 CD4+ cells/mm3. AZT is only a first step in developing new therapy for AIDS. Its use is associated with toxicities, particularly bone marrow suppression. Several groups have reported the development of AZT-resistant strains of HIV. Other dideoxynucleosides whose toxicity profiles differ from that of AZT have also shown activity against HIV in early clinical studies. Large-scale, randomized trials of these drugs are now under way. Studies have shown that the binding of HIV to CD4 may be blocked by genetically engineered forms of CD4 and that HIV protease may be inhibited by substrate analogues. Protease inhibitors are an excellent area for further study in patients. Antisense oligonucleotide therapy may target the regulatory genes of HIV and is also being considered. CONCLUSION: With these advances, AIDS is gradually changing from an imminently fatal disease to one that can be managed with the judicious use of drugs and biologics. Progress against AIDS will continue, provided that researchers adhere to the principles of controlled trials.

Acquired Immunodeficiency Syndrome↗

Models for epilepsy and epileptogenesis: report from the NIH workshop, Bethesda, Maryland.

PURPOSE: The workshop explored the current problems, needs, and potential usefulness of existing methods of discovery of new therapies to treat epilepsy patients. Resistance to medical therapy (pharmacoresistance) and the development of epilepsy (epileptogenesis) are recognized as two of the major problems in epilepsy treatment today. At the same time, there is growing awareness that the development of new therapies has slowed, a trend that has economic and scientific roots. To move toward new and more effective therapies, novel approaches to therapy discovery are needed. METHODS: A workshop was held in March 2001 with the charge to develop a plan to move the exploration and discovery process forward. Participants from academia, government, and industry reviewed the current status of epilepsy therapy and explored the identification of potential new therapies. RESULTS: At the end of the 2-day meeting, the panel made a series of recommendations. The two major recommendations were (a) to establish a means for continuing the examination of new approaches to therapy discovery, and (b) to identify models and approaches to therapy discovery that may identify treatments that are more successful than those available. Further recommendations were made to support the development of technology (miniaturization, computerization, video monitoring, etc.) to facilitate the use of the new models and to identify the mechanisms of therapy success and failure. CONCLUSIONS: Understanding the epidemiology of therapy resistance and providing support for new approaches to therapy development were identified as key issues for introduction of new and more effective treatments.

Animals↗

Integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia. NIH Technology Assessment Panel on Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic Pain and Insomnia.

OBJECTIVE: To provide physicians with a responsible assessment of the integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia. PARTICIPANTS: A nonfederal, nonadvocate, 12-member panel representing the fields of family medicine, social medicine, psychiatry, psychology, public health, nursing, and epidemiology. In addition, 23 experts in behavioral medicine, pain medicine, sleep medicine, psychiatry, nursing, psychology, neurology, and behavioral and neurosciences presented data to the panel and a conference audience of 528 during a 1 1/2-day public session. Questions and statements from conference attendees were considered during the open session. Closed deliberations by the panel occurred during the remainder of the second day and the morning of the third day. EVIDENCE: The literature was searched through MEDLINE, and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. ASSESSMENT PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. CONCLUSIONS: A number of well-defined behavioral and relaxation interventions now exist and are effective in the treatment of chronic pain and insomnia. The panel found strong evidence for the use of relaxation techniques in reducing chronic pain in a variety of medical conditions as well as strong evidence for the use of hypnosis in alleviating pain associated with cancer. The evidence was moderate for the effectiveness of cognitive-behavioral techniques and biofeedback in relieving chronic pain. Regarding insomnia, behavioral techniques, particularly relaxation and biofeedback, produce improvements in some aspects of sleep, but it is questionable whether the magnitude of the improvement in sleep onset and total sleep time are clinically significant.

Behavior Therapy↗

NIH conference. Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Congenital adrenal hyperplasia describes a group of inherited autosomal recessive disorders characterized by an enzymatic defect in cortisol biosynthesis, compensatory increases in corticotropin secretion, and adrenocortical hyperplasia. 21-Hydroxylase deficiency is responsible for more than 95% of cases and is one of the most common known autosomal recessive disorders. The classic or severe type presents in the newborn period or early childhood with virilization and adrenal insufficiency, with or without salt loss; the mild or nonclassic form presents in late childhood or early adulthood with mild hyperandrogenism and is an important cause of masculinization and infertility in women. This wide range of phenotypic expression is mostly explained by genetic variation, although genotype-phenotype discrepancies have been described. Reproductive, metabolic, and other comorbid conditions, including risk for tumors, are currently under investigation in both forms of the disease. A high proportion of patients with adrenal incidentalomas may be homozygous or heterozygous for 21-hydroxylase deficiency. Women with congenital adrenal hyperplasia often develop the polycystic ovary syndrome. Ectopic adrenal rest tissue is often found in the testes of men with congenital adrenal hyperplasia; characteristic clinical and radiologic findings help differentiate this tissue from other tumors. Levels of corticotropin-releasing hormone are elevated in patients with depression and anxiety and are expected to be elevated in patients with congenital adrenal hyperplasia; it is unknown whether patients with 21-hydroxylase deficiency have an increased incidence of these psychiatric disorders. Abnormalities in both the structure and function of the adrenal medulla have been shown in patients with classic congenital adrenal hyperplasia, and the degree of adrenomedullary impairment may be a biomarker of disease severity. The 21-hydroxylase-deficient mouse has provided a useful model with which to examine disease mechanisms and test new therapeutic interventions in classic disease, including gene therapy. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace both glucocorticoids and mineralocorticoids. However, clinical management is often complicated by inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. New treatment approaches currently under investigation include combination therapy to block androgen action and inhibit estrogen production, and bilateral adrenalectomy in the most severely affected patients. Other approaches, which are in a preclinical stage of investigation, include treatment with a corticotropin-releasing hormone antagonist and gene therapy.

Adrenal Hyperplasia, Congenital↗

NIH state-of-the-science statement on management of the clinically inapparent adrenal mass ("incidentaloma").

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the management of clinically inapparent adrenal masses ("incidentalomas"). PARTICIPANTS: A non-Federal, nonadvocate, 12-member panel representing the fields of medicine, surgery, endocrinology, pathology, biostatistics, epidemiology, radiology, oncology, and the public. In addition, experts in these same fields presented data to the panel and to a conference audience of approximately 300. EVIDENCE: Presentations by experts; a systematic review of the medical literature provided by the Agency for Healthcare Research and Quality; and an extensive bibliography of incidentaloma research papers, prepared by the National Library of Medicine. Scientific evidence was given precedence over clinical anecdotal experience. CONFERENCE PROCESS: Answering predefined questions, the panel drafted a statement based on the scientific evidence presented in open forum and the scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the experts and the audience for comment. The panel then met in executive session to consider these comments and released a revised statement at the end of the conference. The statement was made available on the World Wide Web at http://consensus.nih.gov immediately after the conference. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: The management of clinically inapparent adrenal masses is complicated by limited studies of incidence, prevalence, and natural history, including the psychologic impact on the patient who is informed of the diagnosis. Improvements in the resolution of abdominal imaging techniques combined with increased use of abdominal imaging suggest that the prevalence of clinically inapparent adrenal masses will continue to escalate. The low prevalence of adrenal cortical carcinomas and the relatively low incidence of progression to hyperfunction call into question the advisability of the current practice of intense, long-term clinical followup of this common condition. All patients with an incidentaloma should have a 1-mg dexamethasone suppression test and a measurement of plasma-free metanephrines. Patients with hypertension should also undergo measurement of serum potassium and plasma aldosterone concentration/plasma renin activity ratio. A homogeneous mass with a low attenuation value (less than 10 HU) on CT scan is likely a benign adenoma. Surgery should be considered in all patients with functional adrenal cortical tumors that are clinically apparent. All patients with biochemical evidence of pheochromocytoma should undergo surgery. Data are insufficient to indicate the superiority of a surgical or nonsurgical approach to manage patients with subclinical hyperfunctioning adrenal cortical adenomas. Recommendations for surgery based upon tumor size are derived from studies not standardized for inclusion criteria, length of followup, or methods of estimating the risk of carcinoma. Nevertheless, patients with tumors greater than 6 cm usually are treated surgically, while those with tumors less than 4 cm are generally monitored. In patients with tumors between 4 and 6 cm, criteria in addition to size should be considered in making the decision to monitor or proceed to adrenalectomy. The literature on adrenal incidentaloma has proliferated in the last several years. Unfortunately, the lack of controlled studies makes formulating diagnostic and treatment strategies difficult. Because of the complexity of the problem, the management of patients with adrenal incidentalomas will be optimized by a multidisciplinary team approach involving physicians with expertise in endocrinology, radiology, surgery, and pathology. The paucity of evidence-based data highlights the need for well-designed prospective studies. Either open or laparoscopic adrenalectomy is an acceptable procedure for resection of an adrenal mass. The choice of procedure will depend upon the likelihood of an invasive adrenal cortical carcinoma, technical issues, and the experience of the surgical team. In patients with tumors that remain stable on two imaging studies carried out at least 6 months apart and do not exhibit hormonal hypersecretion over 4 years, further followup may not be warranted.

Adrenal Gland Neoplasms↗

National Institutes of Health State-of-the-Science Conference Statement: Symptom management in cancer: pain, depression, and fatigue, July 15-17, 2002.

BACKGROUND: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. STATE-OF-THE-SCIENCE PROCESS: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.

Depression↗

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.

Consensus Development Conferences, NIH as Topic↗

National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002.

BACKGROUND: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. State-of-the-Science Process: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.

Biomedical Research↗

A proposal of subcategorization of bacterial prostatitis: NIH category I and II diseases can be further subcategorized on analysis by therapeutic and immunological procedures.

AIM: We propose preliminarily that acute (category I of the NIH consensus definition) and chronic prostatitis (category II) can be subcategorized into primary and recurrent diseases based on the precise analysis of the clinical course and the immunological parameters in prostatic secretions of our cases. METHODS: Five patients with stone-free, acute febrile prostatitis and nine patients with acute episodes of afebrile urinary infection were included. The expressed prostatic secretions (EPS) were collected soon after the acute illnesses subsided after medication administration and they were examined microscopically, bacteriologically, and serologically. First-line medications were cefem antibiotics with conventional doses for febrile cases and low doses for afebrile cases. They were administered for at least 2 weeks. Second-line conventional medication with sulfamethoxazole-trimethoprim or levofloxacin was given only to the patients in whom remaining prostatic infections were revealed. RESULTS: The first-line medications were successful in all patients and they promptly became asymptomatic in 1 week. All the EPS were infected except for two afebrile cases. Prostatic infections were eradicated by second-line conventional medications. In a patient with afebrile prostatitis whose EPS were free of macrophages and immunoglobulin (Ig)M, the eradication of prostatic pathogens was achieved without second-line antibacterial medication. CONCLUSIONS: Bacterial prostatitis could be classified into primary and recurrent chronic infections in each of the febrile (category I) and afebrile (category II) illnesses. A cefem regimen in varying doses was a clue for differential diagnosis as it did not affect the pathogens in the prostatic ducts or acini unless heavy urine reflux occurred in the ductal draining systems. Macrophages and immunoglobulins, especially IgM, in the EPS were useful immunological parameters to differentiate primary and recurrent infections of the prostate. Fluoroquinolones or sulfamethoxazole-trimethoprim should not be employed in acute urinary infections in male patients until the confirmation of prostatic infection to avoid injudicious use of them, which might cause an increasing prevalence of resistant uropathogens in the community. The evacuation of the prostate by repetitive massage seemed to be effective to enhance the prompt eradication of pathogens from the prostatic tissue and to keep patients asymptomatic throughout the course of the disease by preventing tissue pressure elevation.

Adult↗

Workshop on Alcohol Use and Health Disparities 2002: a call to arms.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) sponsored a "Workshop on Alcohol Use and Health Disparities 2002: A Call to Arms," on December 5, 2002, in Bethesda, Maryland, USA. This workshop was part of the NIAAA/NIH comprehensive strategic plan to reduce, and ultimately eliminate, health disparities. Eleven topics were addressed: (1). biomedical risk factors that may contribute to disparities in the toxic effects of alcohol; (2). alcohol and gene-environment interactions that affect the health of diverse groups; (3). alcohol pharmacogenetics in Mexican-Americans; (4). determinants of risk for alcoholism in minority populations; (5). consideration of population groups in linkage-disequilibrium studies to identify genes associated with alcohol dependence; (6). interaction between alcohol dependence and African-American ethnicity in disordered sleep, nocturnal cytokines, and immunity; (7). disparities of brain functional reserve capacity affecting brain morbidity related to substance abuse; (8). alcohol and pregnancy disparities; (9). role of alcohol in cancer risk disparities; (10). ethnic diversity in alcoholic cardiomyopathy; and (11). postmenopausal health disparities. On the basis of these presentations, seven conclusions emerged: (1). Genetic variations in alcohol-metabolizing enzymes exist in various populations. (2). These enzymes play a role in the variation in health effect outcomes seen in different populations, owing to alcohol consumption. (3). Differences between and among population groups can be critically important for the design and interpretation of studies in genetics. These include differences in expression of phenotype, in locus heterogeneity, in risk alleles, and in population structure. (4). Incidence rates for fetal alcohol syndrome and fetal alcohol spectrum disorders are greater in African-Americans and Native-Americans than in Caucasians. Genetic polymorphisms, nutrition, and other factors may account for these differences. (5). The highest mortality rate for cirrhosis has been found in white Hispanic men. (6). Mexican-Americans have a low frequency of the protective alleles ADH1B(*)2 and ALDH2(*)2 and a relatively high frequency of CYP2E1 c2, which is associated with early onset alcoholism. (7). The incidence rate for cancer is greater for African-Americans than for Caucasians, and part of the higher risk may be attributed to heavier drinking.

Alcohol Drinking↗