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Challenging questions in treating bronchitis.

Whatever facts we gather and no matter how many we have, you and I must eventually put the journal down and pick up our stethoscope, pen, and prescription pad and go to work. Hopefully we can do better than, "Therapy is not uniform and specific antibiotic regimens are usually selected based on local tribal custom." We can discard an old paradigm, "The absence of data bears no relation to the strength of opinion." Personally, I have used these new scientific data before I reached my conclusion. I have developed 10 points to structure my new approach. I invite you to compare my conclusions to yours. 1. In acute bronchitis, in otherwise healthy adults, my preference is to not prescribe an antibiotic. If I do, it is not over the phone. You should want to see and examine the patient. If there are no helpful hints to etiology, I choose a newer macrolide for those under age 50 and use a short course, five-seven days. For patients over age 50, especially if they are "healthy smokers," consider a short course of cefuroxime. (You can see, even in these acute bronchitis patients, you want an antibiotic effective against today's pathogens.) 2. In all chronic bronchitis patients, prevention of further damage to the airways should be attempted by instituting a program of smoking cessation and appropriate immunizations against influenza and pneumococcus. 3. Treatment outcomes will also improve if we recognize that in some patients the progressing SOB, cough, and increasing sputum production are due to congestive heart failure and not due to infection. I try to think about congestive heart failure in all of my patients, but especially in those with known heart disease and cardiomegaly on their chest x-ray. 4. Routine pulmonary function testing is important in smoking patients. Physicians underestimate the degree of obstruction present when they rely on physical exam alone. Hopefully long before the patient's acute illness you have established whether or not obstruction is present. This information helps identify the high risk patient for not only recurrent bouts of infection but also those at increased risk for lung cancer. 5. We will have more success in treating AECB when we elect to use an antibiotic only for patients with at least two of the following three cardinal symptoms: increased dyspnea, increased sputum production, and increased purulent sputum. COPD patients have many days when they feel more SOB. To use this or any one sign as the sole indication for starting an antibiotic has been proven not to make a statistically significant difference in outcome in most patients. Also, the value of prophylactic antibiotic therapy has not been established. 6. When airflow obstruction is moderately severe or more pronounced, AECB should usually be treated with oral steroids. Other measures such as chronic bronchodilator therapy, supplemental and home oxygen use, and pulmonary rehabilitation have been extensively reviewed elsewhere.

Acute Disease↗

United States Food and Drug Administration approach to risk evaluation and risk management for foods.

The Food and Drug Administration (FDA) is developing a comprehensive program on risk evaluation and risk management related to foods and food ingredients. Various groups view the FDA differently in terms of potential food hazards, but the regulatory agency is required to follow the laws that reflect a set of social judgments about permissible risks and benefits. The traditional agency approaches to risk management are reviewed and recent plans to consider structural changes in the basic food statute that could lead to greater administrative flexibility are presented. The proposed tentative suggestions discussed embody basic principles that the public health and trust remain the focus of food safety laws. Public confidence in the present system must be retained, it must be a credible system, embody valid scientific data, and the regulatory actions must be taken by FDA scientists who are recognized for their scientific competence. All the proposed actions need to be taken without placing unnecessary economic burdens on industry. The scope of this program is reviewed.

Food Additives↗

WWW creates new interactive 3D graphics and collaborative environments for medical research and education.

Virtual Reality Modelling Language (VRML) is the start of a new era for medicine and the World Wide Web (WWW). Scientists can use VRML across the Internet to explore new three-dimensional (3D) worlds, share concepts and collaborate together in a virtual environment. VRML enables the generation of virtual environments through the use of geometric, spatial and colour data structures to represent 3D objects and scenes. In medicine, researchers often want to interact with scientific data, which in several instances may also be dynamic (e.g. MRI data). This data is often very large and is difficult to visualise. A 3D graphical representation can make the information contained in such large data sets more understandable and easier to interpret. Fast networks and satellites can reliably transfer large data sets from computer to computer. This has led to the adoption of remote tale-working in many applications including medical applications. Radiology experts, for example, can view and inspect in near real-time a 3D data set acquired from a patient who is in another part of the world. Such technology is destined to improve the quality of life for many people. This paper introduces VRML (including some technical details) and discusses the advantages of VRML in application developing.

Computer Communication Networks↗

EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force.

The objectives have been to establish evidence-based guidelines and identify controversies regarding the management of patients with brain metastases. The collection of scientific data was obtained by consulting the Cochrane Library, bibliographic databases, overview papers and previous guidelines from scientific societies and organizations. A tissue diagnosis is necessary when the primary tumor is unknown or the aspect on computed tomography/magnetic resonance imaging is atypical. Dexamethasone is the corticosteroid of choice for cerebral edema. Anticonvulsants should not be prescribed prophylactically. Surgery should be considered in patients with up to three brain metastases, being effective in prolonging survival when the systemic disease is absent/controlled and the performance status is high. Stereotactic radiosurgery should be considered in patients with metastases of 3-3.5 cm of maximum diameter. Whole-brain radiotherapy (WBRT) after surgery or radiosurgery is debated: in case of absent/controlled systemic cancer and Karnofsky Performance score of 70 or more, one can either withhold initial WBRT or deliver early WBRT with conventional fractionation to avoid late neurotoxicity. WBRT alone is the treatment of choice for patients with single or multiple brain metastases not amenable to surgery or radiosurgery. Chemotherapy may be the initial treatment for patients with brain metastases from chemosensitive tumors.

Advisory Committees↗

Newer insights into cisplatin nephrotoxicity.

OBJECTIVE: To review recent advances in the understanding of the mechanisms of cisplatin nephrotoxicity. Factors affecting this toxicity and agents that may protect against it are discussed. DATA SOURCES: A MEDLINE search was used to identify pertinent literature including reviews. A manual search of bibliographies was performed to include all articles on the subject. STUDY SELECTION: All available data relating to the mechanisms, modifying factors, and management of cisplatin nephrotoxicity were assessed. DATA EXTRACTION: As limited human data are available, all animal studies were included. Articles with hypotheses or suggestions not backed by scientific data were excluded from review. DATA SYNTHESIS: Cisplatin is one of the most effective agents available for treating a variety of solid tumors. Nephrotoxicity is the dose-limiting factor for the use of this drug. Mechanisms for renal toxicity range from definitive histologic changes found in the proximal convoluted tubules to physiologic and biochemical alterations involving a decrease in mitochondrial respiratory function, enzymatic activity in the respiratory chain and glutathione peroxidase, and effects on cellular calcium homeostasis. Important factors related to nephrotoxicity include age, renal irradiation, and concurrent alcohol intake. Agents that appear promising in attenuating the nephrotoxic effects of cisplatin include loading with NaCl solution and/or mannitol, sodium thiosulfate, WR 2721, glutathione, probenecid, and many other compounds under active investigation. CONCLUSIONS: Cisplatin is a nephrotoxic drug; however, agents that may make cisplatin therapy more safe and rewarding will be available in the near future.

Amifostine↗

[A new ISO/FDIS 14242-1 compatible hip prosthesis simulator: E-SIM].

The continuing development of new, highly sophisticated materials for the articulating surfaces of total hip endoprostheses involves the need for testing, not only of biocompatibility and dynamic loadability, but also of tribological properties (friction, wear, lubrication). For decades, the wear resistance of these materials has been tested in wear simulators. In consequence of the currently often widely differing test methods, the technical committee (TC 150) of the ISO (International Organization for Standardization) has been concerned to develop an International Standard (ISO/FDIS 14242 1 and 2: Implants for Surgery--wear of total hip joint prostheses--on the basis of kinetic and kinematic data from gait analysis. This new standard will be the basis for ensuring the comparability of scientific data obtained from tribological testing of total hip endoprothesis. The new hip simulator, E-SIM, presented in this paper, complies with the currently published FDIS (Final Draft International Standard), and enables testing in accordance with these specifications.

Equipment Failure Analysis↗

Classification of chemicals for carcinogenic and mutagenic properties.

In the framework of the EC labelling guide, three categories were devised for carcinogenic as well as for mutagenic chemicals. In short, category 1 is for compounds shown to produce these effects in man, whereas category 2 is meant to contain substances that should be regarded as such, generally on the basis of sufficient experimental data. Category 3 is for compounds that cause concern but for which the evidence is not sufficient for 1 or 2. These general statements have been implemented, both for carcinogenicity and mutagenicity, by a set of criteria and considerations of the group of "specialized experts" who are supporting the "national experts" in deciding upon the classification of individual compounds. Essentially, this classification relies on the strength of the experimental or epidemiological evidence rather than on considerations of risk. In other words, it is based on proven intrinsic properties of the substances. Compared to the IARC classification for carcinogens, the EC criteria rely more on mechanistic data and on qualitative considerations concerning the relevance for man, and less on a strict count of the amount of positive experimental evidence. Difficulties of this (and any) classification system include: (1) the problem of classifying with limited data and (2) the fundamental problem involved in forcing sets of multi-facetted, and often unsatisfactory, scientific data into a simple one-dimensional scheme that may have huge economic consequences.

Animals↗

Mercury exposure and child development outcomes.

Mercury is ubiquitous in the global environment, ensuring universal exposure. Some forms of mercury are especially neurotoxic, including clinical signs at high doses. However, typical human exposures occur at low to moderate doses. Only limited data about neurotoxicity at low doses are available, and scientists differ in their interpretation. Dose-response data on neurodevelopment are particularly limited. Despite or perhaps because of the lack of sufficient or consistent scientific data, public concern about a link between mercury exposure and developmental disabilities has been rising. After reviewing the data, the US Environmental Protection Agency proposed a reference dose (an estimate of a daily dose that is likely to be without a risk of adverse effects over a lifetime) for methyl mercury that is substantially lower than previous guidelines from the World Health Organization, the US Agency for Toxic Substances and Disease Registry, and the US Food and Drug Administration. Some questions have been raised about the Environmental Protection Agency's guidelines, but the issue remains unresolved. Meanwhile, consumer groups have raised questions about the potential link between mercury exposure and autism spectrum disorders as well as other adverse neurodevelopmental outcomes. This hypothesis has prompted some parents to seek regulatory, legal, or medical remedies in the absence of firm evidence. This article reviews what is known about mercury neurotoxicity and neurodevelopmental risk. Our intent is to focus the debate about mercury on 1) additional research that should be sought and 2) defining the principal issues that public policy makers face.

Child↗

[Development of impact acceleration measurement facility in return-cabin of spacecraft].

OBJECTIVE: To provide the basis for medical evaluation of spacecraft, and to measure the impact acceleration of return-cabin of spacecraft. METHOD: A facility to measure the impact acceleration of "SZ-3" and "SZ-4" during landing was developed and the acquired test data were analyzed. RESULT: The data of impact acceleration of return-cabins of "SZ-3" and "SZ-4" were accurately recorded during landing. Most reliable and scientific data were gotten. CONCLUSION: This facility could validate and evaluate the specifications of relevant systems of spacecraft, and provided the scientific basis for the decision if "SZ-5", the manned spacecraft, could be launched.

Acceleration↗

Silicone gel breast implant failure: evaluation of properties of shells and gels for explanted prostheses and meta-analysis of literature rupture data.

After 30 years of clinical use, the 1992 Food and Drug Administration moratorium on silicone gel breast implants (SGBIs) resulted from a paucity of scientific data concerning their safety. The frequency of rupture and reoperative procedures was not known, nor were reliable data available for changes in the physical properties of shells and the composition of gels that might lead to SGBI failure. For this reason the authors conducted large-cohort meta-analyses of failure data for SGBIs based on numerous literature reports and also investigated systematically shell and gel properties from explanted SGBIs. They report their failure analysis data for more than 9,770 SGBIs (an update of an earlier study of more than 8,000 implants) as well an examination of the properties of shells and gels for 74 explanted SGBIs that ranged in age from 2 to 19 years (mean implanted age, 9.9 years). The explants tested were from several different manufacturers. For the modest-size explant cohort that was tested, 31 of 74 implants (42%) were found to be ruptured (some extensively). Even many intact shells were so weakened that only 51 shells had sufficient strength to enable preparation of samples for testing of mechanical properties and for analysis of composition by solvent extraction. Shells were found to contain 15 to 25% of extractable silicone. Exhaustive extraction of gels showed that they actually contained very little crosslinked silicone--85 to 95% being extractable soluble silicone fluid. Tensile and tear strengths of explanted silicone elastomer shells were lower than unimplanted prostheses and were generally well below reported manufacturers' values. This updated large-cohort failure analysis continues to show that shell rupture is related directly to implant duration (e.g., from analysis of variance statistics, 26% failure at 3.9 years, 47% at 10.3 years, 69% at 17.8 years; < or = 0.001). However, for the relatively small series of explants for which physical property data are reported, no significant correlation was observed between implant duration and the degradation of implant strength. It therefore appears most reasonable to conclude that after early weakening of shells as a result of swelling of the shell elastomer by diffusion of silicone oil from the gel, SGBI failure can occur in a time-dependent manner as a result of continuing implant motion and cyclic stresses that are exacerbated by stress concentration at thin areas, defects, and folds in the shells.

Breast Implants↗

Analgesia and sedation during mechanical ventilation in neonates.

BACKGROUND: Endotracheal intubation and mechanical ventilation are major components of routine intensive care for very low birth weight newborns and sick full-term newborns. These procedures are associated with physiologic, biochemical, and clinical responses indicating pain and stress in the newborn. Most neonates receive some form of analgesia and sedation during mechanical ventilation, although there are marked variations in clinical practice. Clinical guidelines for pharmacologic analgesia and sedation in newborns based on robust scientific data are lacking, as are measures of clinical efficacy. OBJECTIVE: This article represents a preliminary attempt to develop a scientific rationale for analgesia sedation in mechanically ventilated newborns based on a systematic analysis of published clinical trials. METHODS: The current literature was reviewed with regard to the use of opioids (fentanyl, morphine, diamorphine), sedative-hypnotics (midazolam), nonsteroidal anti-inflammatory drugs (ibuprofen, indomethacin), and acetaminophen in ventilated neonates. Original meta-analyses were conducted that collated the data from randomized clinical comparisons of morphine or fentanyl with placebo, or morphine with fentanyl. RESULTS: The results of randomized trials comparing fentanyl, morphine, or midazolam with placebo, and fentanyl with morphine were inconclusive because of small sample sizes. Meta-analyses of the randomized controlled trials indicated that morphine and fentanyl can reduce behavioral and physiologic measures of pain and stress in mechanically ventilated preterm neonates but may prolong the duration of ventilation or produce other adverse effects. Randomized trials of midazolam compared with placebo reported significant adverse effects (P < 0.05) and no apparent clinical benefit; the findings of a meta-analysis suggest that there are insufficient data to justify use of IV midazolam for sedation in ventilated neonates. CONCLUSIONS: Despite ongoing research in this area, huge gaps in our knowledge remain. Well-designed and adequately powered clinical trials are needed to establish the safety, efficacy, and short- and long-term outcomes of analgesia and sedation in the mechanically ventilated newborn.

Analgesia↗

Protein kinase resource: an integrated environment for phosphorylation research.

The protein kinase superfamily is an important group of enzymes controlling cellular signaling cascades. The increasing amount of available experimental data provides a foundation for deeper understanding of details of signaling systems and the underlying cellular processes. Here, we describe the Protein Kinase Resource, an integrated online service that provides access to information relevant to cell signaling and enables kinase researchers to visualize and analyze the data directly in an online environment. The data set is synchronized with Uniprot and Protein Data Bank (PDB) databases and is regularly updated and verified. Additional annotation includes interactive display of domain composition, cross-references between orthologs and functional mapping to OMIM records. The Protein Kinase Resource provides an integrated view of the protein kinase superfamily by linking data with their visual representation. Thus, human kinases can be mapped onto the human kinome tree via an interactive display. Sequence and structure data can be easily displayed using applications developed for the PKR and integrated with the website and the underlying database. Advanced search mechanisms, such as multiparameter lookup, sequence pattern, and blast search, enable fast access to the desired information, while statistics tools provide the ability to analyze the relationships among the kinases under study. The integration of data presentation and visualization implemented in the Protein Kinase Resource can be adapted by other online providers of scientific data and should become an effective way to access available experimental information.

Amino Acid Sequence↗

Health concerns regarding consumption of irradiated food.

Food irradiation is being promoted as a simple process that can be used to effectively and significantly reduce food-borne illnesses around the world. However, a thorough review of the literature reveals a paucity of adequate research conducted to specifically address health concerns that may directly result from the consumption of irradiated food. Consequently, there is considerable debate on the issue of health concerns from irradiated food among international agencies and between different nations. This report presents a critical review of scientific data and recommendations from different agencies and consumer groups. The objective of this review is to provide the scientific community and the general public with a balanced discussion on irradiated food from the viewpoint of an environmental or public health professional. As a result of this review, the authors conclude that current evidence does not exist to substantiate the support or unconditional endorsement of irradiation of food for consumption. In addition, consumers are entitled to their right of choice in the consumption of irradiated versus un-irradiated food. Different countries should further evaluate their local and global risks and benefits prior to developing and recommending national and international food irradiation policies.

Animals↗

Scientific dishonesty and good scientific practice.

Scientific dishonesty has been the subject of much public interest in recent years. Although the problem has had a low profile in Denmark, there is no reason to believe that it is non-existent. Several preconditions known to be important prevail here as well as in other countries, such as pressure to publish and severe competition for research grants and senior academic positions. The Danish Medical Research Council (DMRC) decided to respond to this problem by preparing a report on scientific dishonesty with suggestions to the research institutions on rules for good scientific practice and procedures for investigation of suspected dishonesty. To this end, an investigatory system was suggested. The system should consist of two regional committees and one national committee. They should be headed by high court judges and experienced health sciences researchers as members. The committees will investigate cases reported to them and conclude on whether dishonesty has been established and on whether the scientific work should be retracted. Sanctions shall remain the task of the institutions. Preventive measures comprise open access to and a long storage period for scientific data.

Denmark↗

Evaluation of risk from space radiation with high-energy heavy ion beams.

The most challenging radiation in space consists of fully ionized atomic elements with high energy for which only the few lowest energy ions can be stopped in shielding materials. The health risk from exposure to these ions and their secondary radiations generated in shield materials is poorly understood since there are few human data and a systematic study in relevant animal model systems has not been made. The accuracy of risk prediction is described as the major limiting factor in the management of space radiation risk. The expected impact of systematic studies is examined using the limited available biological data and models. Given the limitations of current predictions, models must be developed that are able to incorporate the required fundamental scientific data into accurate risk estimates. The important radiation components that can be provided for laboratory testing are identified. The use of ground-based accelerator beams to simulate space radiation is explained and quantitative scientific constraints on such facilities are derived. Three facilities, one each in the United States, in Germany and in Japan, currently have the partial capability to satisfy these constraints. A facility has been proposed using the Brookhaven National Laboratory Booster Synchrotron in the United States; in conjuction with other on-site accelerators, it will be able to provide the full range of heavy ion beams and energies required.

Aerospace Medicine↗

Cardiopulmonary bypass: Evidence or experience based?

OBJECTIVE: Evidence-based medicine is emerging as a new paradigm for medical practice. The purpose of this study was to evaluate the amount and quality of scientific evidence supporting principles that are currently applied for cardiopulmonary bypass performance. METHODS: A survey of all German departments of cardiac surgery regarding cardiopulmonary bypass performance disclosed major differences. Consequently, for 48 major principles of cardiopulmonary bypass performance, relevant Medical Subject Headings were identified, and a literature search of the Medline database was performed. Two sequentially applied sets of inclusion-exclusion criteria were selected to assess the best available evidence. RESULTS: Thirty-three thousand articles relating to the subject were identified. Among these, 1500 fulfilled the first set of inclusion criteria: meta-analysis of (randomized) controlled clinical trials and in vitro and animal studies. Rigorous methodological criteria were then applied to further select remaining publications. Ultimately, 225 articles referring to major cardiopulmonary bypass principles were identified as providing the best available evidence. These were graded according to their methodological rigor (susceptibility to bias). The scientific evidence on the investigated cardiopulmonary bypass principles did not prove to be of a high enough level to allow general recommendations to be made. CONCLUSIONS: The scientific data concerning the effectiveness and safety of key principles of cardiopulmonary bypass are insufficient in both amount and quality of scientific evidence to serve as a basis for practical, evidence-based guidelines.

Acid-Base Equilibrium↗

Raising questions about antidepressants.

Antidepressant medication has apparently become the most popular treatment for depression in the USA. Several beliefs about the efficacy of antidepressant medications prevail among mental health professionals and the public. This paper explores relevant research data and raises questions about these beliefs. Many of the common beliefs about these medications are not adequately supported by scientific data. The following issues are raised: (1) industry-funded research studies which result in negative findings sometimes do not get published; (2) placebo washout procedures may bias results in some studies; (3) there are serious questions about the integrity of the double-blind procedure; (4) the 'true' antidepressant drug effect in adults appears to be relatively small; (5) there is minimal evidence of antidepressant efficacy in children; (6) side effects are fairly common even with the newer antidepressants; (7) combining medications raises the risk for more serious complications; (8) all antidepressants can cause withdrawal symptoms; (9) genetic influences on unipolar depression appear to be weaker than environmental influences; (10) biochemical theories of depression are as yet unproven; (11) biological markers specific for depression have been elusive; (12) dosage and plasma levels of antidepressants have been minimally related to treatment outcome; (13) preliminary evidence suggests that patients who improve with cognitive-behavioral psychotherapy show similar biological changes as those who respond to medication, and (14) the evidence suggests that psychological interventions are at least as effective as pharmacotherapy in treating depression, even if severe, especially when patient-rated measures are used and long-term follow-up is considered.

Adult↗

Urban air pollution and health inequities: a workshop report.

Over the past three decades, an array of legislation with attendant regulations has been implemented to enhance the quality of the environment and thereby improve the public's health. Despite the many beneficial changes that have followed, there remains a disproportionately higher prevalence of harmful environmental exposures, particularly air pollution, for certain populations. These populations most often reside in urban settings, have low socioeconomic status, and include a large proportion of ethnic minorities. The disparities between racial/ethnic minority and/or low-income populations in cities and the general population in terms of environmental exposures and related health risks have prompted the "environmental justice" or "environmental equity" movement, which strives to create cleaner environments for the most polluted communities. Achieving cleaner environments will require interventions based on scientific data specific to the populations at risk; however, research in this area has been relatively limited. To assess the current scientific information on urban air pollution and its health impacts and to help set the agenda for immediate intervention and future research, the American Lung Association organized an invited workshop on Urban Air Pollution and Health Inequities held 22-24 October 1999 in Washington, DC. This report builds on literature reviews and summarizes the discussions of working groups charged with addressing key areas relevant to air pollution and health effects in urban environments. An overview was provided of the state of the science for health impacts of air pollution and technologies available for air quality monitoring and exposure assessment. The working groups then prioritized research needs to address the knowledge gaps and developed recommendations for community interventions and public policy to begin to remedy the exposure and health inequities.

Air Pollution↗