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FDA is beginning to launch its drug review process into cyberspace. This electronic transformation is expected to speed review of new drug applications.
The boundary between therapy and research may at times be difficult to distinguish, and it is, therefore, important for health care professionals to recognize when a clinical activity should be properly classified as research. Research may be subject to federal regulations which require advance review and approval by an Institutional Review Board (IRB) in order to protect the rights and welfare of patients who serve as human subjects. This paper will discuss the criteria health care professionals can use to distinguish between therapy, innovative therapy, and therapeutic or clinical research.
Contribution of one case of renal cells carcinoma, in an adult man, that during evolution developed arachnoid metastasis. The patient was first seen for a brain haemorrhage due to a bleeding metastasis. In later studies, a renal cells carcinoma was found to be the primary site of the brain condition. The evolution showed neurological manifestations in the limbs, and the arachnoid metastasis was detected. The paper includes imaging studies of the referred disease both al brain, renal and spinal level with CT and NMR studies. A revision is made of the different dissemination forms of renal cells tumours, as well as a review of the existing literature with regard to the nervous system metastasis. No case has been found in this review relative to spinal arachnoid dissemination.
INTRODUCTION: Mechanical ventilation is life saving for many very preterm babies but prolonged use can have adverse effects increasing the risk of subglottic injury and chronic lung disease (CLD). Shorter ventilation should reduce these risks and a number of interventions have been tested to facilitate earlier extubation. METHODS: The Cochrane Library was searched for systematic reviews of randomised controlled trials of interventions to facilitate extubation and reduce post-extubation atelectasis. These interventions included nasal continuous positive airway pressure (CPAP), nasal intermittent positive pressure ventilation (NIPPV), chest physiotherapy, intravenous dexamethasone and methylxanthine treatment. Outcomes are given as numbers needed to treat (NNT) with 95% confidence intervals (CI). RESULTS: Nasal CPAP reduces the incidence of adverse effects after extubation including failure (NNT 6; 95% CI 4-15) and CLD at 28 days (NNT 6; 95% CI 3-22). NIPPV is superior to nasal CPAP at preventing extubation failure (NNT 3; 95% CI 2-5). Chest physiotherapy after extubation does not reduce alveolar atelectasis but it decreases need for re-intubation (NNT 6; 95% CI 4-23). Chest physiotherapy needs to be given 1-2 hourly to obtain this effect. Intravenous dexamethasone reduces the need for re-intubation (NNT 6; 95% CI 3-250) but adverse effects preclude its routine use. Methylxanthines also improve the chances of successful extubation (NNT 4; 95% CI 2-7) and the effect is greatest in infants <1000g birthweight and <7 days postnatal age (NNT 2; 95% CI 1-8). CONCLUSIONS: Nasal CPAP, NIPPV and methylxanthines are evidence-based treatments to facilitate weaning and extubation of preterm infants but only the first 2 can be recommended for routine use. Chest physiotherapy and dexamethasone may be effective but should not be used routinely because of serious adverse effects.
A case of non-invasive aspergillosis affecting the maxillary sinus is presented. Reference is made to its possible aetiology (spores introduced to the antrum at the time of a root canal overfilling with a zinc oxide paste). A review is presented and the management of the case is described.
The appropriate utilization and the quality of care in long-term care facilities should be documented and monitored. This is best accomplished at the local level by physicians and other professionals serving on Utilization Review Committees. Paper compliance to regulation of state or federal agencies is a poor substitute for active involvement of the professionals at the local level.
INTRODUCTION: The incidence of condylar fractures is high. Condylar fractures can be extracapsular (condylar neck or subcondylar) or intracapsular, undisplaced, deviated, displaced or dislocated. Treatment depends on the age of the patient, the co-existence of other mandibular or maxillary fractures, whether the condylar fracture is unilateral or bilateral, the level and displacement of the fracture, the state of dentition and the dental occlusion, and the surgeon's experience. PURPOSE: This report presents the experience acquired in the treatment of 466 condylar fractures over 7 years, reviews the pertinent literature and proposes guidelines for treatment. MATERIAL AND METHODS: The archives of KAT, General District Hospital between 1995 and 2002 were scrutinized and the condylar fractures were recorded. The aetiology, age, sex, level of fracture, degree of displacement, associated facial fractures, malocclusion, and type of treatment were noted. RESULTS: Four hundred and sixty-six condylar fractures were admitted, the male:female ratio was 3.5:1. Road traffic accidents were the main cause and most fractures were unilateral, displaced, subcondylar, occurred on the left side and were treated conservatively. CONCLUSIONS: Early mobilization is the key in treating condylar fractures. Whilst rigid internal fixation provides stabilization and allows early mobilization, conservative treatment is the treatment of choice for the majority of fractures. Children and intracapsular fractures are treated conservatively with or without maxillo-mandibular fixation. Open reduction is recommended in selected cases to restore the occlusion, in severely displaced and dislocated fractures, in cases of loss of ramus height, and in edentulous patients. It may be considered in those with 'medical problems' where intermaxillary fixation is not recommended.
To determine level of agreement and correlation between two similar but separate peer review systems, proposals simultaneously submitted during the same funding year to two agencies using the same scoring system were identified and analyzed (n = 248). There was a direct linear relationship between the scores of the two agencies (r = 0.592, p < 0.001). Raw agreement within whole-digit ranges was moderate (53%) but a Cohen's kappa indicated that agreement beyond chance was only fair (kappa = 0.29, 95% CI = 0.198, 0.382). When proposals were arbitrarily categorized as being "clearly fundable" (on a 0-5 scale, score > or = 3.0) or "not clearly fundable" (score < 3.0), raw agreement was 73% and agreement beyond chance was moderate (kappa = 0.444, 95% CI = 0.382, 0.552). In cases where there was inter-agency disagreement on the fundability of the project, the difference in scores was greater than in those in which there was agreement. In a subsample of 128 pairs, variables describing the application and the applicant (i.e., principal investigator) were coded, but none explained inter-agency agreement on the "fundability" of proposals.
Hepatic glycogenolysis and gluconeogenesis are essential processes for the prevention of hypoglycemia during short-term starvation. As has been calculated from stable isotope studies, gluconeogenesis accounts for approximately 35% to 50% of total basal glucose production, glycogenolysis for the other 50% to 65%. In long-term starvation, the kidney also contributes to glucose production by gluconeogenesis. Glucose production is regulated by the interaction of different regulatory mechanisms, eg, by glucoregulatory hormones, glucose itself, and gluconeogenic substrates. In the last decades, more insight has been gained into the importance of the autonomous nervous system and the existence of an extensive paracrine network in the liver that seems to exert a potent glucoregulatory role as well. This review is focused on the regulation of hepatic glucose production by the autonomous nervous system and the paracrine network, with special emphasis on studies carried out in human subjects.
Recently published studies were systematically reviewed to determine whether use of research in clinical practice by nurses, managers and allied health professionals in hospitals is currently sub-optimal, the factors influencing this and possible remedial strategies. The better studies confirmed that use of appropriate research is currently sub-optimal. The nature of the research and access to it is partly responsible for this. However, adoption of research findings is also currently hindered by factors inherent in hospitals and by the skills and attitudes of potential users of the research. Numerous remedial strategies have been suggested and hospitals could take responsibility for implementing many of them. However, most have yet to be evaluated. Studies into the use of research findings by nurses, managers and allied health professionals in Australian hospitals and trials of remedial strategies are recommended.
Consent forms in research are a source of current and retrospective information for the subject, a "prompt" for the person who is obtaining consent, and a documentation of the "informed" consent process and its adequacy. Occasionally, these forms may be administered by inexperienced trainees or ancillary personnel, and thus stand virtually alone. Therefore, the forms must be inherently comprehensible to the subjects. To test whether this is the case, 65 new applications were randomly selected from 13 consecutive IRB agendas, and their consent documents were computer-analyzed (Flesch/Fry scoring) after correction for expected confounding features, such as lists, tables, and polysyllabic proper names and jargon. Mean U.S. school grade for 70% comprehension (Fry score) was 15.03 +/- 0.19 (standard error of the mean), implying readability by 37.4 +/- 1% of the U.S. adult population. In contrast, a consecutive sampling of 21 Ann Landers columns yielded a mean Fry score of 7.67 +/- 0.5 (p < 0.01; readable by 75 +/- 3%). Fifteen Reader's Digest articles yielded a mean Fry score of 9.95 +/- 0.65 (p < 0.01; readable by 59.1 +/- 3%), and 15 "Talk of the Town" columns from The New Yorker averaged a grade level of 13.3 +/- 0.83; p < 0.01; readable by 42.7% +/- 4.8%). No document was improved by more than one grade level by the IRB review process, and most were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
The herbal remedy St John's wort is widely used as an antidepressant but its efficacy has not been systematically investigated. Meta-analyses and systematic reviews of published trials strongly suggest St John's wort is more effective than placebo although comparative efficacy to standard antidepressants is less clearly established. We updated and expanded previous meta-analyses of St John's wort, scrutinised the validity of published reports and examined possible mechanisms of action. Twenty-two randomised controlled trials were identified. Meta-analysis showed St John's wort to be significantly more effective than placebo (relative risk (RR) 1.98 (95% CI 1.49-2.62)) but not significantly different in efficacy from active antidepressants (RR 1.0 (0.90-1.11)). A sub-analysis of six placebo-controlled trials and four active comparator trials satisfying stricter methodological criteria also suggested that St John's wort was more effective than placebo (RR 1.77 (1.16-2.70)) and of similar effectiveness to standard antidepressants (RR 1.04 (0.94-1.15)). There was no evidence of publication bias. Adverse effects occurred more frequently with standard antidepressants than with St John's wort. The mechanism of action of St John's wort remains unknown. Future research should include large scale, appropriately powered comparisons of St John's wort and standard antidepressants.
The health impact of workplace solvent exposure remains an issue of substantial interest and concern to occupational health professionals. As a result of research performed in the 1970s and 1980s, policies and programs were developed throughout the world to control excessive exposure to solvents. To an extent, these programs have been responsible for reduction of the occurrence of solvent-associated encephalopathy and other health effects. In this review of research performed since 1985, particular attention is given to issues of reversibility of neurotoxicity following exposure cessation. Furthermore, health effects involving other organ systems, particularly reproductive, renal, and hepatic disorders, are discussed. Future research directions are discussed. Finally, the practical implications of these recent research findings are described with a focus on the management of prevention programs at the work site.
The incidence of non-steroidal anti-inflammatory drug-related ulcer complications remains high despite the availability of potent anti-ulcer drugs and selective cyclo-oxygenase-2 inhibitors. Non-steroidal anti-inflammatory drug-related ulcer complications can be minimized by prospective assessment of patients' baseline risk, rational choice and use of non-steroidal anti-inflammatory drugs, and selective use of co-therapy strategies with gastroprotectives. Current recommendations regarding strategies using anti-ulcer drugs and cyclo-oxygenase-2 inhibitors for prevention of clinical non-steroidal anti-inflammatory drug upper gastrointestinal events are largely derived from studies using surrogates such as endoscopic ulcers, erosions, and symptoms in low- to average-risk patients. Conclusions based on surrogate and potentially manipulatable end-points are increasingly suspect with regard to applicability to clinical situations. This article reviews the risks associated with non-steroidal anti-inflammatory drugs including aspirin and includes the effect of the patients' baseline risk, and the confounding effects of Helicobacter pylori infection. In addition, uncertainties regarding the clinical efficacy of anti-ulcer drugs and cyclo-oxygenase-2 inhibitors against non-steroidal anti-inflammatory drug-related ulcer complications are put into perspective. We propose management strategies based on the risk category: low risk (absence of risk factors) (least ulcerogenic non-steroidal anti-inflammatory drug at lowest effective dose), moderate risk (one to two risk factors) (as above, plus an antisecretory agent or misoprostol or a cyclo-oxygenase-2 inhibitor), high risk (multiple risk factors or patients using concomitant low-dose aspirin, steroids, or anticoagulants) (cyclo-oxygenase-2 inhibitor alone with steroids, plus misoprostol with warfarin, or plus a proton pump inhibitors or misoprostol with aspirin), and very high risk (history of ulcer complications) (avoid all non-steroidal anti-inflammatory drugs, if possible or a cyclo-oxygenase-2 plus a proton pump inhibitors and/or misoprostol). The presence of H. pylori infection increases the risk of upper gastrointestinal complications in non-steroidal anti-inflammatory drug users by two- to fourfold suggesting that all patients requiring regular non-steroidal anti-inflammatory drug therapy be tested for H. pylori.
BACKGROUND: Movement clumsiness (or Developmental Coordination Disorder--DCD) has gained increasing recognition as a significant condition of childhood. However, some uncertainty still exists about diagnosis. Accordingly, approaches to assessment and treatment are varied, each drawing on distinct theoretical assumptions about the aetiology of the condition and its developmental course. METHOD: This review evaluates the current status of different approaches to motor assessment and treatment for children with DCD. These approaches are divided according to their broad conceptual origin (or explanatory framework): Normative Functional Skill Approach, General Abilities Approach, Neurodevelopmental Theory, Dynamical Systems Theory, and the Cognitive Neuroscientific Approach. CONCLUSIONS: Each conceptual framework is shown to support assessment and treatment methods with varying degrees of conceptual and psychometric integrity. The normative functional skill approach supports the major screening devices for DCD and cognitive (or top-down) approaches to intervention. The general abilities approach and traditional neurodevelopmental theory are not well supported by recent research. The dynamical systems approach supports promising trends in biomechanical or kinematic analysis of movement, ecological task analysis, and task-specific intervention. Finally, and more recently, the cognitive neuroscientific approach has generated some examples of process-oriented assessment and treatment based on validated (brain-behaviour) models of motor control and learning. A multi-level approach to movement assessment and treatment is recommended for DCD, providing a more complete representation of motor development at different levels of function--behavioural, neurocognitive, and emotional.
Mathematicians, physicists, and physical chemists have generated a number of viewpoints related to systems with nonlinearity, multistability, and fluctuations. The viewpoints tend to be characterized by slogans generated by the respective advocates, e.g., Catastrophe Theory, Dissipative Structures, and Synergetics. The advocates also usually stress the applicability of their work to biology and to self-organization. Have the discussions in the semipopular and broader technical journals served to give proper guidance to the outsider through their assessment of these viewpoints? We discuss this, with particular emphasis on book reviews.
The mouse is a proven model for studying human disease. Many strains exist that exhibit either natural or engineered genetic variation and thereby enable the elucidation of pathways involved in the development of cardiovascular disease. Although those mouse models have been fundamental to advancing our knowledge base, we are still at an early stage in understanding how genes contribute to complex disorders. There remains a need for new animal models that closely represent human disease. To expedite their development, we have established the Center for New Mouse Models of Heart, Lung, Blood, and Sleep Disorders at The Jackson Laboratory. We are using a phenotype-driven approach to identify mutations leading to atherosclerosis, hypertension, obesity, blood disorders, lung dysfunction, thrombosis, and disordered sleep. Our high-throughput, comprehensive phenotyping draws from two sources for new models: 1) the natural variation among over 40 inbred mouse strains and 2) chemically induced, whole-genome mutagenized mice. Here, we review our cardiovascular screens and present some hypertensive, obese, and cardiovascular models identified with this approach.
A panel of biomedical and behavioral scientists were charged with the task of critically evaluating all available research and theory linking behavior to coronary heart disease. The task was divided into five topic areas: (1) association of coronary-prone behavior and coronary heart disease; (2) assessment of the "type A" behavior pattern; (3) physiologic mechanisms linking behavior to coronary heart disease; (4) cultural and developmental factors; and (5) intervention strategies. The review panels developed summary statements which delineated the perceived strengths and short-comings of the theory and data for their respective sections and provided recommendations to the National Heart, Lung, and Blood Institute concerning future research.