First clinical experience with a new non-indwelling voice prosthesis (Provox (R) NID (TM)) for voice rehabilitation after total laryngectomy

Conclusion. The new Provox(R) NID (TM) non- indwelling voice prosthesis investigated in this study provides a good option for laryngectomized patients using non- indwelling voice prostheses and can potentially improve safety and increase patients' satisfaction with their voice and speech. Objective. To investigate the feasibility of and patient satisfaction with the Provox NID non- indwelling voice prosthesis. Material and methods. Pre- and post- study questionnaires were used to evaluate the patients' former voice prosthesis and the Provox NID voice prosthesis. In addition, measurements of pull- out force, maximum phonation time and loudness were made for both voice prostheses. In vitro measurements of airflow characteristics were also made. Following a 6- week trial, all patients provided feedback on the new voice prosthesis and the results were used to further improve the Provox NID. This final version of the new voice prosthesis was subsequently trialled and evaluated by 10 patients 6 months later. Results. Overall results showed that patient satisfaction with the Provox NID non- indwelling voice prosthesis was favourable. The pull- out force for the new prosthesis was significantly higher than that for the formerly used prosthesis and its aerodynamic characteristics were better.

Whither our Art? Clinical Wisdom & Evidence-based Medicine

The relationship between evidence-based medicine (EBM) and clinical judgement is the subject of conceptual and practical dispute. For example, EBM and clinical guidelines are seen to increasingly dominate medical decision-making at the expense of other, human elements, and to threaten the art of medicine. Clinical wisdom always remains open to question. We want to know why particular beliefs are held, and the epistemological status of claims based in wisdom or experience. The paper critically appraises a number of claims and distinctions, and attempts to clarify the connections between EBM, clinical experience and judgement, and the objective and evaluative categories of medicine. I conclude that to demystify clinical wisdom is not to devalue it. EBM ought not be conceived as needing to be limited or balanced by clinical wisdom, since if its language is translatable into terms comprehensible and applicable to individuals, it helps constitute clinical wisdom. Failure to appreciate this constitutive relation will help perpetuate medical paternalism and delay the adoption of properly evidence-based practice, which would be both unethical and unwise.

Clinical progression and outcome of dysphagia following paediatric traumatic brain injury: a prospective study

Objectives : To provide a preliminary clinical profile of the resolution and outcomes of oral-motor impairment and swallowing function in a group of paediatric dysphagia patients post-traumatic brain injury (TBI). To document the level of cognitive impairment parallel to the return to oral intake, and to investigate the correlation between the resolution of impaired swallow function versus the resolution of oral-motor impairment and cognitive impairment. Participants : Thirteen children admitted to an acute care setting for TBI. Main outcome measures : A series of oral-motor (Verbal Motor Production Assessment for Children, Frenchay Dysarthria Assessment, Schedule for Oral Motor Assessment) and swallowing (Paramatta Hospital's Assessment for Dysphagia) assessments, an outcome measure for swallowing (Royal Brisbane Hospital's Outcome Measure for Swallowing), and a cognitive rating scale (Rancho Level of Cognitive Functioning Scale). Results : Across the patient group, oral-motor deficits resolved to normal status between 3 and 11 weeks post-referral (and at an average of 12 weeks post-injury) and swallowing function and resolution to normal diet status were achieved by 3-11 weeks post-referral (and at an average of 12 weeks post-injury). The resolution of dysphagia and the resolution of oral-motor impairment and cognitive impairment were all highly correlated. Conclusion : The provision of a preliminary profile of oral-motor functioning and dysphagia resolution, and data on the linear relationship between swallowing impairment and cognition, will provide baseline information on the course of rehabilitation of dysphagia in the paediatric population post-TBI. Such data will contribute to more informed service provision and rehabilitation planning for paediatric patients post-TBI.

Targeting c-Myb expression in human disease

c-Myb is a transcription factor employed in the haematopoietic system and gastrointestinal tract to regulate the exquisite balance between cell division, differentiation and survival. In its absence, these tissues either fail to form, or show aberrant biology. Mice lacking a functional c-myb gene die in utero by day 15 of development. When inappropriately expressed, as is common in leukaemia and epithelial cancers of the breast, colon and gastro-oesophagus, c-Myb appears to activate gene targets of key importance to cancer progression and metastasis. These genes include cyclooxygenase-2 (COX-2), Bcl-2, Bcl-X-L and c-Myc, which influence diverse processes such as angiogenesis, proliferation and apoptosis. The clinical potential for blocking c-Myb expression in malignancies is based upon strong preclinical data and some trial-based evidence. The modest clinical experience to date has been with haematopoietic malignancies, but other disease classes may be amenable to similar interventions. The frontline agents to achieve this are nuclease-resistant oligodeoxynucleotides (ODNs), which are proving to be acceptable therapeutic reagents in terms of tolerable toxicities and delivery. Nevertheless, further effort must be focused on improving their efficacy, eliminating non-specific toxicity and optimising delivery. Optimisation issues aside, it would appear that anti-c-Myb therapies will be used with most success when combined with other agents, some of which will be established cytotoxic and differentiation-inducing drugs. This review will explore the future strategic use of ODNs in vivo, focusing on a wide spectrum of diseases, including several beyond the haematopoietic malignancies, in which c-Myb appears to play a role.

Cochrane systematic reviews of treatments for lung cancer

Morbidity and mortality from lung cancer is a major burden to global health. The integration of expert clinical experience, patient preference and high-quality evidence, including Cochrane systematic reviews, can only help improve outcomes from this highly lethal condition.

Telemedicine and developing countries - successful implementation will require a shared approach

Telemedicine is often proposed as a solution to certain health-care problems in the developing world. There seems to be little published experience on which to make judgements. A literature search revealed 39 articles, of which only two related to any kind of direct clinical work; most of them were review articles or editorials. The majority of the work reported was educational in nature, and there has been little clinical experience. It seems probable that telemedicine can help with the education of health-care workers and patients; it seems likely that it could bring major benefits to the organization of health-care. Without proper trials, it will be impossible to determine the place of health-care in the developing world. Trials are the only way in which rational decisions can ultimately be reached regarding whether scarce resources should be devoted to telemedicine in developing countries, or whether they should be employed in more conventional health-care measures whose outcomes are known to be cost-effective.

Macrolides in cystic fibrosis. Is there a role?

A spectrum of anti-inflammatory properties, evidence of anti-infective action against Pseudomonas aeruginosa at sub-inhibitory concentrations and positive clinical experience in patients with diffuse panbronchiolitis, a disease with features in common with cystic fibrosis (CF), has prompted research to evaluate the role of macrolide therapy in patients with CF. Newer macrolides such as azithromycin have the advantage of improved tolerability and a prolonged intracellular half-life requiring an infrequent dosing regimen. Results from initial studies suggest a benefit from several months of macrolide therapy in patients with CF. An improvement in lung function was initially shown in a small open study in children, while maintenance of lung function compared with placebo, reduced acute respiratory exacerbations, and reduced systemic markers of inflammation were demonstrated in a randomized, placebo-controlled study of macrolide therapy in adult patients with CF. Additional controlled studies are required to determine optimal drug, dosage, and duration of therapy, and long-term adverse effects of prolonged therapy with macrolides in patients with CF. The potential, with long-term use, to induce resistance against other bacteria colonizing the upper respiratory tract e.g. pneumococci has not been explored. Measurement of cytokines and inflammatory mediators from the sputum of patients with CF is technically difficult and does not correlate with disease activity. There is a need for easily measurable, reproducible and clinically meaningful end-points for evaluation of new therapies in CF. The choice of appropriate outcome measures, apart from lung function, to monitor disease activity needs careful consideration in clinical trials determining the efficacy of macrolides in patients with CF. Evidence-based recommendations for the use of macrolides in the treatment of CF are not expected for some years although macrolides are already being prescribed for long-term use in some centers. There is a need for further research into mechanisms of anti-inflammatory action of macrolides in the lungs of patients with CF and whether or not such therapy may be beneficial in the long term. Copyright 2002 Adis International

Perception or synthesized voice quality in connected speech by Cantonese speakers

Perceptual voice analysis is a subjective process. However, despite reports of varying degrees of intrajudge and interjudge reliability, it is widely used in clinical voice evaluation. One of the ways to improve the reliability of this procedure is to provide judges with signals as external standards so that comparison can be made in relation to these anchor signals. The present study used a Klatt speech synthesizer to create a set of speech signals with varying degree of three different voice qualities based on a Cantonese sentence. The primary objective of the study was to determine whether different abnormal voice qualities could be synthesized using the built-in synthesis parameters using a perceptual study. The second objective was to determine the relationship between acoustic characteristics of the synthesized signals and perceptual judgment. Twenty Cantonese-speaking speech pathologists with at least three years of clinical experience in perceptual voice evaluation were asked to undertake two tasks. The first was to decide whether the voice quality of the synthesized signals was normal or not. The second was to decide whether the abnormal signals should be described as rough, breathy, or vocal fry. The results showed that signals generated with a small degree of aspiration noise were perceived as breathiness while signals with a small degree of flutter or double pulsing were perceived as roughness. When the flutter or double pulsing increased further, tremor and vocal fry, rather than roughness, were perceived. Furthermore, the amount of aspiration noise, flutter, or double pulsing required for male voice stimuli was different from that required for the female voice stimuli with a similar level of perceptual breathiness and roughness. These findings showed that changes in perceived vocal quality could be achieved by systematic modifications of synthesis parameters. This opens up the possibility of using synthesized voice signals as external standards or anchors to improve the reliability of clinical perceptual voice evaluation. (C) 2002 Acoustical Society of America.

Keratinocyte Growth factor (KGF) in hematology and oncology

Keratinocyte Growth factor (KGF) is an epithelial cell growth factor of the fibroblast growth factor family and is produced by fibroblasts and microvascular endothelium in response to proinflammatory cytokines and steroid hormones. KGF is a heparin binding growth factor that exerts effects on epithelial cells in a paracrine fashion through interaction with KGF receptors. Preclinical data has demonstrated that KGF can prevent lung and gastrointestinal toxicity following chemotherapy and radiation and preliminary clinical data in the later setting supports these findings. In the experimental allogeneic bone marrow transplant scenario KGF has shown significant ability to prevent graft-versus-host disease by maintaining gastrointestinal tract integrity and acting as a cytokine shield to prevent subsequent proinflammatory cytokine generation. Within this setting KGF has also shown an ability to prevent experimental idiopathic pneumonia syndrome by stimulating production of surfactant protein A, promoting alveolar epithelialization and attenuating immune-mediated injury. Perhaps most unexpectantly, KGF appears able to maintain thymic function during allogeneic stern cell transplantation and so promote T cell engraftment and reconstitution. These data suggest that KGF will find a therapeutic role in the prevention of epithelial toxicity following intensive chemotherapy and radiotherapy protocols and in allogeneic stem cell transplantation.

The therapeutic potential of dopamine modulators on the cardiovascular and renal systems

In the periphery, physiological dopamine increases renal blood flow, decreases renal resistance and acts on the kidney tubule to enhance natriuresis and diuresis. The loss of dopamine function may be involoved in the deterioration in kidney function associated with ageing and may have a role in the pathogenesis of hypertension and diabetes. Intravenous dopamine is used as a positive inotrope in the treatment of acute heart failure and cardiogenic shock and as a diuretic in renal failure. The clinical uses of dopamine are limited, as it must be given intravenously, and also has widespread effects. The levels of peripheral dopamine can be increased by the administration of L-dopa to increase synthesis, prodrugs to release dopamine (docarpamine, glu-dopa) or by inhibiting the breakdown of dopamine (nitecapone). Preliminary clinical trials suggest that docarpamine may be useful in patients with low cardiac output syndrome after cardiac surgery and in refractory cirrhotic ascites. Ibopamine is an agonist at dopamine D1 and D2 receptors, which may retard the progression of chronic renal failure. Gludopa is selective for the kidney thus avoiding widespread side effects. The early clinical studies with ibopamine as a diuretic in heart failure were favourable but the subsequent large mortality study showed that ibopamine increased mortality. Fenoldopam is a selective dopamine D1 receptor agonist. Intravenous fenoldopam may be useful in the treatment of hypertension associated with coronary artery bypass surgery or in hypertensive emergencies. Although our understanding of physiological and pathological roles of peripheral dopamine has been increasing rapidly in recent times, we still need more information to allow the design of clinically useful drugs that modify these roles. One priority is an orally-active selective dopamine D1 receptor agonist.

Perceptions of evidence-based practice: A survey of Australian occupational therapists

Evidence-based practice (EBP) requires clinicians to access, appraise and integrate research literature with clinical experience and clients' perspectives. Currently, little is known about occupational therapists' attitudes to EBP, their perception of implementation barriers or their educational needs. A questionnaire reflecting these issues was sent to a proportionate random sample of 1491 members of the national professional occupational therapy association, OT AUSTRALIA. The questionnaire was completed by 649 (44%) participants. Occupational therapists were positive about EBP with most (96%) agreeing that EBP is important to occupational therapy. Although 56% used research to make clinical decisions, more relied on clinical experience (96%), information from continuing education (82%) and colleagues (80%). Lack of time, evidence and skills were identified as the main barriers to the implementation of EBP. Over half (52%) expressed strong interest in EBP skills training, and most (80%) indicated an interest in the availability of brief summaries of evidence. Targeted educational initiatives, resources and systems are needed to support EBP in occupational therapy.

Hemodynamic and ventilatory effects of manual respiratory physiotherapy techniques of chest clapping, vibration, and shaking in an animal model

Chest clapping, vibration, and shaking were studied in 10 physiotherapists who applied these techniques on an anesthetized animal model. Hemodynamic variables (such as heart rate, blood pressure, pulmonary artery pressure, and right atrial pressure) were measured during the application of these techniques to verify claims of adverse events. In addition, expired tidal volume and peak expiratory flow rate were measured to ascertain effects of these techniques. Physiotherapists in this study applied chest clapping at a rate of 6.2 +/- 0.9 Hz, vibration at 10.5 +/- 2.3 Hz, and shaking at 6.2 +/- 2.3 Hz. With the use of these rates, esophageal pressure swings of 8.8 +/- 5.0, 0.7 +/- 0.3, and 1.4 +/- 0.7 mmHg resulted from clapping, vibration, and shaking respectively. Variability in rates and forces generated by these techniques was 80% of variance in shaking force (P = 0.003). Application of these techniques by physiotherapists was found to have no significant effects on hemodynamic and most ventilatory variables in this study. From this study, we conclude that chest clapping, vibration, and shaking 1) can be consistently performed by physiotherapists; 2) are significantly related to physiotherapists' characteristics, particularly clinical experience; and 3) caused no significant hemodynamic effects.

An 18th century understanding of migraine - Samuel Tissot (1728-1797)

During the period 1778-1780 the Swiss physician Samuel A A D Tissot (1728-1797) published his Traite des nerfs et de leur maladies, a work which continued to be available and widely influential until at least the middle of the following century. It contained a long chapter dealing with migraine, based on the earlier literature on the topic and on Tissot's own clinical experience. The work appeared at the beginning of the modern era of interest in migraine, and provided the first reasonably adequate and systematic account of the disorder to become widely available. Its descriptions of migraine phenomena have an enduring validity, though Tissot's ideas on the pathogenesis of the disorder, viz. that it usually arose from stomach disturbance, were not founded on satisfactory evidence and are long since superseded. (C) 2003 Elsevier Science Ltd. All rights reserved.

Ethical issues in using a cocaine vaccine to treat and prevent cocaine abuse and dependence

A cocaine vaccine'' is a promising immunotherapeutic approach to treating cocaine dependence which induces the immune system to form antibodies that prevent cocaine from crossing the blood brain barrier to act on receptor sites in the brain. Studies in rats show that cocaine antibodies block cocaine from reaching the brain and prevent the reinstatement of cocaine self administration. A successful phase 1 trial of a human cocaine vaccine has been reported. The most promising application of a cocaine vaccine is to prevent relapse to dependence in abstinent users who voluntarily enter treatment. Any use of a vaccine to treat cocaine addicts under legal coercion raises major ethical issues. If this is done at all, it should be carefully trialled first, and only after considerable clinical experience has been obtained in using the vaccine to treat voluntary patients. There will need to be an informed community debate about what role, if any, a cocaine vaccine may have as a way of preventing cocaine addiction in children and adolescents.