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Biomedical subjects

M Sharpe

Publications and source records attributed to M Sharpe.

At least 19 recordsLinked to original sources
PubMed2001

Improvement in dose escalation using the process of adaptive radiotherapy combined with three-dimensional conformal or intensity-modulated beams for prostate cancer.

PURPOSE: Advances in technology allow the creation of complex treatment plans with tightly conforming doses. However, variations in positioning of the organ/patient with respect to treatment beams necessitate the use of an appreciable margin, potentially limiting dose escalation in many patients. To (1) reduce this margin and (2) test the hypothesis that the achievable level of dose escalation is patient dependent, a patient-specific, confidence-limited planning target volume (cl-PTV) was constructed using an adaptive radiotherapy (ART) process for prostate cancer treatment developed in-house. The potential dose escalation achievable with this ART process is quantified for both conformal radiotherapy (CRT) delivery and intensity-modulated radiotherapy (IMRT) delivery. MATERIAL AND METHODS: Patients with organ confined prostate cancer were entered prospectively into an ART process developed in-house. This ART process has been designed to improve accuracy and precision of dose delivery, consequently enhancing dose escalation. In this process, a cl-PTV is constructed for each patient in the second week of treatment based upon on-line portal and CT images acquired during the first week of treatment. The treatment prescription dose, defined as the minimum dose to the cl-PTV, is selected based on predefined dose-volume constraints for rectum/bladder and derived from the pretreatment planning CT image. In addition, the treatment modality (CRT or IMRT) is determined based on the level of dose escalation achievable and the risk of inaccurate targeting. The potential for both dose escalation and the application of IMRT was evaluated by comparing the prescription doses delivered using the ART process, with the cl-PTV, to those in the traditional treatment process, with a conventional generic PTV. In addition, the distributions of potential geometric target underdosing and normal tissue overdosing were also calculated to evaluate the quality of the conventional treatment plans. RESULTS: One hundred and fifty patients have been treated with the ART process. When compared to the treatment dose delivered with the conventional treatment process (generic PTV), an average 5% (2.5--10%) more dose could be delivered using the ART process with CRT, and 7.5% (2.5--15%) more dose could be delivered with IMRT. Of the 150 patients, 70% were treated to a minimum cl-PTV dose > or = 77.4 Gy (81.3 Gy ICRU isocenter dose). Dosimetric analysis revealed that 81 Gy to the cl-PTV (or 86.7 Gy ICRU) could be prescribed to at least 50% of patients if IMRT was applied using the ART process. In contrast, IMRT did not yield an obvious dose escalation gain if patients were treated using the generic PTV. Our results also demonstrate that the cl-PTV is significantly smaller than the conventional generic PTV for most patients, with a mean volume reduction of 24% (range, 5--43%). CONCLUSION: These results support our hypothesis that the achievable level of dose escalation using ART is patient dependent. By using the ART process to develop a cl-PTV, one can (1) optimize the dose level, (2) increase the applicability of IMRT, and (3) improve the quality of dose delivery. The ART process provides the foundation to identify a suitable option (CRT or IMRT) for the delivery of a safe treatment and dose escalation. It is now our standard of practice for prostate cancer treatment.

Adenocarcinoma↗
PubMed2001

"Unexplained" somatic symptoms, functional syndromes, and somatization: do we need a paradigm shift?

Medically unexplained functional or somatization symptoms are somatic disorders that are not adequately explained by physical disease processes. The way in which these disorders have been understood and managed has varied over the history of medicine. However, only in the past 100 years has the "mental" explanation predominated. A benefit of this trend has been the development of effective treatments in the form of "antidepressant" drugs and cognitive-behavioral therapies; a cost has been limited integration of these treatments into medical practice and lack of acceptability to patients. We suggest that there is much to learn from physicians of the pre-Freudian era. Their etiologic theories are now supported by new scientific evidence, and their clinical practice provided ways of making psychological treatment acceptable to patients. We propose a paradigm shift in which unexplained symptoms are remedicalized around the notion of a functional disturbance of the nervous system and treatments currently considered "psychiatric" are integrated into general medical care.

History, 17th Century↗
PubMed2001

Interpretation of symptoms in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is an illness characterised by fatigue and other symptoms. Both psychological and biological aetiological factors have been proposed, but the disorder is of uncertain origin. The aetiology of the symptoms is therefore ambiguous. It has been suggested (a) that patients with CFS tend to interpret their symptoms as indicating physical illness and (b) they tend not to interpret these symptoms in terms of negative emotion. In order to test these hypotheses we developed a self-report questionnaire to assess the interpretation of symptoms in patients with CFS. It was administered to patients with CFS, patients with depression, patients with multiple sclerosis (MS), and normal controls. Preliminary results suggest that the measure has acceptable psychometric properties. Patients with CFS were more likely than either depressed patients or normal controls to interpret symptoms (characteristic of CFS) in terms of physical illness, but did not differ in this from the MS patients. When compared with all three other groups (including the MS patients), the patients with CFS were least likely to interpret symptoms in terms of negative emotional states. The theoretical and clinical implications of the findings are discussed.

Adult↗
PubMed2001

A survey of frequent attenders at a gastroenterology clinic.

OBJECTIVE: To examine a group of patients satisfying criteria for "frequent attending" as part of an audit of an outpatient gastroenterology service, and to note the prevalence of those with no conspicuous organic disease to account for their symptomatology. METHODS: We used the hospital computer (Oxford Patient Administration System, OXPAS) to identify 2530 consecutive patients who were given an appointment to attend the gastroenterology clinic during an 11-month period. Patients designated "frequent attenders" had their notes flagged before the clinic attendance and were examined in more detail. A frequent attender was defined as a patient who had attended any hospital outpatient clinic in the three Oxford general hospitals on four or more occasions in the previous 12 months. The gastroenterologist then interviewed the patients satisfying these criteria and indicated whether he/she was satisfied that there was no relevant organic disease to account for the symptoms. RESULTS: Of the total 2530 patients, 762 (30%) satisfied our criteria for frequent attendance (FA). Of these, 452 (59%) had organic disease, 128 (17%) either did not attend or cancelled and 159 (21%) had no relevant organic disease. The diagnosis was uncertain in 23 patients (3%). Of patients satisfying our criteria for frequent attending, approximately 20-25% had no established gastroenterological disease. CONCLUSIONS: Frequent attenders present formidable management problems for the gastroenterologist. If they can be identified by computer before the outpatient visit then assessment and management might be more appropriately supervised in designated clinics by more experienced gastroenterology staff.

Adolescent↗
PubMed2001

Health-related quality of life in patients with chronic fatigue syndrome: an international study.

OBJECTIVE: Chronic fatigue syndrome (CFS) has been reported worldwide. Our objectives were to determine if patients from different countries have similar profiles of impairments. METHODS: Health-related quality of life (HRQoL) was assessed in 740 CFS patients in the US, 82 in the UK, and 65 in Germany using the eight subscales of the Short-Form General Health Survey (SF-36). To examine the internal structure, factor analyses were performed. RESULTS: Overall, there was a remarkable similarity in HRQoL among all CFS patients, regardless of location. Patients scored two to three standard deviations below normal on six subscales and one standard deviation below normal on the other two subscales. Factor analysis suggested a two-factor model where the same six subscales constitute the first factor and the two others the second factor. CONCLUSION: HRQoL is poor in CFS patients from three countries. This study is a first step towards conducting further comparative cross-cultural and international studies.

Adolescent↗
PubMed2001

Behavioral treatment of insomnia: treatment outcome and the relevance of medical and psychiatric morbidity.

Recently, we undertook a case series study and found that behavior therapy for insomnia was effective as plied in the clinic setting and that the findings were similar to those in the "clinical trial" literature. In the present study, we evaluate a second set of case series data to assess (1) the replicability of our original findings, (2) if our treatment outcomes are statistically comparable to those in the literature, and (3) if medical and psychiatric morbidity influence treatment outcome. It was found that patients who completed four or more sessions of cognitive behavioral therapy for insomnia (CBT) were, on average, 33% improved. This average corresponded to a 56% reduction in wake time after sleep onset, a 34% reduction in sleep latency, a 29% increase in total sleep time, and a 13% decrease in number of awakenings per night. These findings are not significantly different from those reported in literature for both CBT and pharmacotherapy interventions. Medical and psychiatric comorbidity did not influence treatment outcome.

Behavior Therapy↗
PubMed2001

What is chronic fatigue syndrome? Heterogeneity within an international multicentre study.

OBJECTIVE: We sought to compare the characteristics of patients presenting with chronic fatigue (CF) and related syndromes in eight international centres and to subclassify these subjects based on symptom profiles. The validity of the subclasses was then tested against clinical data. METHOD: Subjects with a clinical diagnosis of CF completed a 119-item self-report questionnaire to provide clinical symptom data and other information such as illness course and functional impairment. Subclasses were generated using a principal components-like analysis followed by latent profile analysis (LPA). RESULTS: 744 subjects returned complete data sets (mean age 40.8 years, mean length of illness 7.9 years, female to male ratio 3:1). Overall, the subjects had a high rate of reporting typical CF symptoms (fatigue, neuropsychological dysfunction, sleep disturbance). Using LPA, two subclasses were generated. Class one (68% sample) was characterized by: younger age, lower female to male ratio; shorter episode duration; less premorbid, current and familial psychiatric morbidity; and, less functional disability. Class two subjects (32%) had features more consistent with a somatoform illness. There was substantial variation in subclass prevalences between the study centres (Class two range 6-48%). CONCLUSIONS: Criteria-based approaches to the diagnosis of CF and related syndromes do not select a homogeneous patient group. While substratification of patients is essential for further aetiological and treatment research, the basis for allocating such subcategories remains controversial.

Adult↗
PubMed2001

Negative attitudes among short-term stroke survivors predict worse long-term survival.

BACKGROUND AND PURPOSE: Patients respond to serious illness in different ways. We wished to determine whether different attitudes toward illness are associated with survival after stroke. METHODS: Three hundred seventy-two stroke patients were identified and medically assessed as part of a randomized trial to evaluate a stroke family care worker. They had all survived 6 months from randomization. A research psychologist visited each patient and administered the Mental Adjustment to Stroke Scale (a self-rated attitude scale based on the Mental Adjustment to Cancer Scale). Disability and dependence (Barthel Index, modified Rankin Scale) and mood (Hospital Anxiety and Depression Scale, General Health Questionnaire 30) were also assessed. Patients were followed up in 1998 (3 to 5 years after the initial stroke) to establish their survival. We modeled the relationship between Mental Adjustment to Stroke scores and survival, adjusting for other factors associated with stroke survival. RESULTS: Eighty-two patients (22%) died within 3 years. After adjustment for other significant factors, fatalism and helplessness/hopelessness were both associated with decreased survival (P=0.03 and 0.04, respectively), but fighting spirit, anxious preoccupation, and denial/avoidance were not. Mood was not associated with survival. CONCLUSIONS: Patients' attitudes toward their illness seem to be associated with survival after stroke. Patients who feel that there is nothing they can do to help themselves 6 months after a stroke have a shorter survival. These findings need to be confirmed and any causal relationship between attitude and survival further explored in a randomized controlled trial to "improve" the attitude of stroke patients toward their illness.

Aged↗
PubMed2001

Alendronate: an update of its use in osteoporosis.

UNLABELLED: Alendronate (alendronic acid) is a nitrogen-containing bisphosphonate which binds to bone surfaces and inhibits bone resorption by osteoclasts. Oral alendronate 5 or 10 mg/day produces sustained increases in bone mineral density (BMD) in postmenopausal women with or without osteoporosis, in men with primary osteoporosis and in both men and women with or without osteoporosis receiving systemic corticosteroid therapy. Histomorphometric analyses have found that alendronate does not appear to impair bone quality. Alendronate reduced the risk of radiographic vertebral fracture, clinical vertebral fracture or hip fracture by 47 to 56% in postmenopausal women who had > or = 1 existing vertebral fracture and in those with no existing vertebral fractures but who had osteoporosis. In a number of comparative trials in postmenopausal women with osteoporosis, alendronate 10 mg/day was found to be more effective at inducing sustained increases in BMD than intranasal calcitonin, and at least as effective as conjugated estrogens and raloxifene. Alendronate 70 mg administered once weekly and 35 mg twice weekly are as effective at increasing BMD as 10 mg/day in this patient group. In clinical trials, alendronate was generally well tolerated when taken as recommended. Adverse events tended to be transient and associated with the upper GI tract, most commonly including abdominal pain, nausea, dyspepsia, acid regurgitation and musculoskeletal pain. No statistically significant differences between alendronate 10 mg/day and placebo have been found in the incidence of upper GI adverse events in large clinical trials. However, postmarketing surveillance reported a low incidence of adverse events related to the oesophagus. Specific instructions aimed at reducing the risk of upper GI adverse events have been provided by the manufacturer. CONCLUSIONS: Alendronate is effective and generally well tolerated in the treatment of women or men with primary (including postmenopausal) or corticosteroid-induced osteoporosis and in the prevention of osteoporosis in postmenopausal women. The drug has been associated with upper GI tract adverse events, although the extent to which alendronate is responsible for these events has not been clearly established. Alendronate should be considered a treatment of choice in postmenopausal women with osteoporosis. Alendronate is also a suitable treatment option for primary osteoporosis in men and for corticosteroid-induced osteoporosis in both men and women.

Adult↗
PubMed2001

Inhaled mometasone furoate: a review of its use in adults and adolescents with persistent asthma.

UNLABELLED: Mometasone furoate is a corticosteroid with relatively high in vitro potency. Recent randomised, double-blind, multicentre trials have assessed the efficacy of mometasone furoate delivered by dry powder inhaler over 12 weeks in adults and adolescents with mild to severe persistent asthma. Mometasone furoate 200 microg twice daily or 400 microg once daily in the morning or 200 microg once daily in the evening improved lung function, asthma symptom scores and use of rescue medication to a significantly greater extent than placebo in patients who had previously received only short-acting inhaled beta2-adrenoceptor agonists alone as treatment in 3 trials (n = 195 to 306). In studies in 227 to 733 patients with mild to moderate asthma who were receiving ongoing treatment with inhaled corticosteroids prior to enrolment, mometasone furoate 100 to 400 microg twice daily was consistently better at improving the above indicators of asthma than placebo. Mometasone furoate 100 to 200 microg twice daily was as effective as beclomethasone dipropionate 200 microg twice daily or budesonide 400 microg twice daily and mometasone furoate 200 microg twice daily was as effective as fluticasone propionate 250 microg twice daily. Mometasone furoate 400 or 800 microg twice daily was also consistently more effective than placebo in reducing oral corticosteroid dosages and improving lung function and asthma symptoms in 132 patients with oral corticosteroid-dependent asthma. Once daily administration of mometasone furoate 400 microg appears to be as effective at improving indicators of asthma as twice daily administration of 200 microg. Patients receiving mometasone furoate < or =800 microg/day and recipients of placebo experienced a similar overall incidence of adverse events considered to be related to treatment. The most common of these events were oral candidiasis, headache, pharyngitis and dysphonia. Mometasone furoate 100 to 400 microg twice daily, beclomethasone dipropionate 200 microg twice daily, budesonide 400 microg twice daily or fluticasone propionate 250 microg twice daily were similarly tolerated. CONCLUSION: Inhaled mometasone furoate is well tolerated, with minimal systemic activity and is equally effective when administered as a divided dose or as a single daily dose. Use of the drug can result in a decrease in requirements for oral corticosteroids in patients with oral corticosteroid-dependent asthma and is as effective as other inhaled corticosteroids currently used in the treatment of mild to moderate persistent asthma. Thus mometasone furoate is suitable for the control of mild to severe persistent asthma in adults or adolescents.

Administration, Inhalation↗
PubMed2001

Telmisartan: a review of its use in hypertension.

UNLABELLED: Telmisartan is an angiotensin II receptor antagonist that is highly selective for type 1 angiotensin II receptors. It was significantly more effective than placebo in large (n >100), double-blind, randomised, multicentre clinical trials in patients with mild to moderate hypertension. Telmisartan 20 to 160 mg once daily produced mean reductions in supine trough systolic blood pressure and diastolic blood pressure of up to 15.5 and 10.5 mm Hg, respectively. Maximum blood pressure reduction occurred with a dosage of 40 to 80 mg/day. Telmisartan 40 to 120 mg/day was as effective as amlodipine 5 to 10 mg/day or atenolol 50 to 100 mg/day in dose-titration studies. Telmisartan 20 to 160 mg/day was generally similar in efficacy to enalapril 5 to 20 mg/day or lisinopril 10 to 40 mg/day in both titration-to-response and other studies. Hydrochlorothiazide was coadministered in most of the titration-to-response studies if patients remained hypertensive. Telmisartan 80 mg/day was more effective than submaximal dosages of losartan (50 mg/day) or valsartan (80 mg/day) and was as effective as a fixed-dose combination of losartan 50 mg plus hydrochlorothiazide 12.5 mg over the last 6 hours of the dosage interval and the whole 24-hour postdose interval. In patients with severe hypertension, telmisartan 80 to 160 mg/day was as effective as enalapril 20 to 40 mg/day (both agents could be titrated and combined sequentially with hydrochlorothiazide 25 mg and amlodipine 5 mg). The addition of hydrochlorothiazide to telmisartan was more effective than each agent alone at lowering blood pressure in patients with hypertension. Telmisartan was well tolerated in patients with mild to moderate hypertension and was significantly less likely to cause persistent, dry cough than lisinopril. CONCLUSION: Telmisartan is an effective antihypertensive agent with a tolerability profile similar to that of placebo. Comparative data have shown telmisartan to be as effective as other major classes of antihypertensive agents at lowering blood pressure. Compared with lisinopril, telmisartan is associated with a significantly lower incidence of dry, persistent cough. Therefore, telmisartan is a useful therapeutic option in the management of patients with hypertension.

Angiotensin II↗
PubMed2001

Smart screening.

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Drug Evaluation, Preclinical↗
PubMed2000

Depression after stroke and lesion location: a systematic review.

BACKGROUND: There is conflicting evidence on the hypothesis that the risk of depression after stroke is influenced by the location of the brain lesion. We undertook a systematic review to examine the hypotheses that depression is more commonly associated with left-hemisphere strokes than with right-hemisphere strokes and with lesions of the left anterior brain than with other regions. METHODS: We did a computer-aided search of MEDLINE, BIDS ISI, and PsychLit databases supplemented by hand searches of key journals. We included all reports on the association of depression after stroke with the location of the brain lesion. Studies were systematically and independently examined by two investigators. Fixed-effects and random-effects meta-analyses were done. FINDINGS: 143 reports were identified by the search strategy. 48 were eligible for inclusion. Not all reports included original data. Only two reports of original data supported the hypotheses and seven clearly did not. The pooled (random-effects) relative risk of depression after a left-hemisphere stroke, compared with a right-hemisphere stroke, was 0.95 (95% CI 0.83-1.10). For depression after a left anterior lesion compared with all other brain areas the pooled (random-effects) relative risk was 1-17 (0.87-1.62). Restriction of the analyses to reports from high-quality studies or major depressive disorder did not substantially affect the findings. Nor were they affected by stratification of the time between stroke and the assessment of depression. Multiple publications from the same samples of patients were apparent. INTERPRETATION: This systematic review offered no support for the hypothesis that the risk of depression after stroke is affected by the location of the brain lesion.

Aphasia↗
PubMed2000

EMG and strength correlates of selected shoulder muscles during rotations of the glenohumeral joint.

OBJECTIVE: To identify activation patterns of several muscles acting on the shoulder joint during isokinetic internal and external rotation. DESIGN: Combined EMG and isokinetic strength analysis in healthy subjects. BACKGROUND: EMG studies of the shoulder region revealed intricate muscular activation patterns during elevation of the arm but no parallel studies regarding pure rotations of the joint could be located. METHODS: Fifteen (n=30 shoulders) young, asymptomatic male subjects participated in the study. Strength production during isokinetic concentric and eccentric internal and external rotations at 60 and 180 degrees /s was correlated with the EMG activity of the rotator cuff, biceps, deltoid and pectoralis major. Analysis of the smoothed EMG related to the timing of onset of the signal and to the normalized activity at the angle of the peak moment. Determination of the association between the EMG and the moment was based on strength ratios. RESULTS: Findings indicated that for both types of rotations, the rotator cuff and biceps were active 0.092+/-0.038-0.215+/-0.045 s prior to the initiation of the actual movement and 0.112-0.034 s prior to onset of deltoid and pectoralis major activity. These differences were significant in all of the eight conditions (P<0.05). In terms of the strength ratios, strong association was found between electrical activity and moment production in the subscapularis and infraspinatus (r(2)=0.95 and 0. 72, respectively) at the low and high angular velocities. CONCLUSIONS: Prior to actual rotation of the shoulder joint, normal recruitment of the rotator cuff and biceps is characterized by a non-specific presetting phase which is mainly directed at enhancing the joint 'stiffness' and hence its stability. Once movement is in progress, the EMG patterns of these muscles become movement specific and are correlated with the resultant moment. RELEVANCE: Muscular dysfunction relating to delayed onset activity or altered activation patterns, due to pain, perturbed mechanics or disturbed neural activation have been implicated as concomitant factors in other joint associated pathologies. Through highlighting the role of the rotator cuff in shoulder joint rotations, this study lends further support to the argument that a parallel situation may prevail with respect to shoulder joint dysfunction. This could lead to the development of rehabilitation protocols aimed specifically at redressing such dysfunction.

Adolescent↗