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Biomedical subjects

J Main

Publications and source records attributed to J Main.

At least 19 recordsLinked to original sources

Patient delay in oral cancer: a qualitative study of patients' experiences.

Up to 30% of patients delay seeking the advice of a healthcare professional after self-discovery of symptom(s) of oral cancer. Reasons for this patient delay are poorly understood. The aim of the present study was to explore patients' initial experiences and reactions to developing symptoms of oral cancer, and to identify factors influencing their decision to consult a health care professional. In-depth semi-structured interviews were conducted with 17 consecutive patients who had received a diagnosis of oral squamous cell carcinoma, but had yet to start treatment. Participants were asked about their beliefs about their symptoms over the course of the disease and their decision to seek help. The tape-recorded interviews were transcribed verbatim and analysed using 'Framework analysis'. Oral symptoms were rarely attributed to cancer and were frequently interpreted as minor oral conditions. As a result of these beliefs, patients tended to postpone seeking help or fail to be concerned over their symptoms. Prior to seeking help, patients responded to symptoms by using self-medication, changing the way they ate and disclosing their discovery of symptoms to friends or family. Problems with access to healthcare professionals and patients' social responsibilities acted as barriers to prompt help-seeking. This study has documented that an individual's interpretation of oral cancer symptoms may be misguided and this can adversely affect subsequent help-seeking behaviour.

Adaptation, Psychological↗

Health benefits of antiviral therapy for mild chronic hepatitis C: randomised controlled trial and economic evaluation.

OBJECTIVES: To determine whether combined therapy with interferon-alpha and ribavirin was more effective and cost-effective than no treatment for patients with mild chronic hepatitis C. DESIGN: A multicentre, randomised, controlled, non-blinded trial assessed the efficacy of combination therapy. A Markov model used these efficacy data combined with data on transition probabilities, costs and health-related quality of life (HRQoL) to assess the lifetime cost-effectiveness of the intervention. SETTING: A multicentre NHS setting. PARTICIPANTS: Treatment-naive, adult patients with histologically mild chronic hepatitis C (Ishak necroinflammatory scores <4 and fibrosis scores <3 on liver biopsy). INTERVENTIONS: Patients were randomised to receive interferon-alpha and ribavirin for 48 weeks or no treatment (control). MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients having a sustained virological response (SVR), measured at 6 months after cessation of therapy. Secondary outcome measures were: the ability of early phase kinetics to predict the eventual outcome of treating mild disease; HRQoL measured using the Short Form 36 and EuroQol (5 Dimensions) questionnaires, and the cost per quality-adjusted life-year (QALY) of interferon-alpha and ribavirin for mild disease compared with no treatment. RESULTS: In the treatment group, 32 out of 98 patients (33%) achieved an SVR. Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% versus 49%, p = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved an SVR. HRQoL fell during treatment and rose with treatment cessation. For patients having an SVR there were modest improvements in HRQoL at 6 months post-treatment. The mean cost per QALY gained was 4535 pounds sterling for 40-year-old patients with genotype non-1 and 25,188 pounds sterling for patients with genotype 1. For patients with genotype 1 aged 65, providing interferon-alpha and ribavirin for mild disease led to fewer QALYs gained, and a mean cost per QALY of 53,017 pounds sterling. The model using efficacy estimates from the literature, showed that the cost per QALY gained from providing pegylated interferon alpha-2b and ribavirin at a mild stage rather than a moderate stage was 7821 pounds sterling for patients with genotype non-1 and 28,409 pounds sterling for patients with genotype 1. CONCLUSIONS: Based on the evidence collected in this study, interferon-alpha and ribavirin treatment for mild chronic hepatitis C patients is in general cost-effective at the 30,000 pounds sterling per QALY threshold previously used by policy-makers in the NHS. For patients with chronic hepatitis C aged 65 or over with genotype 1, antiviral treatment at a mild stage does not appear cost-effective. Further research is required on the cost-effectiveness of pegylated interferon and ribavirin, in particular the intervention's long-term impact on HRQoL and health service costs requires further evaluation. Further research is also needed to develop predictive tests, based on pharmacogenomics, that can identify those cases most likely to respond to antiviral therapy. Liver biopsy before treatment no longer appears justified apart from for older patients (aged 65 or over) with genotype 1. However, further research should monitor the impact this strategy would have on costs and outcomes.

Adult↗

Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C.

BACKGROUND: For patients with mild chronic hepatitis C the cost effectiveness of antiviral therapy is unknown. AIMS: To assess whether antiviral therapy (either interferon alpha or peginterferon alpha combined with ribavirin) is cost effective at a mild stage compared with waiting and only treating those cases who progress to moderate disease. PATIENTS: Cases with mild chronic hepatitis C. METHODS: A cost effectiveness model which estimates long term costs and outcomes for patients with mild chronic hepatitis C. The model uses effectiveness and cost data from the UK mild hepatitis C randomised controlled trial, combined with estimates of disease progression and cost from observational studies. RESULTS: Antiviral treatment at a mild rather than a moderate stage improved outcomes measured by quality adjusted life years (QALYS) gained. The mean cost per QALY gained from antiviral treatment with interferon alpha-2b and ribavirin, compared with no treatment at a mild stage, was 4535 pounds sterling (7108 dollars) for patients with genotype non-1 and 25,188 pounds sterling (39,480 dollars) for patients with genotype 1. Providing peginterferon alpha-2b and ribavirin at a mild rather than a moderate stage was also associated with a gain in QALYS; the costs per QALY gained were 7821 pounds sterling (12,259 dollars) for patients with genotype non-1 and 28,409 pounds sterling (44,528 dollars) for patients with genotype 1. CONCLUSIONS: For patients with chronic hepatitis C, it is generally more cost effective to provide antiviral treatment at a mild rather than a moderate disease stage. For older patients (aged 65 years or over) with genotype 1, antiviral treatment at a mild stage is not cost effective.

Adult↗

Discontinuation of pegylated interferon plus ribavirin in patients who are not responding to therapy -- patients' views of early cessation of therapy.

BACKGROUND: Current therapy for chronic hepatitis C infection involves a course of pegylated interferon and ribavirin. Patients who do not show a virological response after 12 weeks of therapy have a low probability of sustained virological response and it is therefore recommended that such patients stop treatment. AIM: To assess patients' views of early treatment cessation. METHODS: We conducted a open-labelled study in three UK centres, in which patients with biopsy-proven chronic hepatitis C requiring therapy were offered the choice of a full course of therapy with 40 kDa pegylated interferon-alpha 2a plus ribavirin (24 or 48 weeks depending on viral genotype) or early cessation if therapy had failed after 12 weeks. RESULTS: Ninety-five participants were enrolled and the majority (69%) did not wish to discontinue therapy even if it had low probability of success. In this unselected UK population, very few patients (4%) did not achieve an early virological response with the 40-kDa pegylated interferon-alpha 2a plus ribavirin and two of the four early virological non-responders decided to continue therapy. CONCLUSION: Early discontinuation of 'ineffective' anti-viral therapy may prove less popular with patients than with health care providers, and further patient-directed education regarding the cost-effectiveness of therapy will be needed if early discontinuation of unsuccessful therapy is to be accepted by patients.

Adult↗

Treatment of histologically mild hepatitis C virus infection with interferon and ribavirin: a multicentre randomized controlled trial.

Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing alpha-interferon (3 MU thrice weekly) + ribavirin (1000-1200 mg/day) for 48 weeks with no treatment in treatment naive, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with alpha-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% vs 49% P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.

Adult↗

Treatment of hepatitis C.

The combination of pegylated interferon alpha and ribavirin has improved treatment success rates in patients with hepatitis C with sustained response rates of just over 50% overall and more than 70% for those with genotypes 2 and 3. This article reviews the use of combination therapy, contraindications, factors influencing response and describes approaches to specific patient groups.

Acute Disease↗

Hepatitis C: How should we manage the patient?

The patient with HCV infection may present with a variety of problems and range from the asymptomatic patient with mild liver damage to a patient presenting with complications of cirrhosis or hepatocellular carcinoma. The diagnosis of hepatitis C may be a complete surprise to the patient or be an expected diagnosis in someone with known risk factors. Similarly the physician may be faced with a patient who knows very little about hepatitis C or someone who has read extensively on the subject. The initial consultation is useful for gaining information on the patient's background, physical examination may give useful clinical clues on the stage of the liver disease. The consultation gives the physician a chance to educate the patient on the current thinking on hepatitis C and to organize confirmatory and other investigations that will help decide on the next line of management, i.e. whether the patient is a candidate for combination therapy of interferon and ribavirin.

Delivery of Health Care↗

Cytomegalovirus infection and thrombosis: a causative association?

Venous thrombosis is a well-organised complication of hospitalisation and has often been reported in the context of HIV infection. Less frequently cytomegalovirus (CMV) has been implicated in the development of thrombosis, although usually in the context of immunosuppression. We report the case of a young, immunocompetent individual who developed pulmonary emboli as a complication of CMV infection and describe the three proposed mechanisms by which this is thought to occur. The probable mechanism in our patient is discussed.

Adult↗

Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterised by fatigue and musculosketetal pain, the severity of which is variable. Simple reaction times (SRTs) and movement times (SMTs) are slowed in CFS. Our objective is to correlate the day-to-day changes in symptomatology with any change in SRT, SMT or corticospinal excitability. Ten CFS patients were tested on two occasions up to two years apart. Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the thenar muscles. Threshold TMS strength to evoke MEPs was measured to index corticospinal excitability. SRTs and SMTs were measured. The percentage change in both SRTs and SMTs between the two test sessions correlated with the percentage change in corticospinal excitability assessed according to threshold TMS intensity required to produce MEPs. This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of SRTs supports the notion of a deficit in motor preparatory areas of the brain.

Adult↗

Relative increase in choline in the occipital cortex in chronic fatigue syndrome.

OBJECTIVE: To test the hypothesis that chronic fatigue syndrome (CFS) is associated with altered cerebral metabolites in the frontal and occipital cortices. METHOD: Cerebral proton magnetic resonance spectroscopy (1H MRS) was carried out in eight CFS patients and eight age- and sex-matched healthy control subjects. Spectra were obtained from 20 x 20 x 20 mm3 voxels in the dominant motor and occipital cortices using a point-resolved spectroscopy pulse sequence. RESULTS: The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No other metabolite ratios were significantly different between the two groups in either the frontal or occipital cortex. In addition, there was a loss of the normal spatial variation of Cho in CFS. CONCLUSION: Our results suggest that there may be an abnormality of phospholipid metabolism in the brain in CFS.

Adult↗

Semiclassical quantization by harmonic inversion: comparison of algorithms.

Harmonic inversion techniques have been shown to be a powerful tool for the semiclassical quantization and analysis of quantum spectra of both classically integrable and chaotic dynamical systems. Various computational procedures have been proposed for this purpose. Our aim is to find out which method is numerically most efficient. To this end, we summarize and discuss the different techniques and compare their accuracies by way of two example systems.

Journal Article↗

Evidence for a cerebral effect of the hepatitis C virus.

Patients with hepatitis C virus (HCV) infection frequently complain of symptoms akin to the chronic fatigue syndrome and score worse on health-related quality of life indices than matched controls. We address the hypothesis that HCV itself affects cerebral function. Using proton magnetic-resonance spectroscopy we have shown elevations in basal ganglia and white matter choline/creatine ratios in patients with histologically-mild hepatitis C, compared with healthy volunteers and patients with hepatitis B. This elevation is unrelated to hepatic encephalopathy or a history of intravenous drug abuse, and suggests that a biological process underlies the extrahepatic symptoms in chronic HCV infection.

Adult↗

Voluntary motor function in patients with chronic fatigue syndrome.

INTRODUCTION: The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. In particular, little is known of the involvement of the motor cortex and corticospinal system. METHODS: Transcranial magnetic stimulation (TMS) was used to assess corticospinal function in terms of latency and threshold of motor-evoked potentials (MEPs) in thenar muscles. Reaction times and speed of movement were assessed using button presses in response to auditory tones. RESULTS: Patients had higher (P<.05) self-assessed indices of fatigue (7/10) than for pain (5/10), anxiety (4/10) or depression (3/10). Mean (+/-S.E.M.) simple reaction times (SRTs) were longer (P<.05) in the patients (275+/-19 ms) than in the controls (219+/-9 ms); choice reaction times (CRTs) were not significantly longer in the patients. Movement times, once a reaction task had been initiated, were longer (P<.05) in the patients in both SRTs (patients, 248+/-13 ms; controls, 174+/-9 ms) and CRTs (patients, 269+/-13 ms; controls, 206+/-12 ms). There was no difference (P>.05) in threshold or latency of MEPs in hand muscles between the patients (threshold, 54.5+/-2.2% maximum stimulator output [% MSO]; latency 22+/-0.3 ms) and controls (threshold 54.6+/-3.6% MSO; latency 22.9+/-0.5 ms). Regression analysis showed no correlation (P>.05) of SRTs with either threshold for MEPs or fatigue index. CONCLUSION: Corticospinal conduction times and excitability were within the normal range despite a slower performance time for motor tasks and an increased feeling of fatigue. This suggests that the feeling of fatigue and the slowness of movement seen in CFS are manifest outside the corticospinal system.

Adult↗

Corticospinal inhibition appears normal in patients with chronic fatigue syndrome.

The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. Thresholds and latencies of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) are normal but intracortical inhibition has not been investigated. Eleven patients with CFS were compared with 11 control subjects. Each patient completed a questionnaire using visual analogue indices of pain, fatigue, anxiety and depression. Subjects released a button to initiate simple (SRTs) and choice reaction time (CRTs) tasks; for each task, movement times were measured between release of the initiation button and depression of a second button 15 cm away. Subjects held a 10 % maximum voluntary contraction in the thenar muscles of their dominant hand while TMS was applied to the motor cortex; the duration and extent of inhibition of surface electromyographic (EMG) activity were assessed at stimulus strengths above and below the threshold for MEPs. Patients had significantly (P < 0.05) higher mean indices of fatigue than of pain, anxiety or depression. Mean (+/- S.E.M.) SRTs (but not CRTs) were longer in patients (309 +/- 45 ms) than in controls (218 +/- 9 ms). Movement times were longer in patients for both SRTs and CRTs. TMS thresholds, expressed as a percentage of the maximum stimulator output, were not significantly (P > 0.05) different in both groups for both MEPs (patients, 34 +/- 3%; controls, 36 +/- 3%) and inhibition of voluntary contraction (patients, 29 +/- 2%; controls, 34 +/- 4%). The duration and extent of inhibition did not differ significantly between groups at any stimulus strength. The pattern of change in duration and extent of inhibition with increasing stimulus intensity was no different in the two groups. The duration and extent of corticospinal inhibition in patients with CFS did not differ from controls, adding further evidence to the notion that the feeling of fatigue and the slowness of movement seen in CFS is not manifest in corticospinal output pathways.

Adult↗

Treatment of chronic viral hepatitis.

Significant advances have been made in the treatment of both hepatitis B and C. Cure for the majority is becoming reality. Combination regimens are now established therapy in hepatitis C and the near future will see the adoption of a similar approach to hepatitis B. Interferon alpha therapy remains important, with the development of more efficacious pegylated forms. In this article we review current therapy and discuss future strategies of the therapy for chronic viral hepatitis.

Amino Acid Sequence↗