Oral transmucosal fentanyl citrate in the management of breakthrough pain in cancer: an open, multicentre, dose-titration and long-term use study.

Sixty-six patients with cancer-related pain entered an open multicentre study to examine the safety and efficacy of oral transmucosal fentanyl citrate (OTFC) in the treatment of breakthrough pain. Patients were eligible for the study if they were stabilized on a long-acting opioid but were experiencing up to four episodes of breakthrough pain a day and achieving at least partial relief from breakthrough pain using conventional medication (normal release oral morphine in the majority of patients). The efficacy of the conventional medication was documented in a run-in phase and patients then changed to OTFC. All patients were treated initially with a 200 mcg unit of OTFC and the dose was increased if necessary to a level that produced relief of breakthrough pain without troublesome adverse effects. Fifty-eight patients completed the run-in phase using their usual medication and entered the dose titration phase with OTFC and 57 patients received at least one dose of OTFC. Forty-two patients (72%) found a successful dose of OTFC. The primary outcome measures were the Summed Pain Intensity Differences (SPID) and Total Pain Relief (TOTPAR) scores at 60 min. There was a significant difference in both measures in favour of OTFC compared with conventional medication in these patients. Twenty-eight of the 42 patients (67%) preferred OTFC to their usual medication. The most common adverse effects attributed to OTFC were nausea, stomatitis, vomiting and dizziness but there were no unpredicted or severe problems. Thirty-seven patients continued into the long-term study and 12 of these completed six months treatment. Most drop-outs in this phase were associated with progression of the underlying disease. No patient stopped using OTFC because of dissatisfaction with the drug. OTFC appears to be a safe and effective treatment for breakthrough pain in cancer patients and may have advantages over currently available opioid formulations.

Influence of treatment with beclomethasone, cromoglycate and theophylline on perception of bronchoconstriction in patients with bronchial asthma.

1. Perception of asthma by patients can be assessed from the relationship between symptom scores and peak expiratory flows. This study was designed to investigate the possibility that medication can affect perception of the sensation of asthma independently of changes in lung function. 2. Twelve subjects whose asthma was inadequately controlled by inhaled bronchodilator alone were studied during four different drug treatments over 3 months. Subjective self-assessment of asthma was scored on a 10 cm visual analogue scale and followed by three consecutive measurements of peak expiratory flow, using a coded electronic peak flow meter. This was recorded not less than three times daily on diary cards. Observations were recorded during the second week of each of four treatments: (i) a run-in period using only inhaled salbutamol as required, (ii) inhaled beclomethasone, (iii) inhaled cromoglycate and (iv) oral theophylline at a dose adjusted to achieve blood levels of 10-20 mg/l. Inhaled salbutamol was permitted during the other treatments as required. Changes in the slope and position of the regression lines of asthma scores on PEF were used to measure changes in perception of asthma on each treatment. Dynamic lung volumes were measured in the clinic before the study and after each treatment period. 3. In the group as a whole, theophylline improved lung function (mean peak flow and dynamic lung volumes) without affecting mean visual analogue scores, beclomethasone improved mean visual analogue scores with much less effect on lung function, while cromoglycate had a small though consistent effect on both. 4. Perception of asthma, measured by the relationship between peak flow rate and visual analogue scores, was unaffected by cromoglycate. On theophylline, perception of asthma was heightened in five subjects despite a definite improvement in their peak flow. On beclomethasone, perception of asthma was reduced in most subjects, often with no discernible improvement in mean peak flow or dynamic spirometry. 5. Perception of bronchoconstriction in asthma can be affected by drugs independently of control of the condition. Theophylline may produce a paradoxical increase in awareness of asthma in some individuals. With beclomethasone therapy a reduction in symptoms of asthma may occur without any improvement in tests of air flow.

Increased detection of hepatitis C virus infection in commercial plasma donors by a third-generation screening assay.

BACKGROUND: Routine screening of blood donations with second-generation hepatitis hepatitis C virus (HCV) assays has substantially reduced the occurrence of posttransfusion hepatitis. However, following the development of third-generation assays, several studies indicated that these assays may identify HCV-infected individuals who are not identified by second-generation assays. STUDY DESIGN AND METHODS: The sensitivity of a third-generation HCV enzyme-linked immunosorbent assay (ELISA-3) was compared with a second-generation ELISA (ELISA-2) in a side-by-side study of 9936 commercial blood donors. ELISA-reactive specimens were subjected to supplemental analysis by third-generation recombinant immunoblot assay and polymerase chain reaction. RESULTS: ELISA-3 demonstrated greater sensitivity than ELISA-2, detecting 1 additional recombinant immunoblot assay-positive specimen per 2000 tested. ELISA-3 also detected 1 additional HCV-infectious polymerase chain reaction-positive unit among approximately 10,000 units screened. CONCLUSION: The incremental sensitivity achieved with ELISA-3 can be expected to eliminate approximately 20 infectious donations per week among those made by commercial donors in the United States. In accordance with previous studies, most of the improved sensitivity of ELISA-3 derives from its increased detection of anti-c33c (NS3), rather than from the inclusion of HCV antigen NS5.

Accuracy of perception of severity of asthma: patients treated in general practice.

OBJECTIVE: To determine the frequency of poor perception of severity of asthma in general practice. DESIGN: Asthmatic patients recorded their perceived severity of asthma, with a visual analogue score, and a coded measurement of their peak expiratory flow up to four times daily for 14 consecutive days. SETTINGS: 11 general practices in and around Bristol. SUBJECTS: 255 asthmatic patients (139 men and 116 women) aged 17-76 who were recruited by random selection from the general practices' disease registers or when they requested prescriptions for inhaled bronchodilators. MAIN OUTCOME MEASURES: Correlation between visual analogue scores and peak expiratory flow (as a percentage of predicted peak flow). RESULTS: 152 (60%) of the patients showed no significant correlation between visual analogue asthma scores and simultaneous peak flow measurements (p > 0.05) and were termed poor discriminators. The distribution of good and poor discriminators within each general practice was similar (chi 2 = 6.11, df = 10). The two groups were not characterised by differences in the maximum, minimum, or standard deviation of peak expiratory flow or visual analogue score; in age; or in the proportion of men and women in each group. CONCLUSIONS: In general practice a high proportion of asthmatic patients do not reliably detect changes in their lung function. This reinforces the need for careful objective assessment of lung function in the management of asthma.

Acceptability of oxygen concentrators: the patient's view.

The impact of the installation of an oxygen concentrator on the lifestyle of 30 patients in two health districts has been investigated using a questionnaire. Marked improvements in general well-being (83% of respondents), breathing (82%), mobility (62%) and sleep pattern (52%) were reported. The long term nature of the aims of treatment were understood by 83% of the respondents and the mean period of time the patients used the concentrator was satisfactory. However, 34% of respondents had a concentrator with only one outlet and 70% had the concentrator situated in a commonly used room with the possibility of problems with noise. Thirty one percent of the respondents were still smoking. The recommendations given to patients for the sitting of the concentrator and the number of outlets should be improved. However, the oxygen concentrator was found to be generally well tolerated and this refutes criticism that patients may find it restricting.

Home blood pressure recording in mild hypertension: value of distinguishing sustained from clinic hypertension and effect on diagnosis and treatment. Bath Health District Hypertension Study Group.

To identify the prevalence and magnitude of clinic changes in blood pressure and determine their effects on the diagnosis and treatment of hypertension, 268 patients with a BP greater than or equal to 160/95 mmHg on three consecutive occasions (twice in the general practitioner's surgery and once in the hospital clinic) recorded a home BP series with an electronic sphygmomanometer. Of these patients, 114 had never received antihypertensive treatment and 154 were receiving treatment. On return to the hospital clinic (second clinic visit) the BP was measured independently by the patient and doctor using electronic and mercury sphygmomanometers respectively and compared with the mean BP of the home series. In some 80% of both untreated and treated patients the second clinic BP was higher than the mean BP of the home series and in some 40% of patients a clinic rise of greater than 20/10 mmHg was recorded. Clinic falls in BP occurred in some 20% of both untreated and treated patients, but averaged only 4/4 mmHg. Treatment decisions based on a mean diastolic blood pressure of greater than or equal to 95 mmHg in the home series resulted in antihypertensive treatment not being started in 38% of untreated patients and not increased in 31% or reduced in 16% of treated patients when treatment would have been started, increased or continued unchanged on the basis of the second clinic (fourth recorded) diastolic blood pressure of greater than or equal to 95 mmHg. A patient recorded home series provides a representative sample of BP which distinguishes patients with sustained hypertension from those with clinic hypertension and may help reduce the overdiagnosis and overtreatment of mild hypertension.

Value of patient-recorded home blood pressure series in distinguishing sustained from office hypertension: effects on diagnosis and treatment of mild hypertension. Bath District Hypertension Study Group.

To identify the incidence and magnitude of office hypertension and determine its effect on diagnosis and treatment, 104 patients with a systolic blood pressure greater than or equal to 160 mmHg and a diastolic blood pressure greater than or equal to 95 mmHg on three consecutive office visits recorded a home BP series with an electronic sphygmomanometer. At the fourth office visit the blood pressure was measured independently by the patient and doctor using electronic and mercury sphygmomanometers, respectively, and compared with the mean blood pressure of the home series. In 80% of patients, the fourth office blood pressure was higher than the mean blood pressure of the home series. An office rise greater than or equal to 10/5 mmHg occurred in some 60% of patients, greater than or equal to 20/10 mmHg in 36% and 30/15 mmHg in 19% of patients. Office falls in blood pressure occurred in 20% of patients but averaged 3/2 mmHg. Treatment decisions based on the mean blood pressure of the home series resulted in treatment not being started in 25 patients (24%) who would have received treatment on their fourth office blood pressures. A patient-recorded home series provides a representative sample of blood pressure distinguishing patients with sustained hypertension from those with office hypertension and reducing the over diagnosis and over treatment of mild hypertension.

Prescription of oxygen concentrators: adherence to published guidelines.

The indications for the prescription of oxygen concentrators have been assessed in 82 patients against the Department of Health guidelines, except that only one set of blood gas and spirometry measurements was required if the patient's condition was stable. Of the 49 patients recommended for this treatment by a chest physician, 41 (82%) fulfilled the requirements, compared with only 11 of 33 patients where the concentrator was recommended by a general practitioner or non-specialist physician. Eleven patients died within one month of prescription. The results show that many patients are being prescribed oxygen concentrators without assessment and underline the importance of full assessment and attention to prognosis before prescription.

Reflex sympathetic dystrophy associated with squamous cell carcinoma of the lung.

Reflex sympathetic dystrophy was the presenting feature in an otherwise occult case of non-metastatic squamous cell carcinoma of the lung which improved on surgical removal of the primary tumour. Reflex sympathetic dystrophy, therefore, should be considered an occasional manifestation of a paraneoplastic syndrome warranting a thorough search for underlying malignancy.

Defense style and the perception of asthma.

Approximately 15% of patients with bronchial asthma are unable to sense marked changes in airway obstruction. We have investigated the hypothesis that inability to sense changes in the severity of bronchial asthma varies with insensitivity to emotional arousal, which in turn is associated with repressive defense styles. Nine asthmatic patients were studied comparing actual changes in peak flow rate using a coded peak flow meter and in arousal during a stress-inducing psycholinguistic protocol with perceived changes. Our hypotheses were confirmed. Ability to perceive changes in asthma could be predicted from performance on the psycholinguistic stress test (Spearman's rho = +0.733, p less than 0.01). Repressors performed significantly worse on the asthma perception task (Spearman's rho = -0.650, p less than 0.05). The results suggest a role for defense pathology in the psychomaintenance of asthma.

Influence of knowledge of peak flow on self assessment of asthma: studies with a coded peak flow meter.

A portable peak flow meter based on a turbine transducer that can display results in code has been developed. Its performance compares well with the Wright peak flow meter. Records of subjective self assessment of asthma on a visual analogue scale and of peak flow (PEF) were compared in 12 subjects with asthma. PEF measurements were made with a coded meter for two weeks and an uncoded meter for two weeks in random order. The correlation between visual analogue scale score and PEF was invariably stronger when PEF was known. Changes in perception of asthma were measured by comparing the slopes and relative positions of the regressions of visual analogue on PEF. When PEF was uncoded awareness of asthma was significantly increased in five patients, predominantly those whose perception was poorest while they were using the coded meter, and decreased in only one patient. In two patients the results were unsuitable for this type of analysis. Knowledge of PEF therefore may influence subjective self assessment in patients with bronchial asthma. For objective studies of symptoms of asthma, PEF readings should be unknown to the patient. Perception of asthma may, however, be improved in patients with poor ability to detect changes in bronchial calibre by uncoded measurement of peak flow at home.

An electronic peak flow meter with optional coded display.

A portable electronic spirometer giving peak expiratory flow rate has been developed and used successfully in studies of asthma. A turbine flow transducer produces a pulsed output whose frequency is proportional to flow. The output was coded to keep the results 'blind' to the patient. The code is suitable for use on other electronic instruments employing a similar display. It has been successfully used to investigate patients' perception of their asthma.

The duration of protection from exercise-induced asthma by inhaled salbutamol, and a comparison with inhaled reproterol.

beta-Adrenergic bronchodilators can prevent the development of exercise-induced asthma (EIA). To investigate the duration of this effect, we determined the time at which the protective effect of salbutamol diminished significantly in six subjects. All had stable asthma known to be triggered by exercise. Following a control exercise test, identical tests were repeated weekly at various times (1-6 hours) after inhalation of 200 micrograms of salbutamol. Significant protection (less than 75%) was lost in two subjects at 2 hours, in two at 4 hours and in two at 6 hours. A further exercise test was performed after inhalation of 1 mg of reproterol, at the time when salbutamol no longer afforded significant protection. There was a significantly smaller fall in peak expiratory flow rate after exercise (P less than 0.01) with reproterol than with salbutamol, at the same time after inhalation. There was no relationship between the degree or duration of protection from EIA and the bronchodilator effect of the drugs, the age and sex of the subjects, the length of asthma history or severity of base-line EIA, except perhaps the requirement for regular treatment with a steroid aerosol or sodium cromoglycate.

The effect of regular inhaled salbutamol on the airway responsiveness of normal subjects.

1. Airway responses to inhaled salbutamol were measured in two groups of six normal non-atopic subjects. In each group there was a dose-dependent increase in specific airways conductance after salbutamol inhaled in cumulative doses from 25 to 600 micrograms. 2. In the first group these studies were repeated weekly during and after the subjects had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 500 micrograms four times daily by week 5. Then, while subjects were continuing to receive regular salbutamol, the studies were repeated after 48 h of inhaled sodium cromoglycate (20 mg four times daily) and again after 48 h of beclomethasone dipropionate (200 micrograms four times daily). 3. In the second group the studies were repeated after 10 days of regular inhaled salbutamol (500 micrograms four times daily). 4. There was no change in airway response to inhaled salbutamol after 4 weeks or 10 days regular salbutamol therapy, or after 48 h of sodium cromoglycate or beclomethasone dipropionate therapy. 5. This study did not show the development of resistance to beta-agonists in the airways of normal subjects. These findings are discussed in the context of other studies which have shown the development of resistance, and we suggest that there may be a spectrum of susceptibility to the development of impaired airway responsiveness following regular treatment with beta-adrenergic drugs.