Relationship between glycaemia and length of hospital stay during an acute exacerbation of chronic obstructive pulmonary disease.

We have assessed whether glucose concentration and patient outcome are related in hospitalised patients when glycaemia is quantified in detail. Continuous glucose monitoring was performed on 47 consecutive subjects with an acute exacerbation of chronic obstructive pulmonary disease. Length of hospital stay increased by 10% for each mmol/L increase in mean glucose (P = 0.01). In a multivariable analysis, mean glucose was independently associated with length of hospital stay (P = 0.02). These data add weight to evidence that hyperglycaemia may adversely affect patient outcomes in hospitalised patients.

Providing reviews of evidence to COPD patients: controlled prospective 12-month trial.

The aim of this study was to evaluate a novel patient-held manual designed to reduce the evidence-practice gap in chronic obstructive pulmonary disease (COPD). The intervention manual contained summaries of research evidence. It was developed using current best practice for patient information materials and designed to cause discussion of evidence between patient and doctor. A controlled before-and-after study was employed in two similar but geographically separate regions of metropolitan Adelaide, South Australia. Participants had moderate to severe COPD, with 249 included at baseline and 201 completing the study. Evidence-based COPD management was measured using an indicator with three components: rates of influenza vaccination, bone density testing, and pulmonary rehabilitation. A survey of behavioral steps leading to practice change was conducted with the trial. Analysis, by median split of socioeconomic disadvantage, showed significant difference between study arms for only one component of the indicator of evidence-based practice, enrollment in pulmonary rehabilitation and only for the most socioeconomically disadvantaged stratum. For both socioeconomic strata, more intervention participants than control participants reported remembering being given the information material, reading part or all, and finding it very or quite helpful. Other significant differences were restricted to the stratum of greatest socioeconomic disadvantage: reading all of the material, learning from it, referring back, and talking to a doctor about a topic from the material. Above 90% of all participants who received the manual reported reading from it, 42% reported discussing topics with a doctor, but only 10% reported treatment change attributable to the manual. We have found that people with COPD will read an evidence manual developed using current best practice. However, the study demonstrated improvement for only one of the three components of an indicator of evidence-based disease management for only the most socioeconomically disadvantaged stratum of participants. Future interventions should be designed to better translate reading uptake into evidence-based disease management.

COPD care in Saudi Arabia: physicians' awareness and knowledge of guidelines and barriers to implementation.

OBJECTIVE: To assess Saudi physicians' awareness and knowledge about chronic obstructive pulmonary disease (COPD) guideline recommendations. METHODS: Cross-sectional study including physicians involved in COPD care in five hospitals in the Eastern Province of Saudi Arabia. The level of physicians' knowledge was considered as satisfactory (score > 80%), fair (score 50-80%) or poor (<50% of total score). RESULTS: Among the 44 physicians included in the study, the mean ± standard deviation knowledge score was 29.5 ± 4.2 out of 45 points (65.5%). Most physicians appeared to be unaware of any COPD guidelines (n = 27, 61.4%), and reported not adhering to guidelines (n = 28, 63.6%). CONCLUSION: Saudi physicians' knowledge about Global Initiative for Chronic Obstructive Lung Disease guidelines was assessed as fair. It is therefore highly recommended to increase physicians' awareness and knowledge about COPD-related guidelines.

Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation.

In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV1) were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p less than 0.01). Changes in FEV1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p less than 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV1. Moreover, in the context of this study, since the beta-blockers were given in doses likely to induce equivalent cardiac beta-blockade, there is no evidence to suggest that any one of them is more "cardioselective" than the others.

Oxitropium bromide. Dose-response and time-response study of a new anticholinergic bronchodilator drug.

The efficacy and side effects of oxitropium bromide, a new anticholinergic bronchodilator drug, were tested in a double-blind placebo-control study. Twenty-four men, aged 58 to 72 years, with chronic partially reversible obstruction of the airways were used as subjects. Three doses of oxitropium were tested (100 micrograms, 200 micrograms, and 300 micrograms) to determine the optimum dose by metered-dose inhaler. A comparison was also made between oxitropium, fenoterol (400 micrograms), and a combination of oxitropium (200 micrograms) and fenoterol (400 micrograms). Fenoterol produced a greater degree of maximal bronchodilatation than each of the three doses of oxitropium, and its effect was more rapid in onset (30 vs 120 minutes to peak effect); however, the duration of action of oxitropium was greater than that of fenoterol (ie, the forced expiratory volume in one second [FEV1] remained within 5 percent of peak FEV1 for three hours, compared to one hour). Oxitropium in the 100 micrograms dose was inferior to 200 micrograms and 300 micrograms in subjective efficacy scores, peak percent change in FEV1, forced vital capacity, (FVC), mean forced expiratory flow over the middle half of the FVC, and duration of action; there was no difference between 200 micrograms and 300 micrograms. The oxitropium-fenoterol combination had a rapid onset of action, and a greater peak effect was achieved than for oxitropium alone. The main unwanted effect was a mildly unpleasant taste. Anticholinergic effects were not seen in this group of elderly men. Oxitropium bromide therefore is an effective bronchodilator with slow onset but prolonged activity and few side effects when used in patients with moderately severe obstruction of the airways. An appropriate dose appears to be 200 micrograms. Addition of oxitropium to fenoterol appears to offer even greater efficacy.

A comparison of two long-acting vasoselective calcium antagonists in pulmonary hypertension secondary to COPD.

UNLABELLED: STUDY OBJECTIVES AND PATIENTS: Pulmonary hypertension (PH) is common in COPD and may predict mortality in this disorder. We have compared the pulmonary vasodilator effects, dose-response characteristics, and tolerability of two calcium channel blockers, amlodipine and extended-release (ER) felodipine, in 10 patients (seven men, age 68+/-4.8 [SD] years) with clinically stable COPD and PH. DESIGN: Drugs were given in equal single daily oral doses (2.5, 5, and 10 mg), increasing weekly for 3 weeks, in a randomized investigator-blinded crossover manner with a 1-week wash-out period between the two treatments. MEASUREMENTS: Doppler measurements of pulmonary hemodynamics were made on the seventh day of treatment at each drug dose. Lung function, arterial blood gases, and adverse events were also monitored weekly. RESULTS: A dose-dependent decline of pulmonary artery pressure (PAP) was observed with each drug. A dose of 2.5 mg produced a significant decrease in PAP compared with baseline (20% amlodipine, 17% felodipine ER). Additional decreases in PAP were observed at 5 mg and 10 mg that were similar for both drugs, but did not reach statistical significance compared with 2.5 mg. There was a dose-related decrease in pulmonary vascular resistance and increase in oxygen delivery with amlodipine and felodipine ER. Lung function and blood gas values were stable throughout. Side effects (headache and ankle edema) were less frequent during amlodipine treatment (p<0.05). CONCLUSIONS: Both amlodipine and felodipine ER, given as a single daily oral dose of > or = 2.5 mg, are effective pulmonary vasodilators in COPD patients with PH. Their dose-response characteristics are similar, but amlodipine treatment was associated with fewer side effects.

Felodipine improves pulmonary hemodynamics in chronic obstructive pulmonary disease.

Pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis. Reduction of pulmonary artery pressure in COPD by prolonged oxygen treatment has been shown to be associated with increased survival. In an attempt to find a suitable pharmacologic method of reducing pulmonary artery pressure and pulmonary vascular resistance in COPD, we enrolled 13 stable pulmonary-hypertensive, hypoxemic COPD patients in a study to test the effects of felodipine, a relatively new, vascular-selective calcium antagonist. Doppler echocardiography was used to estimate pulmonary artery pressure and cardiac output before treatment, 2, 7, and 12 weeks during felodipine treatment (10 to 20 mg/d), and after a 1-week placebo washout period. Measurements of lung function, arterial blood gases, and exercise capacity during an incremental bicycle ergometer test were also performed at intervals during the study period. Three patients withdrew from the study and of the remaining 10, 8 had some side effects of medication (peripheral edema or headache) that improved either spontaneously or following a reduction in drug dose. In the 10 patients who completed the study (8 male; mean age, 67 years), felodipine resulted in significant reductions in mean pulmonary artery pressure (22 percent) and total pulmonary (vascular) resistance (30 percent) and increases in cardiac output (15 percent) and stroke volume (13 percent) compared with baseline measurements and those taken after placebo washout. These effects were sustained over the 12 weeks of felodipine treatment. There was no adverse effect of felodipine treatment on pulmonary gas exchange at rest or during exercise and no change in lung function or exercise capacity. We conclude that in pulmonary hypertensive, hypoxemic COPD patients, felodipine substantially improves pulmonary hemodynamics.

A study of bleeding time in 120 long-term aspirin trial patients.

The bleeding time was measured in 120 patients participating in a longterm randomised double-blind trial of aspirin in thromboembolic prophylaxis (UK-TIA aspirin Study). In 70 patients taking aspirin 300 mg or 1,200 mg daily for a mean duration of 35 months the bleeding time averaged 228 seconds. In comparison with 30 patients randomised to placebo and not taking aspirin whose bleeding time averaged 217 seconds, there was no significant difference. Stratification of bleeding time estimation by duration of treatment suggested no significant trend in either placebo or aspirin groups over several years. These results suggest that the longterm trials of aspirin should be looked at again from the point of view of efficacy of treatment by time from randomisation.

Conjunctival involvement in cicatricial and bullous pemphigoid: a clinical and immunopathological study.

Patients with bullous pemphigoid were found to have significant ocular abnormalities. In a group of 18 patients one had conjunctival shrinkage, and 11 of 15 (73%) had positive linear direct immunofluorescence on conjunctival biopsy from a clinically uninvolved site. Our ocular findings in a group of 14 with cicatricial pemphigoid are also reported and compared with those from a control group of 20. Our findings suggest there is overlap between the pemphigoid groups and raise further questions about the pathogenicity of immunoreactants within the basement membrane zone. Bulbar conjunctival biopsy was simple and well tolerated, and the rate of immunofluorescence positivity of conjunctiva was twice that of skin in both pemphigoid groups.

Characteristics of near-fatal asthma in childhood.

As part of the South Australian asthma mortality survey, we examined 30 cases of near-fatal asthma attacks in children under 15 years of age who were seen over a 3-year period from May 1988 to June 1991. Subjects presented with asthma and either respiratory arrest, PaCO2 above 50 mm Hg, and/or an altered state of consciousness or inability to speak on presentation at a metropolitan Adelaide teaching hospital. A standardized interview and questionnaire was completed with subjects/parents and medical practitioners. Data were reviewed by the assessment panel which made collective judgments based on predetermined criteria. Seventeen patients (57%) were male, 20% were less than 7 years of age, and the majority (53%) were aged between 12 and 15 years. The majority (83%) had severe asthma and only one case (3.3%) had mild asthma. Half of the subjects were waking every night due to asthma and 79% had significant exercise limitation. A quarter of the subjects had a previous ICU admission and 70% had a hospital admission in the last 12 months. Primary care was carried out by a general practitioner in 57% of cases, and 70% of subjects had a crisis plan. Only 46% of those older than 7 years of age had ever used a peak-flow meter. Eighty percent of subjects or their families had high denial scores, and in 73% of cases psychosocial factors were considered to be significant. Eighty percent of cases experienced acute progressive respiratory distress, and 63% of cases delayed seeking medical care.(ABSTRACT TRUNCATED AT 250 WORDS)

Is asthma a psychosomatic illness?

In asthma the bronchial muscle is hyperirritable, making asthmatics susceptible to a wide variety of external and endogenous trigger factors normally experienced by us all. The level of hyperirritability determines the risk of developing bronchospasm on exposure to the trigger factors. Bronchial muscle tone is in part maintained by vagal nerves. Emotional factors can act as triggers for bronchospasm through these nerves, particularly in patients with the greatest hyperirritability. Asthma itself may arouse hostilities in parents, peers, and therapists. By definition asthma can therefore be considered psychosomatic, but because of current usage, this term does not help good medical management. The complex interplay between the organic abnormality in asthma and the psychosocial environment should always be carefully considered.

Compliance with aerosol therapy in chronic obstructive lung disease.

The compliance of 114 patients with chronic airways disease to therapy with aerosol salbutamol and beclomethasone dipropionate was examined over two consecutive periods of approximately four weeks. Values ranging from 90-110 percent compliance were recorded for the two agents and a further increase in compliance was noted with both aerosols during the second month of surveillance. Over-use of salbutamol occurred in those patients who had been recently discharged from hospital. It was concluded that the high level of compliance was due to the symptomatic nature of the illness and the over-use of the bronchodilator was attributed to the usually prompt relief it provided.

Providing patients with reviews of evidence about COPD treatments: a controlled trial of outcomes.

Studies in many countries have identified gaps between what is known from research evidence and what is done in clinical practice. Merely making research evidence available to practitioners does not cause much change in their behaviour, and researchers are now looking for more effective ways to improve the implementation of evidence. We report outcomes at three months of a parallel group trial of an evidence based patient manual designed to improve implementation of evidence by the patient's doctors. The patient manual was produced with extensive patient and professional input. It contained summaries of the evidence for treatments used in COPD (chronic obstructive pulmonary disease) and prompted discussion of evidence with doctors. Participants in the intervention arm of the trial (n = 125) were supplied with the manual and participants in the control arm (n = 124) were supplied with a pamphlet about COPD produced by the Australian Lung Foundation. The primary outcome measure (rates of current influenza vaccination and bone density testing) was an indicator of evidence based management of COPD. Secondary outcomes were quality of life (mastery component), satisfaction with information, communication with usual doctor, and anxiety. At three months no pattern of benefit in outcome measures was found for either group. Process measures showed high levels of personal use of the manual but progression to conversations with doctors for fewer than half of participants, and little treatment change. The findings highlight the difficulties of promoting changes in health behaviour and show that even when all stakeholders are consulted success is not guaranteed. Further research is required to identify those patients most likely to use manuals such as the one reported here, and how to make patient mediated interventions more effective for a greater proportion of the target population.

Barriers to success for an evidence-based guideline for chronic obstructive pulmonary disease.

OBJECTIVES: To evaluate 1) barriers to clinical guideline use and 2) the relationship between guideline use and inpatient outcomes in chronic obstructive pulmonary disease (COPD). METHODS: 1) Four focus groups of specific health professions (n = 30), from three metropolitan hospitals, and interview of 99 medical officers (MOs), linked to 349 admissions, both guided by behavioural modelling theory; 2) association between guideline use and patient outcomes (length of hospital stay > or = 14 days, and readmission within 28 or 90 days) was evaluated in a cohort of 405 COPD patients. RESULTS: 1) In focus groups, nurses and allied health professionals emphasized facilitation issues including paperwork duplication and time limitations as barriers, but considered improved patient care outcomes as the major guideline use determinant. There were similar findings in junior MOs (nonconsultants) by both focus group and interview, with the addition of a need for a sense of ownership. Senior MOs (consultants) greatly emphasized sense of ownership. Barriers to guideline use varied between types of units. Behavioural modelling explained 49% of the variation in intention to use the guideline for MOs. For nonconsultants, habit and intention were significantly associated with extent of guideline use. 2) Patient outcomes: guideline use was not associated with length of stay or readmission. CONCLUSIONS: 1) Guideline implementation should address issues relevant to different health professions, units and seniority of profession. 2) Guideline use was not associated with reductions in readmission or length of stay.

Fluvoxamine-methadone interaction.

OBJECTIVE: The aim of this paper is to report a case of symptomatic methadone toxicity associated with fluvoxamine treatment. CLINICAL PICTURE: A 28-year-old woman was admitted to hospital with severe hypoxaemia and hypercapnia indicating hypoventilation. Medication prior to admission had been stable and included methadone 70 mg daily and diazepam 2 mg twice daily. Three weeks before admission she had commenced treatment with fluvoxamine. TREATMENT: Methadone was decreased to 50 mg daily and diazepam was tapered to zero. OUTCOME: The serum methadone concentration decreased and oxygenation improved considerably. CONCLUSIONS: Clinicians should be aware of the potential for a significant drug interaction between fluvoxamine and methadone.

Airway responsiveness to histamine and methacholine: relationship to minimum treatment to control symptoms of asthma.

We have prospectively examined in 51 patients the relationship between the level of airway responsiveness to histamine and methacholine and the minimum medications required to control asthma. First we determined the least medication that was required to control symptoms so that they did not disturb sleep, were not present on waking, and did not require use of inhaled salbutamol (200 microgram) more than four times daily. When baseline FEV1 was greater than 70% of predicted and when there had been no respiratory infection or allergen exposure for six weeks, histamine and methacholine inhalation tests were carried out on separate days to determine the provocation concentration causing a fall in FEV1 of 20% (PC20). There was a close correlation between the PC20 to the two agents. The patients were grouped into 1, those who required no medication; 2, those who required salbutamol (200 microgram) occasionally but not daily; 3, those who required daily salbutamol; and 4, those who required additional beclomethasone dipropionate. The mean PC20 was highest in group 1 and lowest in group 4; there was a significant difference between each group. The results indicate that airway responsiveness to vasoactive amines is either an important determinant of the severity of asthma and the medication requirements or a consequence of the severity of asthma. They raise the possibility that measurement of responsiveness may be useful in some patients with established asthma to substantiate or question medication needs.

Long-term stability of bronchial responsiveness to histamine.

Bronchial responsiveness to histamine was measured in 35 adult asthmatics whose symptoms were controlled on a minimum of medication. The tests were carried out on two occasions separated by 10-30 months. On each occasion the subjects had no symptoms of respiratory infection and no exposure to relevant allergens for at least six weeks. Bronchial responsiveness did not change in those who required no medication or inhaled salbutamol only to control their symptoms, but was significantly improved in those who required continuous treatment with both beclomethasone and salbutamol (p = 0.03). The results suggest that non-specific bronchial responsiveness remains similar over long periods when exacerbating factors are not present and that treatment with beclomethasone may reduce hyperresponsiveness.

Posterior sub-Tenon's triamcinolone injections in the treatment of uveitis.

PURPOSE: This is the first study reported in the United Kingdom to investigate the efficacy and safety of posterior, sub-Tenon's triamcinolone acetonide injections in the treatment of posterior and intermediate uveitis. METHODS: Twenty-eight posterior sub-Tenon's triamcinolone injections (40 mg) were given and the results analysed with a 6 month prospective follow-up in 13 cases. RESULTS: At 6 weeks follow-up, objective improvement in visual acuity occurred in 25 eyes (p < 0.05). Vitreous cellular activity was diminished in 21 eyes (p < 0.05). In most cases improvement was observed within 2 weeks of injection. No patient required repeat triamcinolone injection within 3 months and all patients previously treated with systemic immunosuppression were able to decrease or discontinue this treatment. Complications included transient elevation of intraocular pressure in 4 patients and persistent mild ptosis in 2 patients. CONCLUSIONS: We have demonstrated that posterior sub-Tenon's triamcinolone injection significantly decreases cystoid macular oedema, with a corresponding increase in visual acuity, in patients with posterior uveitis. Systemic immunosuppression may be reduced or discontinued with the avoidance of associated systemic side effects, and the technique has a high level of patient acceptability.