Biomedical subjects
Mark Weatherall
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COX-2 inhibitors--first, do no harm.
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Functional measures across neurologic disease states: analysis of factors in common.
OBJECTIVE: To describe the underlying dimensions for a range of functional measures across 3 neurologic diseases at different time points. DESIGN: Multiple cohort study. SETTING: Combination of public hospital wards and community. PARTICIPANTS: Patients (N=308) from 3 cohorts: paralytic poliomyelitis (n=38), mean of 25 years previously, assessed once; acute stroke admitted to hospital and followed up for 12 months postdischarge (n=181); and traumatic brain injury (TBI), admitted to hospital and followed up for 12 months postdischarge (n=89). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Barthel Index, FIM instrument, Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) physical component score (PCS) and mental component score (MCS), Community Integration Questionnaire (CIQ), and the London Handicap Score (LHS). Measures were compared at 2 time points: pre-event status for stroke, TBI and the polio cohort, and 12-month postdischarge status for stroke and TBI. RESULTS: The different measures generally correlated highly within disease states at each time point. Principal components analysis revealed 2 underlying dimensions, a physical dimension onto which loaded the Barthel Index, FIM, PCS, and LHS and a cognitive/emotional dimension onto which loaded the MCS and, for subjects with polio, the CIQ. These 2 dimensions accounted for 69% of the variance in measures at the pre-event time point and 85% of the variance at the 12-month time point. CONCLUSIONS: These data suggest 2 basic underlying dimensions across a wide range of measures in 3 different neurologic conditions even at different time points. Most of the variation in the measures can be captured using the 2 component summary scores (PCS, MCS) of the SF-36.
Metered dose inhalers: a need for dose counters.
OBJECTIVES: This study investigated the ability of patients to assess when a metered dose inhaler (MDI) is empty. METHODOLOGY: A total of 17 patients assessed, by shaking, the number of doses remaining in a salbutamol MDI that had been partially emptied. Another 100 patients were asked to collect all salbutamol MDIs they considered to be empty and would have thrown away. These MDI canisters were weighed and the number of doses that had been used was estimated. RESULTS: Using the 'shaking method', patients overestimated the amount remaining by around 40 doses. The mean number of doses delivered from an MDI labelled to contain 200 doses before it was discarded was 224 (range, 155-289). CONCLUSIONS: These findings confirm that patients are unable to determine when an MDI should be discarded, resulting in insufficient drug delivery at the end of the life of an MDI for the majority of patients, and wastage of the drug for others.
Fluticasone given once versus twice a day: meta-analysis.
OBJECTIVE: The aim of this study was to examine the efficacy of fluticasone administered once daily compared to twice daily in asthma. METHODOLOGY: A meta-analysis was performed of randomized double-blind trials of at least 4 weeks duration that compared fluticasone administered once versus twice a day and presented data on at least one clinical outcome measure. RESULTS: Six studies of 1517 children and adults with asthma met the inclusion criteria. Studies were predominantly in subjects with moderate asthma, treated with doses of fluticasone ranging from 200 to 500 microg per day. Twice-daily dosing was associated with significantly greater efficacy compared with once-daily dosing, for all outcome measures except night wakenings. The mean (95% CI) differences between twice and once-daily administration for FEV(1) and peak expiratory flow were 0.11 L (0.07-0.16) and 12.9 L/min (8.6-17.1), respectively. Twice-daily fluticasone was associated with significantly fewer withdrawals due to asthma than once-daily fluticasone, with an odds ratio of 0.44 (0.30-0.67). CONCLUSION: The findings suggest that twice-daily administration of fluticasone will provide greater therapeutic benefit than a once-daily morning regimen.
Fixed and adjustable dose asthma action plans based on combination therapy: a pilot study.
OBJECTIVE: The use of combination inhaled corticosteroid/long-acting beta-agonist therapy within the framework of a self-management plan has yet to be investigated. METHODOLOGY: In this randomized open-label study, 69 adult asthmatic patients taking >or= 1,000 microg per day of beclomethasone dipropionate (BDP) or equivalent were treated for 3 months with Symbicort Turbuhaler (200 microg budesonide/6 microg formoterol). Patients were assigned to one of two self-management plans, based on either a fixed or adjustable dose regimen. The primary outcome variable was episode-free days. RESULTS: Both regimens resulted in good asthma control, at least comparable to that obtained with previous high dose inhaled corticosteroid therapy. There were no significant differences in clinical outcome measures between the regimens. The mean (+/- SD) usage of Symbicort was similar for the fixed and adjustable dose regimens (3.8 +/- 0.68 vs 3.6 +/- 1.54 puffs per day, respectively). CONCLUSION: We conclude that Symbicort is effective when administered as either a fixed or adjustable dose regimen as part of a self-management plan.
Sleep-disordered breathing occurs frequently in stable outpatients with congestive heart failure.
BACKGROUND: Sleep-disordered breathing (SDB) has a potential role in the pathogenesis of congestive heart failure (CHF). High rates of central sleep apnea (CSA) are found in patients with severe CHF, and equal proportions of obstructive sleep apnea (OSA) and CSA in are found CHF patients referred to sleep clinics. The prevalence, type, and severity of SDB in unselected stable outpatients with CHF are unknown. STUDY OBJECTIVES: To determine the frequency and type of SDB in stable CHF outpatients and to examine the relationship between indexes of SDB and impaired cardiac function. PARTICIPANTS: Fifty-three of 87 eligible outpatients (left ventricular ejection fraction [LVEF] < 45%) were predominantly male (77%), with an average age of 60.1 +/- 9.8 years, mean body mass index of 27.9 +/- 5.3 kg/m2, and mean LVEF of 34.0 +/- 8.5% (+/- SD). MEASUREMENTS: Polysomnography, clinical questionnaire, echocardiography, urinary catecholamines, and amino-terminal fragment of pro-brain natriuretic peptide (NT-BNP). RESULTS: SDB (apnea-hypopnea index >10 events/h) was demonstrated in 36 patients (68%) including two subgroups: OSA (n = 28, 53%) and CSA (n = 8, 15%). SDB was associated with atrial fibrillation (0% vs 28%, p = 0.02), more severe oxyhemoglobin desaturation (percentage of time with oxygen saturation < 90%: 0.4% vs 7.9%, p = 0.003), sleep disruption (p = 0.003), and higher urinary noradrenaline levels (p = 0.013) in OSA patients and CSA patients, respectively. Subjective sleepiness (Epworth sleepiness scale, 7.5 vs 8.5; p = 0.11), indexes of impaired cardiac function including Minnesota Living With Heart Failure Questionnaire scores, shuttle walk distance, and NT-BNP levels were not related to the presence of SDB (p > 0.05). CSA patients had lower LVEF (p = 0.0013). CONCLUSIONS: SDB is very common in stable outpatients with CHF, and in our sample OSA predominates. Atrial fibrillation and severe left ventricular impairment increased the likelihood of SDB (particularly CSA), whereas symptom severity, subjective daytime sleepiness, exercise capacity, and NT-BNP levels did not. If specific therapy for SDB such as continuous positive airway pressure can be shown to improve major cardiovascular end points, these results support screening of clinically stable CHF patients.
Specific oral contraceptive use and venous thromboembolism resulting in hospital admission.
OBJECTIVE: To determine whether there is an increased risk of venous thromboembolism (VTE) with anti-androgen oral contraceptives containing cyproterone acetate and ethinyloestradiol. METHODS: Comparison of the frequency of specific oral contraceptive use in patients aged 15 to 55 years discharged from hospital with radiologically confirmed deep vein thrombosis (DVT) and/or pulmonary embolism (PE) with the expected frequency of use derived from national prescription data. MAIN OUTCOME MEASURE: Ratio of observed frequency of specific oral contraceptive use in patients with VTE versus expected frequency of use. RESULTS: The rank order for observed versus expected use was anti-androgen > third-generation, > second-generation, > progestogen-only oral contraceptive agents with ratios of 1.93, 1.36, 0.70, and 0.39, respectively. CONCLUSION: The risk of VTE resulting in hospital admission associated with anti-androgen oral contraceptive use is at least as high as with third generation use.
The 24 h duration of bronchodilator action of the salmeterol/fluticasone combination inhaler.
INTRODUCTION: The duration of bronchodilator action of the long-acting beta agonist salmeterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of salmeterol, administered from the combination salmeterol/fluticasone (SFC) Accuhaler significantly attenuates the circadian rhythm in airway tone over 24 h. METHODS: Eighteen subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, double dummy, placebo controlled, cross-over study. Subjects inhaled, in random order, placebo, salbutamol (200 microg) or SFC (50/100 microg) administered in the evening (2000 h) on three separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h. RESULTS: Compared with placebo, SFC significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.24 l (0.00-0.47 l). SFC abolished the biphasic pattern of the circadian rhythm in airway tone. In contrast, salbutamol had a significant bronchodilator action of 4-8 h, depending on the lung function parameter measured. CONCLUSION: The single evening administration of SFC via the Accuhaler resulted in a duration of bronchodilation of at least 24 h, with the abolition of the accentuated biphasic circadian variation in airway tone observed in asthma.
Risk factors for entry into residential care after a support-needs assessment.
AIMS: To establish the influence of risk factors derived from the national 'Support Needs Assessment Form' for entry into residential care in New Zealand. METHODS: Using a retrospective cohort design, data was obtained for assessments of people aged over 65 years over a 12-month interval (August 2001 to August 2002) from an administrative database developed by the Needs Assessment and Service Co-ordination Service for Wellington, New Zealand. The risk factors for entry into residential care were examined by logistic regression. RESULTS: 2060 assessments were carried out over this period for people were aged over 65 years; 67.9% were female. The median age was 83 years, inter-quartile range 78 to 88 years. For 33.4% of people, residential care was recommended. For those aged 80 years or older, the relative risk of residential care was 2.95 (95% CI: 2.27 to 3.82) if continence problems were present, and 3.75 (95% CI: 2.99 to 4.73) for those aged 80 years or younger if continence problems were present. For those with mobility problems who had cognitive impairment the relative risk of residential care was 2.95 (95% CI: 2.25 to 3.87), and 1.77 (95% CI: 1.35 to 2.33) if there were no mobility problems. CONCLUSIONS: All of older age, continence problems, mobility problems and dementia predicted residential care after assessment. The effect of continence was more prominent for those aged under 80 years of age. The effect of dementia was more prominent for those with mobility problems. Intervention for continence problems and mobility problems has the potential to reduce the use of residential care.
Quality of life of people with rheumatoid arthritis as measured by the World Health Organization Quality of Life Instrument, short form (WHOQOL-BREF): score distributions and psychometric properties.
OBJECTIVE: To assess the psychometric properties, including responsiveness, of the World Health Organization Quality of Life instrument, short form (WHOQOL-BREF) in people with rheumatoid arthritis. METHODS: A sample of 142 persons with rheumatoid arthritis were randomly selected from a regional disease register and completed questionnaires by postal survey. An additional sample of 72 consecutive inpatients completed questionnaires a few days prior to admission, the day of admission, the day of discharge, and 2 weeks following discharge. RESULTS: Test-retest reliability was adequate (intraclass correlation coefficient 0.71-0.91). Internal consistency was adequate except for the social relationships domain (Cronbach's alpha 0.64-0.87). Factor structure was fairly similar to that previously reported. Correlation with other measures of quality of life was supportive of concurrent validity. Indices of responsiveness were satisfactory except for the social relationships and environment domains, although there was actually no statistical difference in the area under a receiver operating characteristic plot between the WHOQOL-BREF domains and the Health Assessment Questionnaire. CONCLUSION: The WHOQOL-BREF has adequate psychometric properties in people with rheumatoid arthritis and should be considered a valid outcome measure for interventions that aim to improve quality of life for people with this disease.
The risk of hyponatremia in older adults using desmopressin for nocturia: a systematic review and meta-analysis.
AIMS: To estimate the incidence of hyponatremia in older adults who use nasal or oral desmopressin to treat nocturia. MATERIALS AND METHODS: A systematic review and meta-analysis of cohort studies and randomised controlled trials of the use of nasal or oral desmopressin for older adults with nocturia. The incidence of hyponatremia was estimated by a random effects model for binomial data. RESULTS: Seventy-five papers were identified by the literature review of which 14 were reports of randomised trials or cohort studies. Seven studies reported the incidence of hyponatremia. The pooled estimate for the incidence of hyponatremia was 7.6% (95% CI 3.7-15.1). CONCLUSIONS: Hyponatremia is a relatively common adverse effect of the use of desmopressin for the treatment of nocturia and caution and regular monitoring should be part of the use of this management option for nocturia in older adults.
The dose-response relationship of inhaled corticosteroids in asthma.
Inhaled corticosteroids are the only class of asthma medication that can reduce symptoms, improve lung function, reduce the frequency of severe exacerbations, including hospital and ICU admissions, and decrease the risk of mortality. The therapeutic dose range for all clinical outcome measures in adults is 100 to 1000 mg/d of beclomethasone dipropionate or budesonide, or 50 to 500 mg/d of fluticasone propionate. Doses in excess of this range are not recommended for routine use because they are likely to increase the risk of systemic side-effects without further major improvement in efficacy. The recommendations are qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids in asthma, which would suggest that some patients might obtain greater benefit at higher doses, just as some might obtain maximum benefit at lower doses.
Community ambulation after stroke: how important and obtainable is it and what measures appear predictive?
OBJECTIVES: To assess how important community ambulation is to stroke survivors and to assess the relation between the level of community ambulation achieved and other aspects of mobility. DESIGN: A multicenter observational survey. SETTING: Community setting in New Zealand. PARTICIPANTS: One hundred fifteen stroke survivors living at home were referred from physical therapy (PT) services at 3 regional hospitals at the time of discharge and were assessed within 1 week after returning home. Another 15 people with stroke who did not require further PT when discharged were assessed within 2 weeks after they returned home to provide insight into community ambulation status for those without mobility impairment, as recognized by health professionals. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self-reported levels of community ambulation ascertained by questionnaire, gait velocity (m/min), Functional Ambulation Categories (FAC) score, and Rivermead Mobility Index (RMI) score. RESULTS: Mean gait velocity for the participants was 53.9 m/min (95% confidence interval [CI], 52.3-61.1); mean treadmill distance was 165.5 m (95% CI, 141.6-189.5); median RMI score was 14; and median FAC score was 6. Mobility scores for the 15 people who did not require PT were within the normal range. Based on self-reported levels of ambulation, 19 (14.6%) participants were unable to leave the home unsupervised, 22 (16.9%) were walking as far as the letterbox, 10 (7.6%) were limited to walking within their immediate environment, and 79 (60.7%) could access shopping malls and/or places of interest. Participants with different levels of community ambulation showed a significant difference in gait velocity (P<.001). The ability to "get out and about" in the community was considered to be either essential or very important by 97 subjects (74.6%). CONCLUSIONS: Community ambulation is a meaningful outcome after stroke. However, despite good mobility outcomes on standardized measures for this cohort of home-dwelling stroke survivors, nearly one third were not getting out unsupervised in the community. Furthermore, gait velocity may be a measure that discriminates between different categories of community ambulation. These findings may have implications for PT practice for people with mobility problems after stroke.
Self-valuation and societal valuations of health state differ with disease severity in chronic and disabling conditions.
OBJECTIVES: We sought to determine the relationship between self-reported ratings of health-related quality of life (HRQoL) by people with 3 chronic and disabling conditions and population estimates of those health states and to model factors that might explain the disagreement between these 2 ratings. RESEARCH DESIGN: A cross-sectional postal survey was sent in which each participant completed a set of questionnaires addressing HRQoL. Data from self-valuation on a visual analog scale (VAS) was compared with a population-based VAS-equivalent valuation, using the EQ-5D instrument. Different ways of scaling the 2 VAS scores were also explored. Data were analyzed using descriptive statistics and analysis of covariance. SUBJECTS: A community sample of 1036 people took part in the study (rheumatoid arthritis n = 142, stroke n = 585, multiple sclerosis n = 309). MEASUREMENT INSTRUMENT: The EQ-5D health state profile and accompanying visual analog scale were used. RESULTS: Self-ratings were significantly different than the population-based ratings, and agreement was poor, both on the original scale of the data and by analyses of rescaled data. On the original scales the mean difference was 0.13 (95% confidence interval 0.117-0.143). Diagnosis, health state severity, and its square explained 35.3% of the variation in the differences between self and population ratings with a curvilinear relationship suggesting that the differences increased as the health state worsened, but at a decreasing rate as health state severity increased. CONCLUSIONS: This study provides evidence that EQ-5D population valuation estimates of treatment benefit for people with disabling and chronic conditions may well be inaccurate representations of the degree of change actually experienced by the individual with the condition. The varying magnitude of difference between the 2 forms of valuation has important implications for interpreting shifts in health status valuation following interventions for these populations.
The pulmonary and extra-pulmonary effects of high-dose formoterol in COPD: a comparison with salbutamol.
OBJECTIVES: Formoterol, a beta(2) agonist with a rapid onset of effect and long duration of action, can be used as maintenance and reliever medication for asthma and COPD. We compared the pulmonary and extra-pulmonary effects of cumulative doses of formoterol and salbutamol in patients with COPD to assess efficacy and safety. METHODOLOGY: In a randomized, double-blind, cross-over study, 12 patients with moderate to severe COPD inhaled, via Turbuhaler, 10 doses of formoterol (total metered dose, 120 microg, equivalent to a 90- microg delivered dose), salbutamol (total metered dose 2000 microg) or placebo at 2-min intervals on separate days. The effects on lung function (FEV(1) and PEF), heart rate, blood pressure, oxygen saturation, corrected QT interval (QTc), T-wave height and plasma potassium were assessed before each dose, 15 min after each dose, and at half-hourly intervals for 3 h following the final dose. RESULTS: Inhalation of formoterol or salbutamol resulted in significant improvement in lung function (measured 30 min after the last dose) when compared with placebo. There were no clinically important or statistically significant changes in heart rate, QTc, T-wave height, plasma potassium, oxygen saturation, or systolic and diastolic blood pressures with formoterol or salbutamol. One patient developed ventricular trigeminy after both formoterol and salbutamol. She had had ventricular ectopics on her screening electrocardiogram. CONCLUSION: Formoterol and salbutamol both produced significant improvement in lung function and were similarly well tolerated in high doses, as might be taken by a patient for relief of COPD symptoms.
Budesonide once versus twice-daily administration: meta-analysis.
OBJECTIVES: The aim of this study was to examine the efficacy of budesonide administered once daily compared to twice daily in asthma. METHODOLOGY: Meta-analysis of randomised controlled trials comparing budesonide administered once versus twice a day that presented data on at least one clinical outcome measure was conducted. RESULTS: A total of 10 studies, with 1922 children and adults with asthma, met the inclusion criteria. These studies were performed predominantly with mild to moderate asthmatic patients, using doses of budesonide ranging from 200 to 800 microg per day. There was no significant difference between daily dosing once or twice for all the clinical outcome variables, including withdrawals due to asthma, for which the odds ratio was 1.0 (95% confidence interval, 0.65-1.52). CONCLUSIONS: In mild to moderate asthma a once-daily budesonide regimen has a similar efficacy to a twice-daily regimen in doses up to 800 microg per day. A once-daily regimen has potential advantages in terms of patient compliance and satisfaction, when used in clinical practice.
Oral iron therapy for anaemia after orthopaedic surgery: randomized clinical trial.
BACKGROUND: Oral iron therapy is often used after orthopaedic surgery to improve haemoglobin levels. The aim of the present trial was to determine if administration of oral iron after orthopaedic surgery results in a better improvement of haemoglobin levels than a control treatment. METHODS: This was a double blind randomized controlled trial at a tertiary referral orthopaedic centre. The participants were patients undergoing elective hip or knee replacement surgery with normal iron and folic acid stores and no history of iron deficiency, and the primary outcome was the haemoglobin level 10 weeks after surgery. RESULTS: At 10 weeks the mean +/- SD haemoglobin in the iron group was 132.8 +/- 13.4 g/L and in the control group it was 128.0 +/- 10.6 g/L, a difference of 4.8 g/L with a 95% confidence interval for the difference of -1.2 to 10.7 g/l, P = 0.12. CONCLUSIONS: Iron taken after elective hip or knee replacement surgery does not result in higher haemoglobin 10 weeks after surgery, or a faster rate of increase in haemoglobin than a control treatment.