Redefinition of the metabolic syndrome--useful or creating illness?
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Cardiovascular Diseases↗
Biomedical subjects
Mark Weatherall
Publications and source records attributed to Mark Weatherall.
External validity of randomized controlled trials in COPD.
BACKGROUND: COPD is a heterogeneous disease comprising a wide range of clinical phenotypes, depending on the degree to which emphysema, chronic bronchitis, reversible bronchospasm and small airways inflammation are present. Not all of these phenotypes may be represented among the subjects included in randomized controlled drug trials (RCTs) in COPD, making it difficult for doctors to know to what extent RCT evidence applies to individual patients. From a respiratory health survey of adults randomly selected from the community, we have estimated the proportion of subjects with COPD who would have been eligible for inclusion in major COPD RCTs. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function tests. Subjects with COPD defined by post-bronchodilator spirometry were assessed against the eligibility criteria of 18 major RCTs cited in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. FINDINGS: Of 749 subjects completing the full survey, 117 had COPD. Of these, a median of 5% (range 0-20%) of subjects met inclusion criteria for the major RCTs. Of 55 subjects with COPD receiving treatment, 0-9% (median 5%) met inclusion criteria for the major RCTs. INTERPRETATION: The major COPD RCTs on which the GOLD treatment guidelines are based may have limited external validity. Over 90% of the COPD subjects in the community who were taking medication, did so on the basis of RCTs for which they would not have been eligible.
Adult↗
External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?
BACKGROUND: Asthma is a heterogeneous disease with a wide range of clinical phenotypes, not all of which may be encompassed in the subjects included in randomised controlled trials (RCTs). This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient. AIM: To calculate the proportion of individuals with asthma who would have been eligible for the major asthma RCTs from the data of a random community survey of respiratory health. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function testing. Participants with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma (GINA) guidelines. FINDINGS: A total of 749 participants completed the full survey, of whom 179 had current asthma. A median 4% of participants with current asthma (range 0-36%) met the eligibility criteria for the included RCTs. A median 6% (range 0-43%) of participants with current asthma on treatment met the eligibility criteria. INTERPRETATION: This study shows that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient populations. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs.
Adult↗
Complete reference ranges for pulmonary function tests from a single New Zealand population.
AIM: Reference equations are prerequisites for interpretation of pulmonary function tests and are important in diagnosis, assessment, and management of a range of respiratory conditions. Such equations should be derived from populations who are closely ethnically and anthropomorphically matched to those in whom the equations will be used. This paper uses measurements from a single cohort of New Zealand adults to derive reference equations for all major pulmonary function tests. METHODS: Detailed pulmonary function test results including measurement of FEV6 and airway resistance were obtained from a cohort of 212 adult New Zealanders of European origin, who were never smokers with no respiratory disease or symptoms. Equations were developed by linear regression, including sex and other candidate variables based on prior univariate analysis. Comparisons between measured and predicted values using the reference equations of the European Respiratory Society (ERS) were made. RESULTS: Reference equations were produced with high values of explained variance (R2) for many commonly used clinical parameters. When compared with ERS equations, measured values for spirometry and most lung volumes were significantly higher than predicted (mean difference FEV1: male 0.48 L, female 0.36 L, mean difference TLC male 1.14 L, female 0.89 L, SVC male and female 0.66 L). CONCLUSIONS: This study provides a complete set of contemporary pulmonary function reference equations for a New Zealand population of European origin.
Adolescent↗
International medical graduates' training needs: perceptions of New Zealand hospital staff.
OBJECTIVE: To determine the opinion of New Zealand doctors and nurses on the possible training needs of international medical graduates (IMGS) in New Zealand hospitals. DESIGN: A postal questionnaire sent to hospital doctors and nurses. METHODS: All doctors working at Wellington, Kenepuru, and Hutt Hospitals in the greater Wellington region, and nurses working in acute medical wards at the same hospitals, were asked to complete a questionnaire based on the Northern Clinical Training Network and Capital Coast District Health Board resident medical officer assessment forms regarding an overseas-trained doctor they had worked with in the last year. RESULTS: The response rate for the doctor's questionnaires was 68/174 (39.1%), with 51 of these from New Zealand doctors rating an international medical graduate. The response rate for the nurses was 58/60 (96.7%). Areas where the median score of the questionnaire was unsatisfactory (less than three out of five on an ordinal scale rating performance) were clinical documentation; communication with patients, families, and other health professionals; knowledge of hospital policies and procedures, and medicolegal matters; and some aspects of patient management. There was no difference in median ratings between doctors and nurses. CONCLUSIONS: More specific training may improve the performance of overseas-trained doctors in the New Zealand health system. A further study of the perceived needs of the overseas-trained doctors themselves may be useful.
Attitude of Health Personnel↗
Nocturia in adults: draft New Zealand guidelines for its assessment and management in primary care.
Nocturia is a common bothersome condition. An ad hoc group of interested clinicians from a variety of backgrounds has developed draft guidelines for the assessment and management of this condition in primary care in New Zealand. The guidelines propose four steps in the assessment and management: clinical evaluation; simple investigations; assignment of a provisional diagnosis; and management based on the provisional diagnosis. For nocturnal polyuria-associated nocturia, the draft guidelines recommend that: lifestyle measures should be used as part of the management; if a patient complaining of nocturia has other features of overactive bladder, then bladder retraining and/or anticholinergics can be used; hypnosedatives should not be used to treat nocturia in older adults because of the increased risk of falls; loop diuretics given in the afternoon should be considered for the treatment; and desmopressin can be considered in the management of nocturnal polyuria associated nocturia but that it should be used cautiously in people aged over 65 because of the risk of hyponatraemia. A draft algorithm based on international guidelines is presented.
Adolescent↗
The effect of environment and task on gait parameters after stroke: A randomized comparison of measurement conditions.
OBJECTIVES: To assess the effect of environment and a secondary task on gait parameters in community ambulant stroke survivors and to assess the contribution of clinical symptoms to gait performance. DESIGN: A 2x3 randomized factorial design with 2 main factors: task (no task, motor task, cognitive task) and environment (clinic, suburban street, shopping mall). SETTING: Subjects were assessed in 1 of 3 settings: 2 in the community (a suburban street and shopping mall) and 1 clinical environment. PARTICIPANTS: Twenty-seven people with stroke (mean age, 61+/-11.6y; mean time since stroke onset, 45.8+/-34.2mo), living at home, were recruited from community stroke groups and from a local rehabilitation unit. Selection criteria included the following: ability to give informed consent, unilateral first ever or recurrent stroke at least 6 months previously, walking independently in the community, a gait speed between 24 and 50 m/min, Mini-Mental State Examination score of 24 or higher, and no severe comorbidity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait speed (in m/min), cadence, and step length were assessed by using an accelerometer with adjustable thresholds. Clinical measures hypothesized to influence gait parameters in community environments were also assessed including fatigue, anxiety and depression, and attentional deficit. RESULTS: Twenty-seven people with a mean baseline gait speed of 42.2+/-5.9 m/min were randomly allocated to 1 of 9 conditions in which the setting and distraction were manipulated. Analysis of variance showed a significant main effect for environment (P = .046) but not for task (P = .37). The interaction between task and environment was not significant (P = .73). Adjusting for baseline gait speed, people walked on average 8.8m/min faster in the clinic (95% confidence interval, 0.3-17.3m/min) than in the mall. Scores for fatigue, anxiety and depression, and attentional deficit were higher than normative values but did not influence gait performance. CONCLUSIONS: This study suggests that people with chronic stroke cope well with the challenges of varied environments and can maintain their gait speed while performing a secondary task. Despite moderate levels of gait impairment, gait automaticity may be restored over time to a functional level.
Analysis of Variance↗
Is implicit sequence learning impaired in Parkinson's disease? A meta-analysis.
The aim of the present study was to examine impairment of implicit learning in Parkinson's disease (PD) by means of a meta-analysis of studies that used the serial reaction time (SRT) task. The authors performed a systematic review and meta-analysis of published journal articles (1987-2005) that used the SRT task with patients with PD. The principal outcome measures used to compare studies were (a) the difference in reaction time between the last block of ordered sequence trials and the randomized block for PD and control participants and (b) fixed and random effects pooled estimates by the inverse weighting method. Six studies, including 67 patients with PD, met the inclusion criteria. The meta-analysis showed that implicit learning was impaired in PD, relative to healthy controls, with a standardized mean difference of 0.73 (95% confidence interval = 0.38, 1.07). Implicit sequence learning appears to be impaired in patients with PD. Some common methodological weaknesses and limitations in the reporting of statistical data are discussed.
Aged↗
Recent air travel and venous thromboembolism resulting in hospital admission.
OBJECTIVE: The objective of the study was to determine the proportion of patients admitted to hospital with a deep vein thrombosis (DVT) or pulmonary embolism (PE) in whom recent air travel was documented in the medical records. METHODS: A retrospective review of the medical records of patients with a primary or secondary discharge diagnosis of DVT or PE in four hospitals in New Zealand was undertaken. From the medical records information was collected on demographic details, documentation of the presence of risk factors and results of radiological investigations. Strict radiological criteria were applied to ensure that the diagnosis of DVT or PE was firmly established. RESULTS: In 60 of 576 (10.4%) patients with a confirmed venous thromboembolism there was documentation of recent air travel; in 31 of these 60 subjects no other risk factors were recorded. In those cases in whom details of the air travel had been recorded, it had been undertaken in the previous 1 week in 65.0%, and in 43.3% the air travel was of at least 10-h duration. CONCLUSION: Long distance air travel is an important risk factor for venous thromboembolism requiring hospital admission and represents a significant public health problem in New Zealand.
Adult↗
Duration of action of the salmeterol/fluticasone combination inhaler administered in the evening: a randomized controlled trial in childhood asthma.
OBJECTIVE AND BACKGROUND: To investigate the duration of bronchodilator action of a salmeterol/fluticasone combination (SFC) inhaler when administered in the evening to children with asthma. METHODOLOGY DESIGN: A double-blind, placebo-controlled, cross-over study. SETTING: Hospital inpatient. SUBJECTS: Fourteen children aged between 4 and 11 years with mild to moderate asthma (FEV(1) > 60% predicted) who exhibited a 15% increase in FEV(1) with bronchodilator. INTERVENTIONS: SUBJECTS inhaled, in random order, either SFC (100/50 microg) or placebo, via accuhaler, at 20.00 hours on two separate occasions with at least 3 days between study days. OUTCOME MEASURES: Lung function measurements including FEV(1), PEF, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity were measured at baseline, 2, 12, 16, 20 and 24 h. RESULTS: For all lung function parameters SFC resulted in significantly greater bronchodilation than placebo for at least 20 h after inhalation. At 24 h, the increase in FEV(1) and PEF compared with placebo was 0.08 L (95% confidence interval: -0.18 to 0.02, P = 0.16) and 27 L/min (95% confidence interval: -47 to -6, P = 0.004), respectively. CONCLUSIONS: The single administration of SFC via an accuhaler in the evening resulted in significant bronchodilation for at least 20 h in children with asthma.
Administration, Inhalation↗
Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis.
OBJECTIVES: To examine whether the increased risk of cardiovascular events with rofecoxib represents a class effect of cyclooxygenase-2 (COX-2) specific inhibitors. DESIGN: Systematic review and meta-analysis of randomized double-blind clinical trials of celecoxib of at least 6 weeks' duration and presented data on serious cardiovascular thromboembolic events. Data sources included six bibliographic databases, the relevant files of the United States Food and Drug Administration, and pharmaceutical company websites. MAIN OUTCOME MEASURES: Pooled fixed effects estimates of the odds ratios for risk of cardiovascular events with celecoxib compared with comparator treatment were calculated using the inverse variance weight method. The main outcome measure was myocardial infarction. RESULTS: Four placebo-controlled trials with 4422 patients were included in the primary meta-analysis comparing celecoxib with placebo. The odds ratio of myocardial infarction with celecoxib compared to placebo was 2.26 (95%confidence interval 1.0 to 5.1). For composite cardiovascular events [odd ratio 1.38 (95% CI 0.91 to 2.10)], cardiovascular deaths [OR 1.06 (95% CI 0.38 to 2.95)] and stroke [OR 1.0(95% CI 0.51 to 1.84)] there was no significant increase in risk with celecoxib. The secondary meta-analysis which included a total of six studies (with placebo, diclofenac, ibuprofen, and paracetamol as comparators) of 12 780 patients, showed similar findings with a significant increased risk with celecoxib for myocardial infarction [OR 1.88 (95% CI 1.15 to 3.08)] but not other outcome measures. CONCLUSION: The available data indicate an increased risk of myocardial infarction with celecoxib therapy, consistent with a class effect for COX-2 specific inhibitors.
Cardiovascular Diseases↗
Inconsistencies in cardiovascular data from COX-2 inhibitor trials--is it a class effect?
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Anti-Inflammatory Agents, Non-Steroidal↗
Is goal planning in rehabilitation effective? A systematic review.
OBJECTIVE: To determine the evidence regarding the effectiveness of goal planning in clinical rehabilitation. DESIGN: Systematic review. METHOD: MEDLINE, EMBASE, PsycINFO, CINAHL, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, American College of Physicians (ACP) Journal Club, and the Database of Abstracts of Reviews of Effects (DARE) were searched for randomized controlled trials on the therapeutic effectiveness of goal planning in the rehabilitation of adults with acquired disability. Studies were categorized by patient population and the clinical context of the study. Data were analysed using best-research synthesis, based on methodological quality determined by Physiotherapy Evidence Database (PEDro) scale scores. RESULTS: Nineteen studies were included in this review. Study populations in these papers included patients with neurological disorders, psychiatric disorders, musculoskeletal disorders, cardiovascular disorders, respiratory disorders and dietary/endocrine disorders. Six studies investigated the immediate effects of goal planning on patient behaviour. Thirteen studies investigated the effects of goal planning in the context of a rehabilitation programme lasting more than one week. Some limited evidence was identified that goal planning can influence patient adherence to treatment regimes and strong evidence that prescribed, specific, challenging goals can improve immediate patient performance in some specific clinical contexts. However, evidence regarding how these effects translated to improved outcomes following rehabilitation programmes was inconsistent. CONCLUSIONS: This review identified that while some studies demonstrated positive effects associated with goal planning in local contexts, the best available empirical evidence regarding the generalizable effectiveness of goal planning was inconsistent and compromised by methodological limitations.
Persons with Disabilities↗
What are open-label extension studies for?
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Antirheumatic Agents↗
Increased risk of cardiovascular events with parecoxib/valdecoxib: a systematic review and meta-analysis.
OBJECTIVE: To determine the risk of serious cardiovascular events associated with the use of the COX-2 inhibitor valdecoxib and its prodrug parecoxib following major surgery. METHODS: A systematic review and meta-analysis of placebo-controlled randomised double-blind clinical trials of IV parecoxib followed by oral valdecoxib treatment, that presented data on serious cardiovascular events. Studies were identified from six databases including Medline and the FDA website on parecoxib/valdecoxib. The main outcome measure was major cardiovascular events. The pooled fixed effects estimates for the odds ratio for risk of cardiovascular events for the use of parecoxib/valdecoxib were calculated using the inverse variance weighting method. RESULTS: Three studies with a total of 2,604 subjects were included in the meta-analysis. Parecoxib/valdecoxib was associated with a significantly increased risk of major cardiovascular events, with an odds ratio of 2.3 (95% CI: 1.1-4.7). CONCLUSION: There is an increased cardiovascular risk associated with parecoxib/valdecoxib therapy in the post-surgical situation. These findings are consistent with a class effect for COX-2 inhibitors increasing the risk of cardiovascular events.
Cardiac Surgical Procedures↗
Systematic review and meta-analysis of the risk of major cardiovascular events with etoricoxib therapy.
OBJECTIVE: To determine the risk of thromboembolic cardiovascular events associated with the use of etoricoxib, a COX-2 inhibitor. DESIGN: Systematic review and meta-analysis of placebo-controlled randomised double-blind clinical trials of etoricoxib that were of at least 6 weeks duration and presented data on cardiovascular thromboembolic events. DATA SOURCES: Six databases including Medline and EMBASE. METHODS: The main outcome measure was cardiovascular thromboembolic events. A secondary analysis was undertaken to identify the presence or absence of predefined features that allowed determination of major cardiovascular events in a clinical trial. RESULTS: There were five studies with a total of 2,919 subjects included in the meta-analysis. There were 7 cardiovascular thromboembolic events in 1,441 patients (0.5%) treated with etoricoxib, and 1 event in 906 patients (0.1%) on placebo. A pooled fixed effect estimate of the absolute risk difference was 0.5% (95% CI 0.1-1.0). The odds ratio for the risk of cardiovascular events with etoricoxib was 1.49 (0.42-5.31). CONCLUSION: The clinical trials of etoricoxib provide limited data on major cardiovascular thromboembolic events as they were neither designed nor powered to assess the potential cardiovascular risks with etoricoxib therapy. However, the limited data that were available provide weak evidence of an increased cardiovascular risk with etoricoxib consistent with a class effect for COX-2 inhibitors.
Cyclooxygenase Inhibitors↗
The 24 h duration of bronchodilator action of the budesonide/formoterol combination inhaler.
INTRODUCTION: The duration of bronchodilator action of the long-acting beta-agonist formoterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of formoterol, administered from the combination budesonide/formoterol (BUD/F) Turbuhaler significantly attenuates the circadian rhythm in airway tone over 24 h. METHODS: Twenty subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, placebo-controlled, cross-over study. Subjects inhaled, in random order, placebo or BUD/F (2x100/6 microg) administered in the evening (2000 h) on two 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, BUD/F significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.20L (0.04-0.35L). BUD/F attenuated the biphasic pattern of the circadian rhythm in airway tone. CONCLUSION: The single evening administration of formoterol from the combination BUD/F inhaler resulted in a duration of bronchodilation of at least 24 h.
Administration, Inhalation↗
Raised plasma homocysteine levels in alcoholism: increasing the risk of heart disease and dementia?
BACKGROUND: Raised plasma homocysteine levels, which may contribute to the increased risk of cardiovascular disease and dementia associated with alcoholism, have been observed in alcohol-dependent male subjects. METHODS: In this study, we measured plasma homocysteine levels in 20 female and 31 male alcoholic subjects admitted to hospital for detoxification. Nutritional status and clinical factors that might predict plasma homocysteine levels were assessed by measurement of red cell folate, vitamin B12, blood alcohol, and liver function tests. RESULTS: The median (interquartile range) plasma homocysteine level on admission was 15.4 micromol/L (11.1 to 19.7), with 27 (53%) subjects having a raised homocysteine level, greater than 15 micromol/L. There was no difference in admission plasma homocysteine levels between the male and female subjects (difference, male versus female 1.9 micromol/L, 95% CI=2.4 to 6.0, p=0.4). Red cell folate, vitamin B12 levels, and blood alcohol level on admission were not significant predictors of admission homocysteine level. CONCLUSION: Severe alcohol dependence is associated with markedly raised plasma homocysteine levels in both females and males. The common condition of alcohol dependence may be an under-recognised risk factor contributing to raised plasma homocysteine levels and the associated risk of vascular and intellectual impairment.
Adult↗