Derek King

Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease

BACKGROUND Respiratory rehabilitation is increasingly recognised as an important part of the management of patients with chronic obstructive pulmonary disease (COPD). The widespread application of such programmes should be preceded by evidence of directly attributable improvements in function. We assessed the effect of respiratory rehabilitation on exercise capacity and health-related quality of life (HRQL) in patients with COPD. METHODS We carried out a meta-analysis of randomised controlled trials of respiratory rehabilitation in patients with COPD that assessed functional or maximal exercise capacity, HRQL, or both. Respiratory rehabilitation was defined as exercise training (for at least 4 weeks) with or without education, psychological support, or both. The most commonly used measure for HRQL was the chronic respiratory questionnaire, in which responses were presented on a 7-point scale. The control groups received no rehabilitation. Within each trial and for each outcome an effect size was calculated; the effect sizes were then pooled by a random-effects model. The overall effect of treatment was compared with its minimum clinically important difference (MCID)--defined as the smallest difference perceived as important by the average patient. FINDINGS We included 14 trials. Significant improvements were found for all the outcomes. For two important features of HRQL, dyspnoea and mastery, the overall treatment effect was larger than the MCID: 1.0 (95% CI 0.6-1.5) and 0.8 (0.5-1.2), respectively, compared with an MCID of 0.5. For functional exercise capacity (6-min walk test), the overall effect was 55.7 m (27.8-92.8), and for maximum exercise capacity (incremental cycle ergometer test), 8.3 W (2.8-16.5). Functional exercise capacity showed heterogeneity that could not be explained by the sensitivity analyses. INTERPRETATION Respiratory rehabilitation relieves dyspnoea and improves the control over COPD. These improvements are clinically important. The value of the improvement in exercise capacity is not clear. Respiratory rehabilitation is an effective part of care in patients with COPD.

Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature.

OBJECTIVE To determine the effect of corticosteroid therapy on morbidity and mortality in patients with sepsis. DATA SOURCES We searched for published and unpublished research using MEDLINE, EMBASE, and the Science Citation Index, manual searching of Index Medicus, citation review of relevant primary and review articles, personal files, and contact with primary investigators. STUDY SELECTION From a pool of 124 potentially relevant articles, duplicate independent review identified nine relevant, randomized, controlled trials of corticosteroid therapy in sepsis and septic shock among critically ill adults. DATA EXTRACTION In duplicate, independently, we abstracted key data on population, intervention, outcome, and methodologic quality of the randomized controlled trials. DATA SYNTHESIS Corticosteroids appear to increase mortality in patients with overwhelming infection (relative risk 1.13, 95% confidence interval 0.99 to 1.29), and have no beneficial effect in the subgroup of patients with septic shock (relative risk 1.07, 95% confidence interval 0.91 to 1.26). Studies with the highest methodologic quality scores also suggest a trend toward increased mortality overall (relative risk 1.10, 95% confidence interval 0.94 to 1.29). A similar trend was observed for patients with septic shock (relative risk 1.12, 95% confidence interval 0.95 to 1.32). No difference in secondary infection rates was demonstrated in corticosteroid-treated patients with sepsis or septic shock. However, there was a trend toward increased mortality from secondary infections in patients receiving corticosteroids (relative risk 1.70, 95% confidence interval 0.70 to 4.12). The occurrence rate of gastrointestinal bleeding was increased slightly in the treatment group (relative risk 1.17, 95% confidence interval 0.79 to 1.73). CONCLUSIONS Current evidence provides no support for the use of corticosteroids in patients with sepsis or septic shock, and suggests that their use may be harmful. These trials underscore the need for future methodologically rigorous trials evaluating new immune-modulating therapies in well-defined critically ill patients with overwhelming infection.

Clinical impact versus factor analysis for quality of life questionnaire construction

OBJECTIVE We have compared two philosophically different methods for selecting items for a disease-specific quality of life questionnaire. The impact method selects items that are most frequently perceived as important by patients whereas the psychometric method (factor analysis) selects items primarily according to their relationships with one another. PATIENTS 150 adults with symptomatic asthma and a wide range of disease severity were enrolled from asthma clinics and notices in the local media. STUDY DESIGN From a list of 152 items that are potentially troublesome to patients with asthma, the patients identified those items they had experienced in the previous year and scored the importance of each on a five-point scale. For the impact method, items that were identified most frequently and that scored the highest were included in the final instrument. For the psychometric method, factor analysis was performed after highly skewed items had been removed. Items with high factor loading were included in the final instrument. RESULTS The impact method resulted in a 32-item instrument and psychometric analysis in one with 36 items. Twenty items were common to both instruments. The psychometric approach discarded the highest impact emotional function and environmental items and included in their place lower impact items mainly associated with fatigue. CONCLUSIONS Although some items were the same for both methods, there were also some important differences. Different approaches to item reduction led to appreciably different instruments.

Impaired gastric emptying in mechanically ventilated, critically ill patients

ObjectiveTo measure gastric emptying in critically ill patients using an acetaminophen absorption model and determine which variables are associated with impaired gastric emptying.DesignA prospective, cohort study.SettingA medical/surgical ICU at a tertiary care hospital: Hamilton General Hospital, Hamilton, Ontario.Patients and participantsWe recruited 72 mechanically ventilated patients expected to remain in the ICU for more than 48h. Our results were compared to those in healthy volunteers.InterventionWithin 48 h of admission to the ICU, 1.6 g acetaminophen suspension were administered via a nasogastric tube into the stomach. Blood samples were drawn at=0, 30, 60, 90, and 120 min for measurement of plasma acetaminophen levels determined by the enzymatic degradation method.Measurements and resultsMaximal concentration of acetaminophen was 94.1 (75.3) μmol/l compared to 208.4 (33.1) μmol/l in a control population (p<0.0001). The time to reach the maximal concentration was 105 min (60–180) compared to 30 min (15–90) in controls (p<0.0001). The area under the time-acetaminophen concentration curvet=120 was 9301 (7343) μmol/min per 1 compared to 11644 (1336) μmol/min per 1 in the controls (p=0.28). The variables associated with delayed gastric emptying were age, sex and use of opioids for analgesia and sedation.ConclusionsGastric emptying is delayed in critically ill patients. The important consequences of this phenomenon include intolerance to enteral nutrition and gastric colonization. Strategies to minimize the use of narcotics may improve gastric emptying. Studies to examine the effect of gastrointestinal prokinetic agents on gastric emptying are needed.

Generic and Specific Measurement of Health-Related Quality of Life in a Clinical Trial of Respiratory Rehabilitation

The purpose of this study was to compare the performance of measures of health-related quality of life in a randomized controlled trial of respiratory rehabilitation versus conventional community care for patients with chronic airflow limitation. The study included 89 stable patients with moderate to severe chronic airflow limitation with measurement of health status at 12, 18, and 24 weeks. Outcomes included two disease-specific (the Oxygen Cost Diagram and the Chronic Respiratory Questionnaire [CRQ]) measures, a generic health profile (the Sickness Impact Profile [SIP]), and two utility measures (the Standard Gamble and the Quality of Well-Being index [QWB]). Of the measures, only the four domains of the CRQ (dyspnea, fatigue, mastery, and emotional function) showed statistically significant differences (P < or = 0.05) between treatment and control groups. Correlation between change in the CRQ and change in other relevant measures, including the 6-minute walk test and global ratings of change in dyspnea, fatigue, and emotional function were generally weak to moderate (from 0.19 to 0.51). All correlations between change in the QWB, SIP, and Standard Gamble and other measures were very weak or weak (up to 0.30). Correlation between change in the three generic measures were all very weak (<0.15). The results suggest that unless investigators include responsive and valid disease-specific measures of health-related quality of life in controlled trials in chronic diseases, they risk misleading conclusions about the effect of treatments on health status.

Discrimination and abuse in internal medicine residency

OBJECTIVE: To survey the extent to which internal medicine housestaff experience abuse and discrimination in their training. DESIGN: Through a literature review and resident focus groups, we developed a self-administered questionnaire. In this cross-sectional survey, respondents were asked to record the frequency with which they experienced and witnessed different types of abuse and discrimination during residency training, using a 7-point Likert scale. PARTICIPANTS: Internal medicine housestaff in Canada. MEASUREMENTS AND MAIN RESULTS: Of 543 residents in 13 programs participating (84% response rate), 35% were female. Psychological abuse, as reported by attending physicians (68%), patients (79%), and nurses or other health workers (77%), was widespread. Female residents experienced gender discrimination by attending physicians (70%), patients (88%), and nurses (71%); rates for males were 23%, 38%, and 35%, respectively. Females reported being sexually harassed more often than males, by attending physicians (35% vs 4%,p<.01), peers (30% vs 6%,p<.01), and patients (56% vs 18%,p<.01). Physical assault by patients was experienced by 40% of residents. Half of the residents surveyed reported racial discrimination and homophobic remarks in the workplace, perpetrated by all groups of health professionals. CONCLUSIONS: Psychological abuse, gender discrimination, sexual harassment, physical abuse, homophobia, and racial discrimination are prevalent problems during residency training. Housestaff, medical educators, allied health workers, and the public need to work together to address these problems in the training environment.

Outcome assessment for clinical trials: How many adjudicators do we need?

Considerable effort is often expended to adjudicate outcomes in clinical trials, but little has been written on the administration of the adjudication process and its possible impact on study results. As a case study, we describe the function and performance of an adjudication committee in a large randomized trial of two diagnostic approaches to potentially operable lung cancer. Up to five independent adjudicators independently determined two primary outcomes: tumor status at death or at final follow-up and the cause of death. Patients for whom there was any disagreement were discussed in committee until a consensus was achieved. We describe the pattern of agreement among the adjudicators and with the final consensus result. Additionally, we model the adjudication process and predict the results if a smaller committee had been used. We found that reducing the number of adjudicators from five to two or three would probably have changed the consensus outcome in less than 10% of cases. Correspondingly, the effect on the final study results (comparing primary outcomes in both randomized arms) would have been altered very little. Even using a single adjudicator would not have affected the results substantially. About 90 minutes of person-time per patient was required for activities directly related to the adjudication process, or approximately 6 months of full time work for the entire study. This level of effort could be substantially reduced by using fewer adjudicators with little impact on the results. Thus, we suggest that when high observer agreement is demonstrated or anticipated, adjudication committees should consist of no more than three members. Further work is needed to evaluate if smaller committees are adequate to detect small but important treatment effects or if they compromise validity when the level of adjudicator agreement is lower.

Inadequacy of intravenous heparin therapy in the initial management of venous thromboembolism

To determine the adequacy of initial anticoagulation by intravenous heparin for patients who have deep venous thrombosis (DVT), and the factors that influence delayed anticoagulation, independent, duplicate chart review of 63 consecutive patients who had venography-proven DVT was conducted. Adequate heparinization (AH) was defined as an activated partial thromboplastin time (PTT) of more than 1.5 times the normal laboratory control. The proportions of patients achieving AH within 24 hours and 48 hours of initial heparin bolus were 46% and 62%, respectively. Patients who weighed more were less likely to achieve AH (p<0.05), while patients receiving care from the thromboembolism service were more likely to achieve AH (p<0.05). Low initial infusion rate was strongly but not significantly predictive of inadequate anti-coagulation (p=0.06). The mean heparin bolus and initial infusion rates were significantly lower than those suggested in the literature (p<0.01). The AH rates were comparable to historical controls but suboptimal compared with the rates of 66% at 24 hours and 81% at 48 hours reported in association with heparin nomogram use (p<0.05). A heparin nomogram is likely to achieve consistently higher rates of adequate heparinization.