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Biomedical subjects

Milo A Puhan

Publications and source records attributed to Milo A Puhan.

13 recordsLinked to original sources

Does the Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy?--A systematic review.

BACKGROUND: Pharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. We conducted a systematic review to assess the effect modification of the insertion/deletion (I/D) polymorphism of the ACE gene on any outcome in patients treated with ACE inhibitors for cardiovascular and/or renal disease. METHODS: Our systematic review involved searching six electronic databases, then contacting the investigators (and pharmaceutical industry representatives) responsible for the creation of these databases. Two reviewers independently selected relevant randomized, placebo-controlled trials and abstracted from each study details on characteristics and quality. RESULTS: Eleven studies met our inclusion criteria. Despite repeated efforts to contact authors, only four of the eleven studies provided sufficient data to quantify the effect modification by genotypes. We observed a trend towards better response to ACE inhibitors in Caucasian DD carriers compared to II carriers, in terms of blood pressure, proteinuria, glomerular filtration rate, ACE activity and progression to end-stage renal failure. Pooling of the results was inappropriate, due to heterogeneity in ethnicity, clinical domains and outcomes. CONCLUSION: Lack of sufficient genetic data from the reviewed studies precluded drawing any convincing conclusions. Better reporting of genetic data are needed to confirm our preliminary observations concerning better response to ACE inhibitors among Caucasian DD carriers as compared to II carriers.

Journal Article↗

A randomized trial of ways to describe test accuracy: the effect on physicians' post-test probability estimates.

BACKGROUND: Some people believe that likelihood ratios provide diagnostic information that is more useful than sensitivity and specificity estimates. OBJECTIVE: To assess how physicians' estimates about probability of illness are affected by the presentation of a diagnostic test's value as an estimate of sensitivity and specificity versus a likelihood ratio or an inexact numerical graphic. DESIGN: Random assignment of vignettes with different presentation formats of diagnostic test accuracy. SETTING: Auditorium at a continuing medical education conference. PARTICIPANTS: 183 physicians. INTERVENTION: After estimating probabilities of 6 common illnesses described in patient vignettes, physicians reviewed pertinent test results presented in 1 of 3 formats. MEASUREMENTS: Physicians' probability estimates of illness before and after receiving test information, and post-test probability estimates based on the Bayes theorem. RESULTS: Absolute percentage point differences between the physicians' estimated and the Bayes-based post-test probabilities varied from -7 to 31, from -7 to 28, and from 1 to 29 for the sensitivity and specificity, likelihood ratio, and graphical groups, respectively. Mean differences of probability estimates between the sensitivity and specificity and the likelihood ratio groups were small for all vignettes (-2 to 3 percentage points; summary mean z value across the 6 vignettes, 0.04 [95% CI, -0.14 to 0.21]). LIMITATIONS: The small pool of participants (who were potentially selected) and the limited number of vignettes prevented a more detailed analysis of relationships between the interpreted strength of diagnostic evidence and estimations of illness probability. CONCLUSIONS: These findings suggest that presenting diagnostic test accuracy with likelihood ratios does not affect some physicians' estimates of illness probability compared with presenting diagnostic test results as sensitivity and specificity.

Adult↗

Respiratory rehabilitation after acute exacerbation of COPD may reduce risk for readmission and mortality -- a systematic review.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems. Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity. To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses. METHODS: Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings. We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation. Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality. We pooled the results using fixed effects models where statistically significant heterogeneity (p < or = 0.1) was absent. RESULTS: We identified six trials including 230 patients. Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12-0.54]) and mortality (0.45 [0.22-0.91]). Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13-1.61) for the fatigue domain, 1.36 (0.94-1.77) for emotional function and 1.88 (1.67-2.09) for mastery. Weighted mean differences for the St. Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7). In all trials, rehabilitation improved exercise capacity (64-215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48-115). CONCLUSION: Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation. Larger trials, however, are needed to further investigate the role of respiratory rehabilitation after acute exacerbation and its potential to reduce costs caused by COPD.

Acute Disease↗

Ultrasonography in screening for developmental dysplasia of the hip in newborns: systematic review.

OBJECTIVE: To assess the accuracy and effectiveness of the screening of all newborn infants for developmental dysplasia of the hip (DDH) using ultrasound imaging, as is standard practice in some European countries but not in the United Kingdom, the United States, or Scandinavia. DESIGN: Systematic review. DATA SOURCES: Twenty three medical, economic, and grey literature databases (to March 2004), with no limitations of design or language; some references were provided by experts. SELECTION OF STUDIES: Only diagnostic accuracy studies and comparative studies conducted in an unselected newborn population were eligible for the review. Two reviewers independently selected the studies and performed the quality assessment. RESULTS: The review identified one diagnostic accuracy study, and this was of limited quality. In this study the reference standard was treatment up to age of 8 months or an abnormal ultrasound finding at age 8 months. Ultrasound screening had a sensitivity of 88.5% (95% confidence interval 84.1% to 92.1%), specificity of 96.7% (96.4% to 97.4%), a positive predictive value of 61.6% and a negative predictive value of 99.4%. Ten studies evaluated the impact of ultrasound in screening, but these too had various methodological weaknesses, limiting the reliability of their findings. Compared with clinical screening, general ultrasound screening in newborns may increase overall treatment rates, but ultrasound screening seems to be associated with shorter and less intrusive treatment. CONCLUSIONS: Clear evidence is lacking either for or against general ultrasound screening of newborn infants for DDH. Studies that investigate the natural course of the disorder, the optimal treatment for DDH, and the best strategy for ultrasound screening are needed.

Clinical Trials as Topic↗

Internal consistency reliability is a poor predictor of responsiveness.

BACKGROUND: Whether responsiveness represents a measurement property of health-related quality of life (HRQL) instruments that is distinct from reliability and validity is an issue of debate. We addressed the claims of a recent study, which suggested that investigators could rely on internal consistency to reflect instrument responsiveness. METHODS: 516 patients with chronic obstructive pulmonary disease or knee injury participating in four longitudinal studies completed generic and disease-specific HRQL questionnaires before and after an intervention that impacted on HRQL. We used Pearson correlation coefficients and linear regression to assess the relationship between internal consistency reliability (expressed as Cronbach's alpha), instrument type (generic and disease-specific) and responsiveness (expressed as the standardised response mean, SRM). RESULTS: Mean Cronbach's alpha was 0.83 (SD 0.08) and mean SRM was 0.59 (SD 0.33). The correlation between Cronbach's alpha and SRMs was 0.10 (95% CI -0.12 to 0.32) across all studies. Cronbach's alpha alone did not explain variability in SRMs (p = 0.59, r2 = 0.01) whereas the type of instrument was a strong predictor of the SRM (p = 0.012, r2 = 0.37). In multivariable models applied to individual studies Cronbach's alpha consistently failed to predict SRMs (regression coefficients between -0.45 and 1.58, p-values between 0.15 and 0.98) whereas the type of instrument did predict SRMs (regression coefficients between -0.25 to -0.59, p-values between <0.01 and 0.05). CONCLUSION: Investigators must look to data other than internal consistency reliability to select a responsive instrument for use as an outcome in clinical trials.

Clinical Trials as Topic↗

The standard gamble demonstrated lower reliability than the feeling thermometer.

BACKGROUND AND OBJECTIVE: Participants rated clinical marker states (CMS) to make respondents familiar with the task of preference instruments, ground their ratings in relation to other health states, and help investigators interpret patient ratings. The objective was to assess the reliability of CMS using appropriate reliability statistics. STUDY DESIGN AND SETTING: Eighty-one patients rated CMSs for mild, moderate, and severe chronic respiratory disease using the feeling thermometer (FT) and the standard gamble (SG) before and after a 3-month respiratory rehabilitation program. To assess reliability we used (a) intraclass correlation coefficients (ICC) with the variance between CMSs as signal and the variance between raters, the variance within raters, and the signal as noise; (b) scatter plots; and (c) Bland-Altman plots. RESULTS: ICCs were 0.47 for the FT and 0.37 for the SG. Scatter and Bland-Altman plots showed large between- and within-person variability; 64.2% and 11.3% of the CMSs ratings were in the correct order on both occasions on the FT and SG, respectively. CONCLUSION: Our results suggest moderate reliability of CMSs ratings for the FT and poor reliability for the SG, which may explain their lack of improving the SG's measurement properties. Investigators should use appropriate reliability statistics when addressing related issues.

Aged↗

Value of supplemental interventions to enhance the effectiveness of physical exercise during respiratory rehabilitation in COPD patients. A systematic review.

BACKGROUND: There is a controversy about the additional benefit of various supplemental interventions used in clinical practice to further enhance the effectiveness of respiratory rehabilitation in patients with Chronic obstructive pulmonary disease (COPD). The aim of this research was to assess randomised controlled trials (RCTs) testing the additional benefit of supplemental interventions during respiratory rehabilitation in COPD patients. METHODS: Systematic review with literature searches in six electronic databases, extensive hand-searching and contacting of authors. Two reviewers selected independently eligible RCTs, rated the methodological quality and extracted the data, which were analyzed considering the minimal important difference of patient-important outcomes where possible. FINDINGS: We identified 20 RCTs whereof 18 provided sufficient data for analysis. The methodological quality was low and sample sizes were too small for most trials to produce meaningful results (median total sample size = 28). Data from five trials showed that supplemental oxygen during exercise did not have clinically meaningful effects on health-related quality of life while improvements of exercise capacity may be even larger for patients exercising on room air. RCTs of adding assisted ventilation, nutritional supplements or a number of anabolically acting drugs do not provide sufficient evidence for or against the use any of these supplemental interventions. INTERPRETATION: There is insufficient evidence for most supplemental interventions during respiratory rehabilitation to estimate their additional value, partly due to methodological shortcomings of included RCTs. Current data do not suggest benefit from supplemental oxygen during exercise, although the methodological quality of included trials limits conclusions. To appropriately assess any of the various supplemental interventions used in clinical practice, pragmatic trials on respiratory rehabilitation of COPD patients need to consider methodological aspects as well as appropriate sample sizes.

Anabolic Agents↗

Interval exercise versus continuous exercise in patients with moderate to severe chronic obstructive pulmonary disease--study protocol for a randomised controlled trial [ISRCTN11611768].

BACKGROUND: Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes. Interval exercise may be an attractive alternative for these COPD patients because it allows high intensity exercise with recovery periods. The aim of this study is to assess if interval exercise compared to high intensity continuous exercise is not of inferior effectiveness in terms of HRQL and exercise capacity improvements but associated with better exercise tolerance in patients with moderate to severe COPD at the beginning of a respiratory rehabilitation. METHODS/DESIGN: We will assign patients with moderately severe to severe COPD to either continuous exercise or interval exercise using a stratified randomisation. Patients will follow 12-15 exercise sessions during a comprehensive inpatient respiratory rehabilitation. Primary end point for effectiveness is HRQL as measured by the Chronic Respiratory Questionnaire (CRQ) two weeks after the end of rehabilitation and secondary endpoints include additional clinical outcomes such as functional exercise capacity, other HRQL measures, patients' experience of physical exercise as well as physiological measures of the effects of physical exercise such as cardiopulmonary exercise testing. Including expected drop-outs, we will need 52 patients per group to show differences corresponding to the minimal clinically important difference of the CRQ. Outcome assessors and investigators involved in data analysis will be blinded to group assignment until analyses have been carried out. DISCUSSION: Clinicians and the scientific community need evidence on the benefits and tolerance of exercise protocols available in clinical practice. The proposed trial will provide important and needed data on interval and continuous exercise for decision making in clinical practice.

Journal Article↗

Self-administration and interviewer-administration of the German Chronic Respiratory Questionnaire: instrument development and assessment of validity and reliability in two randomised studies.

BACKGROUND: Assessment of health-related quality of life (HRQL) is important in patients with chronic obstructive pulmonary disease (COPD). Despite the high prevalence of COPD in Germany, Switzerland and Austria there is no validated disease-specific instrument available. The objective of this study was to translate the Chronic Respiratory Questionnaire (CRQ), one of the most widely used respiratory HRQL questionnaires, into German, develop an interviewer- and self-administered version including both standardised and individualised dyspnoea questions, and validate these versions in two randomised studies. METHODS: We recruited three groups of patients with COPD in Switzerland, Germany and Austria. The 44 patients of the first group completed the CRQ during pilot testing to adapt the CRQ to German-speaking patients. We then recruited 80 patients participating in pulmonary rehabilitation programs to assess internal consistency reliability and cross-sectional validity of the CRQ. The third group consisted of 38 patients with stable COPD without an intervention to assess test-retest reliability. To compare the interviewer- and self-administered versions, we randomised patients in groups 2 and 3 to the interviewer- or self-administered CRQ. Patients completed both the standardised and individualised dyspnoea questions. RESULTS: For both administration formats and all domains, we found good internal consistency reliability (Crohnbach's alpha between 0.73 and 0.89). Cross-sectional validity tended to be better for the standardised compared to the individualised dyspnoea questions and cross-sectional validity was slightly better for the self-administered format. Test-retest reliability was good for both the interviewer-administered CRQ (intraclass correlation coefficients for different domains between 0.81 and 0.95) and the self-administered format (intraclass correlation coefficients between 0.78 and 0.86). Lower within-person variability was responsible for the higher test-retest reliability of the interviewer-administered format while between person variability was similar for both formats. CONCLUSIONS: Investigators in German-speaking countries can choose between valid and reliable self-and interviewer-administered CRQ formats.

Adult↗

Self-administration and standardisation of the chronic respiratory questionnaire: a randomised trial in three German-speaking countries.

The chronic respiratory questionnaire (CRQ) has demonstrated excellent measurement properties in patients with chronic obstructive pulmonary disease (COPD), but in its original form it is limited by the requirement for interviewer-administration and the individualised dyspnoea questions. The objective of this randomised trial was to examine the evaluative properties of the interviewer and self-administered German CRQ as well as of a standardised CRQ dyspnoea domain. In a multinational trial we randomly allocated 71 patients with COPD to complete the interviewer administered CRQ (CRQ-IA) or the self-administered CRQ (CRQ-SA) and other validation measures at the beginning and end of a respiratory rehabilitation program. We assessed and compared responsiveness and longitudinal validity of the CRQ. The change scores of all CRQ domains were above the minimal clinically important difference of 0.5. Responsiveness of the fatigue domain was higher for the CRQ-SA compared to CRQ-IA (P = 0.02), but there was no difference in responsiveness on the other domains. Compared to the standardised dyspnoea domain the individualised dyspnoea questions tended to show greater responsiveness for both the CRQ-IA (P = 0.07) and CRQ-SA (P = 0.10). We found better longitudinal validity for the CRQ-SA represented by larger correlations between CRQ change scores and those of other validation instruments. Taken these results into consideration, researchers in COPD, in particular those in German-language countries can utilise any one of four CRQ formats that have proved both valid and responsive.

Aged↗

Measurement of agreement on health-related quality of life changes in response to respiratory rehabilitation by patients and physicians--a prospective study.

INTRODUCTION: To provide optimal care for patients with chronic obstructive pulmonary disease physicians need to understand if their patients benefit from an intervention. The objective of this study was to assess agreement between patients and physicians on health-related quality of life (HRQL) changes in response to respiratory rehabilitation and to explore sources for disagreement. METHODS: Sixty-one patients rated their health states on a validated preference-based instrument, the feeling thermometer (FT). In an analogous manner, the eight treating physicians rated the patients' health states on the FT. Patients and physicians were blinded to each other's ratings. We calculated intraclass correlation coefficients (ICC) to assess agreement between patients and physicians and used HRQL instruments and the 6-min walking test to assess the evaluative properties of the FT. RESULTS: We found moderate agreement at baseline (ICC 0.40, P = 0.018) and follow-up (ICC 0.49, P = 0.008) but large disagreement about change scores (ICC 0.02, P = 0.46). Patients' FTchange scores correlated well with change scores of the Chronic Respiratory Questionnaire, SF-36 and the Borg scale for dyspnoea whereas physicians' FT change scores correlated significantly with the change score of the 6- min walking test (r = 0.33). Physicians' ratings showed an inconsistent pattern for correlations with HRQL measures. CONCLUSIONS: There is large disagreement between patients and physicians on HRQL changes in response to respiratory rehabilitation. Investigators should assess whether the introduction of HRQL instruments into clinical practice raises the awareness of physicians towards HRQL and improves agreement with their patients.

Adult↗