Lucas M. Bachmann

Minimal Changes of Serum Creatinine Predict Prognosis in Patients after Cardiothoracic Surgery: A Prospective Cohort Study

Acute renal failure increases risk of death after cardiac surgery. However, it is not known whether more subtle changes in renal function might have an impact on outcome. Thus, the association between small serum creatinine changes after surgery and mortality, independent of other established perioperative risk indicators, was analyzed. In a prospective cohort study in 4118 patients who underwent cardiac and thoracic aortic surgery, the effect of changes in serum creatinine within 48 h postoperatively on 30-d mortality was analyzed. Cox regression was used to correct for various established demographic preoperative risk indicators, intraoperative parameters, and postoperative complications. In the 2441 patients in whom serum creatinine decreased, early mortality was 2.6% in contrast to 8.9% in patients with increased postoperative serum creatinine values. Patients with large decreases (DeltaCrea <-0.3 mg/dl) showed a progressively increasing 30-d mortality (16 of 199 [8%]). Mortality was lowest (47 of 2195 [2.1%]) in patients in whom serum creatinine decreased to a maximum of -0.3 mg/dl; mortality increased to 6% in patients in whom serum creatinine remained unchanged or increased up to 0.5 mg/dl. Mortality (65 of 200 [32.5%]) was highest in patients in whom creatinine increased > or =0.5 mg/dl. For all groups, increases in mortality remained significant in multivariate analyses, including postoperative renal replacement therapy. After cardiac and thoracic aortic surgery, 30-d mortality was lowest in patients with a slight postoperative decrease in serum creatinine. Any even minimal increase or profound decrease of serum creatinine was associated with a substantial decrease in survival.

Accuracy of Ottawa ankle rules to exclude fractures of the ankle and mid-foot: systematic review

Abstract Objective: To summarise the evidence on accuracy of the Ottawa ankle rules, a decision aid for excluding fractures of the ankle and mid-foot. Design: Systematic review. Data sources: Electronic databases, reference lists of included studies, and experts. Review methods: Data were extracted on the study population, the type of Ottawa ankle rules used, and methods. Sensitivities, but not specificities, were pooled using the bootstrap after inspection of the receiver operating characteristics plot. Negative likelihood ratios were pooled for several subgroups, correcting for four main methodological threats to validity. Results: 32 studies met the inclusion criteria and 27 studies reporting on 15 581 patients were used for meta-analysis. The pooled negative likelihood ratios for the ankle and mid-foot were 0.08 (95% confidence interval 0.03 to 0.18) and 0.08 (0.03 to 0.20), respectively. The pooled negative likelihood ratio for both regions in children was 0.07 (0.03 to 0.18). Applying these ratios to a 15% prevalence of fracture gave a less than 1.4% probability of actual fracture in these subgroups. Conclusion: Evidence supports the Ottawa ankle rules as an accurate instrument for excluding fractures of the ankle and mid-foot. The instrument has a sensitivity of almost 100% and a modest specificity, and its use should reduce the number of unnecessary radiographs by 30-40%. What is already known on this topic Although most patients with ankle sprains who present to emergency departments undergo radiography, less than 15% have a fracture The Ottawa ankle rules is a clinical decision aid designed to avoid unnecessary radiography What this paper adds The Ottawa ankle rules is highly accurate at excluding ankle fractures after sprain injury

The Role of 11C-Choline and 18F-Fluorocholine Positron Emission Tomography (PET) and PET/CT in Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT The role of positron emission tomography (PET) and PET/computed tomography (PET/CT) in prostate cancer (PCa) imaging is still debated, although guidelines for their use have emerged over the last few years. OBJECTIVE To systematically review and conduct a meta-analysis of the available evidence of PET and PET/CT using 11C-choline and 18F-fluorocholine as tracers in imaging PCa patients in staging and restaging settings. EVIDENCE ACQUISITION PubMed, Embase, and Web of Science (by citation of reference) were searched. Reference lists of review articles and included articles were checked to complement electronic searches. EVIDENCE SYNTHESIS In staging patients with proven but untreated PCa, the results of the meta-analysis on a per-patient basis (10 studies, n = 637) showed pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of 84% (95% confidence interval [CI], 68-93%), 79% (95% CI, 53-93%), and 20.4 (95% CI, 9.9-42.0), respectively. The positive and negative likelihood ratios were 4.02 (95% CI, 1.73-9.31) and 0.20 (95% CI, 0.11-0.37), respectively. On a per-lesion basis (11 studies, n = 5117), these values were 66% (95% CI, 56-75%), 92% (95% CI, 78-97%), and 22.7 (95% CI, 8.9-58.0), respectively, for pooled sensitivity, specificity, and DOR; and 8.29 (95% CI, 3.05-22.54) and 0.36 (95% CI, 0.29-0.46), respectively, for positive and negative likelihood ratios. In restaging patients with biochemical failure after local treatment with curative intent, the meta-analysis results on a per-patient basis (12 studies, n = 1055) showed pooled sensitivity, specificity, and DOR of 85% (95% CI, 79-89%), 88% (95% CI, 73-95%), and 41.4 (95% CI, 19.7-86.8), respectively; the positive and negative likelihood ratios were 7.06 (95% CI, 3.06-16.27) and 0.17 (95% CI, 0.13-0.22), respectively. CONCLUSIONS PET and PET/CT imaging with 11C-choline and 18F-fluorocholine in restaging of patients with biochemical failure after local treatment for PCa might help guide further treatment decisions. In staging of patients with proven but untreated, high-risk PCa, there is limited but promising evidence warranting further studies. However, the current evidence shows crucial limitations in terms of its applicability in common clinical scenarios.

Accuracy of electrocardiography in diagnosis of left ventricular hypertrophy in arterial hypertension: systematic review

Objective To review the accuracy of electrocardiography in screening for left ventricular hypertrophy in patients with hypertension. Design Systematic review of studies of test accuracy of six electrocardiographic indexes: the Sokolow-Lyon index, Cornell voltage index, Cornell product index, Gubner index, and Romhilt-Estes scores with thresholds for a positive test of ≥4 points or ≥5 points. Data sources Electronic databases ((Pre-)Medline, Embase), reference lists of relevant studies and previous reviews, and experts. Study selection Two reviewers scrutinised abstracts and examined potentially eligible studies. Studies comparing the electrocardiographic index with echocardiography in hypertensive patients and reporting sufficient data were included. Data extraction Data on study populations, echocardiographic criteria, and methodological quality of studies were extracted. Data synthesis Negative likelihood ratios, which indicate to what extent the posterior odds of left ventricular hypertrophy is reduced by a negative test, were calculated. Results 21 studies and data on 5608 patients were analysed. The median prevalence of left ventricular hypertrophy was 33% (interquartile range 23-41%) in primary care settings (10 studies) and 65% (37-81%) in secondary care settings (11 studies). The median negative likelihood ratio was similar across electrocardiographic indexes, ranging from 0.85 (range 0.34-1.03) for the Romhilt-Estes score (with threshold ≥4 points) to 0.91 (0.70-1.01) for the Gubner index. Using the Romhilt-Estes score in primary care, a negative electrocardiogram result would reduce the typical pre-test probability from 33% to 31%. In secondary care the typical pre-test probability of 65% would be reduced to 63%. Conclusion Electrocardiographic criteria should not be used to rule out left ventricular hypertrophy in patients with hypertension.

An empirical comparison of methods for meta-analysis of diagnostic accuracy showed hierarchical models are necessary

OBJECTIVE Meta-analysis of studies of the accuracy of diagnostic tests currently uses a variety of methods. Statistically rigorous hierarchical models require expertise and sophisticated software. We assessed whether any of the simpler methods can in practice give adequately accurate and reliable results. STUDY DESIGN AND SETTING We reviewed six methods for meta-analysis of diagnostic accuracy: four simple commonly used methods (simple pooling, separate random-effects meta-analyses of sensitivity and specificity, separate meta-analyses of positive and negative likelihood ratios, and the Littenberg-Moses summary receiver operating characteristic [ROC] curve) and two more statistically rigorous approaches using hierarchical models (bivariate random-effects meta-analysis and hierarchical summary ROC curve analysis). We applied the methods to data from a sample of eight systematic reviews chosen to illustrate a variety of patterns of results. RESULTS In each meta-analysis, there was substantial heterogeneity between the results of different studies. Simple pooling of results gave misleading summary estimates of sensitivity and specificity in some meta-analyses, and the Littenberg-Moses method produced summary ROC curves that diverged from those produced by more rigorous methods in some situations. CONCLUSION The closely related hierarchical summary ROC curve or bivariate models should be used as the standard method for meta-analysis of diagnostic accuracy.

How should COPD patients exercise during respiratory rehabilitation? Comparison of exercise modalities and intensities to treat skeletal muscle dysfunction

Background: Physical exercise is an important component of respiratory rehabilitation because it reverses skeletal muscle dysfunction, a clinically important manifestation of COPD associated with reduced health-related quality of life (HRQL) and survival. However, there is controversy regarding the components of the optimal exercise protocol. A study was undertaken to systematically evaluate and summarise randomised controlled trials (RCTs) comparing different exercise protocols for COPD patients. Methods: Six electronic databases, congress proceedings and bibliographies of included studies were searched without imposing language restrictions. Two reviewers independently screened all records and extracted data on study samples, interventions and methodological characteristics of included studies. Results: The methodological quality of the 15 included RCTs was low to moderate. Strength exercise led to larger improvements of HRQL than endurance exercise (weighted mean difference for Chronic Respiratory Questionnaire 0.27, 95% CI 0.02 to 0.52). Interval exercise seems to be of similar effectiveness as continuous exercise, but there are few data on clinically relevant outcomes. One small RCT which included patients with mild COPD compared the effect of high and low intensity exercise (at 80% and 40% of the maximum exercise capacity, respectively) and found larger physiological training effects from high intensity exercise. Conclusions: Strength exercise should be routinely incorporated in respiratory rehabilitation. There is insufficient evidence to recommend high intensity exercise for COPD patients and investigators should conduct larger high quality trials to evaluate exercise intensities in patients with moderate to severe COPD.

Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis

OBJECTIVE: To estimate the accuracy of endometrial thickness measurement in the detection of endometrial cancer among women with postmenopausal bleeding with individual patient data using different meta-analytic strategies. DATA SOURCES: Original data sets of studies detected after reviewing the included studies of three previous reviews on this subject. An additional literature search of published articles using MEDLINE databases was preformed from January 2000 to December 2006 to identify articles reporting on endometrial carcinoma and sonographic endometrial thickness measurement in women with postmenopausal bleeding. METHODS OF STUDY SELECTION: We identified 90 studies reporting on endometrial thickness measurements and endometrial carcinoma in women with postmenopausal bleeding. TABULATION, INTEGRATION, AND RESULTS: We contacted 79 primary investigators to obtain the individual patient data of their reported studies, of which 13 could provide data. Data on 2,896 patients, of which 259 had carcinoma, were included. Several approaches were used in the analyses of the acquired data. First, we performed receiver operator characteristics (ROC) analysis per study, resulting in a summary area under the ROC curve (AUC) calculated as a weighted mean of AUCs from original studies. Second, individual patient data were pooled and analyzed with ROC analyses irrespective of study with standardization of distributional differences across studies using multiples of the median and by random effects logistic regression. Finally, we also used a two-stage procedure, calculating sensitivities and specificities for each study and using the bivariate random effects model to estimate summary estimates for diagnostic accuracy. This resulted in rather comparable ROC curves with AUCs varying between 0.82 and 0.84 and summary estimates for sensitivity and specificity located along these curves. These curves indicated a lower AUC than previously reported meta-analyses using conventional techniques. CONCLUSION: Previous meta-analyses on endometrial thickness measurement probably have overestimated its diagnostic accuracy in the detection of endometrial carcinoma. We advise the use of cutoff level of 3 mm for exclusion of endometrial carcinoma in women with postmenopausal bleeding.

The role of fear avoidance beliefs as a prognostic factor for outcome in patients with nonspecific low back pain: a systematic review

BACKGROUND CONTEXT Psychological factors including fear avoidance beliefs are believed to influence the development of chronic low back pain (LBP). PURPOSE The purpose of this study was to determine the prognostic importance of fear avoidance beliefs as assessed by the Fear Avoidance Beliefs Questionnaire (FABQ) and the Tampa Scale of Kinesiophobia for clinically relevant outcomes in patients with nonspecific LBP. DESIGN/SETTING The design of this study was a systematic review. METHODS In October 2011, the following databases were searched: BIOSIS, CINAHL, Cochrane Library, Embase, OTSeeker, PeDRO, PsycInfo, PubMed/Medline, Scopus, and Web of Science. To ensure the completeness of the search, a hand search and a search of bibliographies was conducted and all relevant references included. A total of 2,031 references were retrieved, leaving 566 references after the removal of duplicates. For 53 references, the full-text was assessed and, finally, 21 studies were included in the analysis. RESULTS The most convincing evidence was found supporting fear avoidance beliefs to be a prognostic factor for work-related outcomes in patients with subacute LBP (ie, 4 weeks-3 months of LBP). Four cohort studies, conducted by disability insurance companies in the United States, Canada, and Belgium, included 258 to 1,068 patients mostly with nonspecific LBP. These researchers found an increased risk for work-related outcomes (not returning to work, sick days) with elevated FABQ scores. The odds ratio (OR) ranged from 1.05 (95% confidence interval [CI] 1.02-1.09) to 4.64 (95% CI, 1.57-13.71). The highest OR was found when applying a high cutoff for FABQ Work subscale scores. This may indicate that the use of cutoff values increases the likelihood of positive findings. This issue requires further study. Fear avoidance beliefs in very acute LBP (<2 weeks) and chronic LBP (>3 months) was mostly not predictive. CONCLUSIONS Evidence suggests that fear avoidance beliefs are prognostic for poor outcome in subacute LBP, and thus early treatment, including interventions to reduce fear avoidance beliefs, may avoid delayed recovery and chronicity.

Paradigm shift in manual therapy? Evidence for a central nervous system component in the response to passive cervical joint mobilisation.

Segmental neurological modulation, neural hysteresis and biomechanical effects have been proposed as mechanisms underpinning the effects of manual therapy. An increasing number of studies hypothesise activation of the central nervous system resulting in a non-segmental hypoalgesic effect with concurrent activation of other neural pathways as a potential mechanism of action. Whether this model is consistent with the current literature is unknown. This systematic review aims to assess the consistency of evidence supporting an involvement of supraspinal systems in mediating the effects of passive cervical joint mobilisation. We searched randomised trials in three electronic databases from inception to November 2007, without language restriction, and checked reference lists of included studies. We assessed study validity and extracted salient features in duplicate. Fifteen studies met our inclusion criteria. The overall quality was high. We found consistency for concurrent hypoalgesia, sympathetic nervous system excitation and changes in motor function. Pooling of data suggested that joint mobilisation improved outcomes by approximately 20% relative to controls. This specific pattern suggests that descending pathways might play a key role in manual therapy induced hypoalgesia. Our review supports the existence of an alternative neurophysiological model, in which passive joint mobilisation stimulates areas within the central nervous system.

Sample sizes of studies on diagnostic accuracy: literature survey

Abstract Objectives To determine sample sizes in studies on diagnostic accuracy and the proportion of studies that report calculations of sample size. Design Literature survey. Data sources All issues of eight leading journals published in 2002. Methods Sample sizes, number of subgroup analyses, and how often studies reported calculations of sample size were extracted. Results 43 of 8999 articles were non-screening studies on diagnostic accuracy. The median sample size was 118 (interquartile range 71-350) and the median prevalence of the target condition was 43% (27-61%). The median number of patients with the target condition—needed to calculate a tests sensitivity—was 49 (28-91). The median number of patients without the target condition—needed to determine a tests specificity—was 76 (27-209). Two of the 43 studies (5%) reported a priori calculations of sample size. Twenty articles (47%) reported results for patient subgroups. The number of subgroups ranged from two to 19 (median four). No studies reported that sample size was calculated on the basis of preplanned analyses of subgroups. Conclusion Few studies on diagnostic accuracy report considerations of sample size. The number of participants in most studies on diagnostic accuracy is probably too small to analyse variability of measures of accuracy across patient subgroups.