Methods During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. Results Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P = 1.00), and rates of death were 18.4% and 15.5%, respectively (P = 0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. Conclusions Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of poststroke disability and increased the rate of functional independence. (Funded by Fundacio Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.)

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Thrombectomy within 8 hours after symptom onset in ischemic stroke

Background and Purpose— The modified Rankin scale (mRS), a clinician-reported measure of global disability, is widely applied for evaluating stroke patient outcomes and as an end point in randomized clinical trials. Extensive evidence on the validity of the mRS exists across a large but fragmented literature. As new treatments for acute ischemic stroke are submitted for agency approval, an appreciation of the mRS’s attributes, specifically its relationship to other stroke evaluation scales, would be valuable for decision-makers to properly assess the impact of a new drug on treatment paradigms. The purpose of this report is to assemble and systematically assess the properties of the mRS to provide decision-makers with pertinent evaluative information. Methods— A Medline search was conducted to identify reports in the peer-reviewed medical literature (1957–2006) that provide information on the structure, validation, scoring, and psychometric properties of the mRS and its use in clinical trials. The selecti...

Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis.

BACKGROUND Specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran METHODS We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B) The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time A key secondary end point was the restoration of hemostasis RESULTS This interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B) Among 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline, the median maximum percentage reversal was 100% (95% confidence interval, 100 to 100) Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79% of the patients Among 35 patients in group A who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 114 hours Among 36 patients in group B who underwent a procedure, normal intraoperative hemostasis was reported in 33, and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated CONCLUSIONS Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrialsgov number, NCT02104947)

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Idarucizumab for Dabigatran Reversal

Nosology (the systematic classification of diseases) has always fascinated the sick and their would-be healers. Western societies developed an interest in nosology in the seventeenth and eighteenth centuries when they began to track the causes of sickness and death among their citizens. In the twentieth century, when medical insurance programs made payers other than patients responsible for medical care, nosology became a matter of great interest to those public and private payers. The most commonly used nosologies include International Classification of Diseases (ICD), the American Medical Association's Current Procedural Terminology, 4th Edition (CPT-4); the Health Care Financing Administration (HCFA, now known as the Centers for Medicare and Medicaid Services) Health Care Common Procedural Coding System (HCPCS); the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Revision (DSM-IV); Europe's Classification of Surgical Operations and Procedures, 4th Revision (OPCS-4); and the Agency for Healthcare Research and Quality's Clinical Classification Software (CCS).

This paper focuses on the International Classification of Diseases, now in its ninth and soon to be tenth iteration; the most widely used classification of diseases. Beginning in 1900 with the ICD-1 version, this nosology has evolved from 179 to over 120,000 total codes in ICD-10-CM (ICD-10 2003; ICD-10-CM 2003). The use of codes has expanded from classifying morbidity and mortality information for statistical purposes to diverse sets of applications, including reimbursement, administration, epidemiology, and health services research. Since October 1 1983, when Medicare's Prospective Payment System (PPS) was enacted, diagnosis-related groups (DRGs) based on ICD codes emerged as the basis for hospital reimbursement for acute-care stays of Medicare beneficiaries (U.S. Congress 1985). Today the use of ICD coding for reimbursement is a vital part of health care operations. Health care facilities use ICD codes for workload and length-of-stay tracking as well as to assess quality of care. The Veterans Health Administration uses ICD codes to set capitation rates and allocate resources to medical centers caring for its 6 million beneficiaries. Medical research uses ICD codes for many purposes. By grouping patients according to their diagnoses, clinical epidemiologists use ICD codes to study patterns of disease, patterns of care, and outcomes of disease. Health services researchers use the codes to study risk-adjusted, cross-sectional, and temporal variations in access to care, quality of care, costs of care, and effectiveness of care. Medical and health services researchers commonly use ICD codes as inclusion and exclusion criteria to define sampling frames, to document the comorbidities of patients, report the incidence of complications, track utilization rates, and determine the case fatality and morbidity rates (see Calle et al. 2003 for a recent example) (Steinman, Landefeld, and Gonzales 2000; Calle et al. 2003; Charbonneau et al. 2003; Jackson et al. 2003; Martin et al. 2003; Studdert and Gresenz 2003). The widespread and diverse use of ICD codes demonstrates the central role nosology plays in health care.

Increased attention to code accuracy has occurred both as a result of the application of ICD codes for purposes other than those for which the classifications were originally designed as well as because of the widespread use for making important funding, clinical, and research decisions. Code accuracy, defined as the extent to which the ICD nosologic code reflects the underlying patient's disease, directly impacts the quality of decisions that are based on codes, and therefore code accuracy is of great importance to code users. Accuracy is a complicated issue, however, as it influences each code application differently. Using the codes for reporting case fatality rates in persons hospitalized for influenza, for example, might require a different level of accuracy than using codes as the basis for reimbursing hospitals for providing expensive surgical services to insured persons. Therefore, users of disease classifications, just as users of any measure, must consider the accuracy of the classifications within their unique situations. An appreciation of the measurement context in which disease classifications take place will improve the accuracy of those classifications and will strengthen research and health care decisions based on those classifications.

Researchers studying errors in the code assignment process have reported a wide range of errors. Studies in the 1970s found substantial errors in diagnostic and procedure coding. These error rates ranged from 20 to 80 percent (Institute of Medicine 1977; Corn 1981; Doremus and Michenzi 1983; Johnson and Appel 1984; Hsia et al. 1988). Studies in the 1980s reported slightly increased accuracy with average error rates around 20 percent, and most below 50 percent (Lloyd and Rissing 1985; Fischer et al. 1992; Jolis et al. 1993). Studies in the 1990s found rates similar to those of the 1980 studies, with error rates ranging from 0 to 70 percent (Benesch et al. 1997; Faciszewski, Broste, and Fardon 1997; Goldstein 1998). The inconsistency in the error rates and wide range of reported amounts of error is due largely to differences across study methods (i.e., different data sets, versions of the ICD classifications, conditions studied, number of digits compared, codes examined, etc.) (Bossuyt et al. 2004). However, variation in error rates is also influenced by the many different sources of errors that influence code accuracy (Green and Wintfeld 1993). By clearly specifying the code process and the types of errors and coding inconsistencies that occur in each study, researchers can begin to understand which errors are most common and most important in their situation. They can then institute steps for reducing those errors.

If we think of the assignment of ICD codes as a common measurement process, then the person's true disease and the assigned ICD code represent true and observed variables, respectively. One approach to evaluating ICD code accuracy is to examine sources of errors that lead to the assignment of a diagnostic code that is not a fair representation of the patient's actual condition. Errors that differentiate the ICD code from the true disease include both random and systematic measurement errors. By understanding these sources of error, users can evaluate the limitations of the classifications and make better decisions based on them. In this manuscript, we (1) present the history of ICD code use, (2) summarize the general inpatient ICD coding process (from patient admission to the assignment of diagnostic codes), (3) identify potential sources of errors in the process, and (4) critique methods for assessing these errors.

Measuring diagnoses: ICD code accuracy.

Summary No single outcome measure can describe or predict all dimensions of recovery and disability after acute stroke. Several scales have proven reliability and validity in stroke trials, including the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS), the Barthel index (BI), the Glasgow outcome scale (GOS), and the stroke impact scale (SIS). Several scales have been combined in stroke trials to derive a global statistic to better define the effect of acute interventions, although this composite statistic is not clinically tenable. In practice, the NIHSS is useful for early prognostication and serial assessment, whereas the BI is useful for planning rehabilitative strategies. The mRS and GOS provide summary measures of outcome and might be most relevant to clinicians and patients considering early intervention. The SIS was designed to measure the patient's perspective on the effect of stroke. Familiarity with these scales could improve clinicians' interpretation of stroke research and their clinical decision-making.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474442206704951.pdf

Clinical interpretation and use of stroke scales

Background and Purpose— The modified Rankin Scale is widely used to assess changes in activity and lifestyle after stroke, but it has been criticized for its subjectivity. The purpose of the present study was to compare conventional assessment on the modified Rankin Scale with assessment through a structured interview. Methods— Sixty-three patients with stroke 6 to 24 months previously were interviewed and graded independently on the modified Rankin Scale by 2 observers. These observers then underwent training in use of a structured interview for the scale that covered 5 areas of everyday function. Eight weeks after the first assessment, the same observers reassessed 58 of these patients using the structured interview. Results— Interrater reliability was measured with the κ statistic (weighted with quadratic weights). For the scale applied conventionally, overall agreement between the 2 raters was 57% (κw=0.78); 1 rater assigned significantly lower grades than the other (P=0.048). On the structured interv...

Improving the Assessment of Outcomes in Stroke: Use of a Structured Interview to Assign Grades on the Modified Rankin Scale

98 Background & aims: We have recently developed a structured interview for the Modified Rankin Scale (MRS-SI) to improve the inter-rater reliability of this measure of outcome. The purpose of the ...

Validity of a structured interview for the Modified Rankin Scale: Comparison with other stroke assessment scales

P227 Background & aims: The Modified Rankin Scale (MRS) (van Swieten et al, 1988) is widely used in clinical trials to rate disability and handicap after stroke. Although the MRS is a popular measure of functional outcome the categories of the scale are very broadly defined and open to interpretation by raters. Previous work with the Glasgow Outcome Scale indicates that the reliability of functional rating scales may be improved by use of a structured interview (Wilson et al, 1998). The purpose of the present study was to compare the inter-rater reliability of the conventional MRS with the inter-rater reliability of a newly developed structured interview for the MRS (MRS-SI) Methods: A structured interview was devised for the MRS covering five areas of everyday function. 63 patients with stable functional state after stroke (stroke 6 to 24 months previously) were recruited to the study and scored on the conventional MRS by two independent observers. These observers then underwent training in use of the MRS-SI. Eight weeks after the first assessment the same observers reassessed 58 of these patients using the MRS-SI. Results: To allow comparison between the assessments the analysis of results was restricted to the 58 patients who were rated on both the MRS and MRS-SI. Inter-rater reliability was measured using the kappa statistic (unweighted and weighted using quadratic weights). For the MRS, overall agreement between the two raters was 57% (unweighted kappa 0.44, weighted kappa 0.78); using the MRS-SI, overall agreement was 78% (unweighted kappa 0.70, weighted kappa 0.93). Conclusions: Variability between raters in assigning patients to Rankin grades appears to be reduced when using a structured interview for the Modified Rankin Scale. The use of the MRS-SI could potentially improve the quality of results from clinical studies in stroke. A multi-centre study to further establish the improvement in inter-rater reliability is ongoing.

Marie Grant

Papers

Improving the Assessment of Outcomes in Stroke: Use of a Structured Interview to Assign Grades on the Modified Rankin Scale

Validity of a structured interview for the Modified Rankin Scale: Comparison with other stroke assessment scales

Measuring functional outcomes in stroke trials: Improving inter-rater reliability of the Modified Rankin Scale using a structured interview