Elizabeth A. Wright

Validity and Responsiveness of the Knee Society Clinical Rating System in Comparison with the Sf-36 and Womac

Background: The aim of this study was to validate the Knee Society Clinical Rating System (knee and function scores) and to compare its responsiveness with that of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Medical Outcomes Study Short Form-36 (SF-36). Methods: Patients were recruited as part of a prospective observational study of the outcomes of primary total knee arthroplasty for the treatment of osteoarthritis in four centers in the United States, six centers in the United Kingdom, and two centers in Australia. Independent research assistants at each site collected the Knee Society clinical data. The WOMAC, SF-36, patient satisfaction, and demographic data were obtained with self-administered questionnaires. Results: A total of 862 eligible patients were recruited, and complete preoperative and twelve-month data were available for 697 (80.9%) of them. The mean age was seventy years (range, thirty-eight to ninety years), and the majority of the patients (58.9%) were women. Low correlations were found among the items of both the knee and the function score at both assessment times. The Knee Society pain and function scores had moderate-to-strong correlations with the corresponding pain and function domains of the WOMAC and SF-36 (r = 0.31 to 0.72). Measurement of the standardized response mean showed the Knee Society knee score to be more responsive (standardized response mean, 2.2) than the WOMAC (standardized response means, 2.0 for pain and 1.4 for function) and the SF-36 (standardized response means, 1.0 for bodily pain and 1.1 for physical functioning). The Knee Society function score was the least responsive measure (standardized response mean, 0.8). Correlation of changes in scores at twelve months with patient reports of satisfaction and improvement in health status showed the WOMAC and SF-36 to be more responsive than the Knee Society scores. Conclusions: There is a poor correlation among the items of the Knee Society Clinical Rating System, but the rating system has adequate convergent construct validity. The WOMAC and SF-36 are more responsive measures of outcome of total knee arthroplasty. As they are less labor-intensive for researchers to use and as use of these instruments removes observer bias from the study design, they are preferable for knee arthroplasty outcome studies.

Validation of a meta-analysis: The effects of fish oil in rheumatoid arthritis

The purpose of this study was to validate the results of a meta-analysis showing the efficacy of fish oil in rheumatoid arthritis with the results of a re-analysis of the complete primary data set. A Medline search yielded seven published papers. Three additional trials were found by contacting authorities in the field. Inclusion criteria included (1) a double-blind, placebo-controlled study, (2) use of at least one of seven predetermined outcome measures, (3) results reported for both placebo and treatment groups at baseline and follow-up, (4) randomization, and (5) parallel or cross-over design. Papers were scored for quality. Demographic and outcomes variables were collected. For the re-analysis of the primary data, the same variables were abstracted for the 395 individual patients randomized. The meta-analysis demonstrated that dietary fish oil supplementation for 3 months significantly reduced tender joint count (rate difference [RD] [95% CI] = -2.9 [-3.8 to -2.1] [p = 0.001]) and morning stiffness (RD [95% CI] = -25.9 [-44.3 to -7.5] [p < 0.01]) as compared with heterogeneous dietary control oils. The re-analysis of the primary data confirmed a significant reduction in tender joint count (p = 0.001) and in morning stiffness (p < 0.02) in the parallel analysis that ignored interaction terms. The analyses that included an interaction term between site and treatment again confirmed a significant reduction in tender joint count. The results for morning stiffness were similar to the meta-analysis, but did not quite reach statistical significance (p = 0.052-0.083). The relative improvements in the other outcome variables did not reach statistical significance. Use of fish oil improved the number of tender joints and duration of morning stiffness at 3 months as analyzed by both meta- and mega-analysis. The fuller mega-analysis confirmed the results of the meta-analysis. The advantages of mega-analysis were as follows: (1) the ability to analyze the homogeneity of the patient populations, (2) the ability to make clinically sensible adjustments in the form of the comparison, and (3) the ability to examine subsets of the data.

The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study.

Lyme borreliosis is a tick-borne infection caused by the spirochete Borrelia burgdorferi [1-3]. The disease usually begins with erythema migrans accompanied by viral-like or meningitis-like symptoms. Weeks later meningitis, facial palsy, atrioventricular nodal block, or migratory musculoskeletal pain may develop, followed months to years later by episodes of frank arthritis, encephalopathy, polyneuropathy, or acrodermatitis [4]. Lyme disease is now the most common vector-borne disease in the United States; nearly 50 000 patients have been diagnosed with it since 1982 [5]. Musculoskeletal and neurologic sequelae may occur from Lyme disease. Some of the late consequences of Lyme disease, such as oligoarticular arthritis, axonal polyneuropathy, or active encephalopathy, are thought to be caused by persistent spirochetal infection and are amenable to antibiotic treatment [6-8]. Other syndromes such as persistent arthritis, fibromyalgia, subtle joint pain, or mild encephalopathy do not improve with antibiotic treatment, suggesting a mechanism other than active infection [9-12]. We studied persons residing in an endemic coastal area of Massachusetts who were previously infected with B. burgdorferi in the early 1980s [13]. They contracted Lyme disease while the clinical syndromes and optimal antibiotic therapies were still evolving, which offered a natural experiment for the identification of risk factors for Lyme disease sequelae. We ascertained the prevalence of persistent symptoms in unselected patients with a history of Lyme disease; ascertained their rheumatologic, neurologic, and health status outcomes; and identified potential risk factors for these long-term sequelae. Methods Participants In February l991, we did a follow-up analysis of residents of Argylla Road in Ipswich, Massachusetts, an endemic coastal area for Lyme disease. The incidence and clinical course of Lyme disease among residents of this area have been reported previously [13]. Participants were recruited by calling consecutive households located in the Argylla Road area, the epicenter of infection, to ask if they would be interested in enrolling in a study about Lyme disease in their area. Potential participants were told that the study involved a history, physical examination, and serologic analysis for Lyme disease. Information about whether a person ever had a previous diagnosis of Lyme disease was obtained and used to assign tentative status (with or without Lyme disease) for study participants. We recruited participants until we had 50 tentative persons with Lyme disease and 50 tentative controls. Once the potential Lyme disease group was filled, calls were made consecutively to fill the potential control group. Residents 18 years of age or older were invited to participate in the study. This protocol was approved by the Brigham & Womens Hospital Committee for the Protection of Human Subjects. Confirmation of Lyme Disease For inclusion in the Lyme group, persons needed a previous diagnosis of Lyme disease by a physician and needed to fulfill the Centers for Disease Control and Prevention (CDC) criteria for Lyme disease (a history of physician-documented erythema migrans or a late manifestation of Lyme disease confirmed by a positive Lyme serologic test result, or both [14]). This information was obtained through patient interview and then medical record review to determine if patients fulfilled criteria for Lyme disease. Previous study records, local physician reports, and previous serologic test results were available for confirmation of Lyme disease. Persons without a previous clinical history of Lyme disease were classified as controls. The status of the participants (with or without Lyme disease) was determined independent of the clinical assessment, using a protocol that did not include any outcome data. Assessment of Clinical Outcomes A blinded investigator determined outcomes in a standardized manner independent of Lyme disease status. All patients completed a standardized questionnaire, had electrocardiography, and had a neuropsychological battery of tests. The questionnaire included data on demographics, comorbidity, education, review of systems, medications, memory and cognitive function, and the Short Form-36 health status measure (a reliable, previously validated measure of physical, psychological, social, and role functions [15]). A physical examination was done by one observer blinded to Lyme disease status. It included a joint examination (the American College of Rheumatology Glossary examination) that measured swelling and pain through passive range of motion [16] and a neurologic evaluation of strength and deep tendon reflexes, light touch, and vibration sensation with a 128-Hz tuning fork (at the elbow, wrist, fibula, and ankles). Pain and swelling indices from the joint examination (the American College of Rheumatology Glossary examination) were summed and recorded as a global score. A vibration test result of a distal gradient was considered present if the participant reported diminished vibratory sensation at a distal compared with proximal site. Each participant had an electrocardiographic study that was interpreted blindly by a cardiologist uninvolved with the clinical assessment. All outcomes were determined by one investigator who had no knowledge of whether participants were in the Lyme or control groups. The neuropsychological battery of tests measured immediate and delayed verbal memory, attention, conceptualization, fine motor dexterity, and perceptual discrimination. Tests included the California Verbal Learning Test [17], Wechsler Memory Scale (visual reproduction and verbal paired associates subtests [18]), Shipley abstraction subtest [19], Stroop test [20], Trailmaking test [21], and Purdue Pegboard Test [22]. The California Verbal Learning Test measures verbal memory. Participants are asked to learn a list of 16 words during five trials; recall on the fifth trial is recorded (trial 5). This is then followed by a distracter list. The original list is recalled after the distracter list is learned (short recall) and then recalled again after a 20-minute delay (long recall). This is a challenging test of memory for patients with superior premorbid experience. Normative values are available for young and elderly adults [17]; the range of normal is between 11 and 15 words for trial 5 and is between 10 and 15 words for the long-recall subtest for persons between 45 and 54 years of age. A clinically significant change in the California Verbal Learning Test would be recalling 4 more words or 4 fewer words. All tests were administered according to published procedures. Test scores were transformed into standard scores calculated from published, age-corrected normative data. Participants with a score of 2 or more SDs from age-adjusted means were considered impaired. All results were reviewed by a neuropsychologist (RK) who was not involved with the participants evaluation, to determine those patients who were in need of further clinical evaluation. Participants with swelling or pain (joint examination test result), evidence of a distal gradient (vibration test result) or persistent symptoms of paresthesias in an extremity, or impairment on two or more neurocognitive tests were sent for further clinical evaluation. Nine patients were evaluated at the Lyme disease clinic at Tufts-New England Medical Center and 4 were evaluated by other neurologist or rheumatologist consultants to determine if these abnormal screening test results were accompanied by objective findings. This evaluation included lumbar puncture, electrophysiologic studies, magnetic resonance imaging, detailed neuropsychological tests [8], joint radiographs, or arthrocentesis. Serologic Evaluation All patients had serologic testing after the history and examination. Serum samples were stored at 70C and were tested for IgG antibodies to B. burgdorferi by indirect enzyme-linked immunosorbent assay (ELISA [23]); for IgM, IgG, and IgA antibodies to the spirochete by antibody-capture enzyme immunoassays [24]; and for the pattern of IgG reactivity to spirochetal polypeptides by Western blotting. In general, Western blot reactivity varied with the degree and duration of dissemination of Lyme disease. For example, patients with early localized infection or erythema migrans might react to only 2 to 8 B. burgdorferi polypeptides, those with meningitis might react to at least 8 to 14 polypeptides, and those with arthritis or late central nervous system disease might react to as many as 18 to 25 polypeptides (Berardi VP. Personal communication). The isolate used for antigen preparations was the B. burgdorferi G39/40 strain obtained through low passage [24]. Indirect ELISA titers greater than 400 and ELISA capture ratios (sample optical density/control optical density) of 1.0 or more were considered as increased test results. Western blot reactivity to five or more B. burgdorferi-specific polypeptides indicated previous infection [25]. Silver Stain Method The Dieterle silver impregnation stain used was a modification made by one of us (PHD) in 1985 [26]. This standard approach has yielded a constant clean yellow background of cerebral cortex sections with no silver impregnation of anatomic neural processes and dendrites. Spirochetes are easily seen as black to blue-black cells against the yellow tissue. Specificity for nonstaining of normal tissue fibers (procollagen, elastin, basement membrane material, and neural dendrites and filaments) and documentation of the cytologic structure of Borrelia spirochete strains were further tested in a large extended study [27]. Controls routinely used in each stain assay consisted of NP40 strain that was injected into human normal breast tissue removed for cosmetic surgery and was paraffin-embedded in the usual manner (negative control), and rat gonad tissue infected with the Reiter strain of treponemal spirochetes (positive c

A connective tissue disease screening questionnaire for population studies

To develop a technique to screen populations for potential connective tissue disease (CTD), we mailed a 30-item questionnaire to 253 randomly selected patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease (MCTD), or Sjögrens syndrome and to 340 randomly selected control subjects. The response rate after four mailings was 71% for case subjects and 54% for control subjects. Test-retest reliability for detection of any CTD was 0.82. Sensitivity for specific CTDs was 83 to 96% and specificity was 83 to 93%. The positive predictive value for any CTD (assuming an overall prevalence of 1.3%) was 5.5%; negative predictive value was 99.7%. The CTD Screening Questionnaire has high sensitivity and specificity for screening large populations.

The natural history of exercise-induced anaphylaxis: survey results from a 10-year follow-up study.

BACKGROUND Exercise-induced anaphylaxis (EIA) is a unique physical allergy that is triggered by exertion, the clinical spectrum and modifying factors of which have been previously studied. At the time of initial description, it was postulated that other factors contributed to this disorder. OBJECTIVE We sought to determine the clinical course and potential modifying factors in EIA. METHODS In 1993, we conducted a cross-sectional analysis of 671 individuals with exercise-associated symptoms for more than a decade using a validated 75-item questionnaire. Subjects met criteria for EIA if they had anaphylactic symptoms, including hypotension or upper airway obstruction, urticaria, or angioedema with physical exertion but without a passive increase in core body temperature. RESULTS Of 365 (54%) questionnaire respondents, 279 (87%) met criteria for EIA (199 females and 80 males). At the time of study entry, subjects with EIA (mean age, 37.5 years; range, 13 to 77 years) had an average of 10.6 years of symptoms, which were most frequently triggered by aerobic activities such as jogging or brisk walking (78% and 42%, respectively). On average, subjects reported that the frequency of attacks had decreased (47% of subjects) or stabilized (46% of subjects) since onset. One hundred (41%) subjects reported being completely free of attacks in the past year. Subjects reduced their attacks by avoiding exercise during extremely hot or cold weather (44%), avoiding ingestion of certain foods before exercise (37%), and restricting exercise during their allergy season (36%) or humid weather (33%). The most common pharmacologic agents used to manage symptoms were H1 antagonists (56%) and/or epinephrine (31%). However, 28% used no treatment at all. CONCLUSION EIA is an episodic condition in which the frequency of attacks tends to stabilize or decrease over time. Improvement appears to result from individual modification of exercise and avoidance of known environmental and ingestible precipitants.

Validation of a systemic lupus activity questionnaire (SLAQ) for population studies

The goal of this work was to develop an economical way of tracking disease activity for large groups of systemic lupus erythematosus (SLE) patients in clinical studies. A Systemic Lupus Activity Questionnaire (SLAQ) was developed to screen for possible disease activity using items from the Systemic Lupus Activity Measure (SLAM) and tested for its measurement properties. The SLAQ was completed by 93 SLE patients just prior to a scheduled visit. At the visit, a rheumatologist, blinded to SLAQ results, examined the subject and completed a SLAM. Associations among SLAQ, and SLAM (omitting laboratory items) and between individual items from each instrument were assessed with Pearson correlations. Correlations between pairs of instruments were compared using Student’s t-tests. The mean score across all 24 SLAQ items was 11.5 (range 0 -33); mean SLAM without labs was 3.0 (range 0 -13). The SLAQ had a moderately high correlation with SLAM-nolab (r = 0.62, P < 0.0001). Correlations between patient-clinician matched pairs of items ranged from r = 0.06 to 0.71. Positive predictive values for the SLAQ ranged from 56 to 89% for detecting clinically significant disease activity. In studies of SLE, symptoms suggesting disease can be screened by self-report using the SLAQ and then verified by further evaluation.

Responsiveness of Self-Reported and Objective Measures of Disease Severity in Carpal Tunnel Syndrome

Responsiveness, the ability to detect meaningful clinical change, is a critical attribute of instruments used to evaluate outcomes of treatments. The authors hypothesized that self-administered symptom severity and functional status questionnaires are more responsive to clinical improvement after carpal tunnel release than traditional physical examination measures of strength and sensibility. Data were obtained from a randomized clinical trial of endoscopic versus open carpal tunnel release conducted in four university medical centers. Patients were evaluated before surgery and 3 months after surgery. Seventy-four patients indicating that they were more than 80% satisfied with the results of surgery were assumed to have clinically meaningful improvement and were the focus of the analysis. Evaluations included questionnaires assessing symptom severity, functional status, and activities of daily living as well as measurement of grip, pinch, and abductor pollicus brevis strength, and 2-point discrimination and Semmes-Weinstein pressure sensibility. Responsiveness was calculated with the standardized response mean (mean change/standard deviation of change) as well as the effect size (mean change/standard deviation of baseline values). The symptom severity scale was four times as responsive, and the functional status and activities of daily living scales were twice as responsive, as the measures of strength and sensibility. Self-administered symptom severity and functional status scales are much more responsive to clinical improvement than measures of neuromuscular impairment and should serve as primary outcomes in clinical studies of therapy for carpal tunnel syndrome.

Delirium after Elective Orthopedic Surgery: Risk Factors and Natural History:

Forty-six orthopedic patients were studied to determine the incidence, natural history, and risk factors associated with post-operative delirium. Pre-operatively, patients were given a neuropsychological screening evaluation, the Mood Adjective Checklist (MACL), the Zung Depression Scale, the Anxiety Inventory Scale, and the Health Assessment Questionnaire (HAQ). A psychiatrist interviewed each patient on post-op day four for evidence of delirium as defined by DSM III criteria. Of the patients studied, thirteen (26%) were possibly or definitely delirious following surgery. Treatment with propranolol, scopolamine, or flurazepam (Dalmane) conferred a relative risk for delirium of 11.7 (p = 0.0028). Delirium was associated with increased post-operative complications (p = 0.01), poorer post-operative mood (p = 0.06), and an increase of about 1.5 days in length of stay (not significant). Delirious patients were significantly less likely than matched controls to improve in function at six months compared with a pre-operative baseline HAQ (t = 6.43, p < 0.001).

Joint space narrowing and Kellgren–Lawrence progression in knee osteoarthritis: an analytic literature synthesis

OBJECTIVE While the interpretation of cartilage findings on magnetic resonance imaging (MRI) evolves, plain radiography remains the standard method for assessing progression of knee osteoarthritis (OA). We sought to describe factors that explain variability in published estimates of radiographic progression in knee OA. DESIGN We searched PubMed between January 1985 and October 2006 to identify studies that assessed radiographic progression using either joint space narrowing (JSN) or the Kellgren-Lawrence (K-L) scale. We extracted cohort characteristics [age, gender, and body mass index (BMI)] and technical and other study factors (radiographic approach, study design, OA-related cohort composition). We performed meta-regression analyses of the effects of these variables on both JSN and K-L progression. RESULTS Of 239 manuscripts identified, 34 met inclusion criteria. The mean estimated annual JSN rate was 0.13 +/- 0.15 mm/year. While we found no significant association between JSN and radiographic approach among observational studies, full extension was associated with greater estimated JSN among randomized control trials (RCTs). Overall, observational studies that used the semi-flexed approach reported greater JSN than RCTs that used the same approach. The overall mean risk of K-L progression by at least one grade was 5.6 +/- 4.9%, with higher risk associated with shorter study duration, OA definition (K-L > or = 2 vs K-L > or = 1) and cohorts composed of subjects with both incident and prevalent OA. CONCLUSION While radiographic approach and study design were associated with JSN, OA definition, cohort composition and study duration were associated with risk of K-L progression. These findings may inform the design of disease modifying osteoarthritis drug (DMOAD) trials and assist clinicians in optimal timing of OA treatments.

Performance quality, gender, and professional role: A study of physicians and nonphysicians in 16 ambulatory care practices

The quality of medical care has rarely been evaluated in relation to practitioner or patient gender. Moreover, comparisons between physicians and nonphysicians typically are confounded by practitioner gender. In this study gender and professional role effects were analyzed separately for 162 male and female staff physicians, 191 male and female residents, and 73 female nonphysicians delivering adult and pediatric primary care in 16 ambulatory care practices. Analyses addressed influences of patient and practitioner gender as well as differences between physicians and nonphysicians. Results showed that female staff physicians performed better than male staff physicians for cancer screening in women by breast examination and Pap smears, but that female residents performed worse than male residents for urinary tract infections in children. Patient gender effects occurred for two tasks; for these, superior care was rendered to the gender with higher prevalence for the condition (girls for urinary tract infections, boys for otitis media). The results are considered in the context of the gender-relevance of particular medical tasks or conditions. Comparisons between physicians and nonphysicians were limited to female practitioners. Comparable or superior performance for nonphysicians was found for all tasks but one (cancer screening in women).