Barry P. Katz

Quadriceps Weakness and Osteoarthritis of the Knee

Osteoarthritis of the knee is the most common cause of chronic disability among older persons in the United States [1]. In persons with symptomatic osteoarthritis of the knee, quadriceps muscle weakness is common and is widely believed to result from disuse atrophy secondary to joint pain. Although exercises to strengthen the quadriceps may relieve joint pain in persons with osteoarthritis of the knee [2-6], the role of periarticular muscle weakness in the pathogenesis of joint pain and disability in these persons is poorly understood. The basis for the beneficial effect of strengthening exercises is unclear, and the duration of the improvement has not been studied. Furthermore, the possibility that muscle weakness is an etiologic factor underlying the pathologic changes of osteoarthritis has seldom been considered. Elucidation of the role of muscle weakness in osteoarthritis is particularly important given our growing understanding of safe and effective methods for increasing strength in elderly persons [7, 8]. A substantial proportion of persons who have radiographic evidence of osteoarthritis of the knee have no joint pain [9]. Because asymptomatic persons with radiographic changes seldom seek medical attention for osteoarthritis, muscle weakness has not been studied previously in this group. Thus, it is not known whether quadriceps weakness precedes or follows joint pain or (if it follows joint pain) whether it is mediated by disuse atrophy or by physiologic mechanisms that may inhibit muscle contraction [10]. To address this issue, we studied the relation among lower-extremity muscle strength, lower-extremity lean tissue mass, and osteoarthritis of the knee in men and women 65 years of age and older. Methods Study Group To obtain a sample of elderly persons living in the community, we conducted brief telephone interviews with residents of households in central Indiana. Potential participants were selected through modified random-digit dialing to increase the sampled proportion of persons 65 years of age and older. Persons were eligible if they met the minimal criteria for participation: They were willing and able to provide informed consent and to undergo the necessary strength assessments and other evaluations. Persons were excluded if they had had amputations of both lower extremities, had undergone total knee arthroplasty, or had recently had a cerebrovascular accident or myocardial infarction. A total of 462 persons (approximately 55% of all who were eligible) agreed to participate and completed the following evaluations. Evaluations Radiography of the Knee Standing anteroposterior and lateral radiographs of both knees of each study participant were obtained, and the severity of osteoarthritis in the tibiofemoral compartment was graded by a musculoskeletal radiologist according to the criteria of Kellgren and Lawrence. Similar criteria, based on the presence of osteophytes and joint space narrowing, were used for the patellofemoral compartment [11]. The radiologist was blinded to the clinical status and characteristics of all patients. A participant had to have a Kellgren and Lawrence grade of 2 or more in either knee to be classified as having osteoarthritis. Knee Pain and Function The Western Ontario and McMaster Universities Arthritis Index was used to evaluate knee pain and function [12]. This index assesses the severity of knee pain during 5 activities or situations (walking on a flat surface, going up or down stairs, at night while in bed, sitting or lying, and standing upright) and the severity of impairment of lower-extremity function during 17 activities. Pain and functional impairment were assessed in each knee separately. Responses to each question about the severity of knee pain and level of impairment were recorded on a categorical scale as none, mild, moderate, severe, or extreme. Each category was assigned a corresponding numeric score from 1 to 5 (5 = extreme). Hence, the range on the pain scale was 5 to 25 and the range on the physical impairment scale was 17 to 85 (85 = greatest functional limitation). For the purposes of analysis, participants who rated the severity of their knee pain as moderate or greater (3) with any of the 5 activities on more than half of the days in the month preceding the evaluation were considered to have knee pain. Thus, pain in the more distant past that had resolved was not included. Participants were also questioned about current and previous regular (5 times per week) or occasional use of over-the-counter and prescription analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) in the past year. Lower-Extremity Muscle Strength The strength of each leg was evaluated by using an isokinetic dynamometer (KIN-COM 500H, Chattecx Corp., Hixson, Tennessee). Peak torque was recorded in both the concentric (contractions during muscle shortening) and eccentric (contractions during muscle lengthening) modes. Participants were allowed several submaximal or maximal practice efforts to familiarize themselves with the operation of the dynamometer. Once formal testing began, the best of three maximal efforts was recorded for flexion and extension at both 60 degrees per second and 120 degrees per second. Aborted efforts were repeated in order to obtain the best possible representation of strength for each participant. Concentric and eccentric testing yielded similar results, but because of greater variability in eccentric testing, only the concentric test results are shown. Lower-Extremity Lean Tissue Mass Total-body dual-energy x-ray absorptiometry was done in all participants by using a Lunar-DPX-L instrument (Lunar Corp., Madison, Wisconsin). Results were analyzed for total and regional body composition, including body fat, mineral, and lean components (lean components were components other than fat or mineral). The right and left lower extremities were analyzed separately. The lower extremity was defined as all tissue below a diagonal line drawn outward and upward from the groin area through the femoral neck. Statistical Analysis Participants were divided into four groups on the basis of presence or absence of radiographic evidence of osteoarthritis of the knee and presence or absence of knee pain, as defined above. Men and women were compared by using the t-test. Comparisons of Arthritis Index pain and functional impairment scores were done by using nonparametric approaches. For analyses of continuous data involving more than two groups of participants (for example, osteoarthritis with or without knee pain), analysis of variance was used to determine whether an overall difference was present. The Fisher protected least-significant-difference procedure was used for pairwise comparisons. Comparisons within participants (for example, comparison of the two legs in a person with unilateral osteoarthritis of the knee) were done by using paired t-tests. Regression models were constructed with the generalized estimating equations approach of Zeger and Liang [13]. This approach inflates the standard errors to adjust for correlations in both independent variables (such as strength) and dependent variables (such as radiographic grade) within participants. Statistically significant differences (P < 0.05) in the above analyses are specifically noted below. Results The characteristics of the 462 men and women in the cohort are shown in Table 1. As expected, men were taller, were heavier, and had greater lower-extremity strength and lean tissue mass in the lower extremities compared with women (P < 0.001 for all comparisons). Table 1. Age, Height, Weight, and Lower-Extremity Strength and Lean Tissue Mass* One hundred forty-five participants (31%; 33% of the women and 30% of the men) had radiographic evidence of osteoarthritis involving the tibiofemoral compartment, the patellofemoral compartment, or both. In 62 participants (43%), the radiographic changes were unilateral. Table 2 shows the association between osteoarthritis and obesity [14-16]. Women in the cohort who had osteoarthritis were approximately 15% heavier than women with normal radiographs and no knee pain. Men with osteoarthritis were also slightly heavier than men without osteoarthritis. Table 2. Body Weight and Summed Arthritis Index Scores for Recent Pain and Function in the Left Knee in Participants with and without Radiographic Evidence of Osteoarthritis* Among those with radiographic evidence of tibiofemoral osteoarthritis, women were slightly more likely than men to report knee pain (P = 0.10; Table 3). Table 3. Radiography and Recent Pain in the Left Knee Table 2 also shows the mean summed and the distribution of scores for left knee pain and functional impairment (data for the right knee were similar). Among men and women with radiographic evidence of osteoarthritis who reported having knee pain, the mean summed pain score for the knee with osteoarthritis was approximately 12 (median score, 2 of 5). In comparison, the mean pain score of participants who reported knee pain but did not have radiographic evidence of osteoarthritis in the painful knee was approximately 10 (median score, 2 of 5)-only slightly lower than the mean pain score of participants with radiographic changes. Consistent with their relatively low pain scores, these community-dwelling participants with osteoarthritis reported moderately low use of NSAIDs (Table 4). Table 4. Participants Reporting Regular Current or Previous Use of Analgesics and Nonsteroidal Anti-inflammatory Drugs Related to the Presence of Radiographic Evidence of Osteoarthritis of the Knee and Recent Knee Pain* Arthritis Index scores for functional impairment paralleled those for pain (Table 2). Participants with osteoarthritis had the greatest functional impairment (P < 0.001 for the comparison with patients who did not have pain or radiographic evidence of osteoarthritis). Functional impairment in participants who had pain but no radiographic evidence of osteoarthrit

Comparison of an Antiinflammatory Dose of Ibuprofen, an Analgesic Dose of Ibuprofen, and Acetaminophen in the Treatment of Patients with Osteoarthritis of the Knee

BACKGROUND The optimal short-term, symptomatic therapy for osteoarthritis of the knee has not been fully determined. Accordingly, we compared the efficacy of a nonsteroidal antiinflammatory drug, ibuprofen, given in either an antiinflammatory dose (high dose) or an analgesic dose (low dose), with that of acetaminophen, a pure analgesic. METHODS In a randomized, double-blind trial, 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day. They were evaluated after a washout period of three to seven days before the beginning of the study, and again after four weeks of treatment. The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Questionnaire (range of possible scores, 0 to 3), scores on the visual-analogue scales for pain at rest and pain while walking, the time needed to walk 50 ft (15 m), and the physicians global assessment of the patients arthritis. RESULTS Seventy-eight percent of the patients completed four weeks of therapy. No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events. All three groups had improvement in all major outcome variables, and the groups did not differ significantly in the magnitude of improvement in most variables. The mean improvement (change) in the scores on the pain scale of the Health Assessment Questionnaire was 0.33 with acetaminophen (95 percent confidence interval, 0.14 to 0.52), 0.30 with the low dose of ibuprofen (95 percent confidence interval, 0.09 to 0.51), and 0.35 with the high dose of ibuprofen (95 percent confidence interval, 0.13 to 0.57). Side effects were minor and similar in all three groups. CONCLUSIONS In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose.

Reduced quadriceps strength relative to body weight: A risk factor for knee osteoarthritis in women?

OBJECTIVE To determine whether baseline lower extremity muscle weakness is a risk factor for incident radiographic osteoarthritis (OA) of the knee. METHODS This prospective study involved 342 elderly community-dwelling subjects (178 women, 164 men) from central Indiana, for whom baseline and followup (mean interval 31.3 months) knee radiographs were available. Lower extremity muscle strength was measured by isokinetic dynamometry and lean tissue (i.e., muscle) mass in the lower extremities by dual x-ray absorptiometry. RESULTS Knee OA was associated with an increase in body weight in women (P = 0.0014), but not in men. In both sexes, lower extremity muscle mass exhibited a strong positive correlation with body weight. In women, after adjustment for body weight, knee extensor strength was 18% lower at baseline among subjects who developed incident knee OA than among the controls (P = 0.053), whereas after adjustment for lower extremity muscle mass, knee extensor strength was 15% lower than in the controls (P not significant). In men, in contrast, adjusted knee extensor strength at baseline was comparable to that in the controls. Among the 13 women who developed incident OA, there was a strong, highly significant negative correlation between body weight and extensor strength (r = -0.740, P = 0.003), that is, the more obese the subject, the greater the reduction of quadriceps strength. In contrast, among the 14 men who developed incident OA, a modest positive correlation existed between weight and quadriceps strength (r = 0.455, P = 0.058). No correlation between knee flexor (hamstring) strength and knee OA was seen in either sex. CONCLUSION Reduced quadriceps strength relative to body weight may be a risk factor for knee OA in women.

Condom Use as a Function of Time in New and Established Adolescent Sexual Relationships

OBJECTIVES This study sought to describe condom use over time in new and established adolescent relationships. METHODS The outcome variable was time (in days) until first unprotected coital event. Analyses involved comparisons of Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS Survival functions for the 2 relationship groups were significantly different. However, by 21 days the curves had converged: 43% of new and 41% of established relationships involved no unprotected coital events. Time to first unprotected coital event was significantly longer in new than in established relationships. CONCLUSIONS Prolongation of condom use in ongoing relationships may be a useful intervention to prevent sexually transmitted diseases.

Repeated Chlamydia trachomatis Genital Infections in Adolescent Women

BACKGROUND Repeated Chlamydia trachomatis infections are common among young sexually active women. The relative frequency of reinfection and antibiotic treatment failure is undefined. METHODS Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessments performed every 3 months, including amplification tests for C. trachomatis, ompA genotyping, and interviews and diary entries to document sex partner-specific coitus and event-specific condom use. Repeated infections were classified as reinfection or treatment failure by use of an algorithm. All infections for which treatment outcomes were known were used to estimate the effectiveness of antibiotic use. RESULTS We observed 478 episodes of infection among 210 study participants; 176 women remained uninfected. The incidence rate was 34 episodes/100 woman-years. Of the women who were infected, 121 experienced 1 repeated infections, forming 268 episode pairs; 183 pairs had complete data available and were classified using the algorithm. Of the repeated infections, 84.2% were definite, probable, or possible reinfections; 13.7% were probable or possible treatment failures; and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated 92.2% effectiveness of antibiotic use. CONCLUSIONS Most repeated chlamydial infections in this high-incidence cohort were reinfections, but repeated infections resulting from treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.

Subsequent sexually transmitted infections among adolescent women with genital infection due to Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis.

OBJECTIVE To identify factors associated with subsequent sexually transmitted infection (STI) (within 1 year of initial infection) due to Chlamydia trachomatis, Neisseria gonorrhoeae or Trichomonas vaginalis. DESIGN Prospective cohort study. SETTING A sexually transmitted diseases clinic and four community-based primary care clinics for adolescents. PARTICIPANTS Female patients (ages 15 to 19 years) with initial diagnosis of chlamydia, gonorrhea, or trichomonas. MAIN OUTCOME MEASURES Subsequent infection by chlamydia, gonorrhea, or trichomonas. RESULTS More than 40% of subjects were subsequently infected by at least one STI. Reinfection was common, but infections with sexually transmitted organisms other than the initial infecting organism were also common. Predictors of subsequent infection were black race, gonorrhea as the initial infection, two or more sex partners in the previous 3 months, and inconsistent condom use. CONCLUSIONS Subsequent STI frequently follow an initial STI, but there is substantial variation in the causal organism. These data suggest the importance of comprehensive STI prevention programs for adolescents rather than organism-specific interventions.

Selecting a patient characteristics index for the prediction of medical outcomes using administrative claims data

Recently, there has been a great deal of discussion regarding the use of administrative databases to study outcomes of medical care. A major issue in this discussion is how to classify patients in terms of characteristics such as disease-severity, comorbidities, resource needs, stability, etc. Different indices have been developed in an attempt to provide a common classification scheme in terms of these characteristics. In this paper, we examine the utility of four indices in the prediction of length of stay and 30-day mortality for patients undergoing total knee replacement surgery between 1985 and 1989. The indices that we compare are the Deyo-adapted Charlson Index, the Relative Intensity Score derived from Patient Management Categories (PMCs), the Patient Severity Level derived from PMCs, and the number of diagnoses (up to five) listed in the Medicare claims data. The first three of these indices represent measures of comorbidity, resource use, and severity of illness, respectively. The number of diagnoses is likely to capture aspects of each of these characteristics. We find that all of the indices improve (in terms of model fit) over the baseline (no index) models of length of stay and mortality, and the Relative Intensity Score and Patient and Severity Level result in the greatest improvement in measures of model fit. We found, however, that these two indices have a non-monotonic relationship with length of stay and mortality. The Deyo-adapted Charlson Index performed least well of the four indices in terms of explanatory ability. The number of diagnoses performed well, and does not suffer from problems associated with miscoding on claims data.

Partner‐specific relationship characteristics and condom use among young people with sexually transmitted diseases

This study describes associations of partner‐specific relationship characteristics with consistent condom use among 297 young people (ages 13–24) with sexually transmitted diseases (STD). Relationship‐specific variables were relationship quality, reasons for sex, relationship duration, duration of sexual relationship, coital frequency, “established” versus “new” sexual partner, cohabitation, children, sexual coercion, and drug or alcohol use associated with coitus. Relationship characteristics associated with consistent condom use included lower relationship quality, lower emotional reasons for sex, lower coital frequency, sex with a new partner, noncohabitation, and not having a child with the partner. Controlling for sociodemographic variables, factors exhibiting independent associations with consistent condom use were lower relationship quality, lower coital frequency, and not having a child with the partner. While condom use with potentially high risk new partners is important, other types of relationships are also risky but associated with lower likelihood of consistent condom use. Better understanding of complex relationship characteristics is necessary to improve STD intervention programs.

Behavioral intervention to increase condom use among high-risk female adolescents.

OBJECTIVE To determine whether condom use among high-risk female adolescents could be increased by a behavioral intervention, with the use of infection with Chlamydia trachomatis as a biomarker of condom practices. DESIGN Prospective, randomized, controlled intervention. SETTING Urban family planning and sexually transmitted disease clinics. PARTICIPANTS Two hundred nine female adolescents, aged 15 through 19 years, who were treated for C. trachomatis genitourinary infection, were randomly assigned to standard (control) or experimental (behavioral intervention) groups. One hundred twelve subjects returned for follow-up 5 to 7 months after enrollment and comprise the study subjects. MEASUREMENTS Subjects completed a multiinstrument questionnaire measuring sexual behavior, condom practices, attitudes and beliefs, cognitive complexity, sociodemographics, and motivation at enrollment and follow-up. Endourethral and endocervical sites were sampled for C. trachomatis. RESULTS Among the 112 subjects who returned for repeated examination, those who had received the experimental intervention reported increased use of condoms by their sexual partners for protection against sexually transmitted diseases (odds ratio = 2.4; p = 0.02) and for vaginal intercourse (odds ratio = 3.1; p = 0.005) at the 6-month follow-up. Multivariable logistic regression analysis controlling for condom use at enrollment demonstrated that the experimental intervention (odds ratio = 2.8; p = 0.03) and the higher cognitive complexity (odds ratio = 4.6; p = 0.02) independently contributed to greater condom use at follow-up. Despite greater use of condoms among the group who had received the intervention, use remained inconsistent and rates of reinfection with C. trachomatis were not significantly different (26% vs 17%; p = 0.3). CONCLUSION Although a brief behavioral intervention among high-risk female adolescents can increase condom use by their sexual partners, incident infection does not appear to be reduced, because condom use remained inconsistent.

Standardization of the experimental model of Haemophilus ducreyi infection in human subjects

Human volunteers were challenged with Haemophilus ducreyi. Twenty subjects were inoculated with 2 doses (approximately 30 cfu) of live and 1 dose of heat-killed bacteria at 3 sites on the arm. Eight subjects were assigned to biopsy 1 or 4 days after inoculation, and 12 were biopsied after they developed a painful pustular lesion or were followed until disease resolved. Papules developed at 95% of 40 sites infected with live bacteria (95% confidence interval [CI], 83. 1%-99.4%). In 24 sites followed to end point, 27% of the papules resolved, 69% (95% CI, 47.1%-86.6%) evolved into pustules, and 4% remained at the papular stage. Recovery rates of H. ducreyi from surface cultures ranged from 13% to 41%. H. ducreyi was recovered from biopsies of 12 of 15 pustules and 1 of 7 papules, suggesting that H. ducreyi replicates between the papular and pustular stages of disease.