Katherine M. Skinner

The association of bone marrow lesions with pain in knee osteoarthritis.

Knee osteoarthritis affects 11% to 15% of the U.S. population 65 years of age or older (1) and is a leading cause of disability in the elderly. The major source of disability and care seeking for patients with osteoarthritis is pain in the knee (2). The cause of knee pain in patients with osteoarthritis is unclear. Osteoarthritis has been considered a disease whose characteristic pathologic feature is loss of hyaline articular cartilage, but that tissue contains no pain fibers. Pain fibers are present in several other structures, however, that are often affected by pathologic processes in knee osteoarthritis, including the joint capsule, ligaments in and around the knee joint, the outer third of the meniscus, and possibly the synovium (although for this last tissue, evidence is conflicting [3, 4]). In addition, bone in the periosteum and bone marrow is richly innervated with nociceptive fibers and represents a potential source of pain in patients with knee osteoarthritis. In athletes and younger adults who do not have osteoarthritis, traumatic knee injuries produce high-signal lesions in the medullary space extending to subcortical bone according to T2-weighted magnetic resonance imaging (MRI). These lesions are thought to represent contusions within the bone marrow and have been correlated with the occurrence of pain in athletes (5). Bone marrow lesions that are similar in appearance to those contusions have been noted (6) in patients with knee osteoarthritis, but their association with the occurrence of pain in this disease is unknown. The treatment of pain in osteoarthritis has been frustrating, in part because the target of therapy is unclear. Creamer and colleagues (7) injected intra-articular anesthetic into joints and found that only 6 of 10 persons with painful osteoarthritis had pain relief. This suggests that in some patients, pain originates from extraarticular, noncapsular sources, one of the most likely of which is bone. If pain in some patients does emanate from bone, this finding would have important therapeutic implications and suggests that for these patients, anti-inflammatory treatments targeted at synovitis or intra-articular drainage to relieve capsular distention would be ineffective. We sought to evaluate whether persons with knee pain and osteoarthritis were more often affected by bone marrow lesions than similarly aged persons without knee pain, many of whom also had radiographic knee osteoarthritis. We tested whether pain in the knee was associated with the presence of bone marrow lesions after adjustment for the severity of radiographic osteoarthritis. In addition, among persons with symptomatic knee osteoarthritis, we evaluated whether the severity of their pain was associated with the presence of these lesions. Methods Patient Selection The minimum age for entry into the study was 45 years for men and 50 years for women. The entry age for women was chosen to lessen the chance of inadvertently obtaining radiographs in pregnant women. Male participants were drawn from the Veterans Health Study (VHS), a prospective observational study of health outcomes in 2425 veterans (8). Participants in the VHS were recruited from all men receiving ambulatory care between August 1993 and March 1996 at four Veterans Administration system facilities in the Boston area. Veterans who indicated that they could not read, were identified as unable to answer questions by an accompanying proxy, were disoriented, or did not complete the screening questionnaire were ineligible. A random sample of eligible respondents was contacted by telephone and recruited for the VHS. Of the 4137 patients who were telephoned, 2425 (59%) participated in the VHS. Participant age ranged from 22 to 91 years (mean, 62.4 years). The VHS was designed to be representative of users of ambulatory care in the Veterans Administration system. Compared with all utilizers of the Veterans Administration health care system, the sample underrepresented patients with less education or limitations in literacy or cognitive functioning. Patients in the VHS had lower functional status scores on the physical and mental health components of the Short Form-36 survey (a measure of health status) and had more comorbid conditions (8) than do men 45 years of age or older in the general U.S. population. Male participants were also drawn separately from Veteran Affairs clinics and from the community. Female participants were drawn from clinics at Boston Medical Center and the Veterans Affairs Medical Center; from advertisements in local newspapers; and from a study of women veterans, the Veterans Administration Womens Health Project (n = 719), that was designed to describe the health status of female veterans using ambulatory health care services. The human studies committee and the institutional review board approved protocols. Informed consent was obtained from all participants. All participants were surveyed about knee symptoms. They were asked two questions: Do you have pain, aching, or stiffness in one or both knees on most days? and Has a doctor ever told you that you have knee arthritis? For persons interested in participating in our study of knee pain and osteoarthritis, we conducted a follow-up interview in which those who answered yes to both questions were asked about other types of arthritis that could cause knee symptoms. If no other forms of arthritis were identified in the interview, the person was eligible for recruitment as a participant with knee pain (which we characterize here as knee symptoms). Figure 1 is a flow diagram of the source of participants. Of our male participants, 151 came from the Veterans Health Study, 76 came from Veterans Administration ambulatory clinics, and 8 came from the community. Of our female participants, 18 came from the Veterans Administration Womens Health Project, 9 came from ambulatory clinics, and 89 came from the community. Figure 1. Sources of study participants. We recruited participants from the VHS and the Veterans Administration Womens Health Project without knee pain from among those who answered no to both of the above screening questions (Figure 1). We also asked participants to evaluate the severity of pain in each knee, which they scored by using a 100-mm visual analogue scale (generating a score of 0 [no pain] to 100 [most severe pain possible]). Participants also filled out the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) questionnaire (9), a validated instrument that assesses knee pain and disability during various activities; we analyzed their WOMAC pain subscale score. Radiographic Evaluation All participants underwent weight-bearing posteroanterior radiography by using the protocol of Buckland-Wright (10 and weight-bearing skyline [9] and weight-bearing lateral radiography (11). For the posteroanterior view, the knee was positioned and radiographed under fluoroscopy so that the anterior and posterior medial tibial plateaus were superimposed; this was done to optimize measurement of joint space. Radiographs were read for the presence of definite osteophytes and other features by one radiologist using an atlas. If a definite osteophyte was present in a knee (including the patella) on any one of the three views, the knee was characterized as having osteoarthritis regardless of whether the participant experienced symptoms. This definition of radiographic disease has been recommended by other investigators (22). On the basis of responses to the screening questions, we defined a knee as symptomatic if the participant stated that he or she had pain or aching in that knee on most days. This definition of symptomatic osteoarthritis meets American College of Rheumatology criteria (12). We identified too few symptomatic persons without a radiographic osteophyte to include them as a separate study group (n = 4) and therefore excluded them; we also excluded 16 participants without knee pain whose radiographs showed no osteophytes. Kellgren and Lawrence grades have been developed for the anteroposterior (posteroanterior) view. We therefore assigned Kellgren and Lawrence grades (0 to 4) on this view only. In addition, we read posteroanterior, skyline, and lateral radiographic views and scored them for individual radiographic featuresosteophytes (scale of 0 to 3), joint space narrowing (scale of 0 to 3), cysts (scale of 0 to 1), and sclerosis (scale of 0 to 3)by using the Framingham Osteoarthritis Study atlas (13). The reproducibility of readings of these features and of the Kellgren and Lawrence scale is reported elsewhere (14). Magnetic Resonance Imaging Each person with knee pain underwent MRI of the more symptomatic knee. For persons without knee pain, the dominant knee was selected for imaging. All studies were performed on a General Electric Signa 1.5-Tesla MRI system (GE Medical Systems, Milwaukee, Wisconsin) using a phased-array knee coil. A positioning device for the ankle and knee was used to ensure uniformity between patients. Coronal, sagittal, and axial images were obtained in each participant. Coronal spin-echo fat-saturated proton-density and T2-weighted fat-saturated images (repetition time, 2200 ms; echo time, 20/80 ms) with a slice thickness of 3 mm, a 1-mm interslice gap, 1 excitation, a field of view of 11 to 12 cm, and a matrix of 256 128 pixels were obtained. To evaluate bone marrow lesions on MRI, we used coronal spin-echo T2-weighted fat-saturated images. Each femur and tibia was divided into medial, central, and lateral quadrants, resulting in six potential sites of lesions in each knee. We defined bone marrow lesions as discrete areas of increased signal adjacent to the subcortical bone in either the femur or the tibia, and we scored each bone marrow lesion from 0 to 3 on the basis of lesion size (Figure 2). Lesions with a score of at least 1 were considered definite bone marrow lesions, and lesions with a score of at least 2 were considered larg

Prevalence of depressive and alcohol abuse symptoms among women VA outpatients who report experiencing sexual assault while in the military

Among a national sample of 3,632 women VA outpatients, we determined self-reported prevalence of sexual assault experienced during military service and compared screening prevalence for current symptoms of depression and alcohol abuse between those who did and did not report this history. Data were obtained by mailed questionnaire. Military-related sexual assault was reported by 23%. Screening prevalence for symptoms of current depression was 3 times higher and for current alcohol abuse was 2 times higher among those who reported experiencing military-related sexual assault. Recent mental health treatment was reported by 50% of those who reported experiencing sexual assault during military service and screened positive for symptoms of depression, and by 40% of those who screened positive for symptoms of alcohol abuse.

Improving the response choices on the veterans SF-36 health survey role functioning scales: results from the Veterans Health Study.

Abstract:Role functioning and its limitations due to ones health is an important aspect of health-related quality of life (HRQoL). The Medical Outcomes Study (MOS) SF-36 includes 2 role functioning scales: role limitations due to physical health problems (RP) or emotional problems (RE). Although they capture important concepts of HRQoL, these 2 scales have some limitations in their measurement properties. Using dichotomized sets of response choices, the scales are limited in their distributional properties (eg, higher standard deviation than other SF-36 scales) and ability to discriminate between clinically relevant groups. In this study, we ascertain the improvements to these 2 scales using 5-point ordinal response choices for each of the scale items. Two thousand one hundred sixty-two patients from the Veterans Health Study (VHS), an observational study of health outcomes in patients receiving ambulatory care, completed a health status questionnaire and a medical history. The health questionnaire included (1) the MOS SF-36, in which the RP and RE items used dichotomized yes/no responses; and (2) a set of modified RP and RE items that used 5-response choices for each of the items, ranging from “no, none of the time” to “yes, all of the time.” We compared the original and modified RP and RE scales using internal consistency reliability and factor analysis. We tested item convergent and discriminant validity using multitrait scaling, and scale discriminant validity using ordinary least squares regression. Results indicate that the modifications to the original RP and RE scales accomplish important gains in the distributional properties of the scales. The floor and ceiling effects of the 2 scales have been reduced and the reliability of the RP scale has increased (0.87–0.95). Factor analysis and multitrait scaling tests indicate that the modified items have the same interpretation as the original items. Tests of discriminant validity indicate that the modified RP and RE scales have greater explanatory power for measures of disease burden, depression, and disease severity. The modified SF-36 role scales are clearly superior to the original versions. The modifications have increased the explained variability, suggesting greater explanatory power and more information obtained by the role functioning measures. The modified RP and RE are capturing a wider spectrum of disease severity, in part due to the lowering of the floor and raising of the ceiling of the scales. Additional work needs to test these improvements in other populations and to expand the analysis to track the responsiveness of the modified scales to clinically and socially important changes over time.

Social support, social selection and self-assessed health status : results from the veterans health study in the United States

This study provided a comprehensive assessment of the association between social support and health using longitudinal data from the Veterans Health Study. Unlike previous studies which examined the relationship between one single domain of social support with either mental or physical health, the present study assessed the effects of three different domains of social support on multiple measures of health. The findings of the study indicated that social support tended to mediate the deleterious effects of non-military traumatic events; whereas the adverse consequences of traumatic events experienced in the military were not affected by social support, suggesting that stressors associated with combat had a long lasting effect on the health status of veterans. The study results revealed that compared with those with better health, respondents with poor health were more likely to have lower levels of social support, suggesting that poor health might be a barrier to a persons ability to participate and/or maintain social relationships. The study also showed that different types of social support had varying beneficial effects on different measures of health. While perceived support had a strong effect on all the measures of health (except alcoholism) included in the study, living arrangement had a significant effect on post-traumatic stress disorder or physical health and participation in group activities had a strong effect only on physical functioning. The results of the study highlight the need for future research to determine whether particular types of social support affect various aspects of health differently. This simultaneous focus on multiple support functions and health outcomes is important because it provides insight into the mechanisms linking social support to health.

Patient-reported measures of health: The Veterans Health Study.

Abstract:The goal of the Veterans Health Study (VHS) was to extend the work of the Medical Outcomes Study (MOS) into the VA, by developing methodology for monitoring patient-based outcomes of care for use in ambulatory outpatient care. The principal objective of the VHS was developing valid and reliable measures to assess general health-related quality of life (HRQoL) and identifying the presence of selected health conditions, their severity, and their impact on HRQoL. In this article, we provide an overview of the historical context, framework, objectives, and applications of the VHS for the purpose of assessing the health outcomes of veteran patients. The VHS is a prospective observational study that has followed 2425 VA patients for up to 2 years. The patients were sampled from users of the Veterans Affairs (VA) ambulatory care system in the Boston area. The health conditions selected were hypertension, diabetes, chronic lung disease, osteoarthritis of the knee, chronic low-back pain, and alcohol-related problems. These conditions were chosen because they are both prevalent in the VA and have measurable impacts on HRQoL. One of the cornerstones of the VHS was the development of the Veterans SF-36, modified from the MOS SF-36 for use in veteran ambulatory populations. Other key accomplishments included the development of patient-based disease-specific measures of health and the establishment of methods and logistics for comprehensive health outcomes research in large health care systems such as the VA, using these patient-based measures. Selected measures developed in the VHS, eg, the Veterans SF-36, have been integrated into the VA outcomes measurement system. The scope of the VHS is unique; it resulted in the development of a broad range of patient-focused process and outcome measures, as well as methodologies for assessing large numbers of patients, that have been widely used in the VA outpatient health care system for monitoring health outcomes across the nation.

Health status among 28,000 women veterans. The VA Women's Health Program Evaluation Project.

AbstractBACKGROUND: Male veterans receiving Veterans Health Administration (VA) care have worse health than men in the general population. Less is known about health status in women veteran VA patients, a rapidly growing population. OBJECTIVE: To characterize health status of women (vs men) veteran VA patients across age cohorts, and assess gender differences in the effect of social support upon health status. DESIGN AND PATIENTS: Data came from the national 1999 Large Health Survey of Veteran Enrollees (response rate 63%) and included 28,048 women and 651,811 men who used VA in the prior 3 years. MEASUREMENTS: Dimensions of health status from validated Veterans Short Form-36 instrument; social support (married, living arrangement, have someone to take patient to the doctor). RESULTS: In each age stratum (18 to 44, 45 to 64, and ≥65 years), Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were clinically comparable by gender, except that for those aged≥65, mean MCS was better for women than men (49.3 vs 45.9, P<.001). Patient gender had a clinically insignificant effect upon PCS and MCS after adjusting for age, race/ethnicity, and education. Women had lower levels of social support than men; in patients aged <65, being married or living with someone benefited MCS more in men than in women. CONCLUSIONS: Women veteran VA patients have as heavy a burden of physical and mental illness as do men in VA, and are expected to require comparable intensity of health care services. Their ill health occurs in the context of poor social support, and varies by age.

Comparing the health status of VA and non-VA ambulatory patients: the veterans' health and medical outcomes studies.

Abstract:The purpose of this study was to compare health status and disease profiles of ambulatory patients in specific Veterans Administration (VA) and civilian healthcare settings. A random sample of 2425 male veterans seeking care at 4 Boston-area VA outpatient clinics, who took part in the Veterans Health Study (VHS) in 1993–1995, were compared to 1318 male patients seeking civilian outpatient care in 3 major metropolitan areas covered in the Medical Outcomes Study (MOS) in 1986. The MOS sampled patients who had 1 of 5 conditions—hypertension, non–insulin-dependent diabetes, recent myocardial infarction, congestive heart failure, or depression. These 2 samples were age adjusted and compared in terms of the SF-36 Health Status/Quality of Life measures, and a list of 100 clinical variables (diagnostic, symptom, and medical event reports) collected with comparable instruments by a trained clinical observer. Individual odds ratios (VHS to MOS) were calculated for each measure and clinical variables. SF-36 measures of patient health in the VHS were lower than those in the MOS by more than one half of a standard deviation (SD) on 4 of 8 scales, by more than one quarter of a SD on the other 4, by 58% of a SD on the physical health summary scale, and by 37% of a SD on the mental health summary scale (P < .0001 in all cases). The median odds ratio was 2.2 among the SF-36 scales and 1.9 among clinical variables. Outpatients in the 4 VA clinics had more than twice the illness burden than did patients in the MOS. Current economic condition and service-connected disability explain most, if not all, of the differences. The differences were clinically and socially meaningful and would be consistent with substantially higher expected healthcare use.

Health Status among Women with Menstrual Symptoms

PURPOSE Chronic diseases have been associated with decrements in health status, as measured by the Medical Outcomes Studys Short Form-36 (SF-36). Menstrual symptoms (including irregular menses, menorrhagia, dysmenorrhea and premenstrual symptoms) are common, but little is known about their impact on health status. We sought to determine the prevalence of menstrual symptoms and the degree to which these symptoms affect health status. METHODS This was a mailed survey including questions about sociodemographic characteristics, military experiences, current physical symptoms and medical conditions, mental health, health status (SF-36), and life experiences. The participants were a nationally representative, randomly selected sample of women veterans who had made at least one ambulatory visit to a Veterans Affairs facility between July 1, 1994 and June 30, 1995. The main outcome measures were eight domains of the SF-36 health status questionnaire. RESULTS Among 3632 respondents (58.4% response rate), 1744 were menstruating women and formed the analytical sample for this study. Among these women (mean age 35.8), 67% reported one or more menstrual symptoms. Women with menstrual symptoms had significantly lower scores for all domains of the SF-36 (p < 0.01), except energy and vitality (p < 0.05), both before and after adjusting for sociodemographic, psychosocial, and comorbidity variables. CONCLUSIONS Women veterans who report one or more menstrual symptoms have significantly lower health status compared with those reporting none. Clinicians providing care for women should be attuned to the potential impact of menstrual symptoms on the lives of their patients.

Applications of methodologies of the Veterans Health Study in the VA healthcare system: conclusions and summary.

The Veterans Health Study (VHS) had as its overarching goal the development, testing, and application of patient-centered assessments for monitoring patient outcomes in ambulatory care in large integrated care systems such as the Department of Veterans Affairs (VA). Unlike other previous studies, the VHS has capitalized on rich administrative databases restricted to the VA and linked to patient-centered outcomes. The VHS has developed a comprehensive set of general and disease-specific measures for use by systems of care for ambulatory patients. Chief among these assessments is the Veterans SF-36 Health Survey for measuring health-related quality of life in veteran ambulatory populations. The Veterans SF-36 Health Survey provides the cornerstone for this study and historically has been extensively disseminated and used in the VA with close to 2 million administrations nationally as part of its quality management system. National surveys administered by the VA since 1996 using the Veterans SF-36 Health Survey indicate important regional differences with implications for varying resource needs. Based upon the rich foundation provided by the VHS methodology, the VA has implemented some of these approaches as part of its quality monitoring system and can serve as a model for other large integrated systems of care.

Comparing generic and disease-specific measures of physical and role functioning: results from the Veterans Health Study.

OBJECTIVES This study compared the performance of generic measures of Medical Outcome Study Short Form 36-Item Health Survey physical functioning and role limitations with disease-specific measures of physical functioning and role limitations using specific disease attributions for chronic lung disease, chronic low back pain, and osteoarthritis of the knee. METHODS Data were analyzed from the Veterans Health Study among patients receiving Veterans Administration ambulatory care. Patients identified as having one of the three study conditions were included in the study (n = 932). RESULTS The study revealed that the generic physical functioning and role limitations scales had higher correlations with other generic SF-36 scales, whereas disease-specific attribution measures had larger R2 values in explaining variability in symptom-based disease severity and larger t statistic values in discriminating the impacts of patients taking medications and having surgery. CONCLUSIONS The generic measures of physical functioning and role limitations were more applicable in assessing a broad array of health-related quality-of-life issues, whereas disease-specific measures of physical functioning and role limitations were more useful in evaluating clinical management and limitations associated with specific disease conditions. The results of the study suggest that the use of disease-specific attribution assessments was more cost-efficient than the development of new disease-specific instruments. Disease-specific attribution could be used to complement generic measures in assessing patient outcomes.