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Biomedical subjects

S A Mazzuca

Publications and source records attributed to S A Mazzuca.

At least 19 recordsLinked to original sources
PubMed2006

Association between concentrations of urinary type II collagen neoepitope (uTIINE) and joint space narrowing in patients with knee osteoarthritis.

OBJECTIVE: To examine whether urine concentrations of type II collagen neoepitope (uTIINE) distinguish subjects with progressive radiographic and/or symptomatic knee osteoarthritis (OA) from those with stable disease. METHODS: Subjects were 120 obese middle-aged women with unilateral knee OA who participated in a 30-month randomized-controlled trial of structure modification with doxycycline, in which a standardized semiflexed anteroposterior view of the knee was obtained at baseline, 16 months and 30 months. Subjects were selected from a larger sample to permit a priori comparisons between 60 OA progressors and 60 nonprogressors, as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment. Each group contained 30 subjects who exhibited clinically significant increases in knee pain over 30 months and 30 who did not. Urine samples were obtained every 6 months for determination of the creatinine (Cr)-adjusted uTIINE concentration. RESULTS: Baseline uTIINE levels were unrelated to JSN in the placebo group. However, among subjects in the active treatment group, a 1-standard deviation increment in baseline uTIINE (68 ng/mM Cr) was associated with a marginally significant, two-fold increase in the odds of progression of JSN (odds ratio 2.04, 95% confidence interval 0.98-4.28). The within-subject mean of uTIINE values at baseline, 6 months and 12 months was associated with concurrent JSN measured at 16 months (0.10mm of JSN per 69 ng/mM Cr, P=0.008). Similar results were seen in the interval between months 16 and 30 and in analyses using the maximum of intercurrent uTIINE levels. CONCLUSION: Baseline uTIINE was not a consistent predictor of JSN in subjects with knee OA. However, serial measurements of uTIINE reflect concurrent JSN.

Anti-Bacterial Agents↗
PubMed2005

Urinary levels of type II collagen C-telopeptide crosslink are unrelated to joint space narrowing in patients with knee osteoarthritis.

OBJECTIVE: To determine whether urinary concentrations of the cross linked C-telopeptide of type II collagen (CTx-II) distinguish subjects with progressive radiographic or symptomatic knee osteoarthritis from those with stable disease. METHODS SUBJECTS: were 120 obese women with unilateral knee osteoarthritis who participated in a 30 month, randomised, placebo controlled trial of structure modification by doxycycline, in which a standardised semiflexed anteroposterior view of the knee was obtained at baseline and 30 months. Subjects were selected from a larger sample to permit comparisons of urinary CTx-II levels between 60 progressors and 60 non-progressors with respect to medial joint space narrowing. Each group contained 30 subjects who, across five semi-annual assessments, reported on at least two occasions an increase of > or =20% in 50 ft walk pain (minimum = 1 cm on a 10 cm visual analogue scale), relative to the previous visit. The remainder reported no increases in knee pain. Urine samples were obtained semi-annually for determination of the CTx-II and creatinine concentrations. RESULTS: In an analysis of the placebo group only, the frequency of radiographic progressors in the upper and middle tertiles (48% and 60%, respectively) of the baseline CTx-II distribution was not significantly different than that in the lower tertile (64%). These results were unchanged after inclusion of data from subjects in the doxycycline group. Furthermore, serial CTx-II levels did not distinguish subjects with progressive radiographic or symptomatic knee osteoarthritis from those with stable disease. CONCLUSIONS: In this pilot study, urinary CTx-II concentration was not a useful biomarker of osteoarthritis progression.

Biomarkers↗
PubMed2005

Risk factors for progression of tibiofemoral osteoarthritis: an analysis based on fluoroscopically standardised knee radiography.

OBJECTIVE: To evaluate risk factors for progressive radiographic changes of knee osteoarthritis using a standardised fluoroscopically assisted protocol for knee radiography. METHODS SUBJECTS: (n = 319) with unilateral or bilateral knee osteoarthritis underwent a fluoroscopically standardised x ray examination of the knees (semiflexed AP view) and assessment with the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index at baseline and at 30 months. Tibiofemoral joint space narrowing and osteophytosis were graded in randomly ordered serial radiographs by consensus of two readers using standard pictorial atlases. RESULTS: Progression of joint space narrowing was inversely related to baseline joint space width (odds ratio (OR) = 0.67/1.4 mm (95% confidence interval (CI), 0.49 to 0.91)) and positively associated with patellofemoral osteoarthritis (OR = 3.36 (1.83 to 6.18)). Osteophyte growth was inversely related to overall severity (number and size) of osteophytosis at baseline (OR = 0.47/1.8 points on a 12 point osteophyte severity scale (95% CI, 0.33 to 0.66)), and directly related to baseline stiffness (OR = 1.39/2.1 WOMAC scale points (95% CI, 1.09 to 1.77)) and the presence of patellofemoral osteoarthritis at baseline (OR = 2.31 (1.37 to 3.88)). CONCLUSIONS: Progression of both joint space narrowing and osteophyte growth are predicted by the severity of the respective radiographic features of osteoarthritis at baseline and by the presence of patellofemoral osteoarthritis. In addition, knee stiffness is a risk factor for progressive osteophyte growth.

Aged↗
PubMed2005

Comparison of quantitative and semiquantitative indicators of joint space narrowing in subjects with knee osteoarthritis.

OBJECTIVE: To compare quantitative estimates of change in joint space width (JSW) with semiquantitative ratings of the progression of joint space narrowing (JSN) with respect to sensitivity to change over time. METHODS: 431 obese women 45 to 64 years old with unilateral radiographic knee osteoarthritis were randomised to 30 months' treatment with doxycycline 100 mg twice daily or placebo. Quantitative estimates of change in JSW in the medial tibiofemoral compartment from fluoroscopically assisted semiflexed AP radiographs were obtained at baseline and 16 and 30 months after randomisation. Radiographic JSN was rated (0-3 scale) in the same images by two readers using a standard atlas. Changes in overall severity of knee osteoarthritis were derived from gradings of conventional standing AP radiographs at baseline and 30 months, with blinding to treatment group and chronological order of examination. RESULTS: Follow up radiographs were obtained from 381 subjects (88%) at 16 months and from 367 (85%) at 30 months. The treatment groups did not differ in the frequency of significant loss of JSW by dichotomous criteria (> or =0.5 mm, > or =1.0 mm, > or =20%, or > or =50% of baseline JSW). Progressors and non-progressors, as defined by each of the dichotomous outcomes, differed significantly in mean value for quantitative measurement of change in JSW at 30 months (p< or =0.001). CONCLUSIONS: Quantitative and semiquantitative indicators of progression of osteoarthritis in fluoroscopically standardised radiographs of osteoarthritic knees are highly related, but the effect of doxycycline on articular cartilage thickness was more easily detected with quantitative measurements of change in JSW than with semiquantitative ratings of JSN.

Cartilage, Articular↗
PubMed2003

Development of radiographic changes of osteoarthritis in the "Chingford knee" reflects progression of disease or non-standardised positioning of the joint rather than incident disease.

OBJECTIVE: To ascertain the extent to which the "Chingford knee" (that is, contralateral knee of the middle aged, obese, female patient with unilateral knee osteoarthritis (OA)) is a high risk radiographically normal joint as opposed to a knee in which radiographic changes of OA would have been apparent in a more extensive radiographic examination. METHODS: Subjects were 180 obese women, aged 45-64 years, with unilateral knee OA, based on the standing anteroposterior (AP) view. Subjects underwent a series of radiographic knee examinations: semiflexed AP, supine lateral, and Hughston (patellofemoral (PF)) views. Bony changes of OA were graded by consensus of two readers. Medial tibiofemoral joint space width was measured by digital image analysis. Knee pain was assessed by the WOMAC OA Index after washout of all OA pain drugs. RESULTS: Despite the absence of evidence of knee OA in the standing AP radiograph, only 32 knees (18%) were radiographically normal in all other views. Ninety four knees (52%) exhibited TF knee OA in the semiflexed AP and/or lateral view. PF OA was seen in 121 knees (67%). Subjects with PF OA reported more severe knee pain than those without PF OA (mean WOMAC scores 9.9 v 8.3, p<0.05). CONCLUSION: The Chingford knee is not a radiographically normal joint. The high rate of incidence of OA reported previously for this knee ( approximately 50% within two years) may also reflect progression of existing OA or changes in radioanatomical positioning at follow up that showed evidence of stable disease that was present at baseline.

Acute Disease↗
PubMed2001

Effect of alignment of the medial tibial plateau and x-ray beam on apparent progression of osteoarthritis in the standing anteroposterior knee radiograph.

OBJECTIVE: Previous studies of knee osteoarthritis (OA) have yielded variable estimates of the rate of joint space narrowing (JSN) in the standing anteroposterior (AP) radiograph, due largely to longitudinal changes in the alignment of the medial tibial plateau (MTP) and x-ray beam. To characterize this bias, we examined serial radiographs of subjects with knee OA in population-based and clinical OA cohorts from 3 locations in the United States and the United Kingdom. METHODS: Radiographic features of knee OA (e.g., osteophytosis, JSN) and MTP alignment in 428 OA knees were evaluated by consensus of 2 readers. Alignment was considered satisfactory if the anterior and posterior margins of the MTP were superimposed within 1 mm. Readers were blinded to subject identity, and films were read in random order. The minimum medial joint space width was also measured manually (standard error of repeated measurements 0.20 mm) in serial knee images. RESULTS: Only 14% of serial radiographs exhibited alignment of the MTP in both images. In OA knees with satisfactory alignment in both images, the mean rate of JSN over 2-3 years (0.26 mm/year) was significantly larger (P = 0.004) than that in OA knees with misalignment in 1 or both radiographs and was 86% more rapid than the mean JSN in all OA knees. Moreover, the within-group standard deviation of JSN was significantly smaller among knees with reproduced alignment of the MTP than in knees in which misalignment occurred in 1 or both images (P = 0.006). CONCLUSION: Poor standardization of knee positioning in serial standing AP radiographs in previous studies of OA progression has obscured the rate and variability of articular cartilage loss in subjects with knee OA. True JSN (i.e., JSN that is not attributable to longitudinal changes in the alignment of the MTP with the x-ray beam in serial radiographic examinations) may occur more rapidly, and with less between-subject variability, than that previously thought to be characteristic of knee OA.

Aged↗
PubMed1999

Reduced utilization and cost of primary care clinic visits resulting from self-care education for patients with osteoarthritis of the knee.

OBJECTIVE: To determine the extent to which the cost of an effective self-care intervention for primary care patients with knee osteoarthritis (OA) was offset by savings resulting from reduced utilization of ambulatory medical services. METHODS: In an attention-controlled clinical trial, 211 patients with knee OA from the general medicine clinic of a municipal hospital were assigned arbitrarily to conditions of self-care education (group E) or attention control (group AC). Group E (n = 105) received individualized instruction and followup emphasizing nonpharmacologic management of joint pain. Group AC (n = 106) received a standard public education presentation and attention-controlling followup. A comprehensive clinical database provided data concerning utilization and cost of health services during the following year. RESULTS: Only 25 subjects (12%) were lost to followup. The 94 subjects remaining in group E made 528 primary care visits during the year following intervention, compared with 616 visits by the 92 patients remaining in group AC (median visits 5 versus 6, respectively; P < 0.05). Fewer visits translated directly into reduced clinic costs in group E, relative to controls (median costs [1996 dollars] $229 versus $305, respectively; P < 0.05). However, self-care education had no significant effects on utilization and costs of outpatient pharmacy, laboratory, or radiology services over the ensuing year. The cost per patient to deliver the self-care intervention was estimated to be $58.70. CONCLUSION: Eighty percent of the cost of delivering effective self-care education to the knee OA patients in this study was offset within 1 year by the reduced frequency and costs of primary care visits. For >50% of patients receiving the intervention, the savings associated with fewer primary care visits exceeded the cost of self-care education.

Aged↗
PubMed1999

Plain radiography as an outcome measure in clinical trials involving patients with knee osteoarthritis.

The identification of pharmacologic agents that inhibit matrix metalloproteinase activity and may serve as effective disease-modifying osteoarthritis drugs (DMOADs) in humans has led to interest in the ability of plain radiographic methods to detect early cartilage damage and assess progressive cartilage changes of knee osteoarthritis (OA). Conventional knee radiography lacks sufficient standardization of key elements of the radioanatomic positioning of the knee to avoid significant, probably insurmountable, error variation in the measurement of tibiofemoral joint space width (JSW), the surrogate for the thickness of articular cartilage in radiographic images. Recently, several protocols for the use of fluoroscopy to standardize the radioanatomic position of the knee in a plain radiograph have been shown to afford notably more precise measurement of medial tibiofemoral JSW than can be derived from unstandardized, conventional techniques. A field test of one of these protocols suggests that DMOAD trials with respect to sample size or duration of treatment necessary to detect true OA progression and demonstrate a drug effect may be more feasible.

Antirheumatic Agents↗
PubMed1999

Field test of the reproducibility of automated measurements of medial tibiofemoral joint space width derived from standardized knee radiographs.

OBJECTIVE: To estimate the reproducibility of computerized measurements of minimum joint space width (JSW) in the medial tibiofemoral compartment in knee radiographs (semiflexed AP view) obtained from clinical radiology units. METHODS: Technologists from 5 clinical radiology units were trained in the performance of the fluoroscopically assisted semiflexed AP knee examination. Each of 44 subjects (34 with knee osteoarthritis, OA, 10 with bilaterally normal knees) were examined within 7 days in 2 of the 5 units. The examination in each unit was repeated 1 week later. Minimum JSW was measured on digitized radiographic images with computer software that corrected for radiographic magnification. RESULTS: Despite ongoing quality control by technologists, 11% of radiographs were flawed with respect to the protocol standard for knee rotation and 36% with respect to the standard for knee flexion. The standard error of measurement (SEm) of JSW in 174 knees that were examined twice in the same unit was 0.32 mm (SEm = 0.25 mm for the subset of 76 paired radiographs with uniformly high quality). The overall between-unit SEm was 0.45 mm. Within-unit, but not between-unit, precision was related to the technical quality of the radiographs. Precision was unrelated to subject age, sex, race, weight, and radiographic severity of knee OA. CONCLUSION: The within-unit precision of JSW measurements from all pairs of semiflexed views (irrespective of technical quality) represented a notable improvement over that observed in radiographs with flawed knee rotation or flexion (as would be the case in conventional extended knee views). In future applications of this technique, assurance of technical quality by an independent observer should result in a level of measurement precision that will permit the design of clinical trials of disease modifying OA drugs with fewer subjects and/or shorter duration of treatment than is possible with conventional knee radiography.

Female↗
PubMed1999

Quadriceps strength in women with radiographically progressive osteoarthritis of the knee and those with stable radiographic changes.

OBJECTIVE: To explore the relationship between lower extremity weakness and the progression of established radiographic changes of knee osteoarthritis (OA). METHODS: The study cohort of 342 elderly subjects was recruited from central Indiana by random digit dialing. We analyzed 79 subjects who had definite radiographic changes of unilateral or bilateral knee OA at baseline and for whom baseline data for lower extremity muscle strength and lean tissue mass and baseline and followup assessments of knee pain were available. Radiographs were graded for severity of OA at baseline and again about 2.5 years later (mean 31.5 months). Knee pain was evaluated at the same examination. Strength of the knee flexors and extensors was assessed bilaterally at baseline by isokinetic dynamometry and lower extremity muscle mass by dual energy x-ray absorptiometry. RESULTS: Mean peak knee extensor strength of women with progressive OA, before and after adjustment for lower extremity muscle mass, was about 9% lower than that in those with stable radiographic changes, but this difference was not statistically significant. No difference was apparent between the 2 groups with respect to knee flexor (hamstring) strength. The decrease in quadriceps strength among women with progressive OA, relative to those with stable OA, did not appear to be attributable to knee pain, and knee extensor strength at baseline bore no apparent relationship to the development or progression of knee pain among those with OA. CONCLUSION: We have shown previously that quadriceps weakness may be of etiologic importance in development of knee OA. The absence of a significant difference in quadriceps strength between subjects with radiographically stable OA and those whose joint damage progressed suggests that factors other than quadriceps weakness are more important determinants of OA progression.

Aged↗
PubMed1998

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.

Aged↗
PubMed1997

Effects of self-care education on the health status of inner-city patients with osteoarthritis of the knee.

OBJECTIVE: To evaluate a concise program of self-care education delivered by an arthritis nurse specialist as an adjunct to primary care for inner-city patients with knee osteoarthritis (OA). METHODS: An attention-controlled clinical trial; 211 inner-city patients with knee OA were assigned arbitrarily to education (E) or attention-control (AC) conditions. Group E received an individualized 30-60-minute educational intervention that emphasized nonpharmacologic management of joint pain, preservation of function by problem-solving, and practice of principles of joint protection. Brief telephone contacts 1 week and 4 weeks later monitored and reinforced new self-care activities. Group AC viewed a 20-minute standardized public education presentation on arthritis and received followup telephone calls (only to encourage continued participation in the study). Outcomes included the Health Assessment Questionnaire (HAQ) Disability and Discomfort Scales, 10-cm visual analog scales measuring knee pain at rest and while walking, and the Quality of Well-Being (QWB) scale. Assessments were made at baseline and at 4-month intervals for 1 year. RESULTS: A total of 165 subjects (78%) completed all assessments. After control for baseline status, group E had significantly lower scores for disability and resting knee pain throughout the year of postintervention followup (P < 0.05 for both). Effects were somewhat discordant. By 12 months, functional benefits had begun to wane, while the effect on resting knee pain had grown. The overall effects of education on walking knee pain, overall joint pain (by HAQ), and general health status (by QWB) were not significant. CONCLUSION: Self-care education for inner-city patients with knee OA, delivered as an adjunct to primary care, was found to result in notable preservation of function and control of resting knee pain. The magnitude of the observed effects compares well with those of more labor-intensive and time-consuming intervention models. However, more sustained preservation of function and consistent effects on pain may require prolonged, more proactive followup, either by the patient educator or by a trained clinical assistant dedicated to the task of supporting self-care by patients with knee OA.

Aged↗
PubMed1997

Comparison of general internists, family physicians, and rheumatologists managing patients with symptoms of osteoarthritis of the knee.

OBJECTIVE: To evaluate the nature, risks, and benefits of osteoarthritis (OA) management by primary care physicians and rheumatologists. METHODS: Subjects were 419 patients followed for symptoms of knee OA by either a specialist in family medicine (FM) or general internal medicine (GIM) or by a rheumatologist (RH). Management practices were characterized by in-home documentation by a visiting nurse of drugs taken to relieve OA pain or to prevent gastrointestinal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and by patient report (self-administered survey) of nonpharmacologic treatments. Changes in outcomes (knee pain and physical function) over 6 months were measured with the Western Ontario and McMaster Universities Osteoarthritis Index. RESULTS: Patients of RHs were 2-3 years older (P = 0.035) and tended to exhibit greater radiographic severity of OA (P = 0.064) and poorer physical function (P = 0.076) at baseline than the other 2 groups. In all 3 groups, knee pain and physical function improved slightly over 6 months; however, between-group differences were not significant. Compared to drug management of knee pain by FMs or RHs, that by the GIMs was distinguished by greater utilization of acetaminophen and nonacetylated salicylates (P = 0.008), lower prescribed doses of NSAIDs (P = 0.007), and, therefore, lower risk of iatrogenic gastroenteropathy (P < 0.001). In contrast, patients of RHs were more likely than those of FMs and GIMs to report that they had been instructed in use of isometric quadriceps and range-of-motion exercises (P < or = 0.001), application of heat (P = 0.051) and cold (P < 0.001) packs, and in the principles of joint protection (P = 0.016). Neither physician specialty nor specific management practices accounted for variations in patient outcomes. CONCLUSION: This observational study identified specialty-related variability in key aspects of the management of knee OA in the community (i.e., frequency and dosing of NSAIDs, use of nonpharmacologic modalities) that bear strong implications for long-term safety and cost. However, changes in knee pain and function over 6 months were unrelated to variations in management practices.

Activities of Daily Living↗
PubMed1994

Clinical rheumatology training in an uncertain future. Opinions of recent and current rheumatology fellows about an extended fellowship in musculoskeletal medicine.

OBJECTIVE: To estimate among recent and current rheumatology fellows the appeal of a 3-year rheumatology fellowship emphasizing musculoskeletal medicine. METHODS: A survey of 348 trainee members of the American College of Rheumatology during 1990-1993, by mailed questionnaire. RESULTS: The response rate was 77.8% (n = 271). Both recent and current fellows indicated that they desired more experience in musculoskeletal medicine. Most notably, 50% of current fellows, and a significantly higher proportion of recent fellows (70%; P < 0.005), indicated that they would have opted for a 3-year fellowship in musculoskeletal medicine had one been available to them at the completion of their residency. CONCLUSION: Expertise in musculoskeletal medicine is desired by a sufficient proportion of recent and current rheumatology fellows to warrant the investment in another year of training.

Attitude of Health Personnel↗
PubMed1994

Education and behavioral and social research in rheumatology.

In this review, recent research on educational and psychosocial issues in rheumatology are interpreted in light of the prospects for reforms in health care delivery in the United States. Increased emphasis on primary care will prompt a reappraisal of the training of medical students and primary care residents in the diagnosis, management, and referral of patients with rheumatologic conditions. Evidence of the economic benefits of arthritis self-care education has begun to appear and, if it continues to accumulate, will help assure the availability of such interventions for arthritis patients. Finally, further understanding of the psychosocial impact of musculoskeletal pain and impairment will better enable us to prevent the disability that is a large and growing drain on the American economy.

Delivery of Health Care↗