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Leena Sharma

Publications and source records attributed to Leena Sharma.

At least 19 recordsLinked to original sources
PubMed2006

Lower extremity nerve function in patients with lower extremity ischemia.

BACKGROUND: We determined whether lower extremity ischemia, as measured by the ankle brachial index (ABI), is associated with impaired lower extremity nerve function. METHODS: Participants included 478 persons with peripheral arterial disease (PAD) identified from noninvasive vascular laboratories and 292 persons without PAD identified from a general medicine practice and noninvasive vascular laboratories. Peripheral arterial disease was defined as an ABI lower than 0.90 (mild PAD: ABI, 0.70 to <0.90; moderate PAD: ABI, 0.50 to <0.70; and severe PAD: ABI, <0.50). The ABI and electrophysiologic measures of the peroneal, sural, and ulnar nerves were obtained. RESULTS: Among 546 participants without diabetes, PAD participants had significantly impaired peripheral nerve function in the upper and lower extremities compared with non-PAD participants. After adjusting for age, sex, race, smoking, height, body mass index, recruitment source, alcohol use, disk disease, spinal stenosis, cardiac disease, and cerebrovascular disease, these associations were not statistically significant. After adjusting for confounders among nondiabetic participants, those with severe PAD (ABI, <0.50) had poorer peroneal nerve conduction velocity (NCV) compared with participants without PAD (42.6 vs 44.8 m/s; P = .003) and poorer peroneal NCV compared with participants with mild PAD (42.6 vs 45.0 m/s; P = .001) or moderate PAD (42.6 vs 44.1 m/s; P = .03). Among 224 participants with diabetes, after adjusting for confounders, PAD was associated with poorer peroneal NCV (40.8 vs 43.5 m/s; P = .01), sural nerve amplitude (3.1 vs 4.8 muV; P = .045), and ulnar NCV (47.6 vs 50.2 m/s; P = .03) compared with those without PAD. CONCLUSIONS: Our findings suggest that leg ischemia impairs peroneal nerve function. This association is less strong in patients with diabetes, perhaps because of the overriding influence of diabetes on peripheral nerve function. Clinicians should consider screening for PAD in patients with idiopathic peroneal nerve dysfunction. Peripheral arterial disease-associated nerve dysfunction may contribute to PAD-associated functional impairment.

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PubMed2006

Epidemiology of osteoarthritis: an update.

Osteoarthritis is the most common form of arthritis and is a leading cause of disability in the elderly. Given the anticipated increase in osteoarthritis prevalence, the need to identify risk factors for incident osteoarthritis, osteoarthritis progression, osteoarthritis-associated physical function decline, and disability is an especially high priority. Findings have implicated several factors, including genetic factors, aging, joint deformity and injury, obesity, and hormonal deficiencies in the pathogenesis of osteoarthritis. Recent studies have identified risk factors associated with progression of the disease including varus-valgus alignment, bone marrow edema lesions, varus thrust, a reduced hip abduction moment, and obesity. Predictors of function decline in osteoarthritis include lower self-efficacy, knee laxity, less aerobic exercise, worse joint proprioception, and greater knee pain.

Age Factors↗
PubMed2006

Long-term impact of Fit and Strong! on older adults with osteoarthritis.

PURPOSE: We present final outcomes from the multiple-component Fit and Strong! intervention for older adults with lower extremity osteoarthritis. DESIGN AND METHODS: A randomized controlled trial compared the effects of this exercise and behavior-change program followed by home-based reinforcement (n=115) with a wait list control (n=100) at 2, 6, and 12 months. Fit and Strong! combined flexibility, aerobic walking, and resistance training with education and group problem solving to enhance self-efficacy for exercise and maintenance of physical activity. All participants developed individualized plans for long-term maintenance. RESULTS: Relative to controls, treatment participants experienced statistically significant improvements in self-efficacy for exercise (p=.001), minutes of exercise per week (p=.000), and lower extremity stiffness (p=.018) at 2 months. These benefits were maintained at 6 months and were accompanied by increased self-efficacy for adherence to exercise over time (p=.001), reduced pain (p=.040), and a marginally significant increase in self-efficacy for arthritis pain management (p=.052). Despite a substantially smaller sample size at 12 months, significant treatment-group effects were maintained on self-efficacy for exercise (p=.006) and minutes of exercise per week (p=.001), accompanied by marginally significant reductions in lower extremity stiffness (p=.056) and pain (p=.066). No adverse health effects were seen. Effect sizes for self-efficacy for exercise and for maintenance of physical activity were 0.798 and 0.713, and 0.905 and 0.669, respectively, in the treatment group at 6 and 12 months. IMPLICATIONS: This consistent pattern of benefits indicates that this low-cost intervention is efficacious for older adults with lower extremity osteoarthritis.

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PubMed2006

Epidemiology of osteoarthritis: an update.

PURPOSE OF REVIEW: As the most common arthritis and a leading cause of chronic disability, osteoarthritis is associated with substantial cost to the individual and to society. Epidemiologic studies have supplied, in addition to incidence, prevalence and risk factor data, much of what is known about the natural history of osteoarthritis. RECENT FINDINGS: Especially given the anticipated increase in osteoarthritis prevalence, the need to identify risk factors for incident osteoarthritis, osteoarthritis progression, osteoarthritis-associated physical function decline, and disability is a high priority. As this review illustrates, the emphasis has shifted in osteoarthritis epidemiology towards the identification of risk factors for osteoarthritis progression rather than incidence. SUMMARY: Several risk factors for progression are emerging, many of which are impairments or pathology in the local joint organ environment. This shift in focus relates in part to the concept that local risk factors might ultimately be targeted to delay osteoarthritis progression or to enhance the effect of a disease-modifying drug.

Aging↗
PubMed2005

Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment. METHODS: In this placebo-controlled trial, obese women (n = 431) ages 45-64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6-month intervals. RESULTS: Seventy-one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean +/- SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 +/- 0.42 mm versus 0.24 +/- 0.54 mm); after 30 months, it was 33% less (0.30 +/- 0.60 mm versus 0.45 +/- 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a > or = 20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a > or = 20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase. CONCLUSION: Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.

Anti-Infective Agents↗
PubMed2005

The natural history of anteroposterior laxity and its role in knee osteoarthritis progression.

OBJECTIVE: To test the hypotheses that 1) osteoarthritic (OA) knees at more advanced stages have less anteroposterior (AP) laxity compared with OA knees at milder stages, 2) AP laxity decreases over time, and 3) the absence of a decrease in AP laxity is associated with greater progression of medial tibiofemoral OA. METHODS: The study group comprised 230 patients with knee OA (75% women, mean age 64 years, mean body mass index [BMI] 30 kg/m(2)). At baseline and 18 months, AP laxity was measured (in millimeters of tibial translation, under AP shear loading), and semiflexed AP knee radiographs (with knee position confirmed by fluoroscopy) were obtained. Osteophytes were graded for each compartment, using a scale of 0-4. Disease progression was measured as the amount of medial joint space loss between baseline and followup, using linear regression with generalized estimating equations. RESULTS: At baseline, measurements of AP laxity were lower in knees with a Kellgren/Lawrence (K/L) score of 4 (mean +/- SD 5.0 +/- 2.1 mm) than in those with a K/L score of 0-1 (mean +/- SD 7.1 +/- 2.6 mm). There was a weak negative correlation between osteophyte grade and AP laxity. In knees with a K/L score of 0-2, AP laxity was slightly lower at 18 months than at baseline. AP laxity at baseline was not a predictor of progression of OA. Knees without a decrease in AP laxity had a greater loss of medial joint space (0.22 mm greater, after adjusting for age, sex, and BMI) than did knees in which laxity decreased. CONCLUSION: AP laxity at baseline is not predictive of progression of OA. Although knees with a K/L score of 4 had less AP laxity than those with a K/L score of 0-1, most of this difference was attributable to the significant difference in AP laxity between knees with a K/L score of 0-1 and knees with a K/L score of 2 (i.e., definite osteophytes). Knees in which AP laxity decreased had less medial joint space loss than did knees without a decrease in AP laxity. The knee joint may successfully compensate for AP laxity; the absence of such compensation may have a deleterious effect.

Arthrography↗
PubMed2005

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage in knee osteoarthritis: findings at different radiographic stages of disease and relationship to malalignment.

OBJECTIVE: Delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) is used to examine the distribution of glycosaminoglycan in cartilage. This study sought to characterize dGEMRIC in the evaluation of knee osteoarthritis (OA) according to various radiographically determined disease parameters, and to examine the relationship between alignment of the knee joint and the lateral:medial dGEMRIC ratio. METHODS: Thirty-one patients with knee OA underwent MRI with a dGEMRIC protocol at 1.5T. Semiflexed knee radiographs and full-limb radiographs were also obtained for assessment of alignment. RESULTS: Compartments of the knee joint without joint space narrowing had a higher dGEMRIC index than those with any level of narrowing (mean 408 msec versus 365 msec; P = 0.001). In knees with 1 unnarrowed (spared) and 1 narrowed (diseased) compartment, the dGEMRIC index was greater in the spared versus the diseased compartment (mean 395 msec versus 369 msec; P = 0.001). In spared compartments, there was a trend toward a lower dGEMRIC index with increasing Kellgren/Lawrence (K/L) radiographic severity grade; the spared compartments of knees with a K/L grade 2 had a higher dGEMRIC index than those of knees with a K/L grade 4 (mean 425 msec versus 371 msec; P < 0.05). There was a range of dGEMRIC values in the spared compartments within a given K/L grade, demonstrating biochemical differentiation of disease in radiographically comparable compartments. Almost all compartments with narrowing had dGEMRIC indices of <400 msec. Valgus-aligned knees tended to have lower dGEMRIC values laterally, and varus-aligned knees tended to have lower dGEMRIC values medially; as a continuous variable, alignment correlated with the lateral:medial dGEMRIC ratio (Pearson's R = 0.43, P = 0.02). CONCLUSION: The biochemical information provided by dGEMRIC scans may augment radiography by improving the differentiation of disease status within a given radiographic grade, especially in early OA.

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PubMed2005

Hip abduction moment and protection against medial tibiofemoral osteoarthritis progression.

OBJECTIVE: To test the hypothesis that a greater peak internal hip abduction moment is associated with a reduced likelihood of ipsilateral medial tibiofemoral osteoarthritis (OA) progression. METHODS: Fifty-seven persons with knee OA (by definite osteophyte presence and symptoms) were evaluated. Baseline assessments included kinematic and kinetic gait parameters, obtained with an optoelectronic camera system and force platform, with inverse dynamics used to calculate 3-dimensional moments at the joints; pain, using a separate visual analog scale for each knee; and alignment, using full-limb radiographs. Radiographs of the knee in a semiflexed position, with fluoroscopic confirmation of tibial rim alignment, were obtained at baseline and 18 months later. Disease progression was defined as worsening of the grade of medial joint space narrowing. Logistic regression obtained with generalized estimating equations was used to estimate odds ratios (ORs) for progression per unit of hip abduction moment, after excluding knees with the worst joint space grade at baseline (which could not progress). RESULTS: The 57 participants (63% women) with mild to moderate OA had a mean age of 67 years and a mean body mass index of 29. A greater internal hip abduction moment during gait was associated with a reduced likelihood of medial tibiofemoral OA progression, with OR/unit hip abduction moment of 0.52 and a 95% confidence interval (95% CI) of 0.32-0.85. This protective effect persisted after adjustment for age, sex, walking speed, knee pain severity, physical activity, varus malalignment severity, hip OA presence, and hip OA symptom presence, with an adjusted OR of 0.43 a 95% CI of 0.22-0.81. CONCLUSION: A greater hip abduction moment during gait at baseline protected against ipsilateral medial OA progression from baseline to 18 months. The likelihood of medial tibiofemoral OA progression was reduced 50% per 1 unit of hip abduction moment.

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PubMed2005

Severity of joint pain and Kellgren-Lawrence grade at baseline are better predictors of joint space narrowing than bone scintigraphy in obese women with knee osteoarthritis.

OBJECTIVE: To compare the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a baseline late-phase bone scan and assessments of the radiographic and symptomatic severity of knee osteoarthritis (OA) at baseline as predictors of loss of articular cartilage thickness, as reflected in joint space narrowing (JSN) in the medial tibiofemoral compartment. METHODS: Subjects (174 obese women, 45-64 yrs of age, with unilateral knee OA) were a subset of a larger cohort who participated in a placebo controlled trial of a disease modifying OA drug. Uptake of technetium medronate (99mTc-MDP) in anteroposterior (AP) and lateral views of a late-phase bone scan was measured at baseline in a region of interest drawn around the medial tibia, and was adjusted for (i.e., expressed as a ratio to) uptake in a reference segment of the tibial shaft, which served as an internal standard. Each subject underwent a fluoroscopically standardized radiographic examination of the knees (semiflexed AP view) and a pain assessment with the WOMAC OA Index at baseline, 16 months, and 30 months. RESULTS: Controlling for baseline joint space width and treatment group, multiple linear regression models showed that the adjusted 99mTc-MDP uptake at baseline was a significant predictor of joint space narrowing (JSN) in the index knee at 16 months (b = 0.180, p = 0.015) and 30 months (b = 0.221, p = 0.049). In the contralateral knee, uptake was only a marginally significant predictor of JSN at 30 months (b = 0.246, p = 0.083). Uptake in the upper and middle tertiles of the distribution predicted subjects who would exhibit JSN >/= 0.50 mm within 16 months with 65% sensitivity (PPV 23%) and 36% specificity (NPV 77%). In contrast, a prediction rule based solely on the presence of Kellgren-Lawrence grade 3 OA severity and greater than median WOMAC Pain score identified progressors with 65% sensitivity (PPV 48%) and 79% specificity (NPV 88%). CONCLUSION: Although the level of adjusted 99mTc-MDP uptake was significantly associated with JSN in knees with established radiographic OA, baseline bone scintigraphy is inferior to the radiographic severity of OA and knee pain (alone or in combination) as a predictor of loss of articular cartilage in subjects with knee OA.

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PubMed2004

Subject retention and adherence in a randomized placebo-controlled trial of a disease-modifying osteoarthritis drug.

OBJECTIVE: To describe the methods by which remarkable levels of subject retention and adherence were achieved in a 30-month multicenter randomized placebo-controlled trial (RCT) of a disease-modifying osteoarthritis drug (DMOAD). METHODS: Subjects were obese 45-64-year-old women with unilateral knee osteoarthritis. Before randomization, each volunteer completed a 4-week "faintness-of-heart" (FOH) test, during which she was required to demonstrate reliable appointment keeping and > or =80% adherence to the dosing regimen. Subjects who passed the FOH test were randomized to treatment with doxycycline or placebo for 30 months. The double-blind phase entailed 15 bimonthly followup visits; intervisit adherence data were downloaded from the dosing monitor and used to estimate therapeutic coverage and to identify correctable patterns of nonadherence. Subjects received token incentives and a small cash payment at each followup visit. Measures to prevent or treat side effects of doxycycline were dispensed free of charge. Study coordinators monitored safety and reinforced participation through between-visit telephone calls. RESULTS: Of 463 eligible volunteers, 32 (7%) failed the FOH test and were excluded from the double-blind phase. Among the 431 subjects randomized to treatment groups, 307 (71%) completed the 30-month RCT and 124 discontinued the study drug prematurely. Nearly half of the dropouts returned for their 16- and 30-month radiographs, resulting in loss to followup of 14.8% of randomized subjects. The 2 treatment groups did not differ significantly with respect to rates of discontinuation or retention. Therapeutic coverage over 30 months was very high in both groups. CONCLUSION: The rate of discontinuation in this 30-month RCT (29%) was lower than that of any DMOAD trial of > or =2 years duration published to date. The proportion of subjects for whom 30-month radiographs were available (85%) and adherence to the dosing regimen (mean >80%) also were remarkably high.

Antirheumatic Agents↗
PubMed2004

Potential strategies to reduce medial compartment loading in patients with knee osteoarthritis of varying severity: reduced walking speed.

OBJECTIVE: To determine whether reducing walking speed is a strategy used by patients with knee osteoarthritis (OA) of varying disease severity to reduce the maximum knee adduction moment. METHODS: Self-selected walking speeds and maximum knee adduction moments of 44 patients with medial tibiofemoral OA of varying disease severity, as assessed by using the Kellgren/Lawrence grade, were compared with those of 44 asymptomatic control subjects matched for sex, age, height, and weight. RESULTS: Differences in self-selected normal walking speed explained only 8.9% of the variation in maximum knee adduction moment for the group of patients with knee OA. The severity of the disease influenced the adduction moment-walking speed relationship; the individual slopes of this relationship were significantly greater in patients with less severe OA than in asymptomatic matched control subjects. Self-selected walking speed did not differ between patients with knee OA, regardless of the severity, and asymptomatic control subjects. However, knees with more-severe OA had significantly greater adduction moments (mean +/- SD 3.80 +/- 0.89% body weight x height) and were in more varus alignment (6.0 +/- 4.5 degrees ) than knees with less-severe OA (2.94 +/- 0.70% body weight x height; and 0.0 +/- 2.9 degrees, respectively). CONCLUSION: Patients with less-severe OA adapt a walking style that differs from that of patients with more-severe OA and controls. This walking style is associated with the potential to reduce the adduction moment when walking at slower speeds and could be linked to decreased disease severity.

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PubMed2004

Varus-valgus alignment in the progression of patellofemoral osteoarthritis.

OBJECTIVE: To test the hypotheses that lateral patellofemoral (PF) osteoarthritis (OA) progression is more common than medial PF OA progression, that varus alignment increases the likelihood of medial PF OA progression, and that valgus alignment increases the likelihood of lateral PF OA progression. METHODS: Patients with knee OA were recruited from the community. Inclusion criteria were definite osteophyte presence (i.e., Kellgren/Lawrence radiographic grade >/=2) in 1 or both knees and at least some difficulty with knee-requiring activity. Varus-valgus alignment (the angle formed by the intersection of the mechanical axes of the femur and tibia) was measured on a full-limb radiograph at baseline. To assess PF OA progression, weight-bearing skyline views of the PF compartment were obtained at baseline and at 18-month followup. Knees with the highest grade of PF narrowing at baseline were excluded from analysis. Logistic regression and generalized estimating equations were used; odds ratios (ORs) were adjusted for age, sex, and body mass index. RESULTS: Lateral PF OA progression, which occurred in 120 (30%) of 397 knees, was more common than was medial PF OA progression, which occurred in 60 knees (15%). Varus (versus nonvarus) alignment increased the odds of PF OA progression isolated to the medial PF compartment (adjusted OR 1.85, 95% confidence interval [95% CI] 1.00-3.44). Valgus alignment increased the odds of PF OA progression isolated to the lateral compartment (adjusted OR 1.64, 95% CI 1.01-2.66). CONCLUSION: Lateral PF OA progression was more common than medial progression, and varus-valgus alignment influenced the likelihood of PF OA progression in a compartment-specific manner. Interventions that address the stress imposed by alignment on the PF compartments may delay PF OA progression and should be developed.

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PubMed2004

Thrust during ambulation and the progression of knee osteoarthritis.

OBJECTIVE: To determine whether the presence of varus thrust at baseline increases the risk of progression of medial tibiofemoral osteoarthritis (OA), whether knees with thrust have a greater adduction moment, whether thrust has any additional impact on top of static varus, and whether thrust is associated with poor physical function outcome. METHODS: Two hundred thirty-seven patients with knee OA (definite osteophytes and symptoms) underwent baseline gait observation to assess varus thrust and full-limb radiography to assess alignment. Sixty-four of these 237 patients also underwent quantitative gait analysis to determine the maximum knee adduction moment. Two hundred thirty patients (97%) returned for followup at 18 months. At baseline and 18 months, the 230 participants had semiflexed, fluoroscopically confirmed knee radiographs (with progression defined as worsening of medial joint space grade); self-reported and performance-based measures of function were also assessed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) for medial OA progression, after excluding knees that were not at risk for progression. RESULTS: Varus thrust was present in 67 of 401 knees. Thrust increased 4-fold (age-, sex-, body mass index-, and pain-adjusted OR 3.96, 95% confidence interval [95% CI] 2.11-7.43) the odds of medial progression, with some reduction after further adjustment for varus alignment severity. In varus-aligned knees, thrust increased the odds of OA progression 3-fold (adjusted OR 3.17, 95% CI 1.60-6.31). In the gait substudy, the adduction moment was greater in knees with a thrust compared with knees without a thrust. Having a thrust in both knees versus neither knee was associated with a 2-fold increase in the OR for poor physical function outcome (P not significant). CONCLUSION: Varus thrust is a potent risk factor, identifiable by simple gait observation, for disease progression in the medial compartment, the most common site of OA involvement at the knee. Varus thrust may also predict poor physical function outcome. Varus thrust increased the odds of progression among varus-aligned knees considered separately, suggesting that knees with a thrust are a subset of varus-aligned knees at particularly high risk for progression of OA.

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PubMed2004

Impact of the fit and strong intervention on older adults with osteoarthritis.

PURPOSE: This study assessed the impact of a low cost, multicomponent physical activity intervention for older adults with lower extremity osteoarthritis. DESIGN AND METHODS: A randomized controlled trial compared the effects of a facility-based multiple-component training program followed by home-based adherence (n = 80) to a wait list control group (n = 70). Assessments were conducted at baseline and at 2 and 6 months following randomization. The training program consisted of range of motion, resistance training, aerobic walking, and education-group problem solving regarding self-efficacy for exercise and exercise adherence. All training group participants developed individualized plans for posttraining adherence. RESULTS: Relative to the persons in the control group, individuals who participated in the exercise program experienced a statistically significant improvement in exercise efficacy, a 48.5% increase in exercise adherence, and a 13.3% increase in 6-min distance walk that were accompanied by significant decreases in lower extremity stiffness at 2 and 6 months. Program participants also experienced a significant decrease in lower extremity pain and a borderline significant improvement in efficacy to adhere to exercise over time at 6 months (p =.052). In contrast, persons in the control group deteriorated over time on the efficacy and adherence measures and showed no change on the other measures. No adverse health effects were encountered. IMPLICATIONS: These benefits indicate that this low-cost intervention may hold great promise as one of a growing number of public health intervention strategies for older adults in the United States with osteoarthritis.

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PubMed2004

Glycosaminoglycan distribution in cartilage as determined by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): potential clinical applications.

OBJECTIVE: We sought to describe a range of in vivo observations of glycosaminoglycan distribution in knee cartilage using the delayed gadolinium-enhanced MRI of cartilage technique. CONCLUSION: The index of glycosaminoglycan distribution, T1(Gd), can exceed 500 msec (denoting high glycosaminoglycan) or can be less than 300 msec, with focal areas as low as 240 msec. Compartmental differences, as well as focal defects within the knee, were observed in patients who had sustained injuries to the ligaments and menisci of the knee or who had chronic osteoarthritis. Overall, these results suggest the need for further research into the biochemical changes seen during disease progression and the effects of therapeutic interventions.

Adult↗