Biomedical subjects

M LaValley

Publications and source records attributed to M LaValley.

10 recordsLinked to original sources

PubMed2003

Symmetry and clustering of symptomatic hand osteoarthritis in elderly men and women: the Framingham Study.

OBJECTIVE: While symmetry and clustering of radiographic hand osteoarthritis (OA) have been described in middle-aged women, these have not been studied in elderly individuals and similar investigations are lacking for symptomatic hand OA. The goal of this study was to study patterns of joint involvement in symptomatic hand OA among elderly Caucasian men and women. METHODS: Using data from the Framingham Osteoarthritis Study, we defined a joint as having symptomatic OA if it had symptoms and radiographic OA (Kellgren and Lawrence grade > or =2). We assessed clustering of symptomatic OA using a chi(2)-test and evaluated the interrelationship of occurrence of symptomatic OA among different joints with generalized estimating equations. RESULTS: Of 976 subjects (age 71-99 yr, 36% men) examined, symptomatic OA more often affected multiple hand joints in an individual than would be expected by chance (P<0.001). The presence of symptomatic OA at a particular joint was strongly associated with symptomatic OA in the same joint of the opposite hand, followed by other joints in the same row of the same hand, and then other joints in the same ray of the same hand. The symmetrical pattern of symptomatic OA was more apparent in women than in men. CONCLUSION: Our study demonstrates that symptomatic OA often affects multiple hand joints, and is more likely to cluster by row than by ray. The disease also occurs in a remarkably symmetrical pattern, especially in women.

Age Distribution↗

PubMed2001

Effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on al amyloidosis-associated renal disease.

BACKGROUND: Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation induces remission of the plasma cell dyscrasia in a substantial proportion of patients with AL amyloidosis. The impact of this treatment on associated renal disease is not known. OBJECTIVE: To determine the effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on AL amyloidosis-associated renal disease. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: 65 patients with AL amyloidosis and urinary protein excretion greater than 1 g/24 h who received dose-intensive intravenous melphalan and autologous blood stem-cell transplantation between 1 July 1994 and 30 June 1998. MEASUREMENTS: 24-hour urinary protein excretion, serum cholesterol level, serum albumin level, creatinine clearance, urine and serum immunoelectrophoresis, and bone marrow biopsy. Renal response was defined as a greater than 50% reduction in urinary protein excretion in the absence of a 25% or greater reduction in creatinine clearance. Complete hematologic response was defined as absence of detectable monoclonal protein in serum and urine and a bone marrow specimen containing less than 5% plasma cells without clonal dominance of kappa or lambda isotype. RESULTS: Among the 50 patients who survived for at least 12 months, proteinuria, hypoalbuminemia, and hypercholesterolemia improved during follow-up; 36% met criteria for a renal response. Median 24-hour urinary protein excretion decreased from a baseline value of 9.6 g/24 h to 1.6 g/24 h at 12 months among patients with complete hematologic response, and 71% met criteria for a renal response. Twenty-hour urinary protein excretion did not decrease during follow-up among patients with persistent plasma cell disease, and only 11% had a renal response at 12 months (P < 0.001 for hematologic responders vs. nonresponders). CONCLUSION: Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation improves the nephrotic syndrome in patients with AL amyloidosis-associated renal disease. The benefit is largely limited to patients achieving eradication of the underlying plasma cell dyscrasia.

Adult↗

PubMed2001

Problems in the development and validation of questionnaire-based screening instruments for ascertaining cases with symptomatic knee osteoarthritis: the Framingham Study.

OBJECTIVE: To determine if screening for symptomatic knee osteoarthritis (OA) for clinical trials and epidemiologic studies could be satisfactorily done without performing knee radiographs and to develop efficient screening instruments for symptomatic knee OA based on self-reported symptoms and functional limitations. METHODS: We administered a mailed questionnaire containing many different questions on knee symptoms and functional limitations to 1,921 participants of the Framingham Study who had previously been screened for symptomatic OA with a history and knee radiographs. Recursive partitioning methods (using the Classification and Regression Trees [CART] program) were used to create a set of screening instruments for symptomatic knee OA, which was defined as knee symptoms on most days and radiographic evidence of OA. Three screening instruments were developed to maximize the sensitivity, specificity, and efficiency. RESULTS: The sensitive instrument had 84% sensitivity and 73% specificity. The specific instrument had 46% sensitivity and 94% specificity. The efficient instrument had 56% sensitivity and 85% specificity. Sensitivity was lower and specificity was higher when these instruments were used to screen for radiographic OA. All instruments had higher sensitivity but lower specificity when used for older subjects (age >60) with greater disease prevalence. However, using any of these instruments as a single-step screening mechanism resulted in considerable misclassification. CONCLUSION: We conclude that none of these instruments has adequate diagnostic test performance to serve as a single-step evaluation of the presence or absence of symptomatic knee OA.

Age Factors↗

PubMed2000

Improving the selective use of plain radiographs in the initial evaluation of shoulder pain.

OBJECTIVE: In a previous retrospective study, we had found that shoulder radiographs were overused in the initial evaluation of patients presenting to the emergency department with shoulder pain. Our objective was to prospectively define clinical criteria that identify patients who have a low risk of radiographic findings that influence the management of the initial evaluation of shoulder pain in the emergency department. METHODS: All adult patients presenting to the emergency department of a university teaching hospital with shoulder pain were eligible to participate. Patients with deformities, penetrating wounds, referred pain, and those presenting for followup were excluded. Data were recorded prospectively using a standardized form. All radiographs were classified as therapeutically uninformative (TU) except fracture, acromioclavicular joint separation (> or =Grade 3), infection, or malignancy. A classification tree was used for analysis. RESULTS: Two hundred six patients had shoulder radiographs, of which 88% were TU. The model yielded 3 sets of low risk patients with a high percentage of TU radiographs: (1) no fall, no swelling (99% TU: 106 TU, 1 radiograph with lytic lesions in a cancer patient); (2) a fall, but no swelling, and no pain at rest (100% TU, n = 18); (3) a fall and pain at rest, but no swelling and normal range of motion (100% TU, n = 10). Not performing radiographs on these low risk patients would have decreased radiograph utilization from 52 to 18% of all shoulder patients seen. CONCLUSION: Our findings suggest that specific clinical criteria are able to identify patients who do not need radiographs as part of the initial management of shoulder pain. Prospective validation of these criteria are needed to confirm that these low risk patients can be safely evaluated without radiographs.

Adult↗

PubMed1998

Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients.

AL (amyloid light-chain) amyloidosis is an uncommon plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure and death in a median of 13 months. Autologous stem-cell transplantation is effective therapy for multiple myeloma and therefore, we evaluated its efficacy for AL amyloidosis. Patients with adequate cardiac, pulmonary, and renal function had stem cells mobilized with granulocyte-colony stimulating factor and were treated with dose-intensive intravenous melphalan (200 mg/m2). Response to therapy was determined by survival and improvement of performance status, complete response or persistence of the clonal plasma cell disorder, and change in the function of organs involved with amyloid at baseline. We enrolled 25 patients with a median age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with clonal plasma cell disorders. Twenty-two (88%) were Southwest Oncology Group performance status 1 or 2 within a year of diagnosis, and 16 (64%) had received no prior therapy. Predominant amyloid-related organ involvement was cardiac (n = 8), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1). Fifteen patients had one or two organ systems involved, whereas 10 had three or more involved. With a median follow-up of 24 months (12-38), 17 of 25 patients (68%) are alive, and the median survival has not been reached. Thirteen of 21 patients (62%) evaluated 3 months posttransplant had complete responses of their clonal plasma cell disorders. Currently, two thirds of the surviving patients (11 of 17) have experienced improvements of amyloid-related organ involvement in all systems, whereas 4 of 17 have stable disease. The improvement in the median performance status of the 17 survivors at follow-up (0 [range, 0-3]) is statistically significant versus baseline (2 [range, 1-3]; P < . 01). Significant negative prognostic factors with respect to overall survival include amyloid involvement of more than two major organ systems and predominant cardiac involvement. Three patients have experienced relapses of the clonal plasma cell disorder at 12 and 24 months. Dose-intensive therapy should currently be considered as the preferred therapy for patients with AL amyloidosis who meet functional criteria for autologous transplantation.

Adult↗

PubMed1998

Evidence for a Mendelian gene in a segregation analysis of generalized radiographic osteoarthritis: the Framingham Study.

OBJECTIVE: To investigate the inheritance of generalized osteoarthritis (OA). METHODS: OA was identified on hand and knee radiographs obtained from members of the Framingham Study cohort (the parents) in 1967-1970 and 1992-1993, and from their adult children in the Framingham Offspring Study in 1993-1994. All hand and knee radiographs evaluated for OA were graded using the Kellgren and Lawrence (K/L) scale. A measure of generalized OA was defined as the count of the number of hand and knee joints affected, as determined by the proportion of joints with a K/L grade > or =2. The OA count, treated as a continuous variable, was adjusted for age, body mass index, and a measure of physical activity for each joint area (hand or knee). Calculations were made separately for each generation and each sex, and correlations were analyzed against the standardized residual of OA. Segregation analysis was used to test whether OA aggregated in families, and if its transmission fit a Mendelian pattern. RESULTS: A total of 337 nuclear families with 2 parents and at least 1 biologic offspring were studied. In parents, the mean age was 61.2 years at the time of hand radiographs and 72.8 years at the time of knee radiographs, which were mostly obtained at a later examination. The mean age at the time of radiographs in offspring was 53.9 years. Using standardized residuals, parent-offspring and sibling-sibling correlations ranged from 0.115 to 0.306. In segregation analyses, models testing the hypotheses of no familial aggregation, no familial transmission, or a Mendelian gene alone were all rejected (P < 0.001 for each of these models). The best-fitting models were mixed models with a Mendelian mode of inheritance and a residual multifactorial component. The Mendelian recessive model provided the best fit. CONCLUSION: These analyses support a significant genetic contribution to OA, with evidence for a major recessive gene and a multifactorial component, representing either polygenic or environmental factors.

Adult↗

PubMed1998

The association of peripheral monocyte derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist, and tumor necrosis factor-alpha with osteoarthritis in the elderly.

OBJECTIVE: To examine the association of peripheral blood mononuclear cell (PBMC) derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor alpha (TNF-alpha), and radiographic osteoarthritis (OA) in the elderly. METHODS: A total of 703 subjects (436 women, 267 men, mean age 78.5+/-4.5 yrs) had both knee and hand radiographs, and cytokines were measured during the 22nd biennial examination of the Framingham Cohort. PBMC derived IL-1beta , IL-1Ra, and TNF-alpha production was assessed using a non-cross reacting polyclonal radioimmunoassay. Knee OA was defined as a score of > 2 using a modified Kellgren and Lawrence scale. The presence of osteophytes and joint space narrowing were scored separately on a 0-3 scale, in which disease was defined a priori as a score > 0 for each feature. Sex-specific odds ratios were calculated for knee OA after adjusting for weight, history of knee injury, and use of estrogen and nonsteroidal antiinflammatory drugs. RESULT: No uniform associations were found for IL-1beta or IL-1Ra in men, or for TNF-alpha production and radiographic OA in either sex. We found possible associations for the highest levels of IL-1beta production and the presence of knee osteophytes [OR=2.0 (1.2-3.5)] and joint space narrowing [OR=1.7 (1.1-2.8)] in women. Our data suggested a possible protective effect for IL-1Ra production and hand OA in women [OR=0.6 (0.4-1.0)]. CONCLUSION: We found no consistent association of PBMC cytokine production and radiographic OA. However, women with the highest production of IL-1beta and IL-1Ra had respectively higher rates of knee OA and lower rates of hand OA than expected.

Aged↗

PubMed1997

A consumer's guide to meta-analysis.

The same proponent of meta-analysis who feels that it offers the highest level of evidence of treatment efficacy has also warned that "it is easy to do a meta-analysis; it is hard to do one well" (1). This paper has listed a series of issues that should be addressed in the construction of a good meta-analysis. A meta-analysis protocol needs to be prepared. A concerted effort should be made to capture all published and unpublished studies that address the research question. These studies should then be compared to the inclusion and exclusion criteria from the protocol to determine which will be used in the meta-analysis. A random effects analysis should be performed on the studies. A test of the homogeneity of studies should be done. Funnel plots and the tolerance for null results should be computed to assess publication biases. Finally, sensitivity analyses should be performed. All of these issues need to be discussed in the report of the meta-analysis so that readers can judge the validity of the conclusions.

Clinical Protocols↗

PubMed1997

Signal-averaged electrocardiography in patients with AL (primary) amyloidosis.

One hundred thirty-three patients with biopsy-proven AL amyloidosis were studied with echocardiography, Holter recording, 12-lead electrocardiography, and signal-averaged electrocardiograms. Features from these tests were analyzed in relation to their effect on mortality. Late potentials were more frequent in patients with echocardiographic evidence of cardiac amyloidosis (31%) compared with patients with normal echocardiograms (9%, p < 0.003). One hundred six of the 133 patients died during follow-up, of which 34 were nonsudden cardiac deaths and 33 were sudden deaths. Abnormal echocardiograms and signal-averaged electrocardiograms were each predictive of all-cause cardiac death (p < 0.0001 ) and sudden cardiac death (p < 0.0001). Abnormal signal-averaged electrocardiograms were also independently predictive of sudden death in the subgroup of patients with an abnormal echocardiogram (p < 0.05). Thus late potentials are predictive of sudden death in patients with AL amyloidosis and provide independent prognostic information in patients with echocardiographic evidence of amyloid involvement.

Adult↗

PubMed1997

Familial and primary (AL) cardiac amyloidosis: echocardiographically similar diseases with distinctly different clinical outcomes.

OBJECTIVE: To determine whether patients with myocardial amyloidosis due either to AL (primary) amyloid or familial amyloid have distinguishing echocardiographic or electrocardiographic features; and to compare the prevalence of heart failure and survival in the two types of amyloidosis in relation to echocardiographic findings. DESIGN: Blinded group comparison of randomly selected cases of cardiac amyloidosis. SETTING: International referral centre for amyloid research and treatment. PATIENTS: 36 patients with cardiac amyloid heart disease, of whom 12 had familial and 24 had primary AL amyloidosis. RESULTS: Familial and AL echocardiograms were morphologically indistinguishable, with similar left ventricular wall thickness, mean (SD) 15.4 (2.3) nu 15.8 (2.5) mm, respectively; right ventricular wall thickness was also similar between amyloid types: 9.6 (2.8) nu 9.7 (6.5) mm, respectively. Doppler indices of left and right ventricular function, left ventricular volume, and ejection fraction were also similar. Low voltage electrocardiograms (< 0.5 mV) were more common in the AL (16/24, 67%) than in the familial group (4/12, 25%), P < 0.05. The one year survival for familial and AL forms was 92% (11/12) nu 38% (6/24), respectively, with virtually all deaths due to cardiac causes. CONCLUSIONS: Although cardiac involvement is echocardiographically indistinguishable, cardiac mortality is very different between the two forms of amyloidosis. Preservation of electrocardiographic voltage in familial amyloidosis suggests that the particular biochemical characteristics of distinct types of amyloid fibril have different pathological effects on the myocardium. This distinction becomes critical in the evaluation, treatment, and management of patients who have a diagnosis within the spectrum of the protein deposition diseases.

Amyloidosis↗