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PubMed2000

Visual field progression in patients with initially unilateral visual field loss from chronic open-angle glaucoma.

PURPOSE: To investigate visual field progression in patients with initially unilateral glaucomatous visual field loss, and to determine risk factors for progression. DESIGN: Retrospective observational case series. PARTICIPANTS: Forty-eight consecutive patients with primary open-angle glaucoma, pseudoexfoliative glaucoma, or pigmentary glaucoma, seen over an 18-month period, who initially had unilateral visual field loss as defined by use of modified Anderson criteria. Patients were followed with standard Humphrey perimetry for a minimum of 2 years. METHODS: Progression was defined by use of modified Anderson criteria, and Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study scores. MAIN OUTCOME MEASURE: Visual field progression. RESULTS: Three patients (6.2%) had fellow eye progression over a mean follow-up of 76 months and duration of disease of 8.7 years. Fellow eye progression correlated with progression of the first-affected eye (P = 0.044). Ten patients (21%) had progression of the first-affected eye; these eyes had a larger initial cup/disc ratio compared with stable eyes (P = 0.041). Increasing initial AGIS score was associated with progression (P: = 0.003). Kaplan-Meier survival analysis estimated the risk of progression at 5 years to be 25% in first-affected eyes and 7.2% in fellow eyes. CONCLUSIONS: In this population, the risk of fellow eye progression in patients with initially unilateral visual field loss from open-angle glaucoma is low. Progression is higher in eyes with visual field loss at initial testing, and the risk of progression increases as the level of initial visual field loss increases.

Adult↗

PubMed2004

Osteophytes and progression of knee osteoarthritis.

OBJECTIVES: Osteophytes are thought to stabilize an osteoarthritic joint, thereby preventing structural progression. Meagre longitudinal data suggest, however, that they are associated with an increased risk of structural progression. Our objective was to evaluate the effect of osteophyte size on radiographic progression in osteoarthritis (OA). METHODS: Using data from a natural history study of persons with symptomatic knee OA, we obtained fluoroscopically positioned postero-anterior (PA) radiographs at baseline, 15 and 30 months. Using an atlas, osteophyte size was scored on a scale of 0-3 at each of four sites on the PA film and, for each knee, both compartment-specific (i.e. medial; lateral) and overall osteophyte scores were computed. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semiquantitative grading. Mechanical alignment was assessed using long limb films at the 15 month examination. Logistic regression was used to evaluate the relation of osteophyte size with progression, adjusting for age, gender and body mass index, and with and without adjustment for alignment. RESULTS: Of 270 subjects who had 470 eligible knees with follow-up, 104 (22%) knees showed progression. Overall, osteophyte score modestly increased the risk of progression [odds ratio (OR) per S.D. increase of osteophyte score=1.4 (95% CI 1.1, 1.8, P=0.02)], but this effect weakened and became non-significant after adjustment for limb alignment (OR=1.3). Compartment osteophyte score was strongly associated with malalignment to the side of the osteophyte (e.g. medial osteophyte and varus). Compartment-specific osteophyte score markedly increased the risk of ipsilateral progression (e.g. medial osteophytes --> medial progression) [OR per S.D.=1.9 (95% CI 1.5, 2.5, P<0.001)] and decreased the risk of contralateral progression [OR per S.D.= 0.6 (95% CI 0.5, 0.8, P=0.002)], but these associations diminished when we adjusted for limb alignment (OR=1.5 and 0.7 respectively). CONCLUSIONS: Large osteophytes do not affect the risk of structural progression. They are strongly associated with malalignment to the side of the osteophyte, and any relation they have with progression is partly explained by the association of malalignment with progression.

Aged↗

PubMed1996

A new method using top views of the spine to predict the progression of curves in idiopathic scoliosis during growth.

STUDY DESIGN: A prospective longitudinal study of 51 patients with idiopathic scoliosis using spinal stereoradiographs was performed. The top view, which was obtained from stereoscopic anteroposterior and lateral radiographs, was analyzed for predicting the progression of spinal deformity. OBJECTIVES: To show that the top view facilitates prediction of curve progression in idiopathic scoliosis at the initial examination. SUMMARY OF BACKGROUND DATA: Four progression factors were set up using the top view and were analyzed statistically for predicting progression. No previous study has assessed this concept. METHODS: Fifty-one patients with idiopathic thoracic scoliosis or combined thoracic and lumbar scoliosis were studied longitudinally. There were 24 untreated patients and 27 patients treated with braces. Four potential progression factors were evaluated using the top view: 1) the ratio of the frontal size and the sagittal size in the top view, 2) the magnitude and direction of the vector describing the plane of maximum curvature in the thoracic spine, 3) the magnitude and direction of the vector describing the plane of maximum curvature in the lumbar spine, and 4) the balance of these vectors between the thoracic and lumbar curve. All cases were classified into five groups according to these four factors. RESULTS: The probability of the progression was evaluated statistically, and the prevalence of curve progression was found in each group. The probability of progression of a scoliosis curve increased according to the increase of these four factors. No significant difference was found between Cobb angle at the initial examination and that at skeletal maturity in untreated patients with a small risk of progression. The patients with a large risk of progression and who were treated with braces showed progression of curvature despite brace treatment. CONCLUSION: The present study has evaluated factors relating to progression in scoliosis using the top view. These results may help predict the risk of progression in idiopathic scoliosis.

Adolescent↗

PubMed2000

Comparison of visual field progression in patients with normal pressure glaucoma between eyes with and without visual field loss that threatens fixation.

AIM: To compare the frequency and site of visual field progression and changes in visual acuity in patients with normal pressure glaucoma (NPG) with and without pre-existing visual field loss. METHOD: Patients with normal tension glaucoma were selected who had at least 10 visual fields over 5 or more years of follow up and no other condition that might influence the visual field or visual acuity. Alternate left and right eyes were selected from patients in random order. These eyes were then subdivided according to visual field defect threatening fixation, visual field defect not threatening fixation, and no visual field defect (fellow eyes). Eyes were defined as showing a threat to fixation according to the presence of a visual field defect involving one of more of four paracentral visual field locations. Pointwise linear regression analysis was applied to each visual field series using PROGRESSOR software. Progression of visual field loss was defined as the appearance of a regression slope 1 dB per year or more with a significance of p<0.01, which remained consistent with the addition of two of three successive visual fields to the series. The number of patients showing progression and the number where progression occurred in one of the four paracentral visual field locations was noted. The number of eyes losing two or more lines of Snellen visual acuity over the follow up period was also noted. RESULTS: 174 eyes of 174 patients were selected. 106 eyes had visual field loss threatening fixation, 46 eyes had visual field loss that did not threaten fixation, and 22 were fellow eyes with normal visual fields. The median follow up was 7.2 years. Eight eyes (36.4%) in the "normal visual fields" group, 31 eyes (67.4%) in the "visual field loss away from fixation" group, and 87 eyes (82.1%) in the "threat to fixation" group showed progression in any part of the visual field. Two eyes (9.1%) in the "normal visual fields" group, nine eyes (19.6%) in the "visual field loss away from fixation" group, and 45 eyes (42.5%) in the "threat to fixation" group showed progression at "threat to fixation". The Cox proportional hazards regression model showed an increased risk of progression at any part of the visual field for female sex and a decreased risk for eyes with normal visual fields. For progression at threat to fixation this model showed an increased risk with pre-existing threat to fixation. Eyes from older patients and those that went on to have progressive visual field loss at fixation were more likely to lose two lines of Snellen visual acuity over the follow up period. CONCLUSION: Since 20-30% of previously field damaged eyes and over 60% without prior field loss fail to demonstrate progressive visual field damage over a long follow up it is recommended that normal pressure glaucoma patients be monitored for progression and that potentially harmful therapy be withheld until progression is demonstrated. Although the presence of visual field loss that threatens fixation does not constitute an increased risk of visual field progression it does indicate an increased risk of further loss of visual field close to fixation which is in turn associated with loss of central acuity. In the light of this finding, patients with visual field loss that threatens fixation should be managed more aggressively.

Aged↗

PubMed2000

Treatment of primary progressive Hodgkin's and aggressive non-Hodgkin's lymphoma: is there a chance for cure?

PURPOSE: To determine differences in prognosis between primary progressive Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL), we retrospectively analyzed patients with progressive lymphoma who were treated with different salvage chemotherapy regimens including high-dose chemotherapy (HDCT) followed by autologous stem-cell support (ASCT). PATIENTS AND METHODS: One hundred thirty-one patients with primary progressive lymphoma (HD, n = 67; NHL, n = 64) were enrolled. Primary progressive disease was defined as disease progression during first-line chemotherapy or only transient response (complete or partial response lasting </= 90 days) after induction treatment. Patients 60 years or younger with progressive lymphoma were eligible to receive HDCT with ASCT. RESULTS: The overall response rate after salvage chemotherapy for patients with primary progressive HD and NHL was 33% and 15%, respectively. Twenty-five HD patients (37%) received HDCT. Most patients with NHL had progressive disease under salvage treatment, with only six patients (10%) receiving HDCT. Of those, only two patients were alive and in continuous complete remission 3 and 12 months after HDCT. No patient with NHL survived longer than 26 months after first diagnosis. Actuarial OS after 5 years was 19% for all HD patients; 53% for HD patients receiving HDCT, and 0% for patients who did not receive HDCT. In HD patients, multivariate regression analysis identified chemosensitive disease on salvage treatment (P =.0001) and HDCT (P =.031) as significant prognostic factors for freedom from treatment failure. Significant prognostic factors for OS are chemosensitive disease (P =.0005), HDCT (P =.039), and B symptoms at the time of progress (P =.046). CONCLUSION: There are striking differences in the prognosis of patients with progressive HD and aggressive NHL. The prognosis of progressive NHL patients is dismal. Most patients have rapidly progressive disease after salvage treatment and are, therefore, excluded from HDCT programs. In contrast, progressive HD patients can achieve long-term survival after HDCT.

Adolescent↗

PubMed1999

Progressive motor deficits in lacunar infarction.

OBJECTIVE: To study the clinical characteristics of the progression of motor deficits in lacunar stroke patients. BACKGROUND: Some patients with lacunar infarction have progression of their neurologic deficits, but it is not known which patients will progress or why they progress. METHODS: The authors evaluated 92 consecutive patients (47 men, 45 women; age, 69.4 +/- 10.9 years [mean +/- SD]) with first-ever stroke due to supratentorial lacunes in the internal capsule or the corona radiata. By defining lacunar infarction in which motor deficits progressed between admission and the day after admission as progressive lacunar infarction, the authors compared progressive lacunar infarction with stable lacunar infarction. RESULTS: Of 92 patients, 25 (27%) had progression of deficits. Diabetes mellitus (p = 0.02) and severity of motor deficit on admission (p = 0.006) were related independently to progression in a logistic multiple regression analysis. Size of the infarct was slightly larger (1.2 +/- 0.4 cm2 versus 0.9 +/- 0.5 cm2; p = 0.01) and functional status at discharge was worse (median Barthel index, 45 versus 100; p < 0.001) in patients with progressive infarction than in those without progression. There were no significant differences between the two groups regarding the site of the infarct or blood pressure or hematocrit levels on or after admission. CONCLUSIONS: The progression of motor deficits is associated with a relatively poor functional outcome. Diabetes mellitus and the severity of motor deficit on admission may predict progression of motor deficits.

Activities of Daily Living↗

PubMedDate not supplied

[Evaluation of the rate of progression of chronic renal transplant rejection using the proliferating cell nuclear antigen ].

UNLABELLED: Since the introduction of kidney transplantation, the short-term patient and graft survival have been progressively improving, but the long-term graft survival and half-life of transplants have not. Beyond doubt, chronic rejection (CR) remains the major cause of chronic graft failure and is responsible for the loss over 10 years of 50% of grafts. (1-4). CR is characterized clinically by proteinuria, hypertension and declining renal function, and pathologically by arteriosclerosis, glomerulosclerosis and interstitial fibrosis. The progressive morphological changes of glomerular, vascular and tubulointerstitial (TIN) compartments in renal allografts experiencing chronic rejection correlate directly with declining renal function and the eventual graft loss [5]. In consideration of this fact and using proliferating cell nuclear antigen (PCNA) as a marker of cell proliferation, a retrospective analysis of renal allograft biopsies was carried out with the aim to determine whether quantification of the cell proliferation activity in three tissue compartments may be used as a prognostic index of CR progression. SUBJECTS AND METHODS: Clinical course and biopsy specimens of 27 patients with clinically and morphologically confirmed (Banff schema) diagnosis of CR were retrospectively evaluated. Patients were transplanted between 1988 and 1994 at our Institute and regularly followed-up for at least 2 years after transplantation (14 patients), or till haemodialysis has been resumed (11 patients) or till death (2 patients). The progression rate of renal graft function deterioration was estimated by slopes of regression lines obtained by plotting 1/sCr vs time. According to the progression rate after biopsy patients were divided into two groups: fast progression group (10 patients) and slow progression group (17 patients). Immunosuppressive regimens included induction with anti-lymphocyte globulin followed with cyclosporine, steroids and azathioprine. Immunohistochemistry. Sections of formalin-fixed, paraffinembedded tissue were stained for PCNA with monoclonal mouse anti-proliferating cell nuclear antigen (clone PC 10, Dako) as follows in ref. [6]. PCNA immunoreactivity of smooth muscle cells and lymphocytes in vascular intima, lymphocytes in TIN and glomerular mesangium proliferation was assessed by semiquantitative scoring (scale 0-3). Normal tonsil was used as a positive control. Differences between groups were evaluated using Student's t-test. Pearson's correlation test was used to study the relationship between variables. P values < 0.05 were considered as significant. RESULTS: Data on patients are presented in Table 1. The only statistical difference was in progression of chronic graft failure presented by regression lines obtained by plotting 1/sCr vs time. PCNA protein expressions in vascular, glomerular and TIN compartments for both groups are presented in Figs. 1-3.. PC 10 immunoreactivity was confined to the nucleus. The pattern of staining was granular or diffuse. Individual values of the scores of PCNA immunoreactivity in different tissue compartments for the groups examined are presented in Tables 2 and 3. Comparison of the means of PCNA immunoreactivity scores in different tissue compartments of fast and slow progression group showed that cells proliferation in glomerular, TIN and vascular compartments are significantly higher in the fast than in the slow progression group (Table 4). Besides, significant positive correlation was found between the slopes of the regression lines plotting 1/sCr vs. time and cells proliferation scores for all compartments (Table 5). DISCUSSION: Chronic graft failure may occur due to CR, cyclosporine nephrotoxicity, repeated acute rejection, recurrent glomerular diseases, surgical and urological complications, but CR was recognized as the most common cause of chronic graft failure and renal graft loss [7]. Progression of renal disease reflects the interactive effects of changes in the structure and function. This notion has been examined many times in the native kidneys by studies correlating glomerular filtration rate with architectural deterioration in the glomerular or interstitial compartment [8-10]. Meanwhile, the similar studies in human renal allograft are scarce. Increased PCNA immunodetection in glomerular cells as well as in interstitial infiltrates was described in acute and chronic renal graft rejection and diagnostic value of this finding was analyzed [12, 15]. Similarly, PCNA was often examined immunohistochemically in lymphoma and solid tumours as a marker of cell proliferation, but its reliability as a prognostic factor was also evaluated [18-20]. In the present study the prognostic value of PCNA expression in different tissue compartments of renal grafts experiencing CR was examined for the first time. The present study revealed that two groups examined with the different chronic graft failure progression rate as the main difference had significantly different proliferation of cells in glomerular, TIN and vascular compartments. PCNA immunoreactivity scores in these three compartments were significantly higher in the fast than in slow progression group. The significant positive correlation between the slope of the regression line plotting 1/sCr vs. time and cell proliferation in glomerular, TIN and vascular compartments was also found. Therefore, it was suggested that the measurement of PCNA expression in renal graft tissue might be used as a prognostic index.

Adolescent↗

PubMed2000

Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years.

PURPOSE: Cure from malignancy is commonly defined as a disease-free state lasting 5 years after treatment. We analyzed clinical and biochemical progression rates after radical prostatectomy for men with clinically localized prostate cancer with particular attention to recurrence beyond 5 years. Annual hazard rates of progression were calculated to determine the probability of recurrence at specific intervals following surgery. MATERIALS AND METHODS: The records of 2,782 men with clinically localized prostate cancer (cT1-T2) undergoing radical prostatectomy between 1987 and 1993 were reviewed. All patients were treated in the prostate specific antigen (PSA) era so that serial followup PSA values were available from the time of surgery. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Disease progression was defined as documented local recurrence, systemic progression and/or PSA 0.4 ng./ml. or greater. Lymph node positive cases were eliminated from analysis since almost all received adjuvant hormonal therapy. Annual hazard rates for progression were calculated using the formula: [No. events / No. patients at risk] x 100. Progression-free survival probabilities were determined using the Kaplan-Meier method. RESULTS: Pathological stage was pT2a-b, N0 (68%), pT3a, N0 (21%) and pT3b, N0 (11%). Biochemical progression-free survival at 5 and 10 years was 76% and 59%, respectively, for the entire study population while those with pathologically organ confined (pT2, N0) cancers had progression-free survival rates of 82% and 68% at 5 and 10 years, respectively. A total of 819 patients (29%) eventually had disease progression, including 160 (6%) with progression after 5 years. Annual hazard rates were highest during the first 2 years after radical prostatectomy for the entire population. Patients with adverse prognostic features (pT3b, PSA 10 ng./ml. or greater, Gleason score 8-10 and nondiploid cancers) had high initial hazard rates that decreased with time to lower levels. Those with pathologically organ confined cancer had low but constant hazard rates throughout followup. CONCLUSIONS: Although progression after radical prostatectomy usually occurs early, reflecting the impact of clinical under staging, a significant number of men, including those with organ confined cancers, will continue to have disease progression after 5 years. Patients undergoing radical prostatectomy should be subjected to long-term followup to allow the option of early intervention should progression occur.

Adult↗

PubMed1996

Analysis of progressive change in automated visual fields in glaucoma.

PURPOSE: To detect and estimate the rate of progression of visual field loss in subjects with glaucoma who undergo long-term automated perimetric visual field testing. METHODS: Automated visual field data were obtained for subjects with glaucomatous visual field loss and a minimum of seven threshold field tests over at least 4.5 years. Univariate linear regression was performed with respect to mean deviation (MD), corrected pattern standard deviation (CPSD), mean thresholds of clusters corresponding to the Glaucoma Hemifield Test (GHT), and thresholds of 52 individual test locations. Subjects were classified as progressive or stable (unchanged or improved) based on the slope and statistical significance of these parameters. Adjusted P values were used to maintain the overall type 1 error at 5%. RESULTS: One hundred ninety-one subjects with a mean follow-up period of 7.1 years (range, 4.5 to 10.5 years) and a mean number of visual field tests of 9.5 (range, 7 to 16) were included. Twenty-four subjects (12.6%) showed progression in MD (mean slope [95% confidence interval], -1.26 [-1.50, -1.01] dB/year), and 27 (14.1%) showed progression in CPSD (mean slope [95% confidence interval], 0.71 [0.58, 0.84] dB/year). Thirty-five subjects (18.3%) had > or = 1 progressive GHT cluster. The mean slope in progressive clusters ranged from -1.51 [-1.82, -1.20] to -2.84 [-3.39, -2.29] dB/year. Thirty-six subjects (18.8%) had > or = 1 progressive individual test locations. Fifty-two subjects (27.2%) were classified as progressive based on progression of CPSD, > or = 1 cluster and/or > or = 1 point. CONCLUSIONS: Fewer than 1 in 3 subjects progressed by any one of the criteria for progression over an average of 7.1 years. Rates of progression that could be statistically confirmed were in the range of approximately 1 to 5 dB/year, depending on the number of fields, the variability over time, and the parameter assessed (global indices, GHT clusters, or individual points). No correlation between initial visual field status and the rate of progression was found. A minimum of approximately 5 years of follow-up with annual perimetry would be required to detect significant changes in the visual field by linear regression.

Adolescent↗

PubMed2004

Progression of radiographic hip osteoarthritis over eight years in a community sample of elderly white women.

OBJECTIVE: To describe progression over 8 years in a community-based sample of elderly women with radiographic findings of hip osteoarthritis (RHOA) with or without hip pain. METHODS: Baseline and followup anteroposterior pelvic radiographs were obtained at a mean +/- SD 8.3 +/- 0.4 years of followup in women age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. We evaluated progression in 936 hips of 745 women with one or more baseline findings of RHOA: summary OA grade > or =2, minimum joint space (MJS) < or =1.5 mm, definite femoral or acetabular osteophytes, definite superolateral joint space narrowing (JSN), or moderate or worse superomedial JSN. We separately examined progression in hips with an MJS between 1.5 mm and 2.5 mm. Hip pain and lower extremity disability were assessed by questionnaire and examination. Measures of progression included an increase in summary grade of radiographic findings, increase in total osteophyte score, decrease in MJS of > or =0.5 mm, total hip replacement (THR), and increase in lower extremity disability score. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for baseline radiographic predictors of progression were estimated using general estimating equations. RESULTS: During followup, 12.9% of women with baseline RHOA underwent THR, and 22.8% had substantial worsening of lower extremity disability, while 64.6% of hips with RHOA showed radiographic progression or were replaced. Progression was greater by all measures in the 37% of hips and 47% of women with both RHOA and hip pain at baseline. Of hips with pain, 23.6% progressed to THR compared with 2.7% of hips without pain (OR 8.1 [95% CI 4.2, 15.4], P < 0.001), and MJS decreased > or =0.5 mm in 53.7% of hips with pain compared with 30.7% of hips without pain (OR 1.9 [95% CI 1.4, 2.6], P < 0.001). Women with hip pain were more likely to have worsened lower extremity disability (29.3% versus 17.6%; OR 1.8 [95% CI 1.2, 2.8], P = 0.0053). Hips with an MJS >1.5 mm and < or =2.5 mm (n = 1,868) had primarily superomedial narrowing and comparatively low rates of progression that did not differ by hip pain. Femoral osteophytes, superolateral JSN, and subchondral bone changes were independent predictors of progression. CONCLUSION: Among women recruited from the community, radiographic and clinical progression was greater in those with symptomatic RHOA, but still substantially less frequent than previously reported for hip OA patients in clinical settings. Asymptomatic RHOA and hips with an isolated finding of mild JSN (MJS of 1.5 mm to 2.5 mm) were unlikely to progress over 8 years.

Aged↗

PubMed2004

The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis.

OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients.

Adult↗

PubMed2004

Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years.

OBJECTIVE: In many patients with knee osteoarthritis (OA), the disease progresses, and there is loss of cartilage; in others, the disease stabilizes with time. Previous studies have demonstrated that concentrations of serum proteins that reflect joint tissue metabolism can identify knees that will deteriorate, leading to the suggestion that OA disease activity is phasic or cyclical. The aim of the current study was to determine whether longitudinal measurements of one such protein, serum cartilage oligomeric matrix protein (COMP), are related to disease outcome over a 5-year period. METHODS: Serum COMP levels were measured by enzyme-linked immunosorbent assay at study entry and every 6 months thereafter in 115 patients with knee pain and OA of mainly the tibiofemoral joint. Cartilage loss was determined from knee radiographs taken at entry and at 24, 36, and 60 months. Disease progression was defined as either a reduction in the tibiofemoral joint space width by at least 2 mm or total knee replacement (TKR) in either knee at followup. COMP concentrations at baseline and the area under the curve (AUC) of measurements obtained over 5 years were compared between progressors and nonprogressors by Student's 2-tailed t-test. The patterns and probability of progression according to TKR or > or =2 mm of narrowing of the tibiofemoral joint space were analyzed by logistic regression models. RESULTS: The mean +/- SD ages of the progressors and nonprogressors were 64.2 +/- 7.8 years and 63.3 +/- 10.6 years, respectively, and the proportion of females was 51% and 56%, respectively. Of the 37 patients whose OA progressed (22 by TKR and 15 by > or =2-mm reduction in tibiofemoral joint space), 13 lost cartilage during the first 2 years, and 18 lost cartilage during the last 2 years. The mean +/- SD serum COMP concentration at baseline was significantly higher in the progressors compared with the nonprogressors (14.12 +/- 3.39 units/liter versus 12.62 +/- 3.25 units/liter; P < 0.036). Serum COMP levels rose significantly after TKR; however, after allowing for the effect of TKR, the AUC/month was significantly higher in the progressors compared with the nonprogressors (12.52 +/- 2.71 versus 10.82 +/- 2.71; P < 0.003). Serum COMP concentrations were higher during periods of radiographic progression and identified periods of progression that were nonlinear. Logistic regression analysis showed that on average, a 1-unit increase in serum COMP levels increased the probability of radiographic progression by 15%. CONCLUSION: The data suggest that serum COMP is related to progressive joint damage in knee OA. The patterns of progression for the early and late progressors are consistent with the hypothesis that knee OA progression is episodic or phasic. Large between-subject variation precludes the use of individual values to predict progression with confidence. However, sequential measurements of serum COMP levels may identify patients whose OA is likely to progress over the next year or two.

Aged↗

PubMed1994

Clinical and angiographic variables affecting the progression of coronary artery disease as determined by quantitative angiography.

To assess by serial quantitative angiography, the significance of clinical and angiographic variables that affect the progression of coronary artery disease (CAD). Progression of disease by sequential angiography is unpredictable and the role of clinical risk factors controversial. Various intervention trials have demonstrated less progression and even regression in hyperlipidemic patients. Correlates of progression have included a younger age, unstable angina, and greater involvement of the coronary arteries, with few studies looking at angiographic features of individual lesions. Serial angiograms on 74 patients were analyzed by computer assisted quantitative angiography using absolute measurements. A total of 99 diseased segments were analyzed for progression defined as an absolute reduction of 20% in luminal cross-sectional area. A preliminary correlation coefficient was calculated for each of the clinical and angiographic variables to detect any association with progression, and the odds ratio determined. The presence of any of the clinical risk factors-diabetes, hypertension, serum cholesterol, smoking, and a family history of coronary disease could not predict progression. The use of beta blockers was three times less likely to be associated with progression (odds ratio 0.33). While the presence of distal disease was associated with progression of a more proximal lesion (odds ratio 2.4), eccentricity, branch point location, lesion length, calcification, thrombus, or the presence of collaterals did not influence progression of disease in an individual segment. In conclusion, the presence of any of the clinical risk factors could not predict progression of disease in an individual coronary segment as determined by serial quantitative angiography, and the use of beta blockers and the absence of coexistent distal disease was associated with less progression of disease in an individual coronary segment. This may be related to changes in wall stress, reduced platelet interactions, and the integrity and permeability of the vascular endothelium to lipids.

Adrenergic beta-Antagonists↗

PubMed1998

Follow-up of asbestosis patients and predictors for radiographic progression.

OBJECTIVE: We followed a group of 85 Finnish asbestosis patients radiographically for an average of 6.5 (range 2-10) years to examine the progression of the disease and to assess possible explanations for the progression. METHODS: The examinations included full-size chest radiographs and a blood specimen analysis. The radiographs were classified according to the 1980 International Labor Office (ILO) classification. Progression was accepted if the second or third radiography was estimated (in a side-by-side comparison) to have more profusion of small opacities qualitatively than the first, even if the radiographs were classified into the same profusion category. RESULTS: In all, 38% of the patients showed progression during the follow-up period. The average progression of small opacities ranged from ILO 1/1 to ILO 2/2 (0.4 minor ILO categories/year). The asbestosis was progressive more often among the sprayers than among the insulators and asbestos factory workers [cross-tabulation, odds ratio (OR) 5.0, 95% confidence interval (95% CI) 1.2-20]. In the logistic regression model the ILO classification category at the beginning of the follow-up (OR 1.54; 95% CI 0.96-2.47), the fibronectin (OR 1.01; 95% CI 1.00-1.01) and angiotensin-converting enzyme (ACE; OR 1.10; 95% CI 1.00-1.20) levels, and the erythrocyte sedimentation rate (ESR; OR 1.05; 95% CI 1.00-1.10) were statistically associated with the radiographic progression of small opacities. Abnormalities of the pleura were found to progress more often among the patients with progressive parenchymal opacities. CONCLUSION: For the progression of small-opacity profusion the significant predictors in the logistic regression model were the ILO profusion category at the beginning of the follow-up period, the fibronectin level, the ACE value, and the ESR. The model correctly classified 94% of the patients with progression and 65% of those without progression. The differences in the mean values recorded for the biomarkers between the progressors and nonprogressors, however, were small and may therefore not be of any importance to the clinician.

Adult↗

PubMed2025

A viral clonality evenness score to predict progression to adult T-cell leukaemia in asymptomatic carriers of human T-lymphotropic virus type 1 in Japan: a retrospective longitudinal cohort study.

BACKGROUND: Adult T-cell leukaemia/lymphoma (ATL) is a highly aggressive T-cell malignancy that occurs in approximately 2-7% of individuals with human T-lymphotropic virus type 1 (HTLV-1), after decades of asymptomatic infection. To address the urgent need for predictive biomarkers to identify asymptomatic carriers of HTLV-1 at high risk of progression to ATL, we aimed to evaluate viral clonality sequencing as a potential tool for risk stratification. METHODS: This retrospective longitudinal cohort study involved HTLV-1 carriers enrolled in the Joint Study on Predisposing Factors of ATL Development, a nationwide cohort study initiated in Japan in 2002. Participants were selected from this cohort on the basis of their baseline proviral load at the time of enrolment as an asymptomatic carrier, length of follow-up, and clinical outcome. The cohort was subdivided into three subgroups: the first comprising HTLV-1 carriers who developed ATL, the second comprising carriers with high proviral load (≥4%) who did not progress to ATL, and the third comprising carriers with low proviral load (<4%) who did not progress to ATL. DNA extracted from peripheral blood mononuclear cells collected at enrolment and at least one follow-up visit was analysed by HTLV-1 clonality sequencing and the proviral load was quantified. We calculated a viral clonality evenness (VCE) score, based on the Shannon Evenness Index, to quantify the uniformity of the clonal distribution of samples, for which 0 represents a perfectly monoclonal architecture and 1 indicates a completely polyclonal landscape. We then estimated the performance of proviral load thresholds and VCE scoring to classify the risk of progression to ATL using the area under the receiver operating characteristic curve (AUC), the accuracy, and Matthews correlation coefficient. VCEs were compared between participant subgroups with the Wilcoxon rank sum test. FINDINGS: 56 participants followed up by JSPFAD between Feb 6, 2003, and July 19, 2022, were included in this study: 17 who progressed to ATL (mean follow-up 8·3 years [SD 4·0]), 18 who had a high proviral load and did not progress to ATL (9·7 years [3·4]), and 21 who had a low proviral load and did not progress to ATL (7·5 years [3·0]). Clonality sequencing of samples from 39 participants who did not progress to ATL revealed hundreds to thousands of HTLV-1 integration sites at both timepoints, corresponding to multiple clones of low and uniform abundance, and these participants had high VCE scores (≥0·694) at baseline. By contrast, most participants (14 of 17) who progressed to ATL had a single predominant clone or two to four predominant clones at both timepoints, and lower VCE scores (<0·694) at baseline than those who did not progress (p<0·0001). AUCs were very similar for proviral load thresholds (91 [95% CI 80-98]) and VCE scoring (91 [78-100]), although when using methods that give equal weight to every individual, VCE scoring outperformed proviral load thresholds in predicting progression to ATL (accuracy: proviral load 0·76 [95% CI 0·76-0·77], VCE scoring 1·00 [0·99-1·00]; Matthews correlation coefficient: proviral load 0·23 [95% CI 0·19-0·24], VCE scoring 0·91 [0·80-1·00]). Prediction based on VCE scoring indicated no false positives, compared with 20% when using proviral load, although VCE scoring yields a greater number of false negatives (0·3% vs 0·1%). INTERPRETATION: The implementation of VCE scoring in clinical practice could inform early pre-emptive therapeutic interventions, exclusively targeting individuals with HTLV-1 at high risk and aiming to prevent progression to aggressive, treatment-refractory disease. Further validation, including independent confirmation of the performance of VCE scoring in multiple populations and the characterisation of its temporal dynamics, will be crucial to determine its clinical utility and potential integration into care pathways. FUNDING: Association Jules Bordet, FNRS-Télévie, FCC, WALInnov, FLF, JSPS-KAKENHI, and CoBiA.

Humans↗

PubMed2002

Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community.

OBJECTIVES: This study was designed to analyze the association among cholesterol levels, lipid-lowering treatment, and progression of aortic stenosis (AS) in the community. BACKGROUND: Aortic stenosis is a progressive disease for which there is no known medical treatment to prevent or slow progression. Despite plausible pathologic mechanisms linking hypercholesterolemia to AS progression, clinical studies have been inconsistent and affected by referral bias, and the role of lipid-lowering therapy is uncertain. METHODS: We determined the association between blood cholesterol levels and progression of native AS (assessed by Doppler echocardiography at baseline and at least six months later; mean interval, 3.7 +/- 2.3 years) in a community-based study of 156 patients (age 77 +/- 12 years; 90 men). Thirty-eight patients received statin treatment during follow-up. RESULTS: In untreated subjects, mean gradient increased from 22 +/- 12 mm Hg to 39 +/- 19 mm Hg, and aortic valve area (AVA) decreased from 1.20 +/- 0.35 cm(2) to 0.91 +/- 0.33 cm(2) (both p < 0.001). The annualized change in AVA was -0.09 +/- 0.17 cm(2)/year (-7% +/- 13%/year). Neither total cholesterol (r = -0.01, p = 0.92) nor low-density lipoprotein cholesterol (r = 0.01; p = 0.88) showed a significant correlation to AS progression. Nevertheless, progression of AS was slower in patients receiving statins compared with untreated patients (decrease in AVA -3 +/- 10% vs. -7 +/- 13% per year, respectively; p = 0.04), even when adjusted for age, gender, cholesterol, and baseline valve area (p = 0.04). The association of statin treatment with slower progression was confirmed when analysis was restricted to patients coming for a systematic follow-up (p=0.02). The odds ratio of AS progression with statin treatment was 0.46 (95% confidence interval, 0.21 to 0.96). CONCLUSIONS: In the community, progression of AS shows no trend of association with cholesterol levels. Statin treatment, however, is associated with slower progression, suggesting that the effects of statin treatment on progression of AS should be pursued with appropriate clinical trials.

Adolescent↗

PubMed1999

Progression of mitral regurgitation: a prospective Doppler echocardiographic study.

OBJECTIVES: This study was performed to define the rates and determinants of progression of organic mitral regurgitation (MR). BACKGROUND: Severe MR has major clinical consequences, but the rates and determinants of progression of the degree of regurgitation are unknown. Quantitative Doppler echocardiographic methods allow the quantitation of regurgitant volume (RVol), regurgitant fraction (RF) and effective regurgitant orifice (ERO) to define progression of MR. METHODS: In a prospective study of MR progression, 74 patients had two quantitative Doppler echocardiographic examinations of MR (with at least two methods) 561 +/- 423 days apart without an intervening event. RESULTS: Progression of MR was observed, with increase in RVol (77 +/- 46 ml vs. 65 +/- 40 ml, p < 0.0001), RF (47 +/- 16% vs. 43% +/- 15%, p < 0.0001), and ERO (50 +/- 35 mm2 vs. 41 +/- 28 mm2, p < 0.0001). Annual rates (95% confidence interval) were, respectively, 7.4 ml/year (5.1, 9.7), 2.9%/year (1.9, 3.9) and 5.9 mm2/year (3.9, 7.8). However, wide individual variation was observed, and regression and progression of RVol >8 ml was found in 11% and 51%, respectively. In multivariate analysis, independent predictors of progression of RVol were progression of the lesions, particularly a new flail leaflet (p = 0.0003), and progression of mitral annulus diameter (p = 0.0001). Regression of MR was associated with marked changes in afterload, particularly decreased blood pressure (p = 0.008). No significant effect of treatment was detected. CONCLUSIONS: Organic MR tends to progress over time with increase in volume overload (RVol) due to increase in ERO. Progression of MR is variable and determined by progression of lesions or mitral annulus size. These data should help plan follow up of patients with organic MR and future intervention trials.

Adult↗

PubMed2002

Effect of cataract surgery on the progression of diabetic retinopathy.

PURPOSE: To study the effect of cataract surgery and other factors on the progression of diabetic retinopathy using the nonoperated contralateral eye as a control. SETTING: Department of Ophthalmology, Catholic University Medical College, Uijongbu St. Mary's Hospital, Seoul, Korea. METHODS: Monocular cataract surgery was performed in 75 patients who had the same degree of retinopathy or no retinopathy in both eyes preoperatively. Patients were assigned to 1 of 2 groups as follows: Group A, progression of retinopathy in the operated eye caused by cataract surgery; Group B, no progression of retinopathy bilaterally, comparable level of progression in both eyes, or more progression of retinopathy in the nonoperated eye than in the operated eye. The differences between the 2 groups in age, duration of and treatment methods for diabetes, renal function, and presence of preoperative macular edema were compared. The 1-year follow-up included evaluation of the progression of retinopathy. RESULTS: Surgery caused the retinopathy to progress in 23 patients (30.6%, Group A); 52 patients (69.4%, Group B) had no progression of retinopathy or a comparable level of retinopathy postoperatively. The operated eye had more progression of retinopathy than the nonoperated contralateral eye (P <.05). There was no significant difference between the 2 groups in age, diabetes duration, surgical method, or hypertension. Preoperative macular edema and poor renal function significantly affected the progression of diabetic retinopathy after cataract surgery (P <.05). CONCLUSIONS: Diabetic retinopathy progressed after cataract surgery. The presence of preoperative macular edema and poor renal function increased the progression of retinopathy postoperatively.

Capsulorhexis↗