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PubMed2003

The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis.

BACKGROUND: Some studies suggest that progression of renal disease is slower in women than in men. However, other factors that are also associated with progression of renal disease have not always been taken into account. Therefore, we undertook this analysis to explore the independent association of renal disease progression with gender. METHODS: We analysed a pooled database of patients with non-diabetic renal disease enrolled in 11 randomized controlled trials evaluating the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) for slowing renal disease progression. The primary end point was the combined outcome of doubling of baseline serum creatinine or onset of end-stage renal disease (ESRD). The secondary end point was the onset of ESRD alone. We performed multivariable Cox proportional hazards analysis to study the independent effect of gender on these end points after adjusting for baseline patient characteristics, and changes from baseline to follow-up systolic blood pressure (SBP) and urine protein (UP) excretion. RESULTS: The total number of patients was 1860: 645 (35%) females and 1215 (65%) males. Mean duration of follow-up was 2.2 years. The proportions randomized to ACEI (51%), mean baseline serum creatinine (2.2 mg/dl) and mean age (52 years) were similar for both genders. Mean baseline SBP was greater in women than in men: 151 vs 147 mmHg (P < 0.001). Mean baseline UP was significantly lower in women compared with men: 1.3 vs 2.1 g/day (P < 0.001). A total of 311 (16.7%) patients developed the primary end point, and 176 (9.5%) developed the secondary end point. The unadjusted relative risk (RR) with 95% confidence interval (CI) for the primary end point in women vs men was 0.98 (0.77-1.24). It became 1.32 (1.03-1.69) after adjusting for the baseline variables and interaction between ACEIs and baseline UP, and 1.36 (1.06-1.75) after adjusting for baseline variables and changes in SBP and UP during follow-up. Similar results were found for the outcome of ESRD. CONCLUSIONS: Our findings suggest that the rate of renal disease progression may not be slower, and may even be faster in women compared with men, after adjusting for other factors associated with a faster rate of progression. We caution that most women in our database were of post-menopausal age, and thus our findings may not extend to younger women.

Adult↗
PubMed2004

Determinants of progressive vascular calcification in haemodialysis patients.

BACKGROUND: We determined recently that targeted treatment with calcium-based phosphate binders (calcium acetate and carbonate) led to progressive coronary artery and aortic calcification by electron beam tomography (EBT), while treatment with the non-calcium-containing phosphate binder, sevelamer, did not. Aside from the provision of calcium, we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups. METHODS: We explored potential determinants of progressive vascular calcification in 150 randomized study subjects who underwent EBT at baseline and at least once during follow-up (week 26 or 52). RESULTS: Among calcium-treated subjects, higher time-averaged concentrations of calcium, phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores; no such associations were demonstrated in sevelamer-treated subjects. The relation between parathyroid hormone (PTH) and the progression of calcification was more complex. Lower PTH was associated with more extensive calcification in calcium-treated subjects, whereas higher PTH was associated with calcification in sevelamer-treated subjects. Serum albumin was inversely correlated with progression in aortic calcification. Sevelamer was associated with favourable effects on lipids, although the link between these effects and the observed attenuation in vascular calcification remains to be elucidated. CONCLUSION: Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. Calcium may directly or indirectly (via PTH) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients.

Aged↗
PubMed2004

Chlamydial infection and progression of carotid atherosclerosis in patients on regular haemodialysis.

BACKGROUND: Recent findings have suggested a possible contribution of chlamydial infection to the pathogenesis of atherosclerosis in the general population. However, the role that chlamydial antibody status plays in atherosclerosis generation in haemodialysis (HD) patients remains uncertain. METHODS: We measured carotid artery intima medial thickness (IMT) over 4 years in 100 HD subjects (age: 58+/-10 years; time on HD: 13+/-7 years; male/female: 67/33) and examined potential associations between Chlamydia pneumoniae (Cp) antibody seropositivity and changes in carotid artery IMT. RESULTS: During 4 years, carotid artery IMT increased significantly from 0.62+/-0.13 to 0.73+/-0.12 mm (P< 0.01). IMT progression was significantly and positively correlated with age (r = 0.37, P<0.01), log-transformed C-reactive protein (CRP; r = 0.33, P<0.01) and log-transformed interleukin-6 (IL-6; r = 0.22, P<0.04), but inversely correlated with blood creatinine (r = -0.36, P<0.01) and albumin (r = -0.24, P<0.02). IMT increases were more prominent in patients positive for IgA antibodies (0.039+/- 0.022 mm/year, n = 52) compared with those without IgA antibodies (0.025+/-0.032 mm/year, n = 48) (P<0.01). IgA seropositivity did not accelerate IMT progression in patients with increased CRP (>0.11 mg/dl, n = 53), but significantly increased IMT to a greater extent in IgA-positive subjects than in IgA-negative subjects having lower CRP (</=0.11 mg/dl, n = 47) (0.017+/-0.024 vs 0.034+/- 0.021 mm/year; P = 0.01). Multivariate regression analysis revealed that serum creatinine, log-transformed CRP and IgA Cp seropositivity were independent risk factors for IMT progression (P<0.01). In contrast, IgG Cp antibody did not affect IMT progression or carotid plaque formation. CONCLUSIONS: IMT progression is associated with inflammation and malnutrition. In addition, persistent chlamydial infection may be associated with IMT progression, but only in HD patients having low blood CRP.

Aged↗
PubMed2005

Monoclonal antibody 1-22-3-induced glomerulonephritis in uninephrectomized rats as a model of progressive renal failure.

BACKGROUND: At present, there are few available animal models of progressive renal failure originating from mesangial proliferative glomerulonephritis (GN). In the current study, we examined the usefulness of anti-Thy-1 monoclonal antibody (mAb) 1-22-3-induced GN in uninephrectomized rats as a model of progressive renal failure by analysing the similarities to human disease. METHODS: GN was induced by intravenous injection of mAb 1-22-3 into uninephrectomized male Wistar rats. The natural course of the disease was analysed in this model for 47 weeks. The effect of treatment with the angiotensin-converting enzyme inhibitor, captopril, on renal functional outcome was also examined in this model for 23 weeks, beginning from 1 week after antibody injection. RESULTS: Injection of mAb 1-22-3 induced a persistent proteinuria during the entire study period. Animals showed a progressive decline in renal function and 63% died by week 47. Severe glomerular and tubulointerstitial lesions were consistently observed. Treatment with captopril significantly inhibited increases in proteinuria and blood pressure, and attenuated renal injury. Captopril also retarded the progression of renal failure, and decreased mortality. Finally, the level of proteinuria was significantly correlated with the rate of decline in renal function, and the reduction in proteinuria by captopril was accompanied by a slower progression of renal failure. CONCLUSIONS: The mAb 1-22-3-induced GN in a uninephrectomized rat model simulates the clinical manifestations of human disease, indicating that this model may be useful for studying progressive renal failure and for investigating new therapeutic strategies against renal failure.

Animals↗
PubMed1997

The effect of simvastatin on progression of coronary artery disease. The Multicenter coronary Intervention Study (CIS).

BACKGROUND: In several angiographic trials, HMG-CoA reductase inhibitors have shown a beneficial effect on the progression of coronary artery disease. Using 20 mg simvastatin, day-1, a treatment period of up to 4 years was necessary to show a significant reduction in coronary artery disease progression. The question remains however whether higher dosages of simvastatin would be more advantageous in respect to the magnitude of the effect and the required time interval to demonstrate treatment efficacy. METHODS AND RESULTS: In the Coronary Intervention Study (CIS), a multicentre randomized double-blind placebo-controlled study, the effects of lipid-lowering therapy with simvastatin on progression of coronary artery disease in 254 men with documented coronary artery disease and hypercholesterolaemia were investigated. Following a period of lipid-lowering diet, treatment with 40 mg simvastatin or placebo was maintained for an average of 2.3 years. Two primary angiographic endpoints were chosen: the global change score (visual evaluation according to the method of Blankenhorn) and the per patient mean change of minimum lumen diameter (evaluated by the CAAS I system). The mean simvastatin dose was 34.5 mg day-1. In the placebo group, the serum lipids remained unchanged; in comparison to the placebo group the simvastatin group showed a 35% LDL-cholesterol decrease. Coronary angiography was repeated in 205 patients (81%) and 203 film pairs (80%,) were evaluable by quantitative coronary angiography. In the simvastatin and placebo groups, the mean global change scores were +0.20 and +0.58 respectively, demonstrating a significantly slower progression of coronary artery disease in the treatment group (P = 0.02). The change in minimum lumen diameter assessed by computer-assisted quantitative evaluation with the CAAS I system was -0.02 mm in the simvastatin group and -0.10 mm in the placebo group (P = 0.002). In the simvastatin group, there was a significant correlation between the LDL cholesterol levels achieved therapeutically and the per patient mean loss of minimum lumen diameter (r = 0.29; P = 0.003). During the study period, there was no significant difference in the incidence of serious cardiac events (15 of 129 patients in the simvastatin group and 19 of 125 patients in the placebo group, ns). CONCLUSION: Treatment with 40 mg simvastatin day-1 reduces serum cholesterol and slows the progression of coronary artery disease significantly within a short period of treatment time. In the treatment group, retardation of progression is inversely correlated to the LDL-cholesterol levels achieved.

Adult↗
PubMed1998

Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group.

OBJECTIVE: This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis. SUMMARY BACKGROUND DATA: Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome. METHODS: Variables analyzed for their impact on progression-free survival in a multi-institutional cohort of 329 patients included age, antecedent thyroid irradiation, extrathyroidal tumor extension, size, nodal involvement, distant metastases, technique of thyroid surgery and lymphatic dissection, initial treatment with 131Iodine, residual cervical disease, and histopathologic subtype. Surgical complications were correlated with the specific procedures completed on the thyroid gland or cervical lymphatics. RESULTS: The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at 10 years with 2 disease-related deaths. Regional lymph node and distant metastases were present in 74% and 25% of patients, respectively. Progression-free survival was less in younger patients (p = 0.009) and those with residual cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was more frequent after total or subtotal thyroidectomy (p = 0.001) while wound complications increased after radical neck dissections (p < 0.00001). CONCLUSIONS: The progression-free survival rate was better after a complete resection and in older patients. Progression-free survival rate was the same after lobectomy or more extensive thyroid procedures, but comparison was confounded by the increased use of total or subtotal thyroidectomy in patients with advanced disease. The risk of permanent hypocalcemia increased when total or subtotal thyroidectomy was done. Thyroid lobectomy alone may be appropriate for patients with small localized lesions while total or subtotal thyroidectomy should be considered for more extensive tumors.

Adolescent↗
PubMed2003

Prediction of sites of coronary atherosclerosis progression: In vivo profiling of endothelial shear stress, lumen, and outer vessel wall characteristics to predict vascular behavior.

PURPOSE OF REVIEW: Native atherosclerosis and in-stent restenosis are focal and evolve independently. The endothelium regulates arterial behavior by responding to its local environment of hemodynamic stresses, in particular, shear stress. Identification of endothelial shear stress and arterial wall characteristics may allow for the prediction of the progression of atherosclerosis. Accurate identification of arterial segments at high risk for progression may permit preemptive intervention strategies to avoid adverse coronary events. RECENT FINDINGS: In vitro studies indicate that low endothelial shear stress upregulates the genetic and molecular responses leading to the initiation and progression of atherosclerosis, and promotes inflammation and formation of other features characteristic of vulnerable plaque. Physiologic endothelial shear stress is vasculoprotective and fosters quiescence of the endothelium and vascular wall. High endothelial shear stress promotes platelet aggregation. Recent studies have now provided evidence that endothelial shear stress and vascular wall morphology along the course of human coronary arteries can be characterized in vivo, and, in serial studies, may actually predict the focal areas in which atherosclerosis progression occurs. SUMMARY: Rapidly evolving methodologies are able to characterize the arterial wall and the local hemodynamic environmental factors likely responsible for progression of coronary disease in humans. These new diagnostic modalities allow for identification of plaque progression. Future studies need to identify the factors responsible for vulnerable plaque formation. The current availability of drug-eluting stents with a low risk of restenosis allows for consideration of preemptive intervention strategies for these high-risk vascular sites such that future adverse coronary events can be averted.

Coronary Artery Disease↗
PubMed1998

The effects of lamivudine treatment on HIV-1 disease progression are highly correlated with plasma HIV-1 RNA and CD4 cell count.

OBJECTIVE: To determine the value of plasma HIV-1 RNA and CD4 cell count as predictors of the clinical benefit of antiretroviral treatment. DESIGN AND SETTING: The CAESAR (Canada, Australia, Europe, South Africa) trial randomized 1840 patients [inclusion CD4 cell count, 25-250 x 10(6)/l] to add either placebo, lamivudine (3TC) or 3TC plus loviride in a double-blinded fashion to baseline treatments (zidovudine, zidovudine-didanosine or zidovudine-zalcitabine) for 1 year. PATIENTS: This analysis included 487 patients with data on CD4 cell count and HIV-1 RNA after 12-20 weeks of treatment and subsequent follow-up for clinical progression. MAIN OUTCOME MEASURES: The correlation between 12-20-week change in CD4 cell count, HIV-1 RNA and progression to AIDS or death in the placebo group was used to predict the clinical benefit of the 3TC-containing arms of the trial, given their effects on CD4 cell count and HIV-1 RNA. RESULTS: After 12-20 weeks of treatment, HIV-1 RNA fell by 0.37 log10 copies/ml in the 3TC arms versus a rise of 0.05 log10 copies/ml in the placebo arm. The 12-20-week CD4 cell count rose by 35 x 10(6)/l in the 3TC arm versus a fall of 8 x 10(6)/l in the placebo arm. After 12-20 weeks of treatment, a reduction in HIV-1 RNA of 1 log10 at 12-20 weeks predicted a 49% reduction in progression [hazard ratio (HR), 0.51; 95% confidence interval (CI), 0.30-0.87] and a rise in CD4 cell count of 50 x 10(6)/l predicted a 51% reduction in progression (HR, 0.49; 95% CI, 0.33-0.73). Using the model from the placebo arm, the rises in CD4 cell count and reductions in HIV-1 RNA during 3TC treatment predicted a 59% reduction in progression to AIDS or death. The observed clinical benefit was a 57% reduction in progression for the 3TC arms versus placebo (HR, 0.43; 95% CI, 0.26-0.71). CONCLUSIONS: Rises in CD4 cell count and reductions in HIV-1 RNA were reliable in predicting the clinical benefit of 3TC in the CAESAR trial.

Acetamides↗
PubMed1998

HIV-1 RNA, CD4 cell count and the risk of progression to AIDS and death during treatment with HIV-1 reverse transcriptase inhibitors.

CONTEXT: There is little information available on the correlation between HIV-1 RNA level, CD4 cell count and the risk of progression to AIDS or death during treatment with reverse transcriptase inhibitors. OBJECTIVES: To define the correlation between HIV-1 RNA level, CD4 cell count and the 1 year risk of progression to AIDS or death. DESIGN: Pooled analysis of six randomized clinical trials of zidovudine/lamivudine versus control treatments. SETTING: Investigational sites in Europe, North America, Australia and South Africa. PATIENTS: The trials recruited 1488 adult HIV-1-infected male and female patients aged > or = 18 years, with inclusion CD4 cell count between 25 and 500 x 10(6) cells/l. Patients were either nucleoside analogue-naive or pre-treated, and at all stages of HIV-1 disease. MAIN OUTCOME MEASURES: : Progression (defined as all new and recurrent AIDS-defining events or death) was correlated with the HIV-1 RNA level and CD4 cell count during the first 8 to 52 weeks of treatment. RESULTS: During a median 1 year follow up, progression was largely restricted to patients with both low CD4 cell count (< or = 200 x 10(6) cells/l) and high HIV-1 RNA level (> 5000 copies/ml). There was an increase in the incidence of progression events with rises in HIV-1 RNA level > 5000 copies/ml and reductions in CD4 cell count under 200 x 10(6) cells/l. The events occurring with HIV-1 RNA < 5000 copies/ml were generally atypical. CONCLUSIONS: Progression to AIDS or death is rare for patients with HIV-1 RNA < or = 5000 copies/ml, particularly when CD4 cell count is more than 200 x 10(6) cells/l.

AIDS-Related Opportunistic Infections↗
PubMed1998

The estimated impact of the CCR-5 delta32 gene deletion on HIV disease progression varies with study design. Oslo HIV Cohort Study Group.

OBJECTIVES: To study the impact of the genotype CCR-5 wild-type +/A32 on the progression rate to AIDS and death, and to discuss sources of bias according to study design. METHODS: A prospective study of 310 HIV-positive subjects with follow-up time from study entry (prevalent cohort), and a prospective study of 105 HIV-positive subjects with well-defined time of HIV seroconversion, with follow-up time from the retrospectively assessed date of HIV seroconversion (retrospective incident cohort). RESULTS: Slower progression to AIDS among subjects with CCR-5 +/delta32 than those with CCR-5 +/+ genotype was estimated in the prevalent cohort (P=0.07, log-rank test). Slower progression to death from any cause was also estimated for subjects with CCR-5 +/delta32 (P < 0.05, log-rank test). No differences in survival after AIDS diagnosis were seen (P=0.89, log-rank test). No differences in the progression rate to AIDS (P=0.82, log-rank test) or death (P=0.78, log-rank test) were estimated in the retrospective incident cohort. CONCLUSIONS: The varying estimates of the impact of CCR-5 genotype on progression to AIDS in this and other studies, may be real and reflect differences in the dependence of HIV on the CCR-5 receptor, or may be due to systematic errors caused by study design. Several methodological difficulties occur when the factor studied, such as CCR-5 genotype, is associated both with the risk of being HIV-infected and the progression of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1999

The influence of nutritional and metabolic status on progression from asymptomatic HIV infection to AIDS-defining diagnosis.

BACKGROUND: Changes in body weight and lean tissue increase morbidity and mortality during AIDS; however there are few data on the effect of alterations in nutrition and metabolism on disease progression at earlier stages of HIV infection. OBJECTIVES: To assess whether change in weight, lean tissue or skeletal muscle affects progression to AIDS; to assess prospectively the effects of recognized alterations in nutrition and metabolism in asymptomatic HIV-seropositive men on disease progression; and to examine prospectively changes in nutrition and metabolism at AIDS-defining diagnosis. METHODS: A group of 104 asymptomatic HIV-seropositive men were recruited and prospectively examined at 3-monthly intervals between April 1993 and September 1995. Nutritional status and metabolism were examined using indirect calorimetry, dual energy X-ray absorptiometry and urine excretion of simple sugars. Time-fixed and time-dependent Cox's proportional hazard models were fitted to calculate risks of developing a first AIDS diagnosis, weight loss or death. RESULTS: During the study period, 31 subjects had a first AIDS diagnosis of whom 26 were fully assessed. Changes in nutrition and metabolism do not affect disease progression in asymptomatic HIV infection. However, subjects with a reduction in body weight and basal metabolic index tend to have a higher risk of progression to AIDS-defining diagnosis, independent of CD4 count. There is a significant decrease in all body tissue compartments, a decrease in excretion of urinary sugars and significant increase in resting energy expenditure and fat oxidation associated with a first AIDS diagnosis. CONCLUSION: Change in metabolic and nutritional status at the asymptomatic stage of HIV infection does not influence disease progression significantly, although there is a trend suggesting weight loss has an independent effect on outcome. There is a cachectic response to AIDS-defining opportunistic infection or tumour.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Relationship between HIV-1 Env subtypes A and D and disease progression in a rural Ugandan cohort.

OBJECTIVE: To investigate the role of HIV-1 envelope subtypes on disease progression in a rural cohort of Ugandan adults where two major HIV-1 subtypes (A and D) exist. METHODS: Participants of a clinical cohort seen between December 1995 and December 1998 had blood collected for HIV-1 subtyping. These included prevalent cases (people already infected with HIV at the start of the study in 1990) and incident cases (those who seroconverted between 1990 and December 1998). HIV-1 subtyping was carried out by heteroduplex mobility assay and DNA sequencing in the V3 env region. Disease progression was measured by the rate of CD4 lymphocyte count decline, clinical progression for the incident cases as time from seroconversion to AIDS or death, to first CD4 lymphocyte count < 200 x 10(6)/l and to the World Health Organization clinical stage 3. All analyses were adjusted for age and sex. RESULTS: One hundred and sixty-four individuals, including 47 prevalent and 117 incident cases, had V3 env subtype data of which 65 (40%) were subtyped as A and 99 as D. In the incident cases, 44 (38%) were subtyped as A and 73 as D. There was a suggestion that for most end-points A had a slower progression than D. The cumulative probability of remaining free from AIDS or death at 6 years post-seroconversion was 0.72 [95% confidence interval (CI), 0.50 to 0.85] for A and 0.58 (95% CI, 0.42 to 0.71) for D, and the adjusted hazard ratio of subtype D compared to A was estimated to be 1.39 (95% CI, 0.66 to 2.94; P = 0.39). The estimated difference in rates of decline in square root CD4 lymphocyte counts was -0.41 per year (95% CI, -0.98 to 0.15; P = 0.15). CONCLUSION: This study suggests that although subtype A may have a slower progression than D, HIV-1 envelope subtype is not a major factor in determining the progression of HIV-1 disease in a rural population in Uganda.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Maternal health factors and early pediatric antiretroviral therapy influence the rate of perinatal HIV-1 disease progression in children.

OBJECTIVE: To determine the relationship of maternal health factors and infant antiretroviral treatment to the risk of pediatric disease progression to AIDS or death by 24 months of age. DESIGN: Prospective perinatal HIV-1 transmission and pediatric natural history study. SETTING: Urban medical centers in four cities in the USA. PARTICIPANTS: A total of 2656 pregnant and postpartum HIV-infected women enrolled in the Perinatal AIDS Collaborative Transmission Study (PACTS) and 360 children determined to be HIV-infected. MAIN OUTCOME MEASURES: Pediatric AIDS or death by 24 months of age. RESULTS: Children born to mothers with class C disease, CD4 cell count < 200 x 106/l, or HIV-1 RNA viral load > 100 000 copies/ml progressed more rapidly than children born to mothers with less advanced disease. In a multivariate analysis, there was an increased risk of progression if mothers had Class C disease [relative risk (RR), 1.7; 95% confidence interval (CI), 1.0-2.7] or HIV-1 RNA > 100 000 copies/ml (RR, 2.4; 95% CI, 1.2-4.6) controlling for child antiretroviral therapy and year of birth. Earlier years of birth significantly increased the likelihood of rapid progression (P = 0.01) in this multivariate model. Children who received combination antiretroviral therapies with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor were significantly less likely to progress compared with those receiving no therapy (P = 0.03). CONCLUSIONS: HIV-1-infected infants born to women with advanced HIV-1 disease were at increased risk for rapid disease progression. More recent birth year and early treatment with potent antiretroviral therapy significantly diminished the likelihood of developing AIDS or dying during early childhood.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Factors associated with clinical progression in HIV-2 infected-patients: the French ANRS cohort.

OBJECTIVES: To identify factors associated with clinical progression in HIV-2 infected patients. DESIGN: French prospective cohort initiated in 1994. METHODS: Follow-up data are collected twice a year; viral load is assessed once a year by cellular viraemia, quantitative proviral DNA and plasma RNA. A Cox proportional-hazards model was used for studying baseline factors associated with clinical progression. RESULTS: By December 2001, 217 patients had been enrolled. At inclusion, 80%, 6% and 14% were Centers for Disease Control and Prevention (CDC) group A, B and C, respectively. Median CD4 cell count was 436 x 10(6)/l. In the 48% of positive specimens, the median plasma RNA titre was 3.0 log10 copies/ml. Mean follow-up of the 179 patients seen at least twice was 34.4 months. Of these 13 died and nine progressed to group C. Ninety-three (52%) received antiretroviral therapy during a mean of 33 months, including a protease inhibitor in 48%. The probability of remaining AIDS-free was 97% and 95% at 1 and 3 years, respectively. Independent variables associated with clinical progression were age > or = 40 years [hazard ratio (HR), 11; 95% confidence interval (CI), 1.4-91.8; P = 0.03] and plasma RNA (HR, 2.5 per additional log10 copies/ml; 95% CI, 1.3-4.7, P < 0.01). Prior group B symptoms and CD4 cell count < 200 x 10(6)/l were associated with progression to AIDS. AIDS and plasma RNA were predictive of death. CONCLUSION: Considering the limited progression rate of HIV-2 infection, combined antiretroviral therapy should be discussed in patients with high plasma RNA titres, which threshold value remains to be defined. It is recommended in case of AIDS, CDC group B symptoms or CD4 cell count < 200 x 10(6)/l.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Progression of joint arthrosis 10 to 15 years after high tibial osteotomy.

Forty-eight knees in 44 patients who had a high tibial osteotomy performed for medial compartment osteoarthritis were reevaluated twice, once at 1 year after surgery and again at 10 to 15 years after the high tibial osteotomy, to determine the effects of high tibial osteotomy on progression of medial and lateral joint arthrosis. Radiologically, although arthrosis significantly increased in the medial and the lateral joint compartment, there was no significant difference in the degree of progression between the two compartments. There was a significant correlation between the progression of medial joint arthrosis evaluated at 10 years or more after surgery and the femorotibial angle measured at 1 year. There was no significant correlation between the progression of lateral joint arthrosis in 10 to 15 years and the femorotibial angle measured at 1 year. The average knee function score improved significantly from 59.1 +/- 5.5 points before surgery to 85.1 +/- 6.1 points at the 1-year followup. At the final followup, the clinical score (80.7 +/- 5.4) had deteriorated relative to the 1-year results but still was significantly better than the preoperative score. The current results indicate that the greater the surgical valgus correction, the slower the progression of medial joint arthrosis. Lateral joint arthrosis did not progress more quickly after high tibial osteotomy, even if an overcorrection was performed.

Aged↗
PubMed2004

American Indian substance use: the hazards for substance use initiation and progression for adolescents aged 14 to 20 years.

OBJECTIVE: To describe the risks and risk factors for substance use initiation and progression among a large sample of American Indian (AI) adolescents. METHOD: Data came from surveys completed by 2,356 AI adolescents aged 14 to 20 years who participated in two or more consecutive waves of a longitudinal study between 1993 and 1996 (response rate 74%). Discrete-time survival analysis was used to describe the risks and risk factors for substance use initiation and progression. RESULTS: The risk for initiating use of any substance accelerated in early adolescence and peaked at age 18. The risk for progression from use of alcohol, marijuana, and/or inhalants to the use of other illicit drugs (e.g., cocaine) increased over the first 4.5 years after initiating substance use, then diminished in subsequent years. The risk of substance use initiation and progression varied across the four participating communities and by season of the year. Compared to adolescents who initiated substance use with alcohol only, adolescents who initiated substance use with marijuana or inhalants were more likely to progress to use other illicit drugs. CONCLUSIONS: Prevention programs for AI communities should be designed to address these community, age, and seasonal variations in the risks for substance use initiation and progression.

Adolescent↗
PubMed2000

Characterization and predictors of prostate specific antigen progression rates after radical retropubic prostatectomy.

PURPOSE: Detectable serum prostate specific antigen (PSA) after radical prostatectomy indicates recurrent disease and treatment failure. We characterized PSA recurrence after prostatectomy and identified predictors of rapid PSA progression. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 165 patients with detectable PSA after radical prostatectomy to characterize the rate of PSA increase and correlate this rate with the possible predictors of rapid PSA progression known at prostatectomy. RESULTS: For a median of 48 months postoperatively we followed 142 patients with PSA recurrence after radical prostatectomy who received no immediate adjuvant therapy. PSA doubling time was less than 6, greater than 6, 12, 18 and 24 months in 46%, 54%, 18%, 11% and 9% of cases, while time to PSA 50 ng./ml. was greater than 5, 10, 15 and 20 years in 69%, 34%, 22% and 9%, respectively. Univariate and multivariate analyses revealed that rapid PSA doubling time was associated with Gleason secondary grade, Gleason score and time to initial detectable PSA (p = 0.019, 0.031 and 0.0001, and p = 0.043, 0.045 and 0.0001, respectively). CONCLUSIONS: PSA recurrence progresses at a greatly variable rate and many recurrences progress slowly with a long doubling time. Gleason secondary grade and score appear to be predictive of rapid PSA progression. No other pathological features were predictive of rapid PSA progression.

Analysis of Variance↗
PubMed1996

Long-term follow-up of patients with meningiomas involving the cavernous sinus: recurrence, progression, and quality of life.

OBJECTIVE: In this report, we evaluate the recurrence- and progression-free survival of patients with meningiomas involving the cavernous sinus. METHODS: The rates of tumor recurrence and progression in 119 patients with meningiomas involving the cavernous sinus treated between 1983 and 1993 were analyzed. RESULTS: The mean follow-up period was 33.8 months. There were seven recurrences of completely resected tumors (7 of 73, 10%) and seven progressions of incompletely resected tumors (7 of 46 15%). Life table analysis of recurrence- and progression-free survival was performed. The recurrence-free survival rate was 94% at 3 years and 81% at 5 years. In contrast, the progression-free survival rate was 87% at 3 years and 62% at 5 years (P = 0.0456). There were two patterns of recurrence or progression. The first group of tumors had an aggressive biological behavior with growth at multiple areas of resection; the second group showed growth at or near the margins of resection. Functional status continued to improve slowly during the follow-up period; however, there was no statistically significant difference between the Karnofsky scores obtained 3 to 12 months postoperatively and the follow-up Karnofsky scores (obtained > 1 yr postoperatively). CONCLUSION: Surgery for meningiomas involving the cavernous sinus seems to provide excellent tumor control. Our experience suggests that for the majority of these tumors, complete tumor resection can be performed with acceptable risks of morbidity and mortality and seems to increase the duration of recurrence-free survival. The long-term quality of life of surviving patients is satisfactory, with the great majority of the patients being independent.

Cavernous Sinus↗