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PubMed2005

Hepatic stellate cells and fibrosis progression in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Many patients with nonalcoholic fatty liver disease (NAFLD) have a benign clinical course, but a subgroup of patients progress to advanced fibrosis and cirrhosis. However, there are no available clinical tools to predict fibrosis progression in this population. Activated hepatic stellate cells (HSCs) are the source of collagen deposition in the liver. We aimed at determining whether an HSC activation score predicts fibrosis progression in NAFLD patients. METHODS: The cohort consisted of 39 untreated patients with NAFLD with paired liver biopsies performed 5-59 months apart (mean, 22 months). Patients were divided into 2 groups on the basis of whether fibrosis progression was noted on their second liver biopsy. Liver tissue was immunostained for alpha-smooth muscle actin, and the HSC score was determined independently by 2 pathologists in the NAFLD population and in control subjects without liver disease. RESULTS: The HSC activation score was significantly increased in patients with fibrosis progression versus patients in whom no fibrosis progression was observed (4.8 +/- 0.5 vs 1.8 +/- 0.6, respectively; P < .001). The HSC score was accurate in predicting fibrosis progression, with a positive predictive value of 90%, specificity of 94%, and an area under the receiver operating characteristic curve of 0.82. However, the negative predictive value and sensitivity were 56% and 41%, respectively. The inter-pathologist agreement for the HSC score was excellent (kappa coefficient, 0.95). CONCLUSIONS: These findings suggest that the HSC activation score is a suitable clinical tool to determine the risk of fibrosis progression in patients with NAFLD.

Adult↗
PubMed2000

Effectiveness of heparin treatment for progressing ischaemic stroke: before and after study.

OBJECTIVES: During the acute phase of stroke, symptoms progress in 25% of patients, resulting in a worse outcome. Could heparin treatment improve the situation? DESIGN: Before and after study. During the first period, no treatment was given to patients with progress of symptoms, whereas heparin was used regularly in the second period. A comparison of outcome was performed. SETTING: Patients with acute stroke cared for in stroke units of two big emergency hospitals in Stockholm. Besides heparin treatment, the groups were taken care of according to the same basic principles. SUBJECTS: Consecutive patients admitted to a stroke unit during two periods of time. The first study comprised 314 patients with ischaemic stroke and the second 907. INTERVENTION: In the treatment period, patients with ischaemic stroke and objectively recognized progression received heparin infusion for at least 5 days. MAIN OUTCOME MEASURES: Continued progression, length of stay, unaided walking at discharge, discharge destination and mortality. RESULTS: The progression rate was non-significantly higher in the first period: 28 vs. 21%. One-third continued to progress regardless of treatment given. Patients with progression, treated and untreated alike, had 40% longer stay in the stroke unit compared with stable patients, whereas mortality was unaffected. Treatment did not reduce the proportion of patients who needed aid for walking at discharge (77 vs. 74%) or those who needed further institutionalized care (65 vs. 66%). CONCLUSION: Progression of focal stroke symptoms still constitutes a serious clinical problem for which heparin has insufficient effectiveness in clinical practice. New therapies, ideally preventive, are needed.

Activities of Daily Living↗
PubMed2000

Internal carotid artery stenosis: rate of progression.

OBJECTIVES: to assess the incidence and the rate of progression of internal carotid artery (ICA) stenosis and to determine the related risk factors. DESIGN: open prospective study. MATERIALS AND METHODS: between 1988-1997, 442 carotid arteries with various degrees of stenosis were followed using colour duplex ultrasonography every 6 months. Of these arteries, 290 (66%) were asymptomatic, 62 (14%) had caused transient ischaemic attack and 90 (20%) a stroke. In 145 cases (33%), there was concomitant coronary artery disease (CAD), in 134 (30%) diabetes mellitus, in 248 (56%) hypertension, in 139 (31%) hypercholesterolaemia and in 370 (84%) history of smoking. Of the plaques, 44 (10%) were uniformly echolucent, 19 (4%) haemorrhagic, 136 (31%) predominantly echolucent, 146 (33%) predominantly echogenic and 97 (22%) uniformly echogenic. RESULTS: significant progression of stenosis occurred in 82 cases (19%). The mean progression rate in these cases was 15% annually (range: 5-50%). There was no statistically significant correlation between the progression of the ICA stenosis and initial neurological status, age, gender, diabetes mellitus, hypertension, hypercholesterolaemia and smoking habit. Stenosis progression was correlated only with CAD and the ultrasonographic characteristics of the plaques. Patients with CAD as well as those with uniformly echolucent plaques presented a higher incidence and rate of stenosis progression (p<0.05). CONCLUSIONS: progression of internal carotid artery stenosis occurred in 19% of cases. The mean progression rate in these patients was 15% annually and was correlated with CAD and the ultrasonographic characteristics of the plaque.

Adult↗
PubMed1998

Components of the insulin resistance syndrome are associated with progression of atherosclerosis in non-grafted arteries 5 years after coronary artery bypass surgery.

AIMS: Risk factors for progression of atherosclerosis in non-grafted coronary arteries were examined in a prospective 5-year follow-up study of 228 consecutive coronary artery bypass surgery patients, with the main emphasis on insulin resistance syndrome. METHODS AND RESULTS: Serum lipids and lipoproteins were measured pre-operatively and 1, 2, 3 and 5 years after surgery; and a baseline oral glucose tolerance test with plasma insulin determinations was performed pre-operatively. Progression of atherosclerosis was assessed by means of computer-based quantitative coronary angiography. Compared to subjects without progression, the patients with progression of atherosclerotic lesions had a higher body mass index both at baseline (P = 0.022) and at 5 years (P = 0.007), were more often treated for hypertension at baseline (P = 0.008) and at 5 years (P = 0.012), used diuretics more often during the follow-up period (P = 0.002), had a larger blood glucose area under the curve (P = 0.015) and a lower insulin sensitivity index (P = 0.006) in the baseline oral glucose tolerance test, had a higher serum total cholesterol concentration at baseline (P = 0.044), and a higher serum triglyceride concentration (P = 0.005) during the whole follow-up period. Clustering of the components of insulin resistance syndrome at baseline was more frequently found in patients with progression of atherosclerotic lesions than in patients without progression (P = 0.025). For example, for patients with < or = 1 component, the risk of progression was 17%, while for patients with > or = 5 components the risk was 67%. As compared to the other patients, those with new atherosclerotic lesions had a lower insulin sensitivity index at baseline (P = 0.033), and a lower serum high density lipoprotein cholesterol concentration during the follow-up period (P = 0.033). CONCLUSION: In addition to high serum cholesterol, the components of the insulin resistance syndrome are associated with progression of atherosclerosis in non-grafted coronary arteries 5 years after coronary artery bypass surgery.

Adult↗
PubMed2002

Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability.

BACKGROUND & AIMS: Current models of colorectal adenoma to carcinoma progression do not fully reflect the genetic heterogeneity and complexity of the disease. The aim of the present study was to identify genetic changes discriminating adenomas that have progressed to carcinoma from adenomas that have not progressed, and to refine the current genetic models of colorectal adenoma to carcinoma progression, based on a genome-wide analysis of chromosomal aberrations. METHODS: Sixty-six nonprogressed colorectal adenomas, 46 progressed adenomas (malignant polyps), and 36 colorectal carcinomas were screened for chromosomal aberrations by comparative genomic hybridization, and for mutations in the adenomatous polyposis coli (APC) and K-ras gene. Data analysis focused on cancer-associated genetic changes in adenomas. RESULTS: Accumulation of losses in 8p21-pter, 15q11-q21, 17p12-13, and 18q12-21, and gains in 8q23-qter, 13q14-31, and 20q13 were strongly associated with adenoma-to-carcinoma progression, independent of the degree of dysplasia. Hierarchic cluster analysis demonstrated the presence of 3 distinct subgroups of adenomas, characterized by unique combinations of genetic aberrations in the adenomas (17p loss and K-ras mutation, 8q and 13q gain, and 18q loss and 20q gain, respectively). CONCLUSIONS: The presence of 2 or more of the aforementioned 7 chromosomal changes was associated with progressed colorectal adenomas and colorectal cancer. In addition, evidence was found that these chromosomal abnormalities occurred in specific combinations of a few abnormalities rather than as a mere accumulation of events, indicating the existence of multiple independent chromosomal instability pathways of colorectal cancer progression.

Adenoma↗
PubMed2005

Area socioeconomic status and progressive CKD: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Individual-level socioeconomic status (SES) has been found to be associated inversely with progressive chronic kidney disease (CKD); the effect of area-level SES on progressive CKD is less known. We conducted a cohort study of 12,856 Atherosclerosis Risk in Communities Study participants to examine the independent risk for progressive CKD associated with living in a low SES area. METHODS: Progressive CKD is defined as a creatinine level elevation of 0.4 mg/dL or greater (> or = 35 micromol/L) during a 9-year follow-up, hospitalization for CKD, or death. Area-level SES was characterized by using measures of income, wealth, education, and occupation for 1990 US Census block groups of residence. RESULTS: Age- and center-adjusted incidence rates (per 1,000 person-years) of progressive CKD by quartiles of area-level SES score showed increasing rates with decreasing SES for African-American women: quartile 1 (Q1; low) = 11.1, Q2 = 10.5, Q3 = 6.4, and Q4 = 7.1 and white men: Q1 = 6.6, Q2 = 4.8, Q3 = 4.0, and Q4 (high) = 3.5, but not for African-American men or white women. Cox proportional hazards models showed that living in the lowest versus the highest SES-area quartile was associated with a 60% greater risk for progressive CKD in white men after adjusting for age, center, baseline creatinine level, body mass index, and individual-level SES (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5). This risk and trend persisted after adjusting for such potential mediators as health awareness, health care access, and behavioral and physiological factors. We found no significant association of progressive CKD risk and area SES in white women, African-American women, or African-American men after adjustment. CONCLUSION: For white men, living in a low SES area is independently associated with greater risk for progressive CKD. Future research is needed to examine this association, considering the disparate effects found by race/sex groups.

Black or African American↗
PubMed2000

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma.

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.

Adult↗
PubMed1997

In utero progression of isolated renal pelvis dilation.

The objective of this study to determine the risk of in uteroprogression of renal pelvis dilation when detected on antenatal ultrasound examination. We reviewed 230 fetuses with evidence of renal pelvis dilation. At least one exam was subsequently performed prior to delivery in all cases. Renal pelvis dilation was defined as an anterior-posterior renal pelvis measurement > 4 mm at < 32 weeks' and > 7 mm at > or = 32 weeks' gestation. Hydronephrosis was considered to be present when the renal pelvis measured +10 mm independent of gestational age. Multiple gestations and fetuses with additional congenital anomalies were excluded. The mean gestational age at diagnosis was 24 weeks. Renal pelvis dilation progressed to hydronephrosis in a total of 10.9% (25 of 230) of fetuses. There was a 3.3% chance of unilateral renal pelvis dilation progressing to hydronephrosis versus 26.0% in bilateral dilation (OR 10.4 [95% Cl 3.5-33.3]). Of those fetuses with progression, 80% had bilateral dilation (p < 0.0001). There was no difference in progression between right and left kidneys. Additionally, gender, gestational age at diagnosis and delivery, and birth weight did not differ between those fetuses with and without progression. The hydronephrosis in 7 of 25 (28%) regressed to pyelectasis on a subsequent ultrasound exam. Thus, the overall rate of progression of renal pelvis dilation to persistent hydronephrosis was 7.8% (18 of 230). In conclusion, the risk of isolated renal pelvis dilation progressing to hydronephrosis is low. Although bilateral pelvis dilation carries a higher risk for progression, no fetus in our study required in utero intervention. A follow up scan prior to delivery may be considered to identify those fetuses who will require postpartum intervention.

Adult↗
PubMed1999

Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group.

BACKGROUND AND METHODS: Cytomegalovirus (CMV) has been implicated as a cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We assessed 440 infants (75 of whom were HIV-1-infected and 365 of whom were not) who had known CMV status and were born to HIV-1-infected women and who were followed prospectively. HIV-1 disease progression was defined as the presence of class C symptoms (according to the criteria of the Centers for Disease Control and Prevention [CDC]) or CD4 counts of less than 750 cells per cubic millimeter by 1 year of age and less than 500 cells per cubic millimeter by 18 months of age. RESULTS: At birth the frequency of CMV infection was similar in the HIV-1-infected and HIV-1-uninfected infants (4.3 percent and 4.5 percent, respectively), but the HIV-1-infected infants had a higher rate of CMV infection at six months of age (39.9 percent vs. 15.3 percent, P=0.001) and continued to have a higher rate of CMV infection through four years of age (P=0.04). By 18 months of age, the infants with both infections had higher rates of HIV-1 disease progression (70.0 percent vs. 30.4 percent, P=0.001), CDC class C symptoms or death (52.5 percent vs. 21.7 percent, P=0.008), and impaired brain growth or progressive motor deficits (35.6 percent vs. 8.7 percent, P=0.005) than infants infected only with HIV-1. In a Cox regression analysis, CMV infection was associated with an increased risk of HIV-1 disease progression (relative risk, 2.59; 95 percent confidence interval, 1.13 to 5.95). Among children infected with HIV-1 alone, but not among those infected with both viruses, children with rapid progression of HIV-1 disease had higher mean levels of HIV-1 RNA than those with slower or no progression of disease. CONCLUSIONS: HIV-1-infected infants who acquire CMV infection in the first 18 months of life have a significantly higher rate of disease progression and central nervous system disease than those infected with HIV-1 alone.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Familial clustering and myopia progression in Singapore school children.

BACKGROUND: Familial factors may be related to the progression of myopia in children. A cohort study was conducted to determine the relationship between familial factors and myopia progression in children. METHODS: From a larger clinical trial (n = 311), 153 Singapore children aged 6--12 years were recruited to participate in a cohort study of the risk factors for myopia progression. An in-person interview was conducted whereby information on the history of myopia in first-degree relatives was obtained. Other information collected included housing type, parental education and income. Cycloplegic refractive error as measured by subjective refraction and autorefraction were ascertained every six months. The average length of follow-up was 28 months. RESULTS: The adjusted mean rate of progression of myopia was -0.60 (95% confidence interval -0.66, -0.55) diopters per year. The average rate of progression of myopia for children with a parental history of myopia was -0.63 (95% confidence interval -0.69, -0.56) diopters per year compared to -0.42 (95% confidence interval -0.57, -0.27) diopters per year for children whose parents were not myopic. The different measures of family history of myopia were related to rate of change in refractive error and refractive error in the final visit. There was no association between close work and myopia progression. CONCLUSIONS: A positive family history is related to the progression of myopia and final refractive error in Singapore children, thus supporting evidence that hereditary factors may play an important role in myopia progression.

Child↗
PubMed2003

Progressive hearing loss after closed head injury: a predictable outcome?

OBJECTIVES: To evaluate the prevalence of progression of closed head injury (CHI)-induced hearing impairment, defined as > or = 15 dB HL deterioration at 1 or more frequencies, and to identify risk factors in patient history and initial status that could predict progression. MATERIAL AND METHODS: A total of 600 patients with major CHI were admitted to 2 Swedish medical centres during a 14-year period. The type of injury was established by means of CT and the severity of head injury was measured using the Swedish Reaction Level Scale (RLS). In 62 of these patients, pure-tone audiometry was performed soon after the injury. Forty-three patients agreed to participate in the present investigation, which was carried out 2-13 years after the injury. Each participant was evaluated using pure-tone audiometry and an itemized anamnesis was obtained. RESULTS: There was a higher prevalence of hearing impairments in the study group compared to a control group. Thirty-two subjects (74%,) showed a progression of > or = 15 dB, which was significantly greater than the spontaneous progression in the control group. Age and temporal bone fracture were risk factors for progression but not brain contusion only or RLS. There was an association between early pure-tone average (PTA) and progression as well as regression, i.e. the poorer the initial PTA the greater the progression as well as regression, indicating increased instability in the auditory system. Examination of patient histories did not reveal any single risk factors for progression. A serendipitous finding was a higher prevalence of reported memory shortcomings among those with post-traumatic tinnitus. CONCLUSION: Especially for those with fracture of the temporal bone the present results stress the importance of audiometric evaluation and follow-up, from both rehabilitation and medicolegal perspectives,

Adult↗
PubMed2003

Vinorelbine and cisplatin for metastatic breast cancer: a salvage regimen in patients progressing after docetaxel and anthracycline treatment.

PURPOSE: To assess the antitumor efficacy and safety of a combination of vinorelbine (VNR) and cisplatin in patients with metastatic breast cancer previously treated with anthracyclines and docetaxel. PATIENTS AND METHODS: Thirty-six patients with assessable metastatic breast cancer previously treated with anthracyclines and docetaxel (adjuvant n = 1, palliative n = 20, both n = 15) were studied. Cisplatin was given at 75 mg/m2 on day 1 followed by 25 mg/m2 VNR on days 1 + 8 in a 5-minute i.v. infusion. Courses were repeated every 3 weeks. Treatment was continued until disease progression, excess toxicity, or patient refusal. Patients were classified according to their response to anthracyclines according to criteria published previously: 1) Anthracycline and/or docetaxel resistant were patients who progressed during treatment with anthracyclines and docetaxel or within 4 months after cessation of treatment (metastatic). In addition, adjuvant patients who progressed within 6 months after completion of chemotherapy belong to this group. 2) Anthracycline and/or docetaxel relapsed were either metastatic patients who responded initially and then progressed after 4 months of completing an anthracycline- and docetaxel-based chemotherapy or patients who progressed after 6 months from completion of anthracycline/docetaxel-based adjuvant chemotherapy. RESULTS: Two patients (5.6%) achieved a complete response (CR) and 15 patients (41.6%) achieved a partial response (PR), for an overall response rate (OR) of 47.2% (95% confidence interval, 31-63). Of 18 patients relapsed to anthracycline/docetaxel, 2 had a CR (11%) and 8 a PR (44.4%), giving an objective response of 55.5%. Stable disease (SD) was observed in one patient (5.5%); seven patients had progressive disease (PD) (39%). Among the 18 resistant patients, 7 PRs (39%) were observed (p = 0.5), one patient (5.5%) had stable disease, 10 patients (55.5%) progressed. The median time to progression (TTP) was 16 weeks and median overall survival 36 weeks. Relapsed patients had a longer TTP than resistant patients (24 vs. 8 weeks, p = 0.05) but similar survival (48 vs. 24 weeks, p = 0.173). All patients were assessed for toxicity. The main toxicity was neutropenia grade 3 and 4 in 47% of patients. Febrile neutropenia requiring hospitalization was absent. There were no treatment-related deaths. Thrombocytopenia grade 3 and 4 occurred in four patients (11%). Phlebitis, orthostatic hypotension, and asthenia, all reversible, were observed in 3% of patients, respectively. CONCLUSION: This cisplatin/VNR regimen is well tolerated and active in patients who failed anthracyclines and docetaxel treatment. The response rate, TTP, and survival data are high and indicate that cisplatin/VNR may have a place as salvage treatment in this group of patients. If these results can be verified in multi-institutional trials, this combination of drugs would merit investigation as part of a first-line therapy in breast cancer.

Adolescent↗
PubMed2005

Exposure to Chlamydia pneumoniae infection and progression of age-related macular degeneration.

Recent studies have found an association between exposure to Chlamydia pneumoniae infection and risk of age-related macular degeneration (AMD). To assess a potential risk of AMD progression posed by exposure to C. pneumoniae, the authors reexamined Australian residents in 2001-2002 who were aged 51-89 years with early AMD at baseline (1992-1995). Examination included macular photography and an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. AMD progression was assessed quantitatively, using both coarse and fine progression steps following an international classification for AMD grading, and also qualitatively, by side-by-side comparison of baseline and follow-up macular photographs. Serologic data were available for 246 of 254 (97%) subjects. AMD progression was associated with a higher antibody titer. After adjustment for age, smoking, family history of AMD, history of cardiovascular diseases, and source study, the subjects in the upper tertiles of antibody titers were 2.1 (95% confidence interval: 0.92, 4.69), 2.6 (95% confidence interval: 1.24, 5.41), and 3.0 (95% confidence interval: 1.46, 6.37) times more at risk of progression than those in the lowest tertile, using three definitions of progression, respectively. The fact that seroreactivity to C. pneumoniae was independently associated with the risk of AMD progression suggests that C. pneumoniae infection may be an additional risk factor for AMD progression.

Aged↗
PubMed2003

Effect of chemopreventive agents on separate stages of progression of benzo[alpha]pyrene induced lung tumors in A/J mice.

The effects of aerosol budesonide and dietary myo-inositol on progression of benzo[alpha]pyrene (B[alpha]P) induced carcinogenesis were studied in A/J mouse lung. First, we determined when to intervene in the carcinogenesis process by exposing several animals to B[alpha]P at 100 and 150 mg/kg of body wt. Groups of these animals were necropsied from 1 to 36 weeks post-carcinogen. The presence of different categories of lung tumors was noted over the 36 week time period. Hyperplasia first appeared approximately 6 weeks post-carcinogen followed by adenoma at 9 weeks, then by carcinoma at 26 weeks. From this temporal sequence we determined we could test for effects of preventive agents on progression to hyperplasia by intervening at 3 weeks, for effects on progression to adenoma by intervening at 6 weeks and for effects on progression to carcinoma by intervention at 12 weeks. Intervention at 3 weeks post-carcinogen with aerosolized budesonide delayed both hyperplasia and adenoma formation. Once hyperplasia appeared in budesonide treated animals, however, it increased at the same rate as in control animals, indicating a delay in progression. Progression from adenoma to carcinoma was reduced when budesonide was given 12 weeks post-carcinogen. Dietary myo-inositol failed to suppress progression from adenoma to carcinoma when started 12 weeks post-carcinogen. In summary, budesonide is a chemopreventive agent that has inhibitory effects on B[alpha]P induced carcinogenesis of the lung in A/J mice at all stages of progression from hyperplasia formation to cancer.

Adenoma↗
PubMed1999

Geographical variation in disease progression in HIV-1 seroconverted injecting drug users in Europe?

BACKGROUND: Human immunodeficiency virus (HIV) disease progression might vary by geographical region due to differences in the spectrum of HIV-related illnesses and (access to) health care. Therefore, the effect of geographical region, next to the effect of other potential cofactors, on disease progression in 664 injecting drug users (IDU) with documented HIV seroconversion from eight cohorts in Europe was studied. METHODS: Kaplan-Meier methods and Cox proportional hazards analysis were performed to assess the effect of geographical region, other sociodemographics, drug use and repeated HIV exposure on progression from HIV seroconversion to immunosuppression, AIDS and death with AIDS. We considered the confounding effect of study-design related factors (e.g. setting of follow-up), and accounted for pre-AIDS death from natural causes by imputing when each endpoint would have occurred, had they not died without AIDS. RESULTS: Estimates of progression to AIDS and death with AIDS were substantially faster after taking pre-AIDS mortality into account. Median incubation time from seroconversion to the first CD4 count < 200 cells/microliter was 7.7 years (95% CI: 7.1-8.3) and to AIDS 10.4 years (95% CI: 9.8-infinity). The 10-year survival was 70.3% (95% CI: 62.8-76.6). The relative hazards (RH) of AIDS for IDU from central and southern Europe compared with IDU from northern Europe was 1.9 (95% CI: 1.2-3.0) and 1.2 (95% CI: 0.6-2.3), respectively, before, and 1.5 (95% CI: 0.7-3.2) and 1.1 (95% CI: 0.6-2.3) after taking differences in study-design related factors into account. Accounting for these factors, the RH of death with AIDS was 0.9 (95% CI: 0.3-2.5) for central and 1.2 (95% CI: 0.4-3.4) for southern Europe compared with northern Europe. For the first CD4 count < 200 cells/microliter these figures were 0.8 (95% CI: 0.5-1.4) and 0.8 (95% CI: 0.5-1.4). Age at seroconversion was the strongest predictor of disease progression. No statistically significant differences in disease progression were found by gender, foreign nationality, drug use and potential repeated HIV exposure. CONCLUSIONS: We found no evidence for regional variability in HIV disease progression among European IDU. Future studies evaluating geographical differences should consider the confounding effect of study-design related factors and differential non-AIDS mortality. As age is an important determinant of disease progression, it should be considered in recommending treatment.

Adult↗
PubMed2000

Carboplatin is effective therapy for young children with progressive optic pathway tumors: a Pediatric Oncology Group phase II study.

The Pediatric Oncology Group conducted a phase II study to evaluate the activity of carboplatin in children 5 years or younger with progressive optic pathway tumors (OPTs). Of the 51 patients accrued to this study, 1 was not eligible because the child was older than 6 years. Fifty patients were eligible and had either neuro-imaging or symptomatic evidence of progressive OPTs. Twenty-one of 50 had evidence of neurofibromatosis type I (NF-1). Therapy consisted of carboplatin 560 mg/m2 at 4-week intervals. Patients with stable disease or better after two courses were continued on therapy for 18 months or until progressive disease. Of the 50 eligible children, 39 had stable disease or better, and 34 completed the 18-month therapy. Our data are sufficient to conclude that the proportion of objective responses (complete, partial, or minor response or stable disease) exceeded 30% (P < 0.00001), and the approximate 95% confidence interval estimate of the objective response rate was 0.665 to 0.895. Twenty-one patients went off protocol because of progressive disease. Fifteen patients progressed during the 18-month therapy, and 6 patients progressed after completing therapy. Six children died with progressive disease. Major toxicities were neutropenia and thrombocytopenia, and 3 children experienced allergic reactions. Carboplatin is active and safe for the treatment of young children with progressive OPTs. The addition of other potentially active drugs may further increase the event-free survival for these children.

Antineoplastic Agents↗
PubMed2000

Methods to quantify the relation between disease progression in paired eyes.

The authors compared, in the context of diabetic retinopathy, alternative methods of quantifying the extent to which disease progression in one eye increases the risk of subsequent progression in the other eye. Data were gathered on 478 US patients with insulin-dependent diabetes mellitus who participated in the 1983-1988 Sorbinil Retinopathy Trial and were followed up for a median of 41 months. During that time, diabetic retinopathy progressed in 93 right eyes and 77 left eyes. Crude incidence rates of progression for right eyes were 7.7 times higher after the left eye had progressed and, for left eyes, were 4.4 times higher after the right eye had progressed. In eye-specific proportional hazards models that adjusted for increasing rates of progression over time and for baseline risk factors, the comparable relative risks associated with progression in the other eye were 2.6 (95% confidence interval (CI): 1.5, 4.7) for right eyes and 1.4 (95% CI: 0.72, 2.9) for left eyes. Two alternative proportional hazards models that included data on both eyes and accounted for their correlation produced estimated relative risks of 1.9 (95% CI: 1.2, 2.9) and 2.7 (95% CI: 1.8, 3.5), respectively. The more complex models for joint survival integrate information on both eyes and provide more stable estimates than do separate analyses of right or left eyes.

Adult↗
PubMed2003

Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting.

OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.

Adult↗