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Progression Rate (progression + rate)
Kinds of Progression Rate Selected AbstractsDistinct Brain Volume Changes Correlating with Clinical Stage, Disease Progression Rate, Mutation Size, and Age at Onset Prediction as Early Biomarkers of Brain Atrophy in Huntington's DiseaseCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 1 2009Ferdinando Squitieri Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross-sectional and longitudinal rate of brain atrophy, quantitatively measured by fully-automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene-positive subjects with presymptomatic to advanced HD, and age-matched healthy controls. Each of the three brain compartments we studied (WM, GM, and CSF) had a diverse role and their time courses differed in the development of HD. GM volume decreased early in life. Its decrease was associated with decreased serum brain-derived-neurotrophic-factor and started even many years before onset symptoms, then decreased slowly in a nonlinear manner during the various symptomatic HD stages. WM volume loss also began in the presymptomatic stage of HD a few years before manifest symptoms appear, rapidly decreasing near to the zone-of-onset. Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG-based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R2= 0.25, P < 0.0001). [source] Longitudinal development of hand function in children with unilateral cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2010MARIE HOLMEFUR PHD REG OT Aim The aim of this study was to describe how the usefulness of the hemiplegic hand develops in children with unilateral cerebral palsy (CP) aged between 18 months and 8 years. Method A prospective longitudinal study of 43 children (22 males, 21 females) with unilateral CP was conducted. Inclusion age was 18 months to 5 years 4 months (mean 2y 8mo [SD 1y 1mo]). Children were assessed with the Assisting Hand Assessment (AHA) 3 to 11 times per child over a mean period of 4 years 6 months. Two models were used for grouping children: by AHA score at 18 months and by Manual Ability Classification System (MACS) levels. Estimated average motor development curves were fitted with a nonlinear mixed-effects model. Results Children with a high AHA score (high ability level) at 18 months reached a significantly higher ability level and at a higher progression rate than children with a low 18-month AHA score. Limits of development differed between the three MACS levels. Interpretation Results indicate that the AHA score at 18 months can be used to discuss future development of affected hand use in bimanual tasks in children with unilateral CP. [source] Clinical outcome after 4 years follow-up of HIV-seropositive subjects with incomplete virologic or immunologic response to HAARTJOURNAL OF MEDICAL VIROLOGY, Issue 2 2005Emanuele Nicastri Abstract The duration of the clinical, virologic, and immunologic response to HAART, is not well defined. In this observational multi-center study 2,143 patients were enrolled classified according to virologic suppression (<500 cp/ml) and immune recovery (>100 CD4+ cells/,l from baseline) at month 12 of HAART as complete responders, virologic only responders, immunologic only responders and non-responders. Kaplan Meyer curves, multivariate and politomous regression analysis were used. Complete responders patients were 781 (36.4%), immunologic only responders 441 (20.6%), virologic only responders 336 (15.7%), and non-responders 585 (27.3%). Using multivariate analysis, being antiretroviral-naïve increased the probability of having both a virologic only or a complete response and reduced the probability of an immunologic only response (P,<,0.001 for all tests). Older age was associated directly with a virologic only response and inversely associated with an immunologic only response (P,=,0.027 and P,=,0.035, respectively). Using politomous analysis, patients baseline HIV-RNA level more than 5 log cp/ml had a 1.9-fold higher probability of an immunologic response than of a complete response (P,=,0.001). After 4 years, the clinical progression rate was six times greater in non-responders, 1.9 times greater in virologic only responders, and 2.3 times greater in immunologic only responders than for responders. However, patients with virologic only response or with immunologic only response had a significantly reduced risk for clinical progression than non-responders (P,<,0.001). After 4 years of HAART, the risk of clinical progression in patients with immunologic only or virologic only response is low but still higher than in complete responder patients. J. Med. Virol. 76:153,160, 2005. © 2005 Wiley-Liss, Inc. [source] Clinical history and new prognostic indicators in metachromatic leukodystrophyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004U Del Carro Objective: To study clinical phenotypes and to increase knowledge of natural history of different variants of metachromatic leukodystrophy (MLD). Background: Little is known about factors influencing age of onset, progression rate and peripheral nerve involvement in MLD due to its rarity, heterogeneity and paucity of serial clinical and instrumental reports. Methods: 15 biochemically and molecularly characterized MLD patients were evaluated along a two-year follow-up period with clinical, electroneurographic (ENG) and brain MRI recordings. Results: Late infantile patients had a progressive and rapid course, whereas juvenile form showed marked variability. Different clinical presentations were associated with similar levels of ARSA activity; mutation screening indicated a high prevalence of rare or private mutations. In all late infantile and in the adult patient, ENG revealed a severe polyneuropathy. In juvenile patients a milder polyneuropathy or even normal tests were found. The earliest MRI change was periventricular white matter signal alterations, with initial involvement of posterior regions in a majority of late infantile patients, while in juvenile forms white matter lesions were mainly anterior. Conclusions: MLD course is highly variable and only partially influenced by age of onset, especially among juvenile patients. No clear-cut correlations exist between clinical phenotype and biochemical or molecular characterization. The presence of peripheral neuropathy at onset seems a strong indicator of a poorer clinical outcome. [source] Impact of interferon-alpha therapy on liver fibrosis progression in patients with HBeAg-negative chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 2 2005G. V. Papatheodoridis Summary., The possible effect of interferon-alpha (IFNa) on liver fibrosis progression has not been adequately studied in chronic hepatitis B. We evaluated 147 patients with HBeAg-negative chronic hepatitis B who had ,2 liver biopsies and had been treated with IFNa (n = 120) or had remained untreated (n = 27). The median interval between the two biopsies was 24 (12,160) months. All biopsies were scored blindly by a single liver histopathologist according to the classification of Ishak et al. (J Hepatol 1995; 22: 696,699). IFNa induced sustained biochemical response in 30, initial response and subsequent relapse in 57 and no response in 33 patients. Fibrosis improved in 17.5% of treated (sustained responders: 40%, relapsers: 9%, nonresponders: 12%) and 4% of untreated patients and worsened in 34% (sustained responders: 7%, relapsers: 40%, nonresponders: 48%) and 70% of cases, respectively (P = 0.002). The annual rate of fibrosis progression was worse in the untreated (0.427 ± 0.119) than in treated patients (0.067 ± 0.052, P = 0.001). However, the fibrosis progression rate in the untreated patients was not significantly different than the net fibrosis progression rate (after subtraction of IFNa duration) in nonresponders or relapsers. In multivariate analysis, worse fibrosis progression rate was associated with older age (P = 0.010), worse baseline grading score (P < 0.001), lower baseline fibrosis (P = 0.035) and the type of response to IFNa (P = 0.032). In conclusion, in HBeAg-negative chronic hepatitis B, IFNa significantly reduces the rate of fibrosis progression, but such an effect is mainly observed in patients with sustained biochemical responses. In relapsers and nonresponders, fibrosis benefit equals the treatment period. The strongest factor associated with fibrosis progression is the change in necroinflammatory activity. [source] Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in Caucasian patients with chronic hepatitis CLIVER INTERNATIONAL, Issue 3 2006Sigal Fishman Abstract: Objective: Previous studies have demonstrated that CYP2D6 polymorphism is associated with liver cirrhosis. The aim of the present study was to find out whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression rate. Methods: Seventy-five Caucasian patients with chronic hepatitis C infection were recruited. They were divided into two groups, ,fast fibrosers' and ,slow fibrosers', according to Poynard's fibrosis progression curves. Sixty-two patients underwent liver biopsy. Twenty healthy neonates were included as control population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by polymer chain reaction using fluorescent hybridization probes in a lightCycler instrument. Results: Forty-two patients were classified as ,fast fibrosers' and 33 patients as ,slow fibrosers'. The frequency of CYP2D6*4 allele in the ,fast fibrosers' (34.5%) was significantly higher compared with the ,slow fibrosers' (15%) (P -value=0.007). There was no significant difference between the frequency of CYP2D6*4 in the ,slow fibrosers' (15%) compared with the controls (12.5%). Carrier state of CYP2D6*4 was the only covariate that was significantly positively correlated with fast progression to cirrhosis (odds ratio=6.5, P=0.01). Conclusion: This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients. [source] Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulationMOVEMENT DISORDERS, Issue 8 2007Ettore Accolla MD Abstract We investigated gender-differences in clinical phenomenology and response to deep brain stimulation (DBS) of the subthalamic nucleus (STN) in a group of patients with advanced Parkinson's disease (PD). Thirty-eight consecutive patients with PD (22 men and 16 women), bilaterally implanted for DBS of the STN, were evaluated 1 month before and 11 to 14 months after surgery. Gender differences in severity of the disease (HY and UPDRS), ability in the activities of daily living (ADL, UPDRS II), tremor and rigidity (UPDRS III), bradykinesia (UPDRS III and hand tapping test), levodopa-induced dyskinesias (LIDs, UPDRS IV), and levodopa equivalent daily dosage (LEDD) were analyzed before and after intervention. We found a predominantly male population, with no gender-related differences in age at onset, disease progression rate, or severity of disease. Nevertheless, women had more severe LIDs than men, only before the intervention. Bradykinesia was significantly less responsive to any kind of treatment (pharmacologic and neurosurgical) in women than in men. Finally, although STN-DBS induced similar total benefits in both genders, postoperative assessment suggested that the ADL improved more in women than in men. Women and men with advanced PD appear to differ in some clinical features and in response to dopaminergic and STN-DBS treatment. © 2007 Movement Disorder Society [source] Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: Meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisonsARTHRITIS & RHEUMATISM, Issue 10 2010Niels Graudal Objective To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents. Methods Randomized controlled trials in RA patients, investigating the effects of drug treatment on the percentage of the annual radiographic progression rate (PARPR) were included in a meta-analysis performed with the use of Review Manager 5.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Results Data from 70 trials (112 comparisons, 16 interventions) were summarized in 21 meta-analyses. Compared with placebo, the PARPR was 0.65% smaller in the single-DMARD group (P < 0.002) and 0.54% smaller in the glucocorticoid group (P < 0.00001). Compared with single-DMARD treatment, the PARPR was 0.62% smaller in the combination-DMARD group (P < 0.001) and 0.61% smaller in the biologic agent plus methotrexate (MTX) group (P < 0.00001). The effect of a combination of 2 DMARDs plus step-down glucocorticoids did not differ from the effect of a biologic agent plus MTX (percentage mean difference ,0.07% [95% confidence interval ,0.25, 0.11]) (P = 0.44). Conclusion Treatment with DMARDs, glucocorticoids, biologic agents, and combination agents significantly reduced radiographic progression at 1 year, with a relative effect of 48,84%. A direct comparison between the combination of a biologic agent plus MTX and the combination of 2 DMARDs plus initial glucocorticoids revealed no difference. Consequently, biologic agents should still be reserved for patients whose RA is resistant to DMARD therapy. Future trials of the effects of biologic agents on RA should compare such agents with combination treatments involving DMARDs and glucocorticoids. [source] A Semiparametric Joint Model for Longitudinal and Survival Data with Application to Hemodialysis StudyBIOMETRICS, Issue 3 2009Liang Li Summary In many longitudinal clinical studies, the level and progression rate of repeatedly measured biomarkers on each subject quantify the severity of the disease and that subject's susceptibility to progression of the disease. It is of scientific and clinical interest to relate such quantities to a later time-to-event clinical endpoint such as patient survival. This is usually done with a shared parameter model. In such models, the longitudinal biomarker data and the survival outcome of each subject are assumed to be conditionally independent given subject-level severity or susceptibility (also called frailty in statistical terms). In this article, we study the case where the conditional distribution of longitudinal data is modeled by a linear mixed-effect model, and the conditional distribution of the survival data is given by a Cox proportional hazard model. We allow unknown regression coefficients and time-dependent covariates in both models. The proposed estimators are maximizers of an exact correction to the joint log likelihood with the frailties eliminated as nuisance parameters, an idea that originated from correction of covariate measurement error in measurement error models. The corrected joint log likelihood is shown to be asymptotically concave and leads to consistent and asymptotically normal estimators. Unlike most published methods for joint modeling, the proposed estimation procedure does not rely on distributional assumptions of the frailties. The proposed method was studied in simulations and applied to a data set from the Hemodialysis Study. [source] Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progressionBJU INTERNATIONAL, Issue 7 2004P. Andius OBJECTIVE To report prognostic factors for time to recurrence and progression after bacillus Calmette-Guérin (BCG) prophylaxis in patients with stage Ta/T1 papillary bladder cancer. PATIENTS AND METHODS The clinical records were assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in situ were excluded. The median (range) follow-up was 44 (4,155) months. The effect of 13 variables on the time to recurrence and progression was evaluated using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS The recurrence rate was markedly reduced for all grades and stages. Patients with a negative first cystoscopy and maintenance BCG had a significantly longer time to recurrence than those treated with an induction course alone (P < 0.001). Thirty-seven patients (16%) progressed in stage. The result of the first cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial instillations (P = 0.002) had prognostic importance for the time to progression. Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3,10 times the expected rate. Age, number of tumours, number of positive cystoscopies, length of tumour history before BCG, BCG strain and treatment year had no influence on time to recurrence and progression. CONCLUSIONS Maintenance treatment does not seem to be necessary among patients with TaG1-G2 disease after a negative first cystoscopy, as the progression rate was very low. One new finding was that BCG seemed to be equally effective among patients with or with no history of an upper tract tumour. Another new and surprising finding was that patients treated with fewer than six induction instillations, because of very bothersome side-effects, had an increased risk of tumour progression and of local failure. [source] Reduced angiotensin II levels in the cerebrospinal fluid of patients with amyotrophic lateral sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009M. Kawajiri Background,,, Recent studies suggest that angiotensin II, a major substrate in the renin,angiotensin system, protects neurons through stimulation of its type 2 receptors. However, quite a few clinical studies of angiotensin II levels have shown their relation to disease severity in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Aims of the study,,, To clarify the significance of angiotensin II in ALS. Methods,,, We assayed angiotensin II concentrations in cerebrospinal fluid (CSF) samples from 23 patients with ALS, nine patients with spinocerebellar degeneration (SCD) and 24 control individuals. We evaluated the disability levels of patients with ALS using the Revised ALS Functional Rating Scale (ALSFRS-R) and calculated the disease progression rate (DPR). Results,,, CSF angiotensin II levels were significantly lower in the ALS group compared with that in the control group (P = 0.00864), and showed a significant positive correlation with scores on the ALSFRS-R, and a significant negative correlation with the DPR. Conclusions,,, In the present study, we reveal for the first time that angiotensin II levels in the CSF from patients with ALS are significantly reduced and significantly associated with disease severity and progression rate. These findings suggest that reduced levels of intrathecal angiotensin II may play a role in ALS. [source] 1334: Autofluorescence: new tool to follow dry eye AMD?ACTA OPHTHALMOLOGICA, Issue 2010MN MENKE Purpose In the pathophysiolgy of dry (atrophic) age related macular degeneration (AMD) aging of the retinal pigment epithelium (RPE) plays a key role. Accumulation of lipofuscin granules in the RPE cells represents a common downstream pathogenetic pathway in AMD. Lipofuscin is derived from chemically modified residues of incompletely digested photoreceptor outer segment discs. Detection of lipofuscin in vivo is possible by using fundus autofluorescence (FAF) imaging. The clinical application and possible implications of autofluorescence imaging in dry AMD will be discussed. Methods When stimulated with light in the blue to green range, lipofuscin granules emit a characteristic yellow fluorescence. FAF imaging using a scanning laser ophthalmoscope allows visualization of the topographic distribution of lipofuscin over large retinal areas. Examples of FAF images will be presented to demonstrate various FAF patterns and to discuss the clinical significance of these findings. Results In areas of geographic atrophy FAF images show very low autofluorescence intensity. This is due to the loss of RPE cells including the lipofuscin granules. In the junctional zone between atrophic and normal retina, levels of increased autofluorescence intensity may occur due to excessive accumulation of lipofuscin in the RPE cells. Longitudinal observations further suggest that the extension of the total area with increased autofluorescence intensity surrounding atrophy at baseline has a strong positive correlation with atrophy progression rate over time. Conclusion FAF imaging is an important diagnostic tool to follow the progression of dry AMD and other degenerative macular diseases and should always be considered in cases were the status of the RPE is unknown. [source] Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-upACTA OPHTHALMOLOGICA, Issue 3 2008Kristina Teär Fahnehjelm Abstract. Purpose:, To present long-term ocular complications and electroretinographic (ERG) findings in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency , a life-threatening metabolic disease , and the relation to age at diagnosis, treatment and other clinical parameters. Methods:, Ten children with LCHAD deficiency underwent repeated ophthalmological evaluations including ERG. Results:, All 10 children developed chorioretinal pathology. Regardless of age at diagnosis, initiation of treatment and age at examination, inter-individual differences were present. Profound chorioretinal atrophy, severe visual impairment and progressive myopia had developed in two teenagers. Milder chorioretinopathy with or without subnormal visual acuity was present in all other children. ERG was pathological in seven children. The chorioretinopathy often started in the peripapillary or perimacular areas. In one patient, unilateral visual impairment was associated with fibrosis. Conclusion:, Early diagnosis and adequate therapy might delay but not prevent the progression of retinal complications. Late diagnosis with severe symptoms at diagnosis, neonatal hypoglycaemia and frequent decompensations may increase the progression rate of the chorioretinopathy. LCHAD deficiency, a potentially lethal disease, is sometimes difficult to diagnose. Unusual chorioretinal findings should alert the ophthalmologist to the long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, especially if there is a history of neonatal hypoglycaemia or failure to thrive. [source] Validation of the HCC-MELD for dropout probability in patients with small hepatocellular carcinoma undergoing locoregional therapyCLINICAL TRANSPLANTATION, Issue 4 2008Teh-Ia Huo Abstract:,Background:, The model for end-stage liver disease (MELD) is used in prioritizing cirrhotic patients awaiting liver transplantation. Patients with small hepatocellular carcinoma (HCC) are eligible candidates. An HCC-MELD equation was recently proposed to predict the dropout rate of HCC patients on the waiting list. This study aimed to validate the accuracy of this equation. Methods:, We investigated 390 patients with small HCC who were candidates for liver transplantation and underwent locoregional therapy. Results:, The estimated probability of dropout according to the equation was 8.2% for T1 stage and 13.5% for T2 stage HCC (p < 0.0001). The actual disease progression rate at three months was 2.1% for T1 and 3.0% for T2 stage HCC. At six months, the progression rate was 5.3% for T1 stage and 6.8% for T2 stage. The area under receiver operating characteristic curve of the HCC-MELD equation was 0.81 at three months and 0.80 at six months. Patients undergoing radiofrequency ablation (RFA) had significantly lower dropout rates compared with other treatment groups according to the equation (p = 0.0007). The actual tumor progression rate was also the lowest for the RFA group at both three and six months. Conclusion:, The HCC-MELD equation is a feasible predictive model for patients with small HCC undergoing locoregional therapy. [source] Distinct Brain Volume Changes Correlating with Clinical Stage, Disease Progression Rate, Mutation Size, and Age at Onset Prediction as Early Biomarkers of Brain Atrophy in Huntington's DiseaseCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 1 2009Ferdinando Squitieri Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross-sectional and longitudinal rate of brain atrophy, quantitatively measured by fully-automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene-positive subjects with presymptomatic to advanced HD, and age-matched healthy controls. Each of the three brain compartments we studied (WM, GM, and CSF) had a diverse role and their time courses differed in the development of HD. GM volume decreased early in life. Its decrease was associated with decreased serum brain-derived-neurotrophic-factor and started even many years before onset symptoms, then decreased slowly in a nonlinear manner during the various symptomatic HD stages. WM volume loss also began in the presymptomatic stage of HD a few years before manifest symptoms appear, rapidly decreasing near to the zone-of-onset. Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG-based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R2= 0.25, P < 0.0001). [source] Disease burden of chronic lymphocytic leukaemia within the European UnionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2008Louise Watson Abstract Objective:, Whilst Chronic lymphocytic leukaemia (CLL) is considered a rare disease, to our knowledge, the current prevalence of CLL within the European Union (EU) member states is not published. Understanding the number of individuals with CLL is vital to assess disease burden within the wider population. Methods:, Using 2002 data from the International Agency for Research on Cancer, we estimated the number of individuals with CLL (ICD-10 C91.1) from those reported for all leukaemias (C91,95) and extrapolated the figures by the population increase within the EU between 2002 and 2006, the last year with fully updated community population estimates. One- and 5-yr partial prevalence estimates are reported (i.e. the number of individuals still living 1,5 yr post-diagnosis). We then applied proportional estimates from the literature to assess those requiring immediate treatment, those under observation and their likely progression rates. Results:, We found that within the 27 EU states plus Iceland, Norway and Lichtenstein, 1- and 5-yr CLL partial prevalence estimates totalled approximately 13 952 and 46 633 individuals respectively in 2006. By applying Binet staging to the 1-yr estimate, 40% of patients will be stage B/C and require immediate treatment. Thus, 5581 individuals may be treated within the first year of diagnosis. Of the 60% (8371) under observation, by 5 yr up to 33% (2763) may have more advanced disease with increased risk of mortality. Conclusion:, Whilst CLL is a rare disease, the number of individuals burdened by the disease within the EU is considerable and thousands of patients require treatment and physician care, which has cost implications for member states. [source] Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: A meta-analysis and meta-regression,HEPATOLOGY, Issue 2 2008Hla-Hla Thein Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage-specific fibrosis progression rates and their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage-specific transition probabilities (F0,F1, , , F3,F4) were derived using the Markov maximum likelihood estimation method and a meta-analysis was performed. The impact of potential covariates was evaluated using meta-regression. A total of 111 studies of individuals with chronic HCV infection (n = 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage-specific transition probabilities were: F0,F1 0.117 (0.104,0.130); F1,F2 0.085 (0.075,0.096); F2,F3 0.120 (0.109,0.133); and F3,F4 0.116 (0.104,0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%,19%) for all studies, 18% (15%,21%) for cross-sectional/retrospective studies, 7% (4%,14%) for retrospective-prospective studies, 18% (16%,21%) for studies conducted in clinical settings, and 7% (4%,12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. Conclusion: Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates. (HEPATOLOGY 2008.) [source] Evidence for prolonged clinical benefit from initial combination antiretroviral therapy: Delta extended follow-upHIV MEDICINE, Issue 3 2001Delta Coordinating Committee Background The findings from therapeutic trials in HIV infection with surrogate endpoints based on laboratory markers are only partially relevant for clinical decisions on treatment. Although the collection of clinical follow-up data from such a trial would be relatively straightforward, this rarely occurs. An important reason for this may be the perception that such data have little value because the number of participants remaining on their original allocated therapy has usually fallen substantially. Methods Delta was an international, multicentre trial in which 3207 HIV infected individuals were randomly allocated to treatment with zidovudine (ZDV) alone, ZDV combined with didanosine (ddI) or ZDV combined with zalcitabine (ddC). Although the trial closed in September 1995, information on vital status, AIDS events, treatment changes and CD4 counts was still collected every 12 months until at least March 1997. This has allowed analyses of the longer term clinical effect of treatment. Results The median follow-up to date of death or last known vital status was 43 months (10th percentile 18 months; 90th percentile 55 months). The proportion of participants remaining on their allocated treatment fell steadily over time; by 4 years after trial entry, 3% remained on ZDV, 20% on ZDV + ddI and 21% on ZDV + ddC. Changes mainly involved the stopping, addition or switching of a nucleoside reverse transcriptase inhibitor (NRTIs). There was little use of protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) before the third year of the trial. Between the third and fourth years, regimens included a drug from one of these classes for approximately 17% of person-time in all treatment groups. Relative to ZDV monotherapy, the beneficial effects of combination therapy on mortality and disease progression rates increased significantly with time since randomization. The maximum effects on mortality were observed between 2 and 3 years, with a 48% reduction for ZDV + ddI and a 26% reduction for ZDV + ddC. These rates were observed when the original allocated treatment was received 42% and 47% of the time in the ZDV + ddI and ZDV + ddC groups, respectively. The mean CD4 count remained significantly higher (approximately 50 cells/,L) in the combination therapy groups 4 years after randomization, suggesting a projection of a clinical benefit beyond this time point. Conclusions The sustained clinical effect of the initial allocation to combination therapy, particularly ZDV + ddI, was remarkable in light of the convergence of drug regimens actually received across the three treatment groups. Interpretation of this finding is not straightforward. One of the possible explanations is that the effectiveness of ddI and ddC is diminished if first used later in infection or with greater prior exposure to ZDV, although the data do not clearly support either hypothesis. This analysis highlights the value of long-term clinical follow-up of therapeutic trials in HIV infection, which should be considered in the planning of all new studies. [source] Memory Complaint Is Not Necessary for Diagnosis of Mild Cognitive Impairment and Does Not Predict 10-Year Trajectories of Functional Disability, Word Recall, or Short Portable Mental Status Questionnaire LimitationsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2006Jama L. Purser PhD OBJECTIVES: To evaluate the prevalence and utility of memory complaint in a geographically representative cohort and, in cases with mild cognitive impairment (MCI), to determine whether memory complaint alters 10-year trajectories of disability in activities of daily living (ADLs), Short Portable Mental Status Questionnaire (SPMSQ) score, and 20-item word recall. DESIGN: Prospective cohort study. SETTING: Washington and Iowa counties, Iowa. PARTICIPANTS: Iowa Established Populations for Epidemiologic Studies of the Elderly (N=3,673; aged ,65; 61.3% female; 99.9% white). MEASUREMENTS: Age, sex, education, SPMSQ score, 20-item word recall, ADL or instrumental ADL disability, and chronic medical conditions. RESULTS: The prevalence of memory complaint was 34%. Although proportionally more cognitively impaired individuals were in the memory complaint group (34% vs 27%), the pattern of subclassification into cognitively intact and MCI Stage 1 and 2 subgroups was similar for people with and without memory complaint. Median SPMSQ score and number of words recalled at baseline were comparable across memory complaint categories in each subgroup. MCI participants without subjective memory complaint constituted a larger proportion of the overall sample than individuals with subjective memory complaint (460 (14%) vs 295 (8.9%)) and of persons objectively classified as having MCI (61% vs 39%). The distribution of individual 10-year change in ADL disability, SPMSQ score, and word recall were similar for those with and without memory complaint across all subgroups of cognitive impairment. CONCLUSION: Memory complaint is not necessary for MCI diagnosis and does not distinguish cases with different progression rates in disability or cognitive impairment. 2006. [source] Forest progression modes in littoral Congo, Central Atlantic AfricaJOURNAL OF BIOGEOGRAPHY, Issue 9 2004Charly Favier Abstract Aim, To understand the persistence of a forest,savanna mosaic in places where rainfall data suggest that forest take-over should take place. To study the various modes of forest encroachment, and the role of human activities to hamper it. Location, Data were collected on several forest,savanna ecotones in the coastal region of the Republic of Congo. The sites were chosen to illustrate the differing principal modes of forest expansion, corresponding to different levels of anthropic pressure. Methods, The study sites were situated on five transects perpendicular to the ecotone (total sampled area: 1.7 ha) and 10 forest clumps in savanna (with diameters from 3 to 20 m). Along the transects botanical identification, diameter measurement and cartography were performed, while leaf area index was measured at a high resolution (every metre) along two of them. Collected data were analysed using a continuous quantification approach, which is much more useful than classical quadrat analysis. Time calibration of progression rates was performed using a simple model of the growth of the characteristic pioneer species, Aucoumea klaineana. Results, The two main different modes are reflected in different successional patterns. The edge diffusion is slow (its rate is evaluated to c. 1 m year,1) and is characterized by a progressive increase in large-diameter tree density and shade-tolerant tree density away from the ecotone. Conversely, savanna to forest phase transition by coalescence of clumps exhibits high tree density remnants distributed in established forest. The composition of these remnants is compatible with that of the forest clumps in savannas. Main conclusions, Three functional groups of pioneer trees are distinguished: some occupy the edge (edge pioneer), others establish clumps of forest in savanna (clump pioneers) and the longer-living A. klaineana ensures the transition to ,mature' forest. The two different observed patterns (linear edge progression and clump coalescence) can be understood with the use of a model of forest,savanna dynamics, ,FORSAT'. The two control parameters are the annual rainfall and the frequency of man-made fires in each savanna. In particular, an increase in the fire frequency can lead to a shift from the coalescence regime to the edge progression one. [source] Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: Results from the trial of etanercept and methotrexate with radiographic and patient outcomesARTHRITIS & RHEUMATISM, Issue 10 2006Robert Landewé Objective To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. Methods Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity × treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. Results GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. Conclusion Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA. [source] Matched-cohort analysis of patients with prostate cancer followed with observation or treated with three-dimensional conformal radiation therapy,BJU INTERNATIONAL, Issue 1 2004Noel M. Kramer OBJECTIVES To compare the outcome of similar patients with prostate cancer treated by either observation or three-dimensional conformal radiation therapy (3-DCRT). PATIENTS AND METHODS The study included 69 patients with nonmetastatic prostate cancer who were observed only; the indications included indolent disease, significant medical comorbidities and refusal of treatment. Of these, 62 patients had palpable T1,T2a and seven T2b,T3a disease, a median Gleason score of 6 and a median initial prostate-specific antigen (PSA) level of 5.3 ng/mL. A matched-cohort analysis of 69 patients, based on palpation T category, Gleason score and initial PSA, was used to compare the outcome between the observation and 3-DCRT groups. The median radiation dose for latter was 72 Gy. RESULTS The median follow-up for the observed patients was 49 months. The 5- and 8-year actuarial rates of freedom from distant metastases were 100% and 93%, respectively, and the actuarial overall survival rates 94% and 73%, respectively. Seven observed patients had local disease progression on physical examination. Four patients who initially were observed received radiation therapy later for a rising PSA and/or local disease progression. For the 69 matched 3-DCRT patients, the overall 5-year rate for no biochemically evident disease was 74%. The respective 5- and 8-year actuarial rates of freedom from distant metastases were 95% and 95%, and actuarial overall survival rates 95% and 75%. There were no significant differences in distant metastasis and overall survival rates between the groups, and no deaths from prostate cancer in either group. CONCLUSIONS Observation is a reasonable alternative to treatment in selected patients. During the 5-year follow-up the progression rates were relatively low, and there was no difference in distant metastasis or overall survival between the groups. As the follow-up was short a longer follow-up is needed to determine whether the outcome of those patients who chose observation will remain comparable to that in those undergoing immediate 3-DCRT. [source] Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)BJU INTERNATIONAL, Issue 6 2002J.N. Kulkarni Objective ,To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guérin (BCG, Danish 1331 strain) after complete transurethral resection. Patients and methods ,Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival. Results ,Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy. During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well. Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR. Conclusion ,This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients. [source] Should we screen for bladder cancer in a high-risk population?CANCER, Issue 5 2006A cost per life-year saved analysis Abstract BACKGROUND. The U.S. Food and Drug Administration recently approved screening high-risk patients for bladder cancer using urine-based markers. The cost and life-years saved associated with bladder cancer screening were evaluated. METHODS. A Markov model was created to estimate cumulative cancer-related costs and efficacy of screening (vs. no screening) of a high-risk population for bladder cancer using a urine-based tumor marker over a 5-year period. Assumptions were based on literature review of survival and progression rates for patients with bladder cancer and costs associated with different bladder cancer disease states. RESULTS. Screening for bladder cancer in a population with a 4% incidence of bladder cancer resulted in a gain of 3.0 life years per 1000 subjects at a cost savings of $101,000 for the population, assuming a 50% downstaging in the screened population from muscle-invasive to nonmuscle-invasive disease. One-way sensitivity analyses found that screening is the most cost-effective strategy if cancer incidence is >1.6%, tumor marker costs <$126, marker sensitivity is >26%, marker specificity is >54%, downstaging with screening is >20%, and office cystoscopy costs <$694. Varying costs of cystectomy, transurethral resection of bladder tumor (TURBT), chemotherapy, end-of-life care, costs of metastatic disease, and a computed tomography scan over a wide range did not affect the superiority of screening. CONCLUSIONS. The model found that urine-based markers are cost-effective in a high-risk population. Prospective randomized trials in a completely asymptomatic high-risk cohort are indicated before bladder cancer screening can be recommended. Cancer 2006. © 2006 American Cancer Society. [source] Until what age should glaucoma be monitored and/or treated?ACTA OPHTHALMOLOGICA, Issue 2009A novel index that facilitates clinical decision making Purpose To calculate for which combinations of age and perimetric disease stage (mean deviation [MD]) treated and untreated glaucoma patients are unlikely to become blind during lifetime. Methods The probability of dying without blindness was calculated using the age and gender adjusted life expectancy values from the Statistics Netherlands and the progression rates of treated and untreated glaucoma patients from the Early Manifest Glaucoma Trial and the Groningen Longitudinal Glaucoma Study. Absence of blindness was defined as an MD better than -20 dB. Because it is difficult - or even impossible , to determine someone's individual life expectancy and rate of progression accurately, patients were assumed to reach the 90th percentile of the adjusted life expectancy and to progress with the 90th percentile of the rate of progression, leaving an a priori probability of becoming blind during lifetime of 2.5%. Results If MD+0.8*age, with MD in dB and age in years, is larger than 59, treated male patients were unlikely to become blind during lifetime. For untreated male patients the cut-off value was 66, and for treated and untreated female patients 61 and 68 respectively. Conclusion With this novel index, MD+0.8*age, the intensity of glaucoma monitoring and/or treatment can be reduced well-founded in the ageing patient. The index can be applied to either the worse or the better eye, depending on what is considered acceptable or possible given limited resources. [source] How should a nonfunctioning pituitary macroadenoma be monitored after debulking surgery?CLINICAL ENDOCRINOLOGY, Issue 6 2009Yona Greenman Summary Transsphenoidal surgery is the treatment of choice for nonfunctioning pituitary macroadenomas but is seldom curative. Tumour progression rates are high in patients with postoperative remnants. Therefore, long-term monitoring is necessary to detect tumour growth, which may be asymptomatic or manifest with visual field defects and/or pituitary dysfunction. In view of the generally slow-growing nature of these tumours, yearly magnetic resonance imaging, neuro-ophalmologic and pituitary function evaluation are appropriate during the first 3,5 years after surgery. If there is no evidence for tumour progression during this period, testing intervals may be extended thereafter. [source] | ||||||||||||||||||||||||||||