Estimates Of Progression Rates Research Articles

DURATION OF ALZHEIMER’S DISEASE IN THE PRECLINICAL, PRODROMAL AND DEMENTIA STAGE: A MULTI-STATE MODEL ANALYSIS

About 25% of the non-demented elderly have evidence of amyloid pathology. The time to and duration of symptomatic disease, dementia and death is not well known. We aim to combine international cohort data to estimate the duration of the preclinical, prodromal and dementia stage according to age, gender and setting. We selected 240 subjects with normal cognition and amyloid pathology (preclinical Alzheimer's Disease (AD)), 626 with MCI and amyloid pathology (prodromal AD) and 2091 subjects with AD-type dementia, of whom 38% had confirmed amyloid pathology, while for 62% amyloid status was unknown. Subjects were selected from the Alzheimer Disease Imaging Initiative (ADNI) and memory clinic based Amsterdam Dementia Cohort, DESCRIPA, and ICTUS studies. Longitudinal data on diagnosis and survival was used to fit a multistate model (MSM) that included four stages: preclinical AD, prodromal AD, AD-type dementia, and death. R-packages msm and ELECT were used to estimate progression rates centered at age 70, hazard ratios per year increase in age, and duration of stages according to age, gender and setting (for preclinical AD population-based versus memory clinic). Figure 1 illustrates the MSM model, including progression rates and hazard ratios per year increase in age. Duration of the preclinical AD stage was on average 8 years and the prodromal AD stage 4.5 years, independent of age. The duration of the dementia stage was shorter with increasing age. (Table 1). Duration of preclinical AD in women was longer than in men, 10.2 and 6.1 years respectively. In addition, in women with prevalent dementia the dementia stage was 3 years longer. The preclinical AD stage in memory clinic subjects (3.3 years) was shorter than population-based subjects (8.5 years, Table 2). Age had an impact on duration of the dementia stage, but not the pre-dementia stages. Disease duration was longer in women than men. The shorter preclinical AD stage in the memory clinic, might be due to a referral bias of subjects close to the prodromal stage. Our MSM model estimates can be used for the planning of future studies and could help to give patients a prognosis. Multi-state model with risk estimates (95% CIs) at age 70, and hazard ratios for a year increase in age (95% CIs), misclassification 1.1% for prodromal AD to dementia.

Blinding Trachoma: Systematic Review of Rates and Risk Factors for Progressive Disease.

BackgroundSight loss from trachoma is the end result of a scarring disease process starting in early childhood and characterised by repeated episodes of conjunctival inflammation (active trachoma). Subsequently, the conjunctiva becomes scarred, causing the eyelashes to turn inwards and scratch the cornea (trichiasis), damaging the corneal surface and leading to corneal opacification and visual impairment. It is thought that this process is initiated and driven by repeated infection with Chlamydia trachomatis. We review published longitudinal studies to re-examine the disease process, its progression rates and risk factors.Methodology/Principal FindingsWe searched PubMed for studies presenting incidence and progression data for the different stages of trachoma natural history. We only included studies reporting longitudinal data and identified 11 publications meeting this criterion. The studies were very heterogeneous in design, disease stage, duration, size and location, precluding meta-analysis. Severe conjunctival inflammation was consistently associated with incident and progressive scarring in five studies in which this was examined. One study reported an association between C. trachomatis infection and incident scarring. No studies have yet demonstrated an association between C. trachomatis infection and progressive scarring. Several studies conducted in regions with low prevalence active disease and C. trachomatis infection found evidence of on-going scarring progression.Conclusions/SignificanceOverall, there are few longitudinal studies that provide estimates of progression rates and risk factors, reflecting the challenges of conducting such studies. Our understanding of this disease process and the long-term impact of control measures is partial. Intense conjunctival inflammation was consistently associated with scarring, however, direct evidence demonstrating an association between C. trachomatis and progression is limited. This suggests that on-going chlamydial reinfection may not be mandatory for progression of established scarring, indicating that sight threatening trichiasis may continue to evolve in older people in formerly endemic populations, that will require service provision for years after active disease is controlled.

USING MULTI-STATE MODELS FOR ANALYSIS

Multi-state models as shown in figure 1 have several strengths for the analysis and summary of a subject's traversal of the path from cognitively normal (CN) through dementia. We will discuss some of these, along with examples and details of their implementation. The Mayo Clinic Study of Aging multi-state transition model. All states can transition to death. The underlying model is a simple diagram of the patient states and possible transitions between them. Software for fitting the models is freely available but not yet widely utilized. The methods fall into two disjoint classes. The first applies to cases where the actual transitions between states are observed, e.g., competing risks (Putter http://dx.doi.org/10.1002/sim.2712). The second applies to cases where a subject’s state is recorded at regular visits but the exact event times are unknown (Satten, Applied Statistics 1996). We fit models of both types using the survival, mstate, and msm packages in R. A primary advantage of this approach is that it views the disease process in toto, and as such can generate results on multiple levels, e.g., the predicted future path for a subject given their starting age and state, the population prevalence across states of living subjects, the lifetime probability of ever being demented, and perhaps most useful, estimates of the underlying event rates. Figures 1-3 below are from the Mayo Clinic Study of Aging (MCSA), a population based study of cognitive aging. Figure 1 shows the underlying multi-state model that was assumed. Figure 2 shows the estimated progression rates from the model as a function of age, and figure 3 the fitted model's predicted distribution of states for living subjects. We see the following: (1) Rates increase exponentially with age, only one plateaus; (2) Simple biology (figure 2) can generate a complex interplay of observed frequency (figure 3); amd (3) Stage 1 NIA-AA pre-clinical AD (A+N-) is not benign. It carries an elevated risk for transition to A+N+ which in turn has the highest rate of transition to dementia. Estimated biomarker transition rates by age. Estimated percentage of participants in each state at a given age among those who are alive. Multi-state models are a worthwhile addition to the analysis toolbox, and can give further insight into underlying disease processes. Computational tools to fit the models are increasingly available.

Estimating the True Distribution of Visual Field Progression Rates in Glaucoma

Bayesian methods allow the distribution of glaucomatous visual field progression rates in the population to constrain individual progression rate estimates. As the true population distribution is never known, it must itself be estimated from a finite number of noisy individual estimates of rate. We used simulations to investigate the relationship between the true distribution of progression rates and that estimated from noisy empirical data. We generated series of visual fields (3-10 per patient) using different variabilities (SD of 0.5-2.0 dB) for the summary index mean deviation (MD) to determine the relationship between the distribution of empirical estimates of progression rates determined by linear regression and the true underlying distribution of progression rates. Estimating the underlying distribution from empirical data produced biases that broadened the distribution and made it more symmetrical, particularly for a short series of variable visual field estimates. Decreasing cohort size increased the variability in distribution parameter estimates, but produced no bias. Variability in distribution tails produced a 3.5-fold variation in the proportion of rapid progressors for the smallest cohort (200), falling to 1.8- and 1.3-fold for cohort sizes of 800 and 3200, respectively. The underlying distribution of glaucomatous visual field progression rates for the population is likely to be narrower, and less symmetric, than that predicted from empirical data. Therefore, care should be exercised when inferring the benefits of Bayesian estimators, particularly where prior information is itself derived from a small sample of noisy empirical estimates.

Pinning Down Cancer Risk in Barrett Esophagus with LGD

The estimated rate of progression of Barrett esophagus (BE) with low-grade dysplasia (LGD) to esophageal adenocarcinoma (EAC) ranges widely from <0.2%

MP45-02 13 YEARS OF EXPERIENCE IN ACTIVE SURVEILLANCE FOR PROSTATE CANCER: MALCOMPLIANCE IS A MAJOR CONCERN IN THE LONG TERM

You have accessJournal of UrologyProstate Cancer: Localized III1 Apr 2014MP45-02 13 YEARS OF EXPERIENCE IN ACTIVE SURVEILLANCE FOR PROSTATE CANCER: MALCOMPLIANCE IS A MAJOR CONCERN IN THE LONG TERM Lukas Hefermehl, Daniel Disteldorf, Scherwin Talimi, Rachel Groebli, Benjamin Lyttwin, and Kurt Lehmann Lukas HefermehlLukas Hefermehl More articles by this author , Daniel DisteldorfDaniel Disteldorf More articles by this author , Scherwin TalimiScherwin Talimi More articles by this author , Rachel GroebliRachel Groebli More articles by this author , Benjamin LyttwinBenjamin Lyttwin More articles by this author , and Kurt LehmannKurt Lehmann More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1199AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Active Surveillance (AS) has become a standard treatment for a defined group of patients. Clinical parameters have been approved in similar protocols at large academic institutions. However, non-clinical parameters such as patient compliance are underrated but crucial parameters, especially in a form of therapy where continuous follow up (FU) is imperative. Furthermore, long term data for AS are still not well known, especially in a community hospital environment. Methods We conducted a prospective study starting in 1999 at our non-academic institution. Inclusion and progression criteria as well as FU schedule met general recommendations for AS. If patients failed to appear they were contacted at least twice by post explaining the importance of FU. Results 157 men have been included at a median age of 67 (61-70) y between 1999 and 2013. Median FU was 36 (24-72) mo 32 (20%) men showed progression after a median FU of 26 (19-35) mo. Progression free survival (PFS) was 65% in 146mo. Of these 32 men 62% underwent radical prostatectomy (RP) and 34% had external beam radiotherapy (EBRT). 1 man required direct androgen deprivation therapy and died consecutively. After RP 37% showed GS 7, 5% GS 8 & 10% GS 9. FU after RP was 52 (12-76) & 21 (15-51)mo after EBRT. Follow-up with no evidence of disease after treatment in these men was 43 (12-71) & 23 (15-50) mo respectively. 2nd line therapy was needed only in 1 man after RP and 1 after EBRT. 13-y Kaplan-Meier analysis revealed an estimated progression rate of 28%, lost to FU rate of 27%, OS of 94%, CSS of 99% and PFS of 98%. After 13y only 50% remained in the AS group. 17 (11%) men were lost to FU. Overall drop-out was 36% (57). According to the protocol median FU would have been 67 (43-118) mo. Due to malcompliance actual FU was 36 (24-72) mo only. 3 mo after diagnosis 19% refused confirmation biopsy. Scheduled number of PSA measurements was 1891 but only 40% were performed. Conclusions Even in a community hospital environment AS seams safe if the protocol is followed. Secondary progression after treatment is low. However, in nearly 1/3 histology after RP revealed an aggressive tumor. After 13y ¼ of all men will need definitive treatment and only ½ will continue AS. Lost to FU rate is considerable. When AS is commenced the problem of malcompliance is often scotomized. Stable disease leads to protocol violation and even complete lost to FU in some men. However, our responsibility remains. Our 13y experience reveals that malcompliance is a major concern: This needs to be taken in consideration for future AS protocols and whenever AS is offered as a treatment option. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e459-e460 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Lukas Hefermehl More articles by this author Daniel Disteldorf More articles by this author Scherwin Talimi More articles by this author Rachel Groebli More articles by this author Benjamin Lyttwin More articles by this author Kurt Lehmann More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of Cryoglobulinemic Syndrome on the Outcome of Chronic Hepatitis C Virus Infection

We evaluated the influence of cryoglobulinemic syndrome (CS) on the outcome of chronic hepatitis C virus (HCV) infection in a 15-year prospective study. We assessed a cohort of 950 chronically HCV-infected patients, collected from the beginning of 1990 to the end of 2010. All patients had received a liver histologic diagnosis. Mixed cryoglobulinemia (MC) was determined in 246 patients (25.8%), of whom 184 also had CS. They were assessed every 3 months for 15 years, at least; 141 patients with CS and 601 without MC completed the study.No spontaneous clearance of cryoglobulins was noted. Type II to type III spontaneous switching was ascertained in 1.6% (0.08%/yr) patients. The estimated progression rate of liver fibrosis was lower in CS(+) than in MC(−) patients (p < 0.05). The 15-year cumulative probability of developing cirrhosis and/or hepatocellular carcinoma was higher in MC(−) than in CS(+) patients (24.9% vs. 14.2%, p < 0.005 and 20.3% vs. 7.5%, p = 0.003, respectively). Renal insufficiency, neurologic impairment, or B-cell non-Hodgkin lymphoma were significantly more frequent in CS(+) than in MC(−) patients (32.6% vs. 3%, p < 0.0001; 31.2% vs. 4.8%, p < 0.0001; and 15% vs. 7.1%, p = 0.003, respectively). However, in spite of different morbidity features and causes of death, the 15-year survival rate was similar in the 2 groups (70.2% vs. 71.7%). Antiviral therapy had an undisputable impact on patient outcome.This 15-year prospective cohort study shows that, although CS has no influence on the overall survival of HCV-infected patients, it significantly modifies the natural history of chronically HCV-infected patients.

Progression rates from HbA1c 6.0–6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis

Precise estimates of progression rates from 'prediabetes' to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals. There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA1c-defined prediabetes ranges, with some favouring 6.0-6.4% (42-46mmol/mol). Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories. Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5.6-6.9mmol/l], WHO-defined IFG [6.1-6.9mmol/l], IGT (7.8-11.0mmol/l) or raised HbA1c [6.0-6.4%/42-46mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models. Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA1c, the pooled incidence rate (95% credible interval) of diabetes was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5 [37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results were seen when the data were analysed by the criteria used to diagnose diabetes. This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA1c 6.0-6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.

NASCA Report 2: Longitudinal Study of Relationship of Exposure to Space Radiation and Risk of Lens Opacity

The NASA Study of Cataract in Astronauts (NASCA) was designed to measure the impact of exposure to space radiation on progression rates of cortical, nuclear, and posterior subcapsular cataract in U.S. astronauts who have flown in space and comparison groups of astronauts who had not flown in space, and subjects with a history of military aviation. We present our analyses of 5 years of data with an average of 3.8 exams per subject. All subjects had digital lens images with the Nidek EAS 1000 Lens Imaging System. Because of high variability and skewness of opacity measures, nonparametric methods were used to test for association between rates of opacification and space radiation exposure. First, median regression was used to collapse longitudinal data into robust estimates of progression rates (opacity severity compare to time for each eye of each subject). To quantify and test for a radiation effect, median regression with the dependent variable being the maximum of the two slopes (OD and OS) per subject was then used, adjusting for the confounding variables of age, nutritional, and sun-exposure histories. Median regression showed evidence of an association between the rate of cortical progression in the worse eye with radiation dose and age. The estimated median progression rate from space radiation being 0.25 ± 0.13% lens area/Sv/year (P = 0.062). We found no relationship between radiation exposure and progression of aggregate area of posterior subcapsular cataract or nuclear progression rates. However, longer follow-up may be needed to further understand any impact of space radiation on progression rates for posterior subcapsular cataracts and nuclear cataracts, and to characterize changes to visual acuity.

Myopia Progression Rates in Urban Children Wearing Single-Vision Spectacles

To conduct a meta-analysis on the rates of myopia progression in urban children of Asian and predominately European ethnicities who are corrected with traditional single-vision spectacles. A search of the National Library of Medicine's PubMed literature database for articles on myopia progression was conducted using the terms "myopi*progression" and MeSH terms "myopia" and "disease progression," and limited to publications from January 1990 and only for articles reporting data for humans <16 years of age. Studies were excluded if they were non-randomized, did not use cycloplegic autorefraction, had a sample size <30 individuals, examined high myopia (worse than -6.0 D) or special subject groups, presented myopia as part of a syndrome or condition, were retrospective, or used controls wearing optical corrections other than spectacles. Of 175 articles identified, 20 remained after applying the exclusion criteria. The estimated myopia progression at a mean age of 9.3 years after 1 year of follow-up was -0.55 D [95% confidence interval (CI), -0.39 to -0.72 D] for populations of predominantly European extraction and -0.82 D (95% CI, -0.71 to -0.93 D) for Asians. The estimated progression rates were dependent on baseline age, with decreasing progression as age increased. The rates also varied with gender. For an average baseline age of 8.8 years, estimated annual progression (combined ethnicities) was -0.80 D/yr for females (95% CI, -0.51 to -1.10), and a significantly slower (p < 0.01) -0.71 D/yr for males (95% CI, -0.42 to -1.00). In children wearing single-vision spectacles, higher myopia progression rates were found in urban Asians compared with urban populations of predominantly European descent. Younger children and females demonstrated greater annual rates of progression of myopia.

Impact of delayed diagnosis time in estimating progression rates to hepatitis C virus-related cirrhosis and death

Delay of the diagnosis of hepatitis C virus (HCV), and its treatment to avert cirrhosis, is often present sincethe early stage of HCV progression is latent. Current methods to determine the incubation time to HCV-related cirrhosis and the duration time from cirrhosis to subsequent events (e.g. complications or death) used to be based on the time of liver biopsy diagnosis and ignore this delay which led to an interval censoring for the first event time and a double censoring for the subsequent event time. To investigate the impact of this delay in estimating HCV progression rates and relevant estimating bias, we present a correlated two-stage progression model for delayed diagnosis time and fit the developed model to the previously studied hepatitis C cohort data from Edinburgh. Our analysis shows that taking the delayed diagnosis into account gives a mildly different estimate of progression rate to cirrhosis and significantly lower estimated progression rate to HCV-related death in comparison with conventional modelling. We also find that when the delay increases, the bias in estimating progression increases significantly.

Probability model for estimating colorectal polyp progression rates

According to the American Cancer Society, colorectal cancer (CRC) is the third most common cause of cancer related deaths in the United States. Experts estimate that about 85% of CRCs begin as precancerous polyps, early detection and treatment of which can significantly reduce the risk of CRC. Hence, it is imperative to develop population-wide intervention strategies for early detection of polyps. Development of such strategies requires precise values of population-specific rates of incidence of polyp and its progression to cancerous stage. There has been a considerable amount of research in recent years on developing screening based CRC intervention strategies. However, these are not supported by population-specific mathematical estimates of progression rates. This paper addresses this need by developing a probability model that estimates polyp progression rates considering race and family history of CRC; note that, it is ethically infeasible to obtain polyp progression rates through clinical trials. We use the estimated rates to simulate the progression of polyps in the population of the State of Indiana, and also the population of a clinical trial conducted in the State of Minnesota, which was obtained from literature. The results from the simulations are used to validate the probability model.

Predictive model for progression of hearing loss: meta‐analysis of multi‐state outcome

To develop a multi-state Markov model to predict multi-state progression of age-related hearing loss (ARHL). A systematic searching of literature from Medline (1966-2005) was performed. The disease process for hearing loss was modelled as a four-state continuous-time Markov process. We estimated the progression rates for each study separately, then calculated weighted averages over all studies across age groups, weighting for each study by the inverse of variance. The pooled estimates were obtained and transition probabilities between states were illustrated. The progression of hearing loss increased with the ascending frequencies across all age groups. Men had significantly faster progression rates in all frequencies and age groups except for the age group of 90 years or older. In comparison between ears, the progression of hearing would be slightly faster in left ears initially in early elder life and did not show any difference in further ageing and later hearing declines. With the pooled estimates of progression rates, the probabilities of hearing deterioration could be obtained. The multi-state model can quantify the nature course of hearing progression in ARHL. Predictions of hearing status can be simulated either at population or individual level with this model.

Re-weighted inference about hepatitis C virus-infected communities when analysing diagnosed patients referred to liver clinics

To project national hepatitis C virus (HCV) burden, unbiased estimation of HCV progression to liver cirrhosis is required for the whole community of HCV-infected individuals. However, widely varying estimates of progression rates to cirrhosis have been produced. This disparity is partly associated with the statistical methods applied, but is mainly due to the differing types of study cohort. We use an inverse probability weighted estimation method to recover the true parameters for the (Weibull regression) model that determines the incubation period from infection to cirrhosis for the community of HCV-infected individuals, when there is cirrhosis-related recruitment bias to the studied cohort. We apply the method to simulated data for a liver clinic which attracts patients from a community of 1000 HCV-infected individuals under different event-biased referral patterns. We investigate how well the method performs in recovering the true community parameters, and then apply it to Edinburgh Royal Infirmary's liver clinic series. The results obtained are compared to those from a Weibull survival analysis which ignores the selection bias.

What Proportion of Advanced Adenomas Progress to Colorectal Cancer

The rate at which advanced adenomas progress to colorectal cancer is largely unknown. Previous estimates of progression rates were based primarily on

Muscle-Invasive Bladder Cancer: Predictive Factors and Prognostic Difference Between Primary and Progressive Tumors

Objectives To establish whether a difference in the clinical outcomes of patients with progressive and primary muscle-invasive bladder cancer exists. Methods The records of patients who had undergone radical cystectomy for bladder urothelial carcinoma from 1990 to 2005 were reviewed. According to our inclusion criteria, 109 patients with primary muscle-invasive tumor (group 1) and 45 patients with progressive tumors were selected (group 2). The correlation of clinical and pathologic variables with survival was investigated using the Cox proportional hazards test. The Kaplan-Meier method was used to estimate progression rates. Multivariate analysis was performed using the Cox regression survival method to investigate possible predictive factors. Results The 2, 3, and 5-year cancer-specific survival rate was 72%, 61%, and 43% for patients with progressive tumor and 75%, 62%, and 54% for patients with primary tumor, respectively ( P >0.05). For lymph node-negative tumors (pN0), the corresponding rates were 77%, 64%, and 56% in group 1 and 73%, 60%, and 39% in group 2 ( P >0.05). On multivariate analysis, lymphovascular invasion and pT stage of the primary tumor remained significant independent prognostic factors for cancer-specific survival. The detection of local and/or distant metastasis during follow-up significantly shortened the cancer-specific survival of patients with muscle-invasive bladder cancer. Conclusions The results of our study have shown that patients with progressive muscle-invasive urothelial tumors do not have a worse prognosis than do those with primary tumors. During the early postoperative years, even patients with progressive tumors had better disease-specific survival rates. For both groups, pT stage and lymphovascular invasion seemed to be independent predictors of decreased cancer-specific survival.

Event-biased referral can distort estimation of hepatitis C virus progression rate to cirrhosis, and of prognostic influences

Objective To investigate how cirrhosis-biased referral to liver clinics can explain the wide variation in progression rates for differently recruited cohorts and, in particular, for liver clinic cohorts compared to community-based studies of the natural history of hepatitis C virus (HCV). Study Design and Setting A simulation was designed to illustrate the sort of referral bias pattern that is capable of converting a 20-year progression rate to cirrhosis of around 5% in the community of HCV-infected individuals into a 20% progression rate for patients who have been selectively referred to a liver clinic. Results We show that event-biased recruitment, such as occurs if referral to liver clinics is increasingly likely the closer a patient is to cirrhosis, can produce severely upwardly biased estimates of progression rates, can dampen the influence of “poor prognostic” factors (such as history of excessive alcohol consumption), but overrepresents the proportion of patients in the community of HCV-infected individuals who have poor prognosis. Conclusion When attempting to establish the natural history of new diseases with long incubation periods, researchers should be on the look out for potential biases that result from the way patients are referred into clinical cohorts.

Estimated progression rates in three United Kingdom hepatitis C cohorts differed according to method of recruitment

Objectives To estimate hepatitis C virus (HCV) progression rates between disease stages prior to cirrhosis, using data from liver biopsies in three observational cohorts. To demonstrate how the method of cohort recruitment can influence the estimation of HCV-progression rates. Study Design and Setting Data came from three United Kingdom observational cohorts, assembled from different referral sources. In total, 987 HCV-infected patients with an estimated (or known) date of infection and at least one histologically scored liver biopsy were eligible for inclusion in the analysis. Liver biopsy scores were used to determine the stage of HCV-related liver disease. A three-state continuous time Markov model was used to estimate covariate-specific average probabilities of progression of disease. Results After adjusting for confounders, considerably different rates of disease progression were estimated in the three cohorts. For a group of patients with the same demographics, the estimated 20-year probability of progression to cirrhosis was 12% (95% confidence interval CI = 6–22) in a hospital-based cohort, 6% (95% CI = 3–13) in a posttransfusion cohort, and 23% (95% CI = 14–37) in a cohort recruited from a tertiary referral center. Conclusion Researchers using estimates of disease progression should be aware that the method of cohort recruitment has considerable influence on the progression rates that are derived.

Effect of antiretroviral therapy on viral load, CD4 cell count, and progression to acquired immunodeficiency syndrome in a community human immunodeficiency virus-infected cohort. Swiss HIV Cohort Study.

To examine the effect of different antiretroviral treatment regimens on viral load, CD4 lymphocyte counts, and rates of progression to clinical acquired immunodeficiency syndrome events among treatment-naive human immunodeficiency virus (HIV)-infected patients enrolled in a large community cohort study. Based in 7 outpatient clinics, the Swiss HIV Cohort Study is a cohort with national coverage. Virological, immunologic, and clinical results of 755 treatment-naive patients (median age, 36 years; 28.2% female) who initiated antiretroviral therapy between July 1, 1995, and June 30, 1997, were analyzed. Patients started undergoing monotherapy with 1 reverse transcriptase inhibitor (RTI), combination therapy with at least 2 RTIs, or highly active antiretroviral therapy (HAART) with RTIs and protease inhibitors. Antiretroviral treatment led to a mean reduction of viremia of 1.8 log10 copies per milliliter with HAART, 1.2 log10 copies per milliliter with RTI combination therapy, and 0.4 log10 copies per milliliter with monotherapy. Virological failure, defined as less than 1 log10 reduction per milliliter in viremia, was present in 45 (20%) patients undergoing HAART, 180 (38%) undergoing RTI combination therapy, and 47 (82%) undergoing monotherapy. The proportion of patients reaching undetectable viremia was 12% (n = 7) for monotherapy, 41% (n = 197) for RTI combination therapy, and 63% (n = 137) for HAART. Similar gains of CD4 cells were achieved with RTI combination therapy and HAART. Kaplan-Meier estimates of progression rates to a new acquired immunodeficiency syndrome event at 18 months were 13.6% (monotherapy), 4.7% (RTI combination therapy), and 3.9% (HAART). The rate of virological failure of antiretroviral treatments was high in this population of treatment-naive patients, even among patients receiving combination regimens. Clinical progression rates were, however, low in patients treated with RTI combination therapy and HAART.

Update of the Swedish Two-County Trial of breast cancer screening: histologic grade-specific and age-specific results.

The benefit of mammographic screening in reducing mortality from breast cancer is well established. Questions remain with respect to the magnitude of the long-term benefit of modern mammography screening, age specific benefits and the timing of these, and histology specific effects. The Swedish Two-County Trial was set up in 1977, with 77,080 women aged 40-74 randomised to invitation to mammographic screening for breast cancer (active study population, ASP) and 55,985 women randomised to no invitation (passive study population, PSP). There is now follow-up for mortality to 31 December 1996, approximately 18 years average follow-up. We investigated the effect of invitation of screening on breast cancer mortality and incidence of advanced tumours by age group (40-49 and 50-74) and histologic type. In addition we estimated progression rates by histologic grade using markov chain models. A significant 29% reduction in breast cancer mortality was observed in association with invitation to screening (relative risk = 0.71, 95% confidence interval 0.60-0.83), maintaining the effect observed at previous stages of follow-up. Age-specific analyses show a smaller and later mortality benefit in women aged 40-49. This is related to the fact that there is a considerable benefit from early detection in terms of mortality from aggressive, poorly differentiated cancers in women aged 50-74, whereas the major effect in women aged 40-49 is on the less aggressive tumours of good or intermediate differentiation. Among women aged 50-74, the incidence of grade III tumours in the ASP is significantly lower than in the PSP, but this is not the case for women aged 40-49. This is related to the greater prevalence and rapidity of progression with respect to histologic grade, as evidenced by the results of markov chain models and the proportions of grade III tumours by time since last screen. The substantial and significant mortality benefit of invitation to mammographic screening in women aged 40-74 is maintained at 18 years of follow-up. To achieve a substantial mortality benefit at an early stage in the screening program in women aged under 50 years, an interscreening interval of 12-18 months would be required.