Cumulative Probability Of Progression Research Articles

Visual Field Progression Pattern Associated With Optic Disc Tilt Morphology in Myopic Open-Angle Glaucoma

To understand the long-term characteristics of visual field (VF) progression in myopic open-angle glaucoma (OAG) according to the morphology of optic disc tilt. Retrospective, comparative, longitudinal cohort study. Myopic OAG eyes were divided into temporally tilted disc and inferiorly tilted disc groups according to optic disc torsional degrees. Kaplan-Meier survival analysis was used to compare the survival rates between nonmyopic OAG, myopic OAG with temporally tilted disc, and myopic OAG with inferiorly tilted disc. The hazard ratio (HRs) for the associations between risk factors and progression were analyzed using Cox proportional hazards modeling. In the inferiorly tilted disc group, subgroups were classified into progression, stationary, and progression-to-stationary groups, and the clinical characteristics of VF progression were compared among the subgroups. A total of 82 eyes in 82 nonmyopic OAG patients and 150 eyes in 150 myopic OAG patients were included. Myopic OAG with inferiorly tilted disc showed significantly more baseline and final 1-hemifield-involvement cases compared with myopic OAG with temporally tilted disc (P < .001, P < .001, respectively). The cumulative probability of progression was shown to be faster for myopic OAG with inferiorly tilted disc compared with temporally tilteddisc and nonmyopic OAG (P= .002, P= .038, respectively). A larger number of medications (HR= 1.339; P= .004), earlier-stage VF defect (HR= 1.217; P < .001), and inferiorly tilted disc (HR= 2.378; P < .001) were predictive of progression. In the analysis of myopic OAG with inferiorly tilted disc, the progression group had younger age and earlier-stage VF defect at baseline compared with the stationary group (P= .01, P < .001, respectively). It is likely that VF progression in myopic OAG is associated with the morphology of the optic disc tilt. Especially in OAG with inferiorly tilted disc, VF is likely not to progress after terminating VF progression at the region associated with optic disc tilt.

Implications of Optic Disc Tilt in the Progression of Primary Open-Angle Glaucoma.

To evaluate the effect of optic disc tilt on the progression of glaucoma in myopic glaucomatous eyes. The disc tilt ratio was estimated on disc photographs. Glaucomatous progression was determined either by stereoscopic optic disc/retinal nerve fiber layer photographs or serial visual field data. All participants were categorized into two groups according to tilt ratio (nontilted [<1.3] or tilted [≥1.3]). Kaplan-Meier life-table analysis was used to compare the survival experiences (time to confirmed glaucomatous progression) between groups. The hazard ratios (HRs) for the associations between potential risk factors and progression were determined by using Cox proportional hazards modeling. A total of 85 eyes in 85 myopic glaucoma patients (axial length > 24 mm; mean follow-up, 4.1 years) were included. Among them, 42 eyes (49.4%) demonstrated progression and 43 eyes (50.6%) were stable on follow-up. The mean disc tilt ratio was significantly smaller, and the prevalence of disc hemorrhage higher, in the progression than the stable group (P = 0.032, P = < 0.001, respectively). The cumulative probability of progression was 24.7% in the tilted group and 68.7% in the nontilted group (P = 0.005). Disc hemorrhage (HR = 3.317; P = 0.001) and the tilt ratio (HR = 0.110; P = 0.046) were predictive of progression. Myopic eyes with tilted disc demonstrated a smaller probability of glaucomatous progression. Optic disc tilt may be protective against glaucoma progression, or tilted myopic glaucomatous eyes may have less progressive characteristic by nature.

O2-4-3 - Characteristics and Risk for Progression of Smoldering Multiple Myeloma: Japanese Nationwide Retrospective Survey

Background: Smoldering multiple myeloma (SMM), defined as serum monoclonal (M) protein >= 3 g/dL and/or clonal bone marrow plasma cells (BMPC) >= 10% with no end-organ damage attributed to plasma cell proliferative disorders, have an indolent clinical course for many years without therapy. The standard therapy for SMM is watchful waiting until progression. However, a recent study demonstrated early treatment provided a survival benefit to high-risk SMM patients. To investigate the risk factors of progression, we underwent a nationwide cohort study.Method: The clinical data of patients diagnosed as having SMM between 2001 and 2012 were reviewed. This study was approved by institutional review boards.Results: Medical records of 291 patients with SMM, median age of 68 years (range 27-85), were collected from 61 hospitals. At a median follow-up of 37 months, 53% progressed to symptomatic. The cumulative probability of progression at 3 years was 57.8% in patients who fulfilled the both criteria of serum M protein >= 3 g/dL and clonal BMPC >= 10%, while was 38.9% in those fulfilled only one of them (P < 0.002). The probability of progression at 3 years was significantly higher in patients with abnormal free light chain (FLC) ratio of <0.125 or >8 (P = 0.036), while there was no significant difference in overall survival (P = 0.3). None of the cytogenetic abnormalities, including del13, t(4;14), t(11;14), t(14;16) and del17p detected by FISH, was statistically correlated with either the probability of progression or survival. When an increasing rate of M protein was calculated at progression to symptomatic myeloma, the median time to progression was shorter (8 months vs. 34 months, P < 10-8>), but the survival difference was not significant (109 months vs. 121 months, P = 0.1) in patients with an increasing rate of >2mg/dL per day.Conclusion: An abnormal FLC ratio and a high increasing rate of M protein were associated with progression to symptomatic myeloma.

Natural History Of Smoldering Monoclonal Gammopathy-Associated Malignancies: A Population-Based Study

BackgroundWe performed a population-based study to determine the natural history of monoclonal gammopathy-associated malignancies (MGAM) including multiple myeloma, lymphoplasmacytic lymphoma, and Waldenstrom's macroglobulinemia that were considered smoldering at the time of cancer diagnosis. We compared the clinical outcomes among those with and without a prior monoclonal gammopathy of undetermined significance (MGUS) follow-up. MethodsData were obtained from the Surveillance Epidemiology and End Results (SEER) database linked to Medicare claims. We considered patients age ≥ 67 years with MGAM diagnosed from 1994-2005. We excluded those who were diagnosed by autopsy or death certificate only, had invasive cancers within 5 years prior to MGAM diagnosis, prior diagnosis of MGAM, lacked date of either diagnosis or death, lacked complete Medicare parts A/B coverage 15 months prior to or 3 months after MGAM diagnosis (or to date of death, if death was within 3 months), and receiving dialysis more than 3 months before MGAM diagnosis. Major complications including acute kidney injury, cord compression, dialysis-requirement, fracture, and hypercalcemia at time of disease progression were obtained from diagnosis and procedure claims. MGUS follow-up was defined as having a diagnosis claim 4-15 months prior to smoldering MGAM diagnosis. Smoldering MGAM was defined as absence of all of the following criteria: any major complication claims, any treatment claims, and death because of MGAM within 12 months of MGAM diagnosis, while progression to active MGAM was defined by the presence of any of these criteria. ResultsAt the time of MGAM diagnosis 2,189 had smoldering disease. Of these, 1,753 (80.1%) progressed to active MGAM with a median time-to-progression of 17 months. Progression to active MGAM were identified by claims reflecting the development of major cancer complications (34.9%), administration of cancer therapy (59.5%), both (0.7%), or report of death from MGAM without major complication or treatment claims (4.9%). The cumulative probability of progression by Kaplan-Meier analysis was 40.2%, 72.9%, 85.7%, and 96.1%, at years 1, 3, 5, and 10, respectively. Among those who progressed, 35.6% developed one or more major complications including acute kidney injury (13.0%), cord compression (1.8%), dialysis-requirement (2.0%), fracture (15.6%), and hypercalcemia (5.6%). A prior MGUS follow-up occurred in 199 (9.1%) smoldering MGAM patients. The time to progression for smoldering MGAM patients with a prior MGUS follow-up was similar to those without MGUS follow-up (P = 0.52). Multivariable analysis factoring in year of smoldering MGAM diagnosis, type of cancer, age, sex, race, place of residence, SEER site, median annual household income, Charlson co-morbidity index, and prior MGUS follow-up showed that older age, higher Charlson co-morbidity scores, and diagnosis of multiple myeloma as independent predictors of progression (Table). ConclusionsOur population-based study shows that most patients with smoldering MGAM diagnosed at age ≥ 67 years progress to active disease within the first three years. Those with a prior history of MGUS follow-up progress at a similar rate compared to those without such a history. The determinants of progression at diagnosis are age, number of co-morbidities, and type of MGAM.VariablesHazard Ratio (95% CI)PAge (years)------67-75Reference---76-851.132 (1.020-1.256)0.020≥ 861.394 (1.207-1.611)< 0.001Charlson Co-Morbidity Index (score)------0Reference---11.058 (0.917-1.221)0.44020.971 (0.788-1.196)0.783≥ 31.497 (0.788-1.196)0.002Diagnosis------Waldenstrom's macroglobulinemiaReference---Lymphoplasmacytic lymphoma1.103 (0.882-1.378)0.391Multiple myeloma1.505 (1.296-1.748)< 0.001 Disclosures:No relevant conflicts of interest to declare.

Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance and Smoldering Waldenström Macroglobulinemia

Monoclonal gammopathy of undetermined significance of the immunoglobulin M class was diagnosed in 213 patients at the Mayo Clinic, 29 (14%) of whom developed lymphoma, Waldenström macroglobulinemia, or a related disorder over 1567 person-years of follow-up. The cumulative probability of progression was 10% at 5 years, 18% at 10 years, and 24% at 15 years, or approximately 1.5% per year. The concentration of serum monoclonal protein at diagnosis and the initial serum albumin value were the only independent predictors of progression with multivariate analysis. By contrast, during 285 person-years of follow-up, 34 (71%) of 48 patients with smoldering Waldenström macroglobulinemia (SWM) progressed to Waldenström macroglobulinemia (WM), which required therapy, along with amyloid light chain (AL) amyloidosis (1) and lymphoma (1). The cumulative probability of progression was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 65% at 10 years. The percentage of lymphoplasmacytic cells in the bone marrow, size of the serum monoclonal (M) spike, and hemoglobin value were significant independent risk factors for progression.

A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial

ObjectiveTo assess whether three novel interventions, formulated based on a systems medicine therapeutic concept, reduced disease activity in patients with relapsing–remitting multiple sclerosis (MS) who were either treated or not...

Abstract 2758: Effect of Catheter Ablation and Antiarrhythmic Drug Therapy on AF Progression. A Long-term Controlled Follow-up Study

Background. In the era of catheter ablation there are no prospective data on AF progression according to AF guidelines classification and management. Methods. Of 402 screened patients with first-detected paroxysmal AF, 106 (mean age, 57.5 years) were enrolled for this prospective study. Of them, 54 (mean age, 53.3 years) had lone AF and 52 (mean age, 62.0 years) had comorbidities. Patients were treated according to recent guidelines management. Primary endpoint of the study was the cumulative probability of progression to permanent AF over a 5-year follow-up among patients who underwent catheter ablation or antiarrhythmic drug therapy alone (ADT). Predictors of progression to permanent AF were also analyzed by multivariate analysis. Results. At the end of the 5-year follow-up, 50 patients with lone AF had no further recurrences after the first episode in the absence of ADT. The remaining 56 patients at a median follow-up of 19 months after the first episode experienced recurrent episodes of paroxysmal AF requiring ADT (45 patients) or catheter ablation (11 patients) because of ADT failure. Patients who underwent ablation had similar clinical characteristics as patients on ADT. K-M curves demonstrated that patients on ADT were more likely to progress to permanent AF than those who underwent catheter ablation (p=0.029, by log-rank test, Figure 1 ). Age (p&lt;0.0001), diabetes (p=0.003) and heart failure (p=0.002) predicted progression to permanent AF. Conclusions. Over a 5-year follow-up, catheter ablation is of benefit in delaying arrhythmia progression. Age, diabetes and heart failure predict progression to permanent AF.

Epidemiology of Plasma Cell Disorders in a General Hospital: A Retrospective Study of 102 Patients.

INTRODUCTION Plasma cell disorders are a group of diseases characterized by the proliferation of a plasma cell clone which produces a monoclonal protein (M protein). The most common type is Monoclonal Gammopathies of Undetermined Significance (MGUS), followed by multiple myeloma (MM) and Waldenstrom's Macroglobulinemia (WM). In particular, the frequency of MGUS increases with age and its rate of progression is approximately 1% per year. Because of the high prevalence and the different fields of clinical practice in which these patients are followed, it could be of great interest to know the epidemiology of these diseases out of the Hematology Units.AIM OF THE STUDY to describe the frequency and the progression risk of plasma cell disorders in a General Hospital during more than a twenty-year period.METHODS We retrospectively reviewed the medical records of patients with diagnosis of MGUS, MM or WM seen at our center from 1984 through 2006. Statistical analysis were performed using GraphPad Prism 4 (GraphPad Software, Inc.).RESULTS The study included 102 patients: 78 affected by MGUS (76%), 14 by MM (14%) and 10 by WM (10%). Patients' clinical features are summarized in the Table. Median follow-up was 48 months (range:12–280). Among the 89 patients with a first diagnosis of MGUS, malignant transformation occurred in 11 patients (7 MM and 4 WM). The median time from diagnosis of MGUS to diagnosis of a lymphoplasma cell proliferative disorder was 60 months (range 12–196). Median time to progression (TTP) was 167 months, as shown in Figure. The cumulative probability of progression was 13.5% at 5 years and 29.2% at 10 years. The amount of serum M protein at diagnosis was a significant predictor of progression.CONCLUSIONS MGUS are very common in clinical practice, accounting in our study for more than 75% of plasma cell disorders. The premalignant nature of this condition is comfirmed by the rate of transformation in lymphoplasma cell proliferative disorders (50% of MM and 40% of WM, in this study). Even if our results may be biased by the short follow-up period, the only significant predictor of progression was the size of serum M protein at presentation.Table:Patients' characteristicsCharacteristicsMGUSMMWMGender male/female41/374/107/3Age at diagnosis median (range)69 yrs (30–91)72 yrs (51–90)75 yrs (67–85)Serum M protein median (range)1.26 g/dl (0.17–2.92)3.85 g/dl (0.62–8.10)3.20 g/dl (2.22–4.9)IsotypeIgG468-IgA146-IgM15-10biclonal3--Immunoparesis yes/no20/5814/010/0BJ proteinuria pos/neg11/6711/31/9 [Display omitted]

Clinical Course and Prognosis of Smoldering (Asymptomatic) Multiple Myeloma

Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder associated with a high risk of progression to symptomatic multiple myeloma or amyloidosis. Prognostic factors for the progression and outcome of this disease are unclear. We searched a computerized database and reviewed the medical records of all patients at Mayo Clinic who fulfilled the criteria of the International Myeloma Working Group for the diagnosis of smoldering multiple myeloma between 1970 and 1995. Bone marrow aspirate and biopsy specimens were studied, and patients were followed throughout the course of disease. During the 26-year period, 276 patients fulfilled the criteria for smoldering multiple myeloma. During 2131 cumulative person-years of follow-up, symptomatic multiple myeloma or amyloidosis developed in 163 persons (59%). The overall risk of progression was 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% per year for the last 10 years; the cumulative probability of progression was 73% at 15 years. At diagnosis, significant risk factors for progression included the serum level and type of monoclonal protein, the presence of urinary light chain, the extent and pattern of bone marrow involvement, and the reduction in uninvolved immunoglobulins. The proportion of plasma cells in the bone marrow and the serum monoclonal protein level were combined to create a risk-stratification model with three distinct prognostic groups. The risk of progression from smoldering multiple myeloma to symptomatic disease is related to the proportion of bone marrow plasma cells and the serum monoclonal protein level at diagnosis.

Suivi évolutif des gammapathies monoclonales de signification indéterminée: Étude rétrospective de 190 patients

Monoclonal gammopathies of undetermined significance (MGUS) occur in up to 1% of persons aged 50 years or older. The risk of its progression to multiple myeloma or related disorders is also approximately 1% per year.Our study had two aims: to describe the risk of malignant progression of patients examined in our center for MGUS, and to identify predictors of this malignant progression.We retrospectively reviewed the medical records of patients with MGUS seen in our center from 1980 through 1995. Information about progression came either from the medical file or from responses to questionnaires sent to patients' general practitioners.The study included 190 patients. Median follow-up was 84 months (range: 12-240 months). MGUS remained stable for 128 patients (67.37%), whose median follow-up was 96 months. Malignant transformations occurred in 41 patients (21.58%). The median interval from diagnosis of MGUS to diagnosis of a lymphoplasma cell proliferative disorder was 49 months. The cumulative probability of progression was 13.05% at 5 years and 25.14% at 10 years. The initial concentration of serum monoclonal protein was a significant predictor of progression (threshold value: 15 g/L).The cumulative probability of progression in our study is higher than that observed elsewhere. Our results may well be biased by the short follow-up period and selective referrals.The initial concentration of serum monoclonal protein is a significant predictor of malignant progression of MGUS.

A long-term study of prognosis in monoclonal gammopathy of undetermined significance.

A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent of persons 50 years of age or older. Reliable predictors of progression have not been identified, and information on prognosis is limited. We identified 1384 patients residing in southeastern Minnesota in whom MGUS was diagnosed at the Mayo Clinic from 1960 through 1994. The primary end point was progression to multiple myeloma or another plasma-cell cancer. During 11,009 person-years of follow-up, MGUS progressed in 115 of the 1384 patients to multiple myeloma, IgM lymphoma, primary amyloidosis, macroglobulinemia, chronic lymphocytic leukemia, or plasmacytoma (relative risk of progression, 25.0, 2.4, 8.4, 46.0, 0.9, and 8.5, respectively). The overall relative risk of progression was 7.3 in these patients as compared with the white population of the Iowa Surveillance, Epidemiology, and End Results program. In 32 additional patients, the monoclonal protein concentration increased to more than 3 g per deciliter or the percentage of plasma cells in the bone marrow increased to more than 10 percent (smoldering multiple myeloma) but without progression to overt myeloma or related disorders. The cumulative probability of progression was 12 percent at 10 years, 25 percent at 20 years, and 30 percent at 25 years. The initial concentration of serum monoclonal protein was a significant predictor of progression at 20 years. The risk of progression of MGUS to multiple myeloma or related disorders is about 1 percent per year.