Predictive Value Of Early Changes Research Articles

The Predictive Value of Early Changes in 18 F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

The aim of this study was to investigate the predictive value of early changes in 18 F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)-positive metastatic breast cancer. Patients underwent 18 F-FES PET/CT scans at both baseline (scan 1) and day 28 (scan 2). The maximum standardized uptake value (SUVmax) of all metastatic sites was determined in each scan, and the percentage reduction in SUVmax (ΔSUVmax) was calculated as [(SUVmax on scan 1-SUVmax on scan 2)/ SUVmax on scan 1] * 100%. In total, 294 18 F-FES-positive lesions from 36 patients were identified. The 18 F-FES SUVmax varied widely among lesions (median 5.7; range 1.8-32.4) and patients (median 5.1; range 2.5-13.2). After treatment, the median SUVmax among lesions and patients was 2.1 and 2.1, respectively. The ΔSUVmax ranged from -5.1% to 100%, with a median reduction of 61.3%. Using receiver operating characteristic analysis, the optimal cutoff point to discriminate patients who could derive clinical benefit from fulvestrant was determined to be 38.0%. Patients with a median ΔSUVmax ≥38.0% experienced significantly longer progression-free survival (PFS) than those with ΔSUVmax <38.0% (28.0 months vs. 3.5 months, p = .003). Multivariate analysis demonstrated that ΔSUVmax ≥38.0% was an independent predictor of PFS benefit in patients receiving fulvestrant therapy. Changes in SUVmax measured by serial imaging of 18 F-FES PET/CT could be used early to predict PFS benefit in patients receiving fulvestrant therapy. The aim of this study was to evaluate the role of 18 F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) in predicting response to fulvestrant 500 mg therapy in patients with hormone receptor-positive/human epidermal growth receptor 2-negative metastatic breast cancer. This study highlights the utility of FES PET/CT as a predictive factor to discriminate patients who might benefit from fulvestrant. Moreover, these findings showed that this molecular imaging technique might be a potential tool for physicians to make individualized treatment strategies.

Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis

BackgroundThe objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA).MethodsThis was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression.ResultsData from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p < 0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p < 0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p < 0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p < 0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression.ConclusionsMRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures.Trial registrationClinicalTrials.gov, NCT01164579.

Early changes in depression predict outcomes of inpatient adolescent anorexia nervosa.

The aim of this study was to investigate the predictive value of early changes in depression levels during inpatient treatment of adolescent anorexia nervosa (AN). Fifty-six adolescents (88% girls) aged 10-18years (M = 15.35, SD = 2.23) diagnosed with AN were assessed at admission and 1month following admission to an inpatient setting. Depression levels and eating disorder symptoms were reported at both assessments. Re-hospitalization within 12months of discharge was documented using official national records. Whereas depression levels at baseline were found equivalent between subsequently re-hospitalized and non-re-hospitalized patients, at 1month after admission patients who were later re-hospitalized had higher levels of depression compared to those who were not re-hospitalized. These differences remained significant after controlling for weight gain and anti-depressant medication intake. We additionally found that the proportion of boys in the non-re-hospitalized group was substantially larger than their proportion in the re-hospitalized group. Our results suggest that depression at the point of hospital admission may not be a reliable predictor of treatment outcomes, and highlight the risk of relapse in AN patients whose depression levels do not alleviate after a month of inpatient treatment. Clinicians should consider providing more adjusted and intensive attention to such patients in their efforts to facilitate remission. Well-designed cohort study.

P127 - The predictive value of early changes in 18F-fluoroestradiol PET/CT during fulvestrant 500 mg therapy in patients with ER-positive metastatic breast cancer

P127 - The predictive value of early changes in 18F-fluoroestradiol PET/CT during fulvestrant 500 mg therapy in patients with ER-positive metastatic breast cancer

The value of early changes in platelet counts in assessing the prognosis of aged patients with severe pneumonia

Objective To explore the predictive value of early changes in platelet counts in the prognosis of severe pneumonia in aged patients. Methods This retrospective study included elderly patients with severe pneumonia, who were ≥65 years old and whose length of ICU stay ≥72 hours, admitted to the intensive care unit(ICU)of NO.2 People's Hospital of Changzhou from January 2014 to January 2017.They were divided into a survival group and a death group according to the 28-day outcome.General information and serum platelet levels at 0, 24, 36, and 72 hours after admission were collected.Receiver operating characteristic curve(ROC)was plotted according to platelet counts, changes in platelet counts and rates of change in platelet counts to evaluate their predictive value for 28-day prognosis.Kaplan-Meier survival curve was used to analyze the 28-day cumulative survival rate between different groups of patients, who were further divided according to platelet counts at 0 and 72 hours after admission to ICU, changes in platelet counts and rates of change in platelet counts at 72 hours after admission. Results (1)One hundred elderly patients with severe pneumonia were enrolled, among whom 41 cases were in the death group, thus with a mortality of 41.0%.The acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ), sequential organ failure assessment(SOFA), C-reactive protein(CRP), and procalcitonin(PCT)in the death group were significantly higher than those in the survival group.2)Serum platelet levels showed a downward trend in both the death group and the survival group.The level of serum platelets at 72 hours after admission to ICU in the death group was significantly lower than that in the survival group(80.00×109/L vs.171.00×109/L, Z=5.786, P<0.05); changes in platelet counts and rates of change in platelet counts in the death group were significantly higher than those in the survival group, especially at 72 hours after admission to ICU(△PLT72: -79.00×109/L vs.-38.00×109/L, Z=4.938, P<0.05; △PLT 72%: -43.6% vs.-17.7%, Z=6.816, P<0.05). (3)ROC curve analysis showed that platelet levels, changes in platelet counts, and rates of change in platelet counts could predict 28-day mortality in aged patients with severe pneumonia.The largest area under ROC curve was 0.902 when plotted with the rate of platelet counts at 72 hours after admission to ICU.Using the cut-off value of -36.14% in the rate of change at 72 hours after admission to evaluate the predictive value in 28-day mortality, the sensitivity and specificity were 89.8% and 75.6%, respectively.(4)Kaplan-Meier survival analysis showed that the 28-day survival rate was significantly higher and the length of survival was significantly greater when platelet counts at 0 and 72 hours after admission to ICU were higher than the cut-off value, and this also occurred in changes in platelet count and rates of change at 72 hours after admission to ICU. Conclusions Continuous decline in serum platelet levels indicates poor prognosis.When combined with platelet counts, changes in platelet counts and rates of change in platelet counts at 72 hours after admission to ICU, it may play an important role in assessing the prognosis of aged patients with severe pneumonia. Key words: Blood platelets; Pneumonia; Prognosis

Dynamics of cerebral perfusion deficits after aneurysmal SAH – predictive value of early MTT for subsequent MTT deterioration

Background and purposeThe pathogenesis of poor functional outcome after aneurysmal subarachnoid hemorrhage (aSAH) is not fully understood. Microcirculatory dysfunction, which can be indirectly measured by CT perfusion (CTP), is assumed to play a central role. We evaluated the predictive value of early changes in microcirculation for secondary critical perfusion changes. Materials and methodsOut of 351 consecutive aSAH patients, 166 patients with ≥1 CTP within 72h of ictus (early CTP) and ≥3 CTPs in total were included in the retrospective analysis (53.2±12.4years of age). Receiver-operating-characteristic (ROC) analysis was performed to identify the mean transit time (MTT) threshold in early CTP with the highest sensitivity and specificity for predicting secondary critical perfusion changes >72h after ictus. The odds ratio was calculated and the threshold for the highest odds ratio was determined. ResultsSecondary critical perfusion changes were observed in 67/166 patients (40.4%). An early MTT 1.3 times the mean normal MTT could predict those changes with an odds ratio of 2.67 (sensitivity 67.2%, specificity 56.6%). Shifting the threshold to 1.26 times the mean normal MTT resulted in an odds ratio of 3.56 (sensitivity 79.1%, specificity 48.5%). ConclusionsEarly MTT is predictive of secondary critical perfusion changes, which could have applications for neuromonitoring and treatment.

Use of Mental Health Telemetry to Enhance Identification and Predictive Value of Early Changes During Augmentation Treatment of Major Depression

Standard clinical trial methodology in depression does not allow for careful examination of early changes in symptom intensity. The purpose of this study was to use daily "Mental Health Telemetry" (MHT) to prospectively record change in depressive and anxiety symptoms for depressed patients receiving augmentation treatment, and determine the extent and predictive capacity of early changes. We report results of a 6-week, open-label study of the addition of quetiapine XR (range, 50-300 mg) for adult patients (n = 26) with major depressive disorder who were nonresponsive to antidepressant treatment. In addition to regular study visits, all participants completed daily, wirelessly transmitted self-report ratings of symptoms on a Smartphone. Daily and 3-day moving average mean scores were calculated, and associations between early symptom change and eventual response to treatment were determined. Improvement in depressive and anxiety symptoms was identified as early as day 1 of treatment. Of the total decline in depression severity over 6 weeks, 9% was present at day 1, 28% at day 2, 39% at days 3 and 4, 65% at day 7, and 80% at day 10. Self-report rating of early improvement (≥20%) in depressive symptoms at day 7 significantly predicted responder status at week 6 (P = 0.03). Clinician-rated depressive and anxiety symptoms only became significantly associated with responder status at day 14. In conclusion, very early changes in depressive symptoms were identified using MHT, early changes accounted for most of total change, and MHT-recorded improvement as early as day 7 significantly predicted response to treatment at study end point.

Limited predictive value of early changes in EEG spectral power for neural injury after asphyxia in preterm fetal sheep

This study examined whether spectral analysis of the electroencephalogram (EEG) can discriminate between mild and severe hypoxic-ischemic injury in the immature brain. Total EEG power was profoundly suppressed after umbilical cord occlusion and recovered to baseline by 5 h after 15-min of occlusion, in contrast with transient recovery in the 25-min (P < 0.05). Power spectra were not different between groups in the first 3 h; α and β power were significantly higher in the 15-min group from 4 h, and Δ and θ power from 5 h (P < 0.05). The 25-min group showed severe neuronal loss in hippocampal regions and basal ganglia at 3 days, in contrast with no/minimal injury in the 15-min group. EEG power after asphyxia did not discriminate between mild and severe injury in the first 3 h in preterm fetal sheep. Severe subcortical neural injury was associated with persistent loss of high-frequency activity. Chronically instrumented fetal sheep at 0.7 gestation (101-104 days; term is 147 days) received either 15-min (n = 13) or 25-min (n = 13) of complete umbilical cord occlusion. The Δ (0-3.9 Hz), θ (4-7.9 Hz), α (8-12.9 Hz), and β (13-22 Hz) components of the EEG were determined by power spectral analysis. Brains were taken at 3 days for histopathology.

The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

IntroductionThe aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).MethodsThis is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.ResultsAfter three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician's global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.ConclusionsThree years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures.

Predictive Value of Early Changes in Triglycerides and Weight for Longer-Term Changes in Metabolic Measures During Olanzapine, Ziprasidone or Aripiprazole Treatment for Schizophrenia and Schizoaffective Disorder

The objective of this study was to determine if early changes in triglycerides and weight may be useful in predicting longer-term changes in weight and other metabolic parameters. Data were from three 24- to 28-week randomized, controlled studies comparing olanzapine to ziprasidone or aripiprazole for treatment of schizophrenia. Analyses were restricted to completers with fasting laboratory data at all protocol specified time points. Analyses were primarily descriptive and included mean changes and categorical outcomes. In all treatment groups, participants who did not experience a 20 mg/dL or greater increase in triglycerides at early time points were unlikely to experience a change of 50 mg/dL or more in triglycerides after 6 months. Negative predictive values were 83% to 95%. However, early change in triglycerides was not useful for predicting later change in glucose, cholesterol, or weight. Similarly, early weight change gave robust negative predictive values for longer-term weight change (≥10 kg), but not for change in glucose or cholesterol. Lack of early elevation in triglyceride concentrations was predictive of later lack of substantial increase in triglycerides in olanzapine-, ziprasidone-, and aripiprazole-treated participants. Lack of early elevation in weight was predictive of later lack of substantial increase in weight in all 3 treatment groups. Early monitoring of triglyceride concentrations and weight may help clinicians assess risk that individuals will experience significant increase in triglycerides or weight gain, allowing assessments of potential risks and benefits earlier in treatment. Clinical monitoring is advised throughout treatment for all patients.

The early non-increase of serum BDNF predicts failure of antidepressant treatment in patients with major depression: A pilot study

In the treatment of patients with major depressive disorder (MDD), early non-improvement of symptoms after initiation of antidepressant treatment is a highly sensitive and specific marker for final treatment failure. On the other hand, meta-analyses of clinical studies investigating serum BDNF (sBDNF) concentration before and after antidepressant treatment showed an increase of sBDNF during treatment, which was correlated with amelioration of depressive symptoms. No study has yet investigated the predictive value of early changes of sBDNF for final treatment outcome of the individual patient. The aim of this study was to investigate in patients with MDD, whether i) the non-increase of sBDNF in the early course of treatment is a specific and sensitive marker for final treatment failure, ii) whether the sensitivity and specificity of early non-improvement for treatment failure can be increased by combining it with the marker "early non-increase of sBDNF". For this purpose, we performed a pilot study with 41 inpatients with MDD according to DSM-IV, who were treated in a naturalistic setting. Depression severity and sBDNF were measured in weekly intervals from baseline to week six with the 21-item Hamilton Depression Rating Scale (HAMD-21) and ELISA, respectively. The individual markers sBDNF non-increase and HAMD-21 non-improvement from baseline to day 7 or 14 predicted later non-response and non-remission with moderate to high specificity. The combined marker sBDNF non-increase plus HAMD-21 non-improvement at day 14 increased the specificity for non-response and non-remission to 100%. Our data provide the first evidence that the absence of an early increase of sBDNF in conjunction with early non-improvement might be a highly specific peripheral marker predictive for treatment failure in patients with MDD. If replicated, this combined marker could be considered useful for prospective confirmatory trials in patients with MDD.

DIFFERENCES BETWEEN EARLY RESPONDERS AND EARLY NON-RESPONDERS TO ATYPICAL ANTIPSYCHOTICS ON SYMPTOM AND FUNCTIONAL OUTCOMES IN THE TREATMENT OF SCHIZOPHRENIA

score reduction) at week 1, 2 and 3 for UR (>30% total PANSS score) or remission (no more than mild symptoms) at endpoint. Results: In 127 adolescents (15.5 years) with schizophrenia (n=54) or psychosis NOS (n=73) treated openly for 3 months, CGI-S and CGAS score reductions were significantly more pronounced in the first 4 weeks vs. the following 8 weeks. CGI-I defined ER at 4 weeks predicted UR with a high sensitivity (83%), moderate specificity (69%) and good Positive Predictive Value (PPV: 78%), and Negative Predictive Value (NPV: 76%). ER patients had significantly greater improvements on the CGI-S and GAF score at 4, 8 and 12 weeks than early non-responders. Early nonresponders had significantly more parkinsonism (44.4% vs. 16.7%, p< .05). In the RCT, 293 adolescents (15.5 years) were randomized to aripiprazole 10 mg (N=99) or 30 mg (N=97), or placebo (N=98). Nearly 50% of the aripiprazole PANSS Total reduction was achieved by week 2; up to 75% by week 3. ER at week 3 had better predictive values than ER at week 2. At week 3, ER predicted UR at 6 week with high sensitivity (88%), specificity (83%), PPV (84%), and NPV (87%). Similarly good predictive values were found for remission: sensitivity=71%, specificity=76.2%, PPV=83%, NPV=62%. Patients achieving ER at week 2 and week 3 had significantly greater reductions in PANSS total, positive and negative scores, CGI-S, CGI-I, and CGAS scores (all p-values<0.001). The incidence of adverse events between ER and ENR patients was not different. Conclusions: Data in adolescents with schizophrenia-spectrum disorders confirm that most of the treatment response occurs early. Early non-response was a better predictor of later non-response in the RCT than in the naturalistic study that used more global outcome measures. Further studies in adolescents and in real-world settings are needed. In addition, the predictive value of early changes in the CGI-I score need to be examined in youth and adults to test if this more easily implementable scale could serve as a reliable, clinical indicator or early and ultimate response.

EARLY RESPONSE TO ANTIPSYCHOTICS – WHAT CHANGES EARLY AND HOW?

score reduction) at week 1, 2 and 3 for UR (>30% total PANSS score) or remission (no more than mild symptoms) at endpoint. Results: In 127 adolescents (15.5 years) with schizophrenia (n=54) or psychosis NOS (n=73) treated openly for 3 months, CGI-S and CGAS score reductions were significantly more pronounced in the first 4 weeks vs. the following 8 weeks. CGI-I defined ER at 4 weeks predicted UR with a high sensitivity (83%), moderate specificity (69%) and good Positive Predictive Value (PPV: 78%), and Negative Predictive Value (NPV: 76%). ER patients had significantly greater improvements on the CGI-S and GAF score at 4, 8 and 12 weeks than early non-responders. Early nonresponders had significantly more parkinsonism (44.4% vs. 16.7%, p< .05). In the RCT, 293 adolescents (15.5 years) were randomized to aripiprazole 10 mg (N=99) or 30 mg (N=97), or placebo (N=98). Nearly 50% of the aripiprazole PANSS Total reduction was achieved by week 2; up to 75% by week 3. ER at week 3 had better predictive values than ER at week 2. At week 3, ER predicted UR at 6 week with high sensitivity (88%), specificity (83%), PPV (84%), and NPV (87%). Similarly good predictive values were found for remission: sensitivity=71%, specificity=76.2%, PPV=83%, NPV=62%. Patients achieving ER at week 2 and week 3 had significantly greater reductions in PANSS total, positive and negative scores, CGI-S, CGI-I, and CGAS scores (all p-values<0.001). The incidence of adverse events between ER and ENR patients was not different. Conclusions: Data in adolescents with schizophrenia-spectrum disorders confirm that most of the treatment response occurs early. Early non-response was a better predictor of later non-response in the RCT than in the naturalistic study that used more global outcome measures. Further studies in adolescents and in real-world settings are needed. In addition, the predictive value of early changes in the CGI-I score need to be examined in youth and adults to test if this more easily implementable scale could serve as a reliable, clinical indicator or early and ultimate response.