A Transformation Class for Spatio-temporal Survival Data with a Cure Fraction

We propose a hierarchical Bayesian methodology to model spatially or spatio-temporal clustered survival data with possibility of cure. A flexible continuous transformation class of survival curves indexed by a single parameter is used. This transformation model is a larger class of models containing two special cases of the well-known existing models: the proportional hazard and the proportional odds models. The survival curve is modeled as a function of a baseline cumulative distribution function, cure rates, and spatio-temporal frailties. The cure rates are modeled through a covariate link specification and the spatial frailties are specified using a conditionally autoregressive model with time-varying parameters resulting in a spatio-temporal formulation. The likelihood function is formulated assuming that the single parameter controlling the transformation is unknown and full conditional distributions are derived. A model with a non-parametric baseline cumulative distribution function is implemented and a Markov chain Monte Carlo algorithm is specified to obtain the usual posterior estimates, smoothed by regional level maps of spatio-temporal frailties and cure rates. Finally, we apply our methodology to melanoma cancer survival times for patients diagnosed in the state of New Jersey between 2000 and 2007, and with follow-up time until 2007

The Choice of Prior Distribution for A Covariance Matrix in Multivariate Meta-Analysis: A Simulation Study

Bayesian meta-analysis is an increasingly important component of clinical research, with multivariate meta-analysis a promising tool for studies with multiple endpoints. Model assumptions, including the choice of priors, are crucial aspects of multivariate Bayesian meta-analysis (MBMA) models. In a given model, two different prior distributions can lead to different inferences about a particular parameter. A simulation study was performed in which the impact of families of prior distributions for the covariance matrix of a multivariate normal random effects MBMA model was analyzed. Inferences about effect sizes were not particularly sensitive to prior choice, but the related covariance estimates were. A few families of prior distributions with small relative biases, tight mean squared errors, and close to nominal coverage for the effect size estimates were identified. Our results demonstrate the need for sensitivity analysis and suggest some guidelines for choosing prior distributions in this class of problems. The MBMA models proposed here are illustrated in a small meta-analysis example from the periodontal field and a medium meta-analysis from the study of stroke

The Choice of Prior Distribution for A Covariance Matrix in Multivariate Meta-Analysis: A Simulation Study

Bayesian meta-analysis is an increasingly important component of clinical research, with multivariate meta-analysis a promising tool for studies with multiple endpoints. Model assumptions, including the choice of priors, are crucial aspects of multivariate Bayesian meta-analysis (MBMA) models. In a given model, two different prior distributions can lead to different inferences about a particular parameter. A simulation study was performed in which the impact of families of prior distributions for the covariance matrix of a multivariate normal random effects MBMA model was analyzed. Inferences about effect sizes were not particularly sensitive to prior choice, but the related covariance estimates were. A few families of prior distributions with small relative biases, tight mean squared errors, and close to nominal coverage for the effect size estimates were identified. Our results demonstrate the need for sensitivity analysis and suggest some guidelines for choosing prior distributions in this class of problems. The MBMA models proposed here are illustrated in a small meta-analysis example from the periodontal field and a medium meta-analysis from the study of stroke

The Effect of Regional Analgesia on Vascular Tone in Hip Arthroplasty Patients

Background: While it is assumed that neuraxial analgesia and pain management may beneficially influence perioperative hemodynamics, few studies provided data quantifying such effects and none have assessed the potential contribution of the addition of a nerve block. Questions/purposes: This clinical trial compared the visual analog scale (VAS) scores and measurement of arterial tone using augmentation index of patients who received combined spinal-epidural (CSE) only to patients who received both CSE and lumbar plexus block. Methods: After obtaining written consent, 92 patients undergoing total hip arthroplasty were randomized to receive either CSE or CSE with lumbar plexus block (LPB). Perioperative pain and arterial tone were measured using VAS scores and augmentation index (AI) respectively, at baseline and at various times postoperatively. Results: After the exclusion of 2 patients, 44 patients received CSE alone and 46 patients received CSE and LPB. Patient demographics and perioperative characteristics were similar in both groups. AI continuously decreased after placement of a CSE with or without LBP, beyond full resolution of neuraxial and peripheral blockade. Although the LPB group demonstrated a statistically significant reduction of VAS pain scores in the postanesthesia care unit (PACU; P \u3c 0.05), overall, the addition of a LPB did not significantly reduce the AI when compared to the control group. Conclusion: The addition of a LPB provided better pain control in the PACU but did not reduce the AI, compared to the control group. We conclude that the addition of a LPB may have limited ability to affect arterial tone in the presence of a continuous infusion of epidural analgesics. In summary, the addition of a LPB in patients undergoing total hip arthroplasty is clinically effective and provided better pain control, especially in the immediate postoperative period. The continuous decrease on the AI in both groups beyond the full resolution of the neuroaxial and LPB will require further studies

MRI Analysis of White Matter Myelin Water Content in Multiple Sclerosis: A Novel Approach Applied to Finding Correlates of Cortical Thinning

A novel lesion-mask free method based on a gamma mixture model was applied to myelin water fraction (MWF) maps to estimate the association between cortical thickness and myelin content, and how it differs between relapsing-remitting (RRMS) and secondary-progressive multiple sclerosis (SPMS) groups (135 and 23 patients, respectively). It was compared to an approach based on lesion masks. The gamma mixture distribution of whole brain, white matter (WM) MWF was characterized with three variables: the mode (most frequent value) m1 of the gamma component shown to relate to lesion, the mode m2 of the component shown to be associated with normal appearing (NA) WM, and the mixing ratio (λ) between the two distributions. The lesion-mask approach relied on the mean MWF within lesion and within NAWM. A multivariate regression analysis was carried out to find the best predictors of cortical thickness for each group and for each approach. The gamma-mixture method was shown to outperform the lesion-mask approach in terms of adjusted R2, both for the RRMS and SPMS groups. The predictors of the final gamma-mixture models were found to be m1 (β = 1.56, p \u3c 0.005), λ (β = −0.30, p \u3c 0.0005) and age (β = −0.0031, p \u3c 0.005) for the RRMS group (adjusted R2 = 0.16), and m2 (β = 4.72, p \u3c 0.0005) for the SPMS group (adjusted R2 = 0.45). Further, a DICE coefficient analysis demonstrated that the lesion mask had more overlap to an ROI associated with m1, than to an ROI associated with m2 (p \u3c 0.00001), and vice versa for the NAWM mask (p \u3c 0.00001). These results suggest that during the relapsing phase, focal WM damage is associated with cortical thinning, yet in SPMS patients, global WM deterioration has a much stronger influence on secondary degeneration. Through these findings, we demonstrate the potential contribution of myelin loss on neuronal degeneration at different disease stages and the usefulness of our statistical reduction technique which is not affected by the typical bias associated with approaches based on lesion masks

CT Angiography in The Detection of Carotid Body Enlargement in Patients with Hypertension and Heart Failure

Introduction: The carotid body (CB) has previously been found to be enlarged and hyperactive in various disease states such as heart failure (HF), hypertension (HTN), and respiratory disease. Evaluation of CB size in these disease states using imaging has not been performed. The purpose of this case–control study was to compare CB sizes in patients with HF and HTN with those of controls using CT angiography. Methods: A retrospective review was performed on 323 consecutive patients who had neck computed tomography angiography (CTA) exams in 2011. Following extensive review, 17 HF and HTN patients and 14 controls were identified. Two radiologists blinded to the patient disease status made consensus bilateral carotid body (CB) measurements on the CTA exams using a previously described standardized protocol. CB axial cross-sectional areas were compared between HF and HTN cases and controls using a paired t test. Results: The right CB demonstrated a mean cross-sectional area of 2.79 mm2 in HF and HTN patients vs. 1.40 mm2 in controls (p = 0.02). The left CB demonstrated a mean cross-sectional area of 3.13 mm2 in HF and HTN patients vs. 1.53 mm in controls (p = 0.03). Conclusion: Our results provide imaging evidence that the carotid bodies are enlarged in patients with HF and HTN. Our case–control series suggests that this enlargement can be detected on neck CTA

Autologous Stem Cell Transplant is Feasible in Very Elderly Patients with Lymphoma and Limited Comorbidity

In patients with recurrent Hodgkin or non-Hodgkin\u27s lymphoma, autologous stem cell transplantation (ASCT) can offer potential for cure or long-term remission. Because of potential toxicity, elderly patients are usually not considered candidates, but data regarding tolerability and efficacy in this group are lacking. The transplant database at Weill Cornell Medical College was reviewed to identify patients with lymphoma undergoing ASCT at age 69 or greater. Clinical data and comorbidities were correlated with outcome. Twenty-one patients were identified. Sixteen of 19 evaluable patients (76%) achieved complete remission following ASCT, while 2 patients died before response assessment. Median progression-free survival following ASCT was 8 months and median overall survival was 18 months. Age was not predictive of overall survival, but patients 75 and older had inferior progression-free survival compared to younger patients. High-risk status by hematopoietic stem cell transplant comorbidity index (HCT-CI) was associated with short overall survival and high transplant-related mortality. ASCT is feasible and of potential benefit in selected elderly lymphoma patients. Consideration of comorbidities, rather than age alone, may allow selection of patients likely to tolerate and benefit from ASCT

Autologous Stem Cell Transplant is Feasible in Very Elderly Patients with Lymphoma and Limited Comorbidity

In patients with recurrent Hodgkin or non-Hodgkin\u27s lymphoma, autologous stem cell transplantation (ASCT) can offer potential for cure or long-term remission. Because of potential toxicity, elderly patients are usually not considered candidates, but data regarding tolerability and efficacy in this group are lacking. The transplant database at Weill Cornell Medical College was reviewed to identify patients with lymphoma undergoing ASCT at age 69 or greater. Clinical data and comorbidities were correlated with outcome. Twenty-one patients were identified. Sixteen of 19 evaluable patients (76%) achieved complete remission following ASCT, while 2 patients died before response assessment. Median progression-free survival following ASCT was 8 months and median overall survival was 18 months. Age was not predictive of overall survival, but patients 75 and older had inferior progression-free survival compared to younger patients. High-risk status by hematopoietic stem cell transplant comorbidity index (HCT-CI) was associated with short overall survival and high transplant-related mortality. ASCT is feasible and of potential benefit in selected elderly lymphoma patients. Consideration of comorbidities, rather than age alone, may allow selection of patients likely to tolerate and benefit from ASCT

CD4 Deficit and Tuberculosis Risk Persist With Delayed Antiretroviral Therapy: 5-Year Data From CIPRA HT-001

SETTING: Port-au-Prince, Haiti. OBJECTIVE: To determine long-term effects of early vs. delayed initiation of antiretroviral therapy (ART) on immune recovery and tuberculosis (TB) risk in human immunodeficiency virus (HIV) infected individuals. DESIGN: Open-label randomized controlled trial of immediate ART in HIV-infected adults with CD4 counts between 200 and 350 cells/mm(3) vs. deferring ART until the CD4 count was \u3c200 cells/mm(3). The primary comparisons were CD4 counts over time and risk for incident TB, with 5 years of follow-up. RESULTS: A total of 816 participants were enrolled, with 408 in each treatment arm. The early treatment group started ART within 2 weeks, while the deferred treatment group started ART a median of 1.3 years after enrollment. After 5 years, the mean CD4 count in the early treatment group was significantly higher than in the deferred treatment group (496 cells/mm(3), 95% confidence interval [CI] 477-515 vs. 373 cells/mm(3), 95%CI 357-389; P \u3c 0.0001). TB risk was higher in the deferred treatment group (unadjusted HR 2.41, 95%CI 1.56-3.74; P \u3c 0.0001) and strongly correlated with lower CD4 counts in time-dependent multivariate analysis. CONCLUSION: Delays in ART initiation for HIV-infected adults with CD4 counts of 200-350 cells/mm(3) can result in long-term immune dysfunction and persistent increased risk for TB. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120510

Improved Left Ventricular Mass Quantification with Partial Voxel Interpolation – In-Vivo and Necropsy Validation of a Novel Cardiac MRI Segmentation Algorithm

Background—CMR typically quantifies LV mass (LVM) via manual planimetry (MP), but this approach is time consuming and does not account for partial voxel components - myocardium admixed with blood in a single voxel. Automated segmentation (AS) can account for partial voxels, but this has not been used for LVM quantification. This study used automated CMR segmentation to test the influence of partial voxels on quantification of LVM. Methods and Results—LVM was quantified by AS and MP in 126 consecutive patients and 10 laboratory animals undergoing CMR. AS yielded both partial voxel (ASPV) and full voxel (ASFV) measurements. Methods were independently compared to LVM quantified on echocardiography (echo) and an ex-vivo standard of LVM at necropsy. AS quantified LVM in all patients, yielding a 12-fold decrease in processing time vs. MP (0:21±0:04 vs. 4:18±1:02 min; pFV mass (136±35gm) was slightly lower than MP (139±35; Δ=3±9gm, pPV yielded higher LVM (159±38gm) than MP (Δ=20±10gm) and ASFV (Δ=23±6gm, both pPV and ASFV correlated with larger voxel size (partial r=0.37, pPV yielded better agreement with echo (Δ=20±25gm) than did ASFV (Δ=43±24gm) or MP (Δ=40±22gm, both pPV and ex-vivo results were similar (Δ=1±3gm, p=0.3), whereas ASFV (6±3g, P\u3c0.001) and MP (4±5 g, P=0.02) yielded small but significant differences with LVM at necropsy