Search

BACKGROUND: Cerebral embolic protection devices (EPDs) were developed to mitigate the risk of stroke during transcatheter aortic valve replacement (TAVR), but their benefit remains unproven. In the PROTECTED-TAVR trial (Stroke Protection With Sentinel During Transcatheter), EPD use did not reduce periprocedural stroke (primary study outcome) but led to a 62% reduction in the secondary end point of disabling stroke. Given these results, the impact of EPDs during TAVR remains unclear. METHODS: We used STS/ACC TVT registry data to examine the association between EPD use and a proxy for disabling stroke among transfemoral TAVR patients between January 2018 and June 2023. The primary outcome was in-hospital disabling stroke--defined as stroke associated with either in-hospital death or discharge to a nonhome location. We evaluated the association between EPD use and disabling stroke using instrumental variable analysis with a site-level preference for EPD use as the instrument--a quasi-experimental approach that can support causal inference. In addition, we performed a propensity score--based comparison using overlap weighting as a secondary analysis. RESULTS: The study population consisted of 414 649 patients of whom 53 389 (12.9%) received an EPD. The unadjusted rate of in-hospital disabling stroke was 0.7% among the EPD group and 0.9% in the no-EPD group. EPD use was associated with a reduction in disabling stroke in both instrumental variable analysis (relative risk, 0.87 [95% CI, 0.73--1.00]) and propensity-weighted analysis (odds ratio, 0.79 [95% CI, 0.70--0.90]) but was not associated with a reduction in nondisabling stroke. In subgroup analyses, the benefit of EPD was greater among those with versus without prior stroke (Pinteraction<0.05 for both instrumental variable and propensity-weighted analyses). CONCLUSIONS: In the largest study to date, among patients undergoing TAVR, EPD use was associated with a small, borderline significant reduction in stroke associated with death or discharge to a nonhome location (a proxy for disabling stroke) that is likely to be causal in nature. Taken together with previous mechanistic and clinical studies, these findings provide credible evidence that EPDs benefit patients undergoing TAVR. GRAPHIC ABSTRACT: A graphic abstract is available for this article. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is characterized by progressive loss or damage to the nervous system which can cause impairment in movement, coordination, and cognition. Due to the complexity of clinical features at different stages of the disease, it may require months for an accurate diagnosis. Oculomotor researchers have demonstrated the utility of examining eye movements for differentiating various neurodegenerative disorders including AD, Parkinson's disease (PD), and other PD mimics (PDM). In this study, we propose an automatic pipeline to identify saccade, fixation, and blinks and extract response‐to‐stimuli‐derived interpretable biomarkers that could inform clinicians in making accurate assessment. Method: Eye tracking data in smooth pursuit, pro‐saccade, and anti‐saccade tasks were recorded from 146 participants ‐ 14 with AD or Mild Cognitive Impairment (MCI), 46 with PD, 16 with PDM, and 70 age‐matched normal controls (CTL). Biomarkers based on the identified eye movement and interaction with the stimuli were extracted with our algorithms. Then, pairwise Kruskal‐Wallis H tests were conducted to determine if there were statistically significant differences between groups. The Benjamini‐Hochberg correction was performed to control the false discovery rate. Result: The results show that, in the smooth pursuit task, the AD/MCI group had a significantly higher (p < 0.05) saccade count than CTL and PD groups. The AD/MCI group also exhibited significantly longer (p < 0.05) average saccade duration than CTL and PDM groups. The mean and standard deviation for the number of saccadic adjustments to reach and stay on the target significantly differed (p < 0.05) between AD/MCI and CTL and between PD and CTL in trials of the pro‐saccade task. The magnitude of overshoot or undershoot was significantly greater (p < 0.05) for AD/MCI, PD, and PDM compared to CTL. Moreover, the number of saccades in the wrong direction was significantly higher (p < 0.05) for AD/MCI and PD compared to CTL in the anti‐saccade task. Conclusion: Oculographic biomarkers can be leveraged within a machine learning framework and may be useful in distinguishing different types of neurodegenerative diseases in their early stages yielding more objective and precise protocols to monitor disease progression than current methods. [ABSTRACT FROM AUTHOR]

Higher anatomical SYNTAX score tercile was associated with a higher risk of all-cause death in US veterans undergoing isolated on-pump coronary artery bypass grafting. [Display omitted] • In the REGROUP trial, higher anatomical SYNTAX score was associated with higher mortality. • These results are discordant with results in non-veterans populations. • Future studies are needed to corroborate these results. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is characterized by progressive loss or damage to the nervous system which can cause impairment in movement, coordination, and cognition. Due to the complexity of clinical features at different stages of the disease, it may require months for an accurate diagnosis. Oculomotor researchers have demonstrated the utility of examining eye movements for differentiating various neurodegenerative disorders including AD, Parkinson's disease (PD), and other PD mimics (PDM). In this study, we propose an automatic pipeline to identify saccade, fixation, and blinks and extract response‐to‐stimuli‐derived interpretable biomarkers that could inform clinicians in making accurate assessment. Method: Eye tracking data in smooth pursuit, pro‐saccade, and anti‐saccade tasks were recorded from 146 participants ‐ 14 with AD or Mild Cognitive Impairment (MCI), 46 with PD, 16 with PDM, and 70 age‐matched normal controls (CTL). Biomarkers based on the identified eye movement and interaction with the stimuli were extracted with our algorithms. Then, pairwise Kruskal‐Wallis H tests were conducted to determine if there were statistically significant differences between groups. The Benjamini‐Hochberg correction was performed to control the false discovery rate. Result: The results show that, in the smooth pursuit task, the AD/MCI group had a significantly higher (p < 0.05) saccade count than CTL and PD groups. The AD/MCI group also exhibited significantly longer (p < 0.05) average saccade duration than CTL and PDM groups. The mean and standard deviation for the number of saccadic adjustments to reach and stay on the target significantly differed (p < 0.05) between AD/MCI and CTL and between PD and CTL in trials of the pro‐saccade task. The magnitude of overshoot or undershoot was significantly greater (p < 0.05) for AD/MCI, PD, and PDM compared to CTL. Moreover, the number of saccades in the wrong direction was significantly higher (p < 0.05) for AD/MCI and PD compared to CTL in the anti‐saccade task. Conclusion: Oculographic biomarkers can be leveraged within a machine learning framework and may be useful in distinguishing different types of neurodegenerative diseases in their early stages yielding more objective and precise protocols to monitor disease progression than current methods. [ABSTRACT FROM AUTHOR]

A 68-year-old woman with positional dizziness and progressive imbalance presented for vestibular evaluation. Examination was notable for spontaneous downbeat nystagmus (DBN), horizontal and vertical gaze-evoked nystagmus (GEN) with centripetal and rebound nystagmus, and positional apogeotropic nystagmus. There was also mild–moderate slowing of saccades horizontally and vertically and poor fast phases with an optokinetic stimulus. Further consultation by a movement disorder specialist uncovered asymmetric decrementing bradykinesia and rigidity, masked facies, and a wide-based stance without camptocormia. Screening serum laboratory results for metabolic, rheumatologic, infectious, heavy metal, endocrine, or vitamin abnormalities was normal. Surveillance imaging for neoplasms was unremarkable, and cerebrospinal fluid (CSF) analysis was negative for 14-3-3 and real-time quaking-induced conversion (RT-QuIC). However, her anti-glutamic acid decarboxylase-65 (GAD65) immunoglobulin G (IgG) level was markedly elevated in serum to 426,202 IU/mL (reference range 0–5 IU/mL) and in CSF to 18.1 nmol/L (reference range <0.03 nmol/L). No other autoantibodies were identified on the expanded paraneoplastic panel. The patient was referred to neuroimmunology, where torso rigidity, spasticity, and significant paravertebral muscle spasms were noted. Overall, the clinical presentation, examination findings, and extensive workup were consistent with a diagnosis of anti-GAD65-associated stiff person syndrome-plus (musculoskeletal plus cerebellar and/or brainstem involvement). She was subsequently treated with intravenous immunoglobulin (IVIg) and has been stable since commencing this therapy. In patients with centripetal nystagmus, especially in association with other cerebellar findings, an autoimmune cerebellar workup should be considered. [ABSTRACT FROM AUTHOR]

Background: Days at home (DAH) quantifies time spent at home after a medical event but has not been fully evaluated for TAVR. We sought to compare 1- and 5-year DAH (DAH365, DAH1825) among high-risk patients participating in a randomized trial of transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR).Methods: We linked data from the U.S. CoreValve High Risk Trial to Medicare Fee-for-Service claims in 456 patients with 450 (234 TAVR/216 SAVR) and 427 (222 TAVR/205 SAVR) analyzed at 1 and 5 years. DAH was calculated as the number of days alive and spent outside of a hospital, skilled nursing facility, rehabilitation, long-term acute care hospital, emergency department, or observation stay.Results: Mean DAH365 was higher in patients who underwent TAVR compared with SAVR (295.1 ± 106.9 vs 267.8 ± 122.3, difference in days 27.2 [95% CI 6.0, 48.5], P = .01). Compared with SAVR, TAVR patients had a shorter index length of stay (LOS) (7.4 ± 4.5 vs 12.5 ± 9.0, difference in days -5.1 [-6.5, -3.8], P < .001). The largest contributions to decreased DAH365 were mortality days and total facility days after discharge from the index hospitalization (mortality days-TAVR: 34.7 ± 93.1 vs SAVR: 48.0 ± 108.8, difference in days -13.3 [95% CI -32.1, 5.5], P = .17; total facility days-TAVR: 27.9 ± 47.4 vs SAVR: 36.7 ± 48.9, difference in days -8.8 [95% CI -17.8, 0.1], P = .05). Mean DAH1825 was numerically but not statistically significantly higher in TAVR (TAVR: 1154.2 ± 659.0 vs SAVR: 1067.6 ± 697.3, difference in days 86.6 [95% CI -42.3, 215.6], P = .19). Landmark analysis showed no difference in DAH from years 1 to 5 (TAVR: 1040.4 ± 477.5 vs SAVR: 1022.9 ± 489.3, P = .74).Conclusions: In the U.S. CoreValve High Risk Trial linked to Medicare, high-risk patients undergoing TAVR spend an average of 27 additional DAH compared with SAVR in the first year after the procedure due to a shorter index LOS and the additive effect of fewer but nonsignificantly different mortality and total facility days after discharge from the index hospitalization compared with SAVR. After the first year, both groups spend a similar number of DAH. These results describe the postprocedural course of high-risk patients from a patient-centered perspective, which may guide expectations regarding longitudinal health care needs and inform shared decision-making. [ABSTRACT FROM AUTHOR]

Background: Similar to other neurological diseases, subtle early neurological changes that occur in Alzheimer's Disease (AD) are difficult to quantify and track objectively. One relevant bio‐signal is eye movement, as it presents a unique window into cognitive processes as a direct measure of real‐time inputs to the brain. Eye‐tracking allows us to estimate timestamped activity of neural function and begin to infer and quantify attention, reprocessing (eg. word revisits), and many other aspects relevant to assessing AD. The goal of this study was to investigate the saccadic movements and trial progress during administration of the Stroop test in AD compared to normal controls. Method: 5 AD subjects and 12 age‐matched cognitively normal controls were recruited from the Johns Hopkins Memory and Alzheimer's Treatment Center and the Movement Disorders Clinic at the Johns Hopkins University School of Medicine. An Eyelink Portable Duo in head‐free‐to‐move mode was used to track eye movements. Movement of the eyes were analyzed by automatically segmenting saccade movements throughout a trial. We then analyzed the eye movements in the context of cognitive performance, by identifying when subjects progress to each word in the Stroop test. We compared the performance of each group using a Wilcoxon RankSum test with the SciPy package using Python. Result: Preliminary results show that 60% (3/5) of AD subjects were unable to complete the Stroop task in 80 seconds. Individuals with AD had more saccades (p=0.105) with greater saccadic overshoot (p=0.092) and a greater maximum saccade velocity (p=0.035) on average compared to cognitively normal controls. AD subjects also took much longer to complete the first (p=0.114) and second lines (p=0.092) compared to healthy controls, suggesting initial confusion and hesitation. Conclusion: AD subjects change their gaze more often with greater speed and less precision than age‐matched controls. These data demonstrate feasibility of using automatic quantitative evaluation of eye movements in AD. In the future, we will determine the utility of using this tool for early detection of AD and tracking its progression, along with combining other measures such as voice and handwriting (multimodal) to provide insights into early physiological changes in AD. [ABSTRACT FROM AUTHOR]

Background: Speech and language problems are one of the earliest signs of neurodegenerative diseases including Alzheimer's disease (AD), but they are often difficult to detect especially in the early stages. Utility of assessing speech and language problems using artificial intelligence (AI) has been examined in the past. However, the accuracy of different methods has been variable, preventing incorporation of these techniques in clinical use. In this study, we present different speech‐based machine learning techniques. We focused on the automatic extraction of a wide array of interpretable features from the speech signals, then compared these features across different neurological disorders. Method: Spoken responses to four different tasks (i.e., Cookie Theft Picture (CTP) and Stroop Task) were recorded from 80 participants, 5 with AD, 28 with Parkinson's disease (PD), 18 normal controls (NCs), and the remaining with other neurological diseases (OTRs). We automatically extracted several acoustic and linguistic features using speech and language technologies. We conducted pairwise Kruskal–Wallis tests to assess how speech and language abilities differed between different neurodegenerative disease vs. control groups. We used SciPy Python library. Result: The total amount of speech time and pauses as well as the average duration and the variance of the number pauses significantly differed between AD and NC and between PD and NC in almost every task (p <0.05). Prosodic features based on F0 contour and F0 on the first and last voiced segment resulted in significant differences across tasks between AD and NC, AD and PD, AD and OTR (p <0.05). The phonological posterior for the phonological classes of consonantal, voiced, labial, nasal, velar, trill, and close significantly differed in almost every task between AD and NC, AD and PD and AD and OTR (p <0.05). Moreover, from the transcriptions of the CTP task, the number of sentences and noun phrases differed significantly between AD and NC, whereas the number of contrastive connectives and the moving average type‐token ratio were significant between NC and OTR (p <0.05). Conclusion: Automated analysis of speech employing machine learning techniques can provide objective assessment of patients with AD that may be useful in distinguishing AD from other neurological disorders. [ABSTRACT FROM AUTHOR]

Background: Regulatory agencies have endorsed more limited approaches to clinical trial site monitoring. However, the impact of different monitoring strategies on trial conduct and outcomes is unclear.Methods: We conducted a patient-level block-randomized controlled trial evaluating the effect of intensive versus limited monitoring on cardiovascular clinical trial conduct and outcomes nested within the CoreValve Continued Access and Expanded Use Studies. Intensive monitoring included complete source data verification of all critical datapoints whereas limited monitoring included automated data checks only. This study's endpoints included clinical trial outcome ascertainment as well as monitoring action items, protocol deviations, and adverse event ascertainment.Results: A total of 2,708 patients underwent transcatheter aortic valve replacement (TAVR) and were randomized to either intensive monitoring (n = 1,354) or limited monitoring (n = 1,354). Monitoring action items were more common with intensive monitoring (52% vs 15%; P < .001), but there was no difference in the percentage of patients with any protocol deviation (91.6% vs 90.4%; P = .314). The reported incidence of trial outcomes between intensive and limited monitoring was similar for mortality (30 days: 4.8% vs 5.5%, P = .442; 1 year: 20.3% vs 21.3%, P = .473) and stroke (30 days: 2.8% vs 2.4%, P = .458), as well as most secondary trial outcomes with the exception of bleeding (intensive: 36.3% vs limited: 32.0% at 30 days, P = .019). There was a higher reported incidence of cardiac adverse events reported in the intensive monitoring group at 1 year (76.7% vs 72.4%; P = .019).Conclusions: Tailored limited monitoring strategies can be implemented without influencing the integrity of TAVR trial outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the applicability of pivotal transcatheter aortic valve replacement (TAVR) trials to the real-world population of Medicare patients undergoing TAVR. It is unclear whether randomized controlled trial results of novel cardiovascular devices apply to patients encountered in clinical practice. Characteristics of patients enrolled in the U.S. CoreValve pivotal trials were compared with those of the population of Medicare beneficiaries who underwent TAVR in U.S. clinical practice between November 2, 2011, and December 31, 2017. Inverse probability weighting was used to reweight the trial cohort on the basis of Medicare patient characteristics, and a "real-world" treatment effect was estimated. A total of 2,026 patients underwent TAVR in the U.S. CoreValve pivotal trials, and 135,112 patients underwent TAVR in the Medicare cohort. Trial patients were mostly similar to real-world patients at baseline, though trial patients were more likely to have hypertension (50% vs 39%) and coagulopathy (25% vs 17%), whereas real-world patients were more likely to have congestive heart failure (75% vs 68%) and frailty. The estimated real-world treatment effect of TAVR was an 11.4% absolute reduction in death or stroke (95% CI: 7.50%-14.92%) and an 8.7% absolute reduction in death (95% CI: 5.20%-12.32%) at 1 year with TAVR compared with conventional therapy (surgical aortic valve replacement for intermediate- and high-risk patients and medical therapy for extreme-risk patients). The trial and real-world populations were mostly similar, with some notable differences. Nevertheless, the extrapolated real-world treatment effect was at least as high as the observed trial treatment effect, suggesting that the absolute benefit of TAVR in clinical trials is similar to the benefit of TAVR in the U.S. real-world setting. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g., depression, psychosis, and anxiety) with the severity of neuropathology in the substantia nigra and locus coeruleus.Methods: The brains of 175 participants with a primary pathologic diagnosis of Parkinson's disease were analyzed semi-quantitatively to ascertain the burden of neuronal loss and gliosis and Lewy body pathology within the locus coeruleus and substantia nigra. Participants' history of anxiety, depression, and psychosis were determined using a chart-extracted medical history or record of formal psychiatric evaluation.Results: Of the sample, 56% (n = 98), 50% (n = 88), and 31.25% (n = 55) of subjects had a diagnosis of psychosis, depression, and anxiety, respectively. Psychosis (χ2 = 7.1, p = 0.008, df = 1) and depression (χ2 = 7.2, p = 0.007, df = 1) were associated with severe neuronal loss and gliosis in the substantia nigra but not in the locus coeruleus. No association was observed between anxiety and neuronal loss and gliosis in either region. No neuropsychiatric symptoms were associated with Lewy body score. After controlling for disease duration and dementia, psychosis (odds ratio [OR]: 3.1, 95% confidence interval [CI]: 1.5-6.4, χ2 = 9.4, p = 0.012, df = 1) and depression (OR: 2.6, 95% CI: 1.3-5.0, χ2 = 7.9, p = 0.005, df = 1) remained associated with severe neuronal loss and gliosis in the substantia nigra.Conclusion: These results suggest that psychosis and depression in Parkinson's disease are associated with the underlying neurodegenerative process and demonstrate that cell loss and gliosis may be a better marker of neuropsychiatric symptoms than Lewy body pathology. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prior studies on the use of multivessel percutaneous coronary intervention (MV PCI) for patients with STsegment-elevation myocardial infarction (STEMI) and multivessel coronary artery disease have yielded heterogeneous results. The recent COMPLETE trial (Complete Versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease After Early PCI for STEMI) demonstrated that MV PCI was superior to culprit-only PCI among patients with STEMI. It is unclear how these trial results apply to clinical decisions encountered in routine practice. METHODS: We studied STEMI admissions among patients >65 years with multivessel disease and Centers for Medicare and Medicaid Services-linked data in the National Cardiovascular Data Registry CathPCI Registry from July 1, 2009 to December 31, 2017. MV PCI was defined as PCI to a nonculprit lesion ≤45 days of the index procedure. The primary outcome was the composite of death, myocardial infarction, and revascularization from 45 days through 1 year. To account for unmeasured confounders, an instrumental variable analysis was used to compare treatment strategies. The instrument was institutional rates of MV PCI. A falsification end point of postdischarge major bleeding was utilized to assess for residual confounding. RESULTS: Of 56 332 admissions from 1102 institutions, 37.7% received MV PCI =45 days of index STEMI PCI. Of those undergoing MV PCI, 74.8% received complete revascularization. In unadjusted analysis, MV PCI was associated with a lower cumulative incidence of the composite outcome between 45 days and 1 year (13.9% versus 18.2% for non-MV PCI, P<0.01). In the instrumental variable analysis, there was no association between MV PCI and the composite outcome (adjusted risk difference, -0.97% [95% CI, -3.52% to 1.59%]; P=0.46). An association between MV PCI and the falsification end point of major bleeding was not observed (adjusted risk difference, -2.54% [95% CI, -5.30% to 0.22%]; P=0.07). CONCLUSIONS: In this large, nationwide analysis, we did not find benefit of MV PCI by 1 year among older STEMI patients. The clinical benefit of MV PCI may not extend equally outside of trials to include all patients, including those with more extreme ages and more complex decision-making. [ABSTRACT FROM AUTHOR]

Background/purpose: Vitamin C has been proposed to prevent the incidence of complex regional pain syndrome, but the results are conflicting. We evaluated the effectiveness of vitamin C in the prevention of complex regional pain syndrome-1 after distal end radius fractures in the aging population. Methods: This was a prospective, randomized study. Patients treated with either conservative or surgical management for distal end radius fracture received Vitamin C (500 mg/day) plus standard therapy or standard therapy alone for a period of 3 months. The presence of complex regional pain syndrome-1 was assessed with Budapest criteria. Results: The complex regional pain syndrome-I occurred in 11.3% in Vitamin C plus Standard in compared to 26% in Standard therapy alone. Vitamin C was significantly associated with a reduction in the likelihood of exhibiting complex regional pain syndrome-1. Conclusion: Vitamin C (500 mg/day) supplementation was effective and associated with a lower occurrence of acute complex regional pain syndrome-1. It can be a promising prophylactic option for the prevention of complex regional pain syndrome-1 after distal end radius fracture. [ABSTRACT FROM AUTHOR]

BACKGROUND: Data from administrative claims may provide an efficient alternative for end point ascertainment in clinical trials. However, it is uncertain how well claims data compare to adjudication by a clinical events committee in trials of patients with cardiovascular disease. METHODS: We matched 1336 patients ≥65 years old who received percutaneous coronary intervention in the DAPT (Dual Antiplatelet Therapy) Study with the National Cardiovascular Data Registry CathPCI Registry linked to Medicare claims as part of the EXTEND (Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data) Study. Adjudicated trial end points were compared with Medicare claims data with International Classification of Diseases, Ninth Revision codes from inpatient hospitalizations using time-to-event analyses, sensitivity, specificity, positive predictive value, negative predictive value, and kappa statistics. RESULTS: At 21-month follow-up, the cumulative incidence of major adverse cardiovascular and cerebrovascular events (combined mortality, myocardial infarction, and stroke) was similar between trial-adjudicated events and claims data (7.9% versus 7.2%, respectively; P=0.50). Bleeding rates were lower using adjudicated events compared with claims (5.0% versus 8.6%, respectively; P<0.001). The sensitivity and positive predictive value of comprehensive billing codes for identifying adjudicated events were 65.6% and 85.7% for myocardial infarction, 61.5% and 47.1% for stroke, and 76.8% and 39.3% for bleeding, respectively. Specificity and negative predictive value for all outcomes ranged from 93.7% to 99.5%. All 39 adjudicated deaths were identified using Medicare data. Kappa statistics assessing agreement between events for myocardial infarction, stroke, and bleeding were 0.73, 0.52, and 0.49, respectively. CONCLUSIONS: Claims data had moderate agreement with adjudication for myocardial infarction and poor agreement but high specificity for bleeding and stroke in the DAPT Study. Deaths were identified equivalently. Using claims data in clinical trials could be an efficient way to assess mortality among Medicare patients and may help detect other outcomes, although additional monitoring is likely needed to ensure accurate assessment of events. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation (KT) is widely accepted as most successful treatment option for patients with end-stage kidney disease (ESKD) for better survival and quality of life for both children as well as adults. Data scarcity on long term outcome of living donor (LD) versus deceased donor (DD) pediatric KT in developing countries prompted us to review our experience. Aims and Objectives: To determine(1) long term graft, (2)patient survival outcome and (3) rejection episodes in LD versus DD pediatric KT in developing country. Patients and Methods: This was a retrospective observational analysis of 151 LD and 37 DD pediatric renal transplants (age ≤18 years) performed at a tertiary care center between 1998 and 2011. This study was under taken to evaluate long term patient and graft survival, rejection episodes and other complications. Demographic details for all patients was retrieved. Kaplan-Meier curves were used for survival analysis. Results: Over a mean follow-up of 4.2 ± 3.61 years, one-, five- and ten- year death-censored graft survival in LDKT was 87.4%, 72.1%, 72.1% and patient survival was 92.5%, 80.9%, 75.1% respectively; 19.8% (n = 30) patients had biopsy proven acute rejection (BPAR) and 17.8% (n = 27) patients died, mainly due to infections (n = 12). In DDKT, over mean follow-up of 3.93 ± 3.5 years, one-, five- and ten-year death-censored graft survival was 90.4%, 86.4% ,73.3% and patient survival was 83.4%, 67.9%, 67.9 %, respectively; 21.6% (n = 8) patients had BPAR and 27% (n =10) patients died, mainly owing to infections (n = 6). Conclusion: LDKT or DDKT in children has acceptable graft function with patient/graft survival over long-term follow-up, encouraging to develop sustained deceased donor program in developing countries. However, infections are major cause of morbidity and mortality. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the performance of administrative claims in ascertaining trial clinical events committee–adjudicated outcomes in the U.S. CoreValve studies. Real-world data offer tremendous opportunity to improve outcome ascertainment in clinical trials. However, little is known about the validity of outcomes ascertained using real-world data to capture trial endpoints. Patients enrolled in 3 pivotal trials and 2 pre-market continued-access studies evaluating transcatheter aortic valve replacement were linked to Medicare fee-for-service inpatient claims. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa agreement statistic of claims to detect clinical endpoints and procedural complications in trial patients were calculated. Claims accurately identified trial-adjudicated deaths (sensitivity, specificity, PPV, and NPV all >99.6%; kappa 1.00). Claims had good performance in identifying trial-adjudicated permanent pacemaker implantation (sensitivity 92.2%, specificity 99.1%, PPV 96.1%, NPV 98.2%, kappa 0.93) and aortic valve reintervention (sensitivity 84.4%, specificity 99.6%, PPV 69.1%, NPV 99.8%, kappa 0.76). Claims had more modest performance in ascertaining trial-adjudicated myocardial infarction (sensitivity 63.6%, specificity 97.2%, PPV 29.9%, NPV 99.3%, kappa 0.39) and acute kidney injury (sensitivity 70.2%, specificity 85.4%, PPV 38.2%, NPV 95.7%, kappa 0.41) and the poorest performance for identifying trial-adjudicated bleeding events (sensitivity 86.4%, specificity 36.8%, PPV 35.0%, NPV 86.3%, kappa 0.16). Compared with trial-adjudicated outcomes, claims data performed well in ascertaining death and outcomes with procedural billing codes and more modestly in identifying other outcomes. Claims may be cautiously and selectively used to augment data collection in future cardiovascular device trials. [ABSTRACT FROM AUTHOR]

To determine the presence of and periprocedural changes caused by aortic regurgitation (AR) in patients supported with an Impella (Abiomed, Danvers, MA) left ventricular assist device. Retrospective. Tertiary academic medical center. Patients who underwent insertion of an Impella device at Allegheny General Hospital from January 2015 to December 2018. Analysis of patient electronic medical records. Demographic information; comorbidities; duration of support; and the presence and severity of AR pre-procedure and post-procedure, as reported by echocardiography, were analyzed. The electronic medical records of 69 patients were included in the present study. Before placement of the Impella device, 25 (35%) patients showed detectable AR, with 18 (26%) showing mild AR and 7 (10%) showing moderate AR. After the removal of the Impella device, AR remained steady or increased in 61 patients. Fifteen patients (22%) demonstrated mild AR, 6 (8.7%) demonstrated moderate AR, and 2 (2.9%) demonstrated severe AR. An increase in severity of AR was noted in 9 patients (14.7%), and 52 patients (85%) had no change in the severity of AR. The duration of support with the Impella device, demographic variables, and comorbidities were not associated with a statistically significant risk for increased severity of post-procedural AR in multiple multivariable logistic regression analyses. The presented data suggest that after Impella device support, a significant proportion of patients may show evidence of increased AR. Additional studies are needed to understand the etiology and significance of this observation. [ABSTRACT FROM AUTHOR]

Adeno-associated viral vectors (AAV) are the leading platform for gene delivery to treat disease. Although AAVs are not known to be pathogenic, patients with high levels of pre-existing neutralizing antibodies (NAbs) to AAVs may fail to achieve desired transgene expression and/or be at increased risk of a systemic inflammatory response. Tenaya Therapeutics is developing TN-201, the first AAV9-mediated gene therapy for the treatment of MYBPC3-associated HCM. To date, there have been no studies to assess pre-existing AAV9 immunity to determine the percentage of MYBPC3-associated HCM patients who may be candidates for this one-time gene therapy treatment. To assess the prevalence of NAbs in MYBPC3-associated HCM patients, Tenaya initiated an observational seroprevalence study, enrolling participants at US HCM clinics. Sites collected medical histories and sera from participants. Serum from each participant was used in an AAV9 NAb assay to assess NAb titer to AAV9, the serotype used in TN-201. Participants with titers <1:20 were classified as seronegative (low pre-existing NAb) to AAV9. Total antibody titer to AAV9 was assessed to compare with NAb titers. As of June 2023, participants have enrolled in this seroprevalence study across 10 clinics. Interim results indicate that 33 of 45 (73%) MYBPC3-associated participants are AAV9 seronegative. AAV9 seronegativity did not vary by age, race, geography, or medical history. Results suggest that MYBPC3-associated HCM patients have low levels of pre-existing NAbs to AAV9 used in TN-201. This finding may indicate that the majority patients could be eligible for TN-201 in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Access to dermatologists is low among Medicaid-insured patients. Higher clinic nonattendance among Medicaid-insured patients might affect provider decisions to accept these patients.Objective: To determine the effect of different scheduling policies on the attendance among children seen at a pediatric dermatology clinic.Methods: In this retrospective review, we compared nonattendance among children for 3 different scheduling policies implemented over 3 consecutive years. The scheduling policies used were a first-available open scheduling policy, a 2-week in advance scheduling policy, and a 4-week in advance scheduling policy. Subset analyses were performed by clinic location and insurance type.Results: The interval between scheduling and appointment date was directly related to nonattendance rates; rates were higher for Medicaid-insured than privately insured patients. Open scheduling was associated with a 37% nonattendance rate for Medicaid-insured patients and 18% nonattendance rate for privately insured patients. A 4-week in advance scheduling policy significantly decreased the nonattendance rate to 19% among Medicaid-insured and 7% among privately insured patients. A 2-week in advance policy further decreased the nonattendance rate to 11% among Medicaid-insured patients and 4% among privately insured patients.Limitations: This is a retrospective study, and same-day cancellations were not tracked.Conclusion: Decreasing the time interval between scheduling and appointment dates can significantly decrease nonattendance. This strategy might help dermatologists incorporate more Medicaid-insured patients into their practices. [ABSTRACT FROM AUTHOR]

In manufacturing processes the automated identification of faulty operating conditions that might lead to insufficient product quality and reduced availability of the equipment is an important and challenging task. This paper proposes a data mining approach to the identification of complex faults, i.e. unplanned machine stops in plastic injection molding. Several data mining methods are considered, with a focus on the abilities to reveal patterns of faulty operating conditions and on the interpretation of the induced models with the objective to find the data mining method that best corresponds to the nature of the plastic-injection-molding process and the related data. Well-known data mining methods, i.e. J48, random forests, JRip rules, naïve Bayes, and k-nearest neighbors are applied to real industrial data. The results show that tested data mining methods can be effectively used to reveal patterns related to faulty operating conditions. The interpretation capacity of the tested methods, their ability to describe the operating conditions, and to reveal patterns related to faulty operating conditions, are demonstrated and discussed. [ABSTRACT FROM AUTHOR]