Response of Central Giant Cell Granuloma of the Jaw to Imatinib.

Central giant cell granuloma of the jaw (CGCJ) can be locally aggressive and result in facial and dental deformity. A child with CGCJ was treated surgically and with denosumab with a response but life-threatening toxicity. Imatinib, a tyrosine kinase inhibitor, was prescribed based on clinical similarities between CGCJ and cherubism, for which Imatinib has been effective. Within 2 months, a computed tomographic scan showed significant ossification, which increased over the following 8 months. This case suggests that tyrosine kinase inhibitors may be an effective option, and one with limited toxicity, for CGCJ.

Clinical Effectiveness of Calcium Oxalate Stone Treatments.

INTRODUCTION: Lowering kidney stone risk and urine calcium oxalate supersaturation is a primary clinical focus for kidney stone prevention and can be achieved with multiple strategies. Common strategies include advice to increase fluid intake, restrict dietary sodium, or prescribing a thiazide-type diuretic. We investigated how physicians make these decisions in real-world practice and evaluate their efficacy based on 24-h urine collections. METHODS: We reviewed medical charts for 203 kidney stone formers with idiopathic calcium stones from University of Chicago Kidney Stone Clinic between 2005 and 2020. Patients had three 24-h urines before an initial pre-treatment clinic visit and one follow-up 24-h urine. We analyzed changes in urine composition based on treatment advice using t tests and ANOVA. RESULTS: Patients who received advice to increase fluid intake had lower urine volume at baseline (1.5 vs. 2.5 L/day, p < 0.001) and larger increase in urine volume at follow-up (0.6 vs. 0.1 L/day, p < 0.001) compared to those who did not receive the advice. Patients who were advised to restrict dietary sodium had a higher urine sodium at baseline (208 vs. 139 mEq/day, p < 0.001), a larger reduction in urine sodium (-28 vs. 13 mEq/day, p = 0.002), and larger reduction in urine calcium (-74 vs. -28 mg/day, p = 0.005) compared with those not advised to restrict dietary sodium. Patients started on a thiazide had a higher baseline urine calcium (281 vs. 213 mg/day) and larger reduction in urine calcium (-83 vs. -9 mg/day, p < 0.001) compared with patients not started on a thiazide. In combination, thiazide prescriptions with dietary sodium restriction reduced urine calcium by 99 mg/day and reduced calcium oxalate supersaturation from 8.0 to 5.5 and calcium phosphate supersaturation from 1.4 to 1.0. CONCLUSION: Providers use 24-h urine data to guide treatment strategy decisions. These strategies achieved the intended effects on urine composition and lowered kidney stone risk.

Comparative effectiveness of revascularization strategies.

BACKGROUND: Questions persist concerning the comparative effectiveness of percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG). The American College of Cardiology Foundation (ACCF) and the Society of Thoracic Surgeons (STS) collaborated to compare the rates of long-term survival after PCI and CABG. METHODS: We linked the ACCF National Cardiovascular Data Registry and the STS Adult Cardiac Surgery Database to claims data from the Centers for Medicare and Medicaid Services for the years 2004 through 2008. Outcomes were compared with the use of propensity scores and inverse-probability-weighting adjustment to reduce treatment-selection bias. RESULTS: Among patients 65 years of age or older who had two-vessel or three-vessel coronary artery disease without acute myocardial infarction, 86,244 underwent CABG and 103,549 underwent PCI. The median follow-up period was 2.67 years. At 1 year, there was no significant difference in adjusted mortality between the groups (6.24% in the CABG group as compared with 6.55% in the PCI group; risk ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00). At 4 years, there was lower mortality with CABG than with PCI (16.4% vs. 20.8%; risk ratio, 0.79; 95% CI, 0.76 to 0.82). Similar results were noted in multiple subgroups and with the use of several different analytic methods. Residual confounding was assessed by means of a sensitivity analysis. CONCLUSIONS: In this observational study, we found that, among older patients with multivessel coronary disease that did not require emergency treatment, there was a long-term survival advantage among patients who underwent CABG as compared with patients who underwent PCI. (Funded by the National Heart, Lung, and Blood Institute.).

Prediction of long-term mortality after percutaneous coronary intervention in older adults: results from the National Cardiovascular Data Registry.

BACKGROUND: The purpose of this study was to develop a long-term model to predict mortality after percutaneous coronary intervention in both patients with ST-segment elevation myocardial infarction and those with more stable coronary disease. METHODS AND RESULTS: The American College of Cardiology Foundation CathPCI Registry data were linked to the Centers for Medicare and Medicaid Services 100% denominator file by probabilistic matching. Preprocedure demographic and clinical variables from the CathPCI Registry were used to predict the probability of death over 3 years as recorded in the Centers for Medicare and Medicaid Services database. Between 2004 and 2007, 343 466 patients (66%) of 518 195 patients aged ≥65 years undergoing first percutaneous coronary intervention in the CathPCI Registry were successfully linked to Centers for Medicare and Medicaid Services data. This study population was randomly divided into 60% derivation and 40% validation cohorts. Median follow-up was 15 months, with mortality of 3.0% at 30 days and 8.7%, 13.4%, and 18.7% at 1, 2, and 3 years, respectively. Twenty-four characteristics related to demographics, clinical comorbidity, prior history of disease, and indices of disease severity and acuity were identified as being associated with mortality. The C indices in the validation cohorts for patients with and without ST-segment elevation myocardial infarction were 0.79 and 0.78. The model calibrated well across a wide range of predicted probabilities. CONCLUSIONS: On the basis of the large and nationally representative CathPCI Registry, we have developed a model that has excellent discrimination, calibration, and validation to predict survival up to 3 years after percutaneous coronary intervention.

User-centered design of a telehealth-enhanced hybrid cardiac rehabilitation program as hospital quality improvement.

Background Innovative program designs and strategies are needed to support the widespread uptake of cardiac rehabilitation (CR) programs in the post-COVID19 era. We combined user-centered design (UCD) and implementation science (ImS) principles to design a novel telehealth-enhanced hybrid (home and clinic-based) CR (THCR) program. Methods As part of a New York Presbyterian Hospital (NYPH) quality improvement initiative (March 2020-February 2022), we designed a THCR program using an iterative 3 step UCD process informed by the Theoretical Domains Framework and Consolidated Framework for Implementation Research to: 1) identify user and contextual barriers to CR uptake (stakeholder interviews), 2) design an intervention prototype (design workshops and journey mapping), and 3) refine the prototype (usability testing). The process was optimized for usability and implementation outcomes. Results Step 1: Semi-structured interviews with stakeholders (n = 9) at 3 geographically diverse academic medical centers revealed behavioral (e.g., self-efficacy, knowledge) and contextual (e.g., social distancing guidelines, physical space, staffing, reimbursement) barriers to uptake. Step 2: Design workshops (n = 20) and journey-mapping sessions (n = 3) with multi-disciplinary NYPH stakeholders (e.g., digital health team, CR clinicians, creative director) yielded a THCR prototype that leveraged NYPH's investment in their remote patient monitoring (RPM) platform to optimize feasibility of home-based CR sessions. Step 3: Usability testing with CR clinicians (n = 2) administering and CR patients (n = 3) participating in home-based sessions revealed usability challenges (e.g., RPM devices/exercise equipment usability; Wi-Fi/Bluetooth connectivity/syncing; patient safety/knowledge and protocol flexibility). Design workshops (n = 24) and journey-mapping sessions (n = 3) yielded design solutions (e.g., onboarding sessions, safety surveys, fully supervised remote sessions) and a refined THCR prototype. Conclusion Combining UCD and ImS methods while engaging multi-disciplinary stakeholders in an iterative process yielded a theory-informed telehealth-enhanced hybrid CR program targeting user and contextual barriers to real-world CR implementation. We provide a detailed summary of the process, and guidance for incorporating UCD and ImS methods in early-stage intervention development. THCR may shrink the evidence-to-practice gap in CR implementation. A future hybrid type I effectiveness-implementation trial will determine its feasibility, acceptability, and effectiveness.

Applying User-Centered Design and Implementation Science to the Early-Stage Development of a Telehealth-Enhanced Hybrid Cardiac Rehabilitation Program: Quality Improvement Study.

BACKGROUND: Cardiac rehabilitation (CR) is an evidence-based intervention that improves event-free survival in patients with cardiac conditions, yet <27% of all eligible patients use CR in the United States. CR is traditionally delivered in clinic-based settings where implementation barriers abound. Innovative nontraditional program designs and strategies are needed to support widespread CR uptake. OBJECTIVE: This study aimed to demonstrate how user-centered design (UCD) and implementation science (IS) principles and methods can be integrated into the early-stage development of nontraditional CR interventions. METHODS: As part of a NewYork-Presbyterian Hospital (NYPH) quality improvement initiative (March 2020-February 2022), we combined UCD and IS principles and methods to design a novel home- and clinic-based telehealth-enhanced hybrid CR (THCR) program. We co-designed this program with multilevel stakeholders using an iterative 3-step UCD process to identify user and contextual barriers and facilitators to CR uptake (using semistructured interviews and contextual inquiry [step 1]), design an intervention prototype that targets contextual and user factors and emulates the evidence-based practice (through design workshops and journey mapping [step 2]), and review and refine the prototype (according to real-world usability testing and feedback [step 3]). The UCD process was informed by the Theoretical Domains Framework and Consolidated Framework for Implementation Research. RESULTS: At step 1, we conducted semistructured interviews with 9 provider- and system-level stakeholders (female: n=6, 67%) at 3 geographically diverse academic medical centers, which revealed behavioral (eg, self-efficacy and knowledge) and contextual (eg, social distancing guidelines, physical space, staffing, and reimbursement) barriers to uptake; hybrid delivery was a key facilitator. Step 2 involved conducting 20 design workshops and 3 journey-mapping sessions with multidisciplinary NYPH stakeholders (eg, digital health team, CR clinicians, and creative director) where we identified key design elements (eg, mix of clinic- and home-based CR and synchronous remote patient monitoring), yielding an initial THCR prototype that leveraged NYPH's telehealth infrastructure. At step 3, we conducted usability testing with 2 CR clinicians (both female) administering home-based sessions to 3 CR patients (female: n=1, 33%), which revealed usability themes (eg, ease of using remote patient monitoring devices or a telehealth platform, technology disruptions, and confidence in using the telehealth platform to safely monitor patients) and design solutions (eg, onboarding sessions, safety surveys, and fully supervised remote sessions) to be included in the final THCR prototype. CONCLUSIONS: Combining UCD and IS methods while engaging multidisciplinary stakeholders in an iterative process yielded a theory-informed THCR program targeting user and contextual barriers to real-world CR implementation. We provide a detailed summary of the process and guidance for incorporating UCD and IS principles and methods into the early-stage development of a nontraditional CR intervention. The feasibility, acceptability, appropriateness, and usability of the final THCR prototype is being evaluated in an ongoing study.

Relative contributions of urine sulfate, titratable urine anion, and GI anion to net acid load and effects of age.

Models of acid-base balance include acid production from (1) oxidation of sulfur atoms on amino acids and (2) metabolically produced organic acid anions. Acid load is balanced by alkali from metabolism of GI anions; thus, net acid production is equivalent to the sum of urine sulfate and organic anion (measured by titration in urine), minus GI anion. However, the relative contributions of these three sources of acid production in people eating free choice diets, and presumably in acid-base balance, have not been well studied. We collected 26 urines from 18 normal subjects (10 male) and 43 urine samples from 34 stone formers (17 male) and measured sulfate, organic anion, and components of GI anion and acid excretion in each; values were expressed as mEq/mmol creatinine. Mean values of the urine components, except creatinine and pH, did not differ between the sexes or groups. Urine organic acid and acid production varied directly with age (p ≤ 0.03). In a general linear model of acid excretion, the coefficients for sulfate, organic anion, and GI anion were 0.34 ± 0.09, 0.49 ± 0.12, and -0.51 ± 0.06, respectively, p ≤ 0.005, and the model accounted for 54% of the variance. A model for urine ammonia gave similar results. Urine organic anion is a significant contributor to total acid production and may be responsible for an increase in acid production with age.

Impact of ethnicity and gender differences on angiographic coronary artery disease prevalence and in-hospital mortality in the American College of Cardiology-National Cardiovascular Data Registry.

BACKGROUND: Although populations referred for coronary angiography are increasingly diverse, there is limited information on coronary artery disease (CAD) prevalence and in-hospital mortality other than for predominately white male patients. METHODS AND RESULTS: We examined gender and ethnic differences in CAD prevalence and in-hospital mortality in a prospective cohort of patients referred for angiographic evaluation of stable angina (n=375,886) or acute coronary syndromes (ACS; unstable angina or myocardial infarction, n=450,329) at 388 US hospitals participating in the American College of Cardiology-National Cardiovascular Data Registry, an angiographic registry. Univariable and multivariable (with covariates that included risk factors, symptoms, and comorbidities) logistic regression models were used to estimate significant CAD, defined as > or = 70% stenosis, and in-hospital mortality. Within stable angina and ACS cohorts, 7% of patients were black, 2% were Hispanic, 0.3% were Native American, 1% were Asian, and 90% were white, respectively. In stable angina, the risk-adjusted OR for significant CAD was 0.34 for women compared with men (P<0.0001), with black women having the lowest risk-adjusted odds (P<0.0001) compared with other females. Among ACS patients, the risk-adjusted OR of significant CAD was 0.47 for women compared with men (P<0.0001); similarly, black women had the lowest risk-adjusted odds (P<0.0001) compared with other females. Higher in-hospital mortality was reported for white women presenting with stable angina (P<0.00001). White women had a 1.34-fold (95% CI 1.21 to 1.48) higher risk-adjusted odds ratio for mortality than white men with stable angina (P<0.0001), with higher rates noted for white women who were older or had significant CAD (both P<0.0001). Lower utilization of elective coronary revascularization, aspirin, and glycoprotein IIb/IIIa inhibitors (all P<0.0001) may have contributed to higher in-hospital mortality for white women. In ACS, higher in-hospital mortality was reported for Hispanic (P=0.015) and white (P<0.0001) women; however, neither white (P=0.51) or Hispanic (P=0.13) women had higher in-hospital risk-adjusted mortality. CONCLUSIONS: The likelihood for significant CAD at coronary angiography and for in-hospital mortality varied significantly by ethnicity and gender. Future clinical practice guidelines should be tailored to gender subsets of the population, in particular for black women, to improve the efficient use of angiographic laboratories and to target at-risk populations of women and men.

Comparison of coronary artery calcium scores between electron beam computed tomography and 64-multidetector computed tomographic scanner.

OBJECTIVE: Because almost all data currently available with coronary calcium scanning are from electron beam tomography (EBT), we assessed whether scores obtained with 64-multidetector computed tomography (CT; MDCT) are similar. We evaluated the interscan variation in coronary artery calcium (CAC), Agatston score (AS), and volume score (VS) between EBT and 64-MDCT (VCT; GE, Milwaukee, Wis). MATERIALS AND METHODS: One hundred two patients (mean age, 61.1 years; 27 women) underwent dual CAC scanning with both EBT and 64-MDCT. The AS and VS were measured with the Aquarius workstation (TeraRecon, Inc, San Mateo, Calif). The correlation coefficient, Bland-Altman analysis, interscanner variation, and agreement in AS and VS scores between EBT and 64-MDCT were computed. RESULTS: Interscan agreement for presence of CAC was 99%. Median values were 286 and 268 mm for AS and 243 and 213 mm for VS with EBT and 64-MDCT, respectively (P > 0.05). There was significant linear relationship between scores from the 2 scanners (R = 0.98 in AS and R = 0.99 in VS; P < 0.001). The interscanner variability between EBT and 64-MDCT was 20.9% and 17.6% in AS and VS, respectively (P = NS). Bland-Altman analysis demonstrated a mean difference in scores of 8.3% for AS and 7.8% by VS. When compared with EBT, there were larger and more prevalent motion artifacts (P < 0.001) and larger mean Hounsfield units using 64-MDCT (P < 0.001). CONCLUSIONS: At CAC scanning, 64-MDCT and EBT were comparable in AS and VS. The interscan variability between scanners is similar to interscan variability of 2 calcium scores done on the same equipment. However, heart rate control was achieved for this study for calcium scores. Whether these results are repeatable without heart rate control needs to be further assessed.

State-wide hospital clinical laboratory plan for measuring cholinesterase activity for individuals suspected of exposure to nerve agent chemical weapons.

BACKGROUND: Hospital laboratories currently lack the capacity to provide emergency determination of cholinesterase activity. METHODS: We have developed a hospital-based 3-tiered system to test plasma for butyrylcholinesterase (BChE) activity and whole blood for red cell acetylcholinesterase (AChE) activity using available technology and personnel. Interagency communications, toxidrome definition, and patient triage will be coordinated by the Connecticut Department of Public Health and the Poison Control Center. DATA: Initial BChE data documents good precision between institutions (coefficient of variation < 8%). SUMMARY: Laboratory testing of plasma or blood for cholinesterase activity is important in the management of nerve agent exposure and in ruling out disease in those with non-specific symptoms in the setting of a terrorist attack or accidental exposure. Rapid availability of strong hospital-based analytic support in a smoothly functioning network of clinical, public health, and laboratory services will facilitate overall regional response to chemical terrorism or large scale HazMat events.

ACMT Position Statement: Alternative or Contingency Countermeasures for Acetylcholinesterase Inhibiting Agents.

First responders and health care providers must prepare to provide care for patients poisoned by acetylcholinesterase (AchE) inhibitor chemical warfare agents or pesticides. However, pre-deployed medical countermeasures (MCMs) may not be sufficient due to production and delivery interruption, rapid depletion of contents during a response, expiration of MCM components, or lack of local availability of approved MCMs. To augment supplies of community-based and forward-deployed nerve agent countermeasures, the American College of Medical Toxicology (ACMT) supports several strategies: (1) The use of expired atropine, diazepam, and pralidoxime auto-injectors and vials if non-expired drugs are unavailable; and (2) Investigation, development, and identification of alternative countermeasures-commonly stocked drugs that are not approved for nerve agent poisoning but are in the same therapeutic class as approved drugs.

Risk-adjusted mortality analysis of percutaneous coronary interventions by American College of Cardiology/American Heart Association guidelines recommendations.

An American College of Cardiology (ACC)/American Heart Association (AHA) task force on practice guidelines in 2001 published evidence-based recommendations for performing percutaneous coronary interventions (PCIs). These guidelines grouped the indications for PCI into 4 classes (I, IIa, IIb, and III) based on analyses of risks and benefits. In a previous study, we found that clinical success and in-hospital adverse events varied by indications class. However, no adjustment for risk was used in those comparisons. The ACC/National Cardiovascular Data Registry (ACC-NCDR) previously developed a risk-adjustment model for the adverse event of in-hospital PCI mortality. We investigated how the 14 individual risk factors in the ACC-NCDR PCI mortality model might differ across the 4 indications classes and whether estimated mortality for each class approximated the observed mortality for that class. We analyzed the ACC-NCDR PCI database for January 1, 2001 to December 31, 2004. We excluded procedures performed for treatment of acute ST-segment elevation myocardial infarction; all others were included, yielding 559,273 procedures for analysis. An algorithm derived from the 2001 guidelines was used to assign procedures to an indications class. Increasing frequencies of risk components were observed across classes I, IIa, IIb, and III. Expected mortalities for each class calculated by the risk-adjustment model were close to observed values (expected 0.52%, 0.59%, 1.72%, and 1.96%, respectively; observed 0.49%, 0.63%, 1.88%, and 1.60%, respectively). In conclusion, the ACC-NCDR risk-adjusted mortality model can be linked to the ACC/AHA PCI guidelines, and together these produce mortality risk estimates by indications classes that are close to actual observed values. With further refinement, these methods should be able to be used as powerful analytic tools for quality assurance and appropriateness purposes.

Retreatment with yttrium-90 ibritumomab tiuxetan in patients with B-cell non-Hodgkin's lymphoma.

There is no data on safety and efficacy of a second course of ibritumomab tiuxetan. In this work, data on patients with B-cell NHL who were treated with two courses of ibritumomab tiuxetan were analyzed. Eighteen such patients were analyzed (age: 58 years, 48 - 91), with a median of four prior regimens (1 - 7), stem cell transplantation (n = 5), and radiation therapy (n = 6). After the first course, G3/4 neutropenia and thrombocytopenia was 35% and 41%; overall response rate (ORR) was 89%; time between courses was 16.6 months (6.0 - 42.7). After the second course, the incidence of G3/4 neutropenia and thrombocytopenia was 28% and 44%; and ORR 77%. There were no infectious or bleeding complications, secondary myelodysplastic syndromes, or leukemias. Retreatment with the ibritumomab tiuxetan regimen was well tolerated, with a safety profile similar to that of the first course. To conclude, patients who benefited from the first course of ibritumomab tiuxetan can benefit from retreatment.

Cardiac CT angiography (CTA) and nuclear myocardial perfusion imaging (MPI)-a comparison in detecting significant coronary artery disease.

RATIONALE AND OBJECTIVES: Endowed with sufficient diagnostic accuracy, electron beam computed tomography angiography (CTA) is being increasingly used to evaluate coronary arteries. However, data on direct comparisons with nuclear myocardial perfusion studies are limited. In this study, we sought to compare the accuracies of CTA and myocardial perfusion imaging (MPI) for identifying symptomatic patients with hemodynamically significant obstructive coronary artery disease (CAD). MATERIALS AND METHODS: In a single-center study, symptomatic outpatients who were scheduled for cardiac catheterization were prospectively enrolled. Only patients with exertional angina or dyspnea were included. After fulfilling the inclusion criteria, 30 patients were enrolled in the study (mean age 54 +/- 9 years and 70% males). Patients underwent MPI, CTA including coronary artery calcification (CAC) measure, and invasive coronary angiography for evaluation of obstructive coronary artery disease. Significant CAD was defined as >50% left main artery stenosis or >70% stenosis of any other epicardial vessel by invasive angiography. The sensitivities, specificities and predictive values of MPI, CAC, and CTA were analyzed per patient RESULTS: CTA demonstrated significant higher sensitivity than MPI (95% vs. 81%, P < .05). CTA demonstrated significantly higher specificity than both MPI (89% versus 78%, P = .04) and CAC (56%, P = .002). CTA also performed better in a per-vessel analysis (sensitivity 94%, specificity 96%) than both nuclear and CAC. There were no significant differences between the sensitivities and specificities of MPI and CAC. CONCLUSION: CTA accurately detects obstructive CAD in symptomatic patients and may be more accurate than MPI or CAC assessment. Larger studies in a more diverse population are needed.

Safety and efficacy of extended-release ranolazine in patients aged 70 years or older with chronic stable angina pectoris.

This analysis examined the safety and efficacy of extended-release ranolazine among patients aged 70 years or older (n=363) compared with patients younger than 70 years (n=1024) enrolled in 2 large multinational prospective clinical trials. The primary end points were exercise capacity and number of weekly angina episodes. Beneficial effects of ranolazine, relative to placebo, were generally similar for each of these outcomes among older and younger participants. For example, at a ranolazine dose of 1000 mg bid, mean exercise duration increased by 19.8+/-13.1 seconds (mean +/- SE) relative to placebo in patients younger than 70 years and by 32.4+/-19.7 seconds relative to placebo in patients 70 years or older. Adverse effects were more common in older than in younger patients, but the incidence of serious adverse effects attributable to ranolazine did not differ significantly between age groups. Outcomes were also similar at dosages of either 750 mg or 1000 mg bid. In conclusion, pooled data from 2 large randomized trials indicate that the efficacy of ranolazine is similar in older and younger patients but that adverse effects are more common in the elderly.