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Aims: Broad molecular profiling of patients with advanced non-small cell lung cancer (NSCLC) is strongly advised to optimize genomic matching with available targeted treatment options or investigational agents. Unlike conventional molecular diagnostic testing, or smaller hotspot panels, comprehensive genomic profiling (CGP) identifies genomic alterations across hundreds of clinically relevant cancer genes from a single tissue specimen. The present study sought to estimate the budget impact of increased use of CGP using a 324-gene panel (FoundationOne) vs non-CGP (represented by a mix of conventional molecular diagnostic testing and smaller NGS hotspot panels) and the number needed to test with CGP to gain 1 life year. Materials and methods: A decision analytic model was developed to assess the budget impact of increased CGP in advanced NSCLC from a US private payer perspective. Model inputs were based on published literature (epidemiology and treatment outcomes), real-world data (testing and rates, medical service costs), list prices for CGP and anti-cancer drugs, and assumptions for clinical trial participation. Results: Among 2 million covered lives, 532 had advanced NSCLC; 266 underwent molecular diagnostic testing. An increase in CGP among those tested, from 2% to 10%, was associated with $0.02 per member per month budget impact, of which $0.013 was attributable to costs of prolonged drug treatment and survival and $0.005 to testing cost. Approximately 12 patients would need to be tested with CGP to add 1 life year. Limitations: The model incorporated certain assumptions to account for inputs with a limited evidence profile and simplify the possible post-CGP treatments. Conclusions: An increase in CGP utilization from 2% to 10% among patients with advanced NSCLC undergoing molecular diagnostic testing was associated with a modest budget impact, most of which was attributable to increased use of more effective treatments and prolonged survival.

Aims: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. Methods: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1–2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010–2014). Results: Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1–22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). Limitations: In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. Conclusions: The low frequency of molecular diagnostic testing suggests there are opportunities to better inform management of patients with advanced cancer, particularly decisions to treat with GMTT.

Bifidobacteria are dominant members of the microbial community in the intestinal tract of infants, and studies have shown that glycolipids extracted from the cell surface of these bacteria elicit beneficial immune responses. Accordingly, the identification and structural characterization of glycolipids from the cell wall of bifidobacteria is the first step in correlating glycolipid structure with biological activity. Using whole cell MALDI as a screening tool, we herein present for the first time the identification and structural elucidation of the major polar lipids from Bifidobacterium longum subs. infantis. The lipids identified include an unprecedented plasmenyl cyclophosphatidic acid and a mixed acetal glycolipid, with the latter subsequently being isolated and found to suppress the innate immune response.

The objective of this study was to estimate the frequency of heart failure (HF) readmissions that can be prevented through a quality improvement (QI) program. All HF patients at the University of Connecticut Health Center who had a readmission within 30 days of discharge in the year before (2008) and the year after (2011) a QI program were studied. Through chart review, the percentage of patients who had preventable readmissions in each year was estimated. Prior to the QI initiative, chart reviewers identified that 20% to 30% of readmissions were preventable. The decrease in readmissions after the QI program was similar at 28%. Fewer readmissions after the QI initiative were deemed preventable compared with before. In conclusion, this study found a percentage of preventable readmissions similar to the actual 28% reduction in readmissions after a QI program was launched. Preventable readmissions were less common after the QI program was in place.

The mainstay of treatment for acute decompensated heart failure (ADHF) is intravenous (IV) diuretic therapy either as a bolus or via continuous infusion. Despite being available for decades, few randomized trials exist to guide dosing and administration of these drugs. In 2011, the Diuretic Optimization Strategies Evaluation (DOSE) trial used a prospective, randomized design to compare bolus versus continuous infusion of IV furosemide, as well as high-dose versus low-dose therapy. The study found no difference in the primary end point for continuous versus bolus infusion. High-dose diuretics were more effective than low dose without clinically important negative effects on renal function. Although limited by patient selection criteria and protocol design, the study challenges long-held beliefs that continuous infusion is more effective than bolus dosing. The study also challenges the notion that high-dose diuretics carry clinically important renal toxicity risks for patients.

Zirconia is currently used as a framework material for posterior all-ceramic bridges. While the majority of research efforts have focused on the microstructure and corresponding mechanical properties of this material, clinical fractures appear to be largely associated with the appliance geometry. Objective The objective of this study was to estimate the maximum stress concentration posed by the connector geometry and to provide adjusted estimates of the minimum connector diameter that is required for achieving 20 years of function. Methods A simple quantitative description of the connector geometry in an all-ceramic 4-unit bridge design is used with published stress concentration factor charts to estimate the degree of stress concentration and the maximum stress. Results The magnitude of stress concentration estimated for clinically relevant connector geometries ranges from 2 to 3. Using previously published recommendations for connector designs, adjusted estimates for the minimum connector diameter required to achieve 20 years of clinical function are presented. Significance To prevent clinical fractures the minimum connector diameter in multi-unit bridges designs must account for the loads incurred during function and the extent of stress concentration posed by the connector geometry.

Since their commercial introduction in 2003, drug-eluting stents (DES) have rapidly altered the management of coronary artery disease. Before their development, the percutaneous management of coronary artery disease was performed predominantly by implantation of bare metal stents (BMS) made of either surgical stainless steel or metal alloys. Although such stents represented a considerable advance over balloon angioplasty alone, they remained limited by restenosis resulting from neointimal proliferation. As a result, ≈15% to 20% of patients treated with BMS required ≥1 repeat revascularization procedure within the 6 to 12 months after stent implantation.1 Despite numerous attempts at systemic pharmacotherapy, device modification, and even use of ionizing radiation, the rate of restenosis after BMS implantation remained largely unaffected. Response by Eisenberg p 1744 Over the past 5 years, effective DES have become the first device to substantially reduce the incidence of restenosis after stent implantation. By delivering high concentrations of either antiproliferative or immunomodulatory compounds directly to the site of arterial injury and by controlling this delivery through polymer-based drug release, both sirolimus- and paclitaxel-eluting stents have safely and effectively inhibited the proliferative process that results in in-stent restenosis. In pivotal clinical trials, both sirolimus- and paclitaxel-eluting stents have reduced rates of angiographic restenosis by 70% to 90% compared with conventional BMS designs, with parallel reductions in the need for clinically driven target vessel revascularization (TVR).2–4 As a result, in April 2003, DES were approved for use in clinical practice in the United States. Within 9 months of their introduction, DES made up 35% of all stent implantations in the United States,5 and their use has increased rapidly since that time. At our own institution, DES comprised >85% of all stents implanted during the past year, and national estimates are that >90% of all percutaneous coronary intervention (PCI) procedures …

Background— Recent studies indicate that a routine invasive approach for patients with unstable angina (UA) and non–ST-segment elevation myocardial infarction (NSTEMI) yields improved outcomes compared with a conservative approach, but the optimal timing of this approach remains open to debate. Methods and Results— We used day of hospital presentation as an instrumental variable to study the impact of timing of cardiac catheterization and revascularization therapy on acute outcomes (death, reinfarction, stroke, cardiogenic shock, or congestive heart failure) among patients with UA and NSTEMI. Between January 2001 and September 2003, 56 352 patients with UA or NSTEMI were treated at 310 US hospitals participating in the CRUSADE national quality improvement initiative. Weekend patients were defined as those who presented to the hospital between 5 pm on Friday and 7 am on Sunday. All other patients were classified as weekday. Weekday patients were similar to weekend patients in terms of demographics, clinical characteristics, and the use of medical therapies in the first 24 hours. Although overall rates of cardiac catheterization and revascularization were similar for the 2 groups, median time to catheterization was significantly longer for weekend than for weekday patients (46.3 versus 23.4 hours, P P =0.23), recurrent MI (2.9% versus 3.0%, P =0.36), or their combination (6.6% versus 6.6%, P =0.86). These findings were not affected by risk adjustment or use of alternative definitions of weekend versus weekday presentation. When weekend presentation was used as the basis for an instrumental variable analysis, we found that catheterization within the first 12 hours of presentation was associated with a nonsignificant trend toward reduced in-hospital mortality (absolute risk reduction 1.9%; 95% CI 6.7% lower to 2.9% higher; P =0.43) that decreased with longer treatment delays. Conclusions— Although weekend presentation is associated with a delay in invasive management among patients with UA and NSTEMI, in the context of contemporary medical therapy, this does not increase adverse events. Weekend presentation appears to fulfill accepted criteria as an instrumental variable for studying the optimal timing of invasive management for acute coronary syndrome patients. Using weekend status as an instrumental variable, we found no significant benefit to early catheterization, although we could not exclude an important risk reduction, particularly for catheterization within 12 hours of presentation.

Background Previous studies have demonstrated low rates of adherence to American College of Cardiology (ACC) and American Heart Association (AHA) guidelines for acute myocardial infarction (AMI). Quality improvement projects increase compliance with recommended therapies, but identification of AMI patients is a major challenge. Objective To determine the utility of a daily troponin list in identifying AMI patients for a quality improvement initiative to increase compliance with ACC/AHA-recommended therapies. Design Quality improvement initiative. Methods and results During a 3-month period, the charts of patients with elevated troponin levels were screened for a diagnosis of AMI. For those patients with AMI, a clinical reminder about ACC/AHA-recommended therapies was placed in the chart. Nearly half (46%) of our hospital population had a troponin level measured during their clinical course. Of these, 26% had elevated troponin levels and 5% had AMI. All patients with AMI were identified using the daily troponin list with a sensitivity of 100% and a specificity of 78.4%. The daily troponin list captured more AMI patients than the admitting diagnosis. Use of the daily troponin list and targeted clinical reminders was associated with maintenance of a high (>95%) compliance with recommended therapies. Conclusions A daily list of inpatients with a positive troponin identified all patients with AMI. Targeted reminders to clinicians regarding ACC/AHA-recommended therapies for AMI were associated with consistent adherence to guideline-recommended therapies.

The Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trial was a prospective, randomized study comparing ultrafiltration versus pharmacological therapy in the treatment of acute decompensated heart failure (ADHF) complicated by cardiorenal syndrome Bart et al. (N Eng J Med 367:2296–2304, 1). The study found that ultrafiltration was inferior to pharmacological therapy, resulting in a significant increase in serum creatinine and serious adverse events while producing no significant difference in weight loss. The CARRESS trial calls into question the viability of ultrafiltration as a preferable treatment strategy in ADHF patients with cardiorenal syndrome.

Planning operations across a number of domains can be considered as resource allocation problems with timing constraints. An unexplored instance of such a problem domain is the aircraft carrier flight deck, where, in current operations, replanning is done without the aid of any computerized decision support. Rather, veteran operators employ a set of experience-based heuristics to quickly generate new operating schedules. These expert user heuristics are neither codified nor evaluated by the United States Navy; they have grown solely from the convergent experiences of supervisory staff. As unmanned aerial vehicles (UAVs) are introduced in the aircraft carrier domain, these heuristics may require alterations due to differing capabilities. The inclusion of UAVs also allows for new opportunities for on-line planning and control, providing an alternative to the current heuristic-based replanning methodology. To investigate these issues formally, we have developed a decision support system for flight deck operations that utilizes a conventional integer linear program-based planning algorithm. In this system, a human operator sets both the goals and constraints for the algorithm, which then returns a proposed schedule for operator approval. As a part of validating this system, the performance of this collaborative human-automation planner was compared with that of the expert user heuristics over a set of test scenarios. The resulting analysis shows that human heuristics often outperform the plans produced by an optimization algorithm, but are also often more conservative., United States. Office of Naval Research (Autonomy Program Contract N000140910625)

The study objectives were to quantify the change in 7-day follow-up visits and 30-day readmissions as part of a hospital quality improvement initiative and to characterize events at 7-day follow-up visits. Some data suggest that outpatient assessments of patients with heart failure within 7 days of hospital discharge may prevent readmissions, although little is known about patient needs at 7-day follow-up visits.We performed a single-center, retrospective chart review of all heart failure discharges at the University of Connecticut Health Center (398 patients) the year before (2008) and the year after (2011) a quality improvement initiative that included mandatory 7-day follow-up visits. We quantified the change in 30-day readmission rate after the initiative, frequency of 7-day follow-up visits, and events at follow-up visits.The average age of patients with heart failure was 79.9 years in 2011, with 45.9% having systolic heart failure. Thirty-day all-cause readmissions decreased from 27.5% to 19.1% after our quality improvement initiative (P = .024). Frequency of 7-day follow-up visits increased from 19.6% to 46.9% (P.01). Eighty-one percent of 7-day visits occurred in the University of Connecticut Heart Failure Center with a cardiologist or heart failure nurse practitioner. Fifty-one percent of patients had blood work drawn, and 26% had a medication dose changed. Only 13% of patients had no discrepancy between the discharge and follow-up medication lists.Our hospital's 30-day readmission rate for patients with heart failure decreased in parallel with an increase in 7-day follow-up visits. Patients with heart failure were complex and often had diagnostic testing and medication changes at follow-up visits.

Introduction Many studies have demonstrated gaps in adherence to American College of Cardiology (ACC)/American Heart Association (AHA) guidelines among patients with acute decompensated heart failure (ADHF). Quality improvement initiatives can improve compliance with guideline-recommended therapy yet a major challenge to such programs is identifying heart failure patients across the many wards and services of the complex hospital environment. Methods and results Using our hospital's electronic order-entry system, we generated a daily list of all hospitalized patients receiving a loop diuretic. Over a 3-month period, each patient on this list was screened through chart review for a diagnosis of ADHF. For those patients with ADHF, a clinical reminder about ACC/AHA recommended therapies was placed in the chart. Patient outcomes were followed using the Get With The Guidelines heart failure database.During the study period, 98.6% of patients with ADHF were identified by the diuretics list. The diuretics list had a sensitivity of 98.6% and specificity of 92.2%. The diuretic list captured more ADHF patients than alternative methods such as chest x-ray and brain natriuretic peptide level. Use of the daily diuretic list and targeted reminders to clinicians was associated with an improvement in recommended therapies including smoking-cessation education and heart failure teaching. Conclusions A daily list of inpatients receiving diuretics allowed real-time identification of most hospitalized heart failure patients at our institution. Targeted reminders to clinicians regarding ACC/AHA-recommended therapies for heart failure were associated with improvements in guideline adherence.

Background— Although drug-eluting stents have been shown to be cost-effective compared with bare-metal stents for select clinical trial patients, whether these findings apply to the general population is unknown. Methods and Results— We used data from the Medicare 5% Standard Analytic Files to compare the practice and outcomes of coronary revascularization (by either percutaneous coronary intervention or coronary artery bypass grafting) in the United States between 2001 (pre–drug-eluting stent era, n=14 362) and 2004 (post–drug-eluting stent era, n=16 374). Between 2001 and 2004, the rate of revascularization increased from 837 to 931 per 100 000, whereas the proportion of patients who underwent percutaneous coronary intervention as an initial revascularization procedure increased from 67.5% to 75.2% ( P P =0.193). Significant decreases were seen, however, in the incidence of repeat revascularization (17.1% versus 16.0%, P =0.012) and myocardial infarction (10.6% versus 8.5%, P P P Conclusions— Among the Medicare population undergoing coronary revascularization, the introduction of drug-eluting stents was associated with increased use of initial percutaneous coronary intervention and reduced bypass surgery along with improved clinical outcomes over ≈2 years of follow-up. Although total cardiovascular-related costs per revascularized patient decreased over this time period, total cost to the Medicare system still increased owing to greater overall use of revascularization procedures.

Drug-eluting stents have been a major advance in percutaneous coronary revascularization. Widespread use of these stents has been spurred by substantial reductions in restenosis rates when compared with bare metal stents. The use of drugeluting stents during ST-segment elevation myocardial infarction has been a common practice and is associated with lower revascularization rates in various studies. Unfortunately, significant concerns regarding the occurrence of late stent thrombosis with this technology persist. A clinical dilemma exists as to whether the benefits of reduced repeat revascularization with DES outweigh the harm caused by a possible increased occurrence of the infrequent but devastating complication of late stent thrombosis. This review with discuss the theoretical risks and benefits of DES for STEMI, the available data regarding their use, and the areas where future studies are needed.

Since their introduction, drug-eluting stents have rapidly altered modern medicine's approach to coronary artery disease. Before the development of drug-eluting stents, standard bare-metal stents were plagued by in-stent restenosis, requiring repeat revascularization in as many as 15-20% of patients during the first 6-12 months following implantation [1]. The currently approved drug-eluting stents have dramatically reduced this complication by using a polymer-impregnated coating that elutes either paclitaxel or sirolimus to inhibit smooth muscle proliferation. The pivotal TAXUS-IV [2] and SIRIUS [3] trials compared drug-eluting stents with standard bare-metal stents and found rates of target vessel revascularization ranging from 3 to 4.1% in stable coronary artery disease patients - far lower than that had been seen previously with conventional standard bare-metal stents. After their approval in April 2003, drug-eluting stents use in clinical practice expanded rapidly. Within 9 months of their introduction, drug-eluting stents comprised 35% of all stent implantations in the United States [4]. In the last year at our own institution, drug-eluting stents comprised over 85% of all stents implanted. Despite their extensive use, data regarding the efficacy and safety of drug-eluting stents in certain clinical scenarios are limited. To date, the only published data supporting drug-eluting stents in ST[corrected]-elevation acute myocardial infarction come from the retrospective Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital registry [5] and the randomized, controlled single high-dose bolus tirofiban and sirolimus-eluting stent vs. abciximab and bare-metal stent in myocardial infarction study [6]. In this chapter, we discuss the theoretical risks and benefits of drug-eluting stents for ST elevation acute myocardial infarction, the available data regarding their use, and the areas in which future studies are needed.

We sought to assess whether statins may decrease cardiac complications in patients undergoing noncardiac vascular surgery.Cardiovascular complications account for considerable morbidity in patients undergoing noncardiac surgery. Statins decrease cardiac morbidity and mortality in patients with coronary disease, and the beneficial treatment effect is seen early, before any measurable increase in coronary artery diameter.A retrospective study recorded patient characteristics, past medical history, and admission medications on all patients undergoing carotid endarterectomy, aortic surgery, or lower extremity revascularization over a two-year period (January 1999 to December 2000) at a tertiary referral center. Recorded perioperative complication outcomes included death, myocardial infarction, ischemia, congestive heart failure, and ventricular tachyarrhythmias occurring during the index hospitalization. Univariate and multivariate logistic regressions identified predictors of perioperative cardiac complications and medications that might confer a protective effect.Complications occurred in 157 of 1,163 eligible hospitalizations and were significantly fewer in patients receiving statins (9.9%) than in those not receiving statins (16.5%, p = 0.001). The difference was mostly accounted by myocardial ischemia and congestive heart failure. After adjusting for other significant predictors of perioperative complications (age, gender, type of surgery, emergent surgery, left ventricular dysfunction, and diabetes mellitus), statins still conferred a highly significant protective effect (odds ratio 0.52, p = 0.001). The protective effect was similar across diverse patient subgroups and persisted after accounting for the likelihood of patients to have hypercholesterolemia by considering their propensity to use statins.Use of statins was highly protective against perioperative cardiac complications in patients undergoing vascular surgery in this retrospective study.

This study investigated the relationship between adolescents' academic performance and participation in physical activity. 232 boys and girls from Years 8–11 (ages 13–16 years) were randomly selected, and their academic performance was assessed on previous examination scores in English, Mathematics, and Science. Participants were also asked to list all the sports-based physical activities in which they normally participated during a typical week and to indicate how many times per week they took part in each activity and the duration of each. Overall, no significant correlations were found, although weak negative correlations were recorded between the amount of time (in minutes) in sport and exercise and English scores for children ages 13, 14, and 16 years. A similar association was also noted for Science scores of children 16 years old.

Among patients with heart failure, neurohormonal blockade with angiotensin-converting enzyme inhibitors, β-adrenergic receptor blockers (BB), and aldosterone antagonists has been shown to improve mortality and hospitalization rates.1–4 Combination therapy with these drugs can reduce mortality more …

It had been a frenetic day for me and my team. We were swamped with patients, and keeping up was exacting, made worse by the pace. But in addition to the volume of admissions, our night felt increa...