Reversing the "Risk-Treatment Paradox" of Bleeding in Patients Undergoing Percutaneous Coronary Intervention: Risk-Concordant Use of Bleeding Avoidance Strategies Is Associated With Reduced Bleeding and Lower Costs.

Background Bleeding is a common, morbid, and costly complication of percutaneous coronary intervention. While bleeding avoidance strategies ( BAS ) are effective, they are used paradoxically less in patients at high risk of bleeding. Whether a patient-centered approach to specifically increase the risk-concordant use of BAS and, thus, reverse the risk-treatment paradox is associated with reduced bleeding and costs is unknown. Methods and Results We implemented an intervention to reverse the bleeding risk-treatment paradox at Barnes-Jewish Hospital, St. Louis, MO, and examined: (1) the temporal trends in BAS use and (2) the association of risk-concordant BAS use with bleeding and hospital costs of percutaneous coronary intervention. Among 3519 percutaneous coronary interventions, there was a significantly increasing trend ( P=0.002) in risk-concordant use of BAS . The bleeding incidence was 2% in the risk-concordant group versus 9% in the risk-discordant group (absolute risk difference, 7%; number needed to treat, 14). Risk-concordant BAS use was associated with a 67% (95% confidence interval, 52-78%; P<0.001) reduction in the risk of bleeding and a $4738 (95% confidence interval, 3353-6122; P<0.001) reduction in per-patient percutaneous coronary intervention hospitalization costs (21.6% cost-savings). Conclusions In this study, patient-centered care directly aimed to make treatment-related decisions based on predicted risk of bleeding, led to more risk-concordant use of BAS and reversal of the risk-treatment paradox. This, in turn, was associated with a reduction in bleeding and hospitalization costs. Larger multicentered studies are needed to corroborate these results. As clinical medicine moves toward personalization, both patients and hospitals can benefit from a simple practice change that encourages objectivity and mitigates variability in care.

Novel Patient-Centered Approach to Facilitate Same-Day Discharge in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Same-day discharge (SDD) after elective percutaneous coronary intervention is safe, less costly, and preferred by patients, but it is usually performed in low-risk patients, if at all. To increase the appropriate use of SDD in more complex patients, we implemented a "patient-centered" protocol based on risk of complications at Barnes-Jewish Hospital. METHODS AND RESULTS: Our objectives were as follows: (1) to evaluate time trends in SDD; (2) to compare (a) mortality, bleeding, and acute kidney injury, (b) patient satisfaction, and (c) hospital costs by SDD versus no SDD (NSDD); and (3) to compare SDD eligibility by our patient-centered approach versus Society for Cardiovascular Angiography and Interventions guidelines. Our patient-centered approach was based on prospectively identifying personalized bleeding, mortality, and acute kidney injury risks, with a personalized safe contrast limit and mitigating those risks. We analyzed Barnes-Jewish Hospital's National Cardiovascular Data Registry CathPCI Registry data from July 1, 2009 to September 30, 2015 (N=1752). SDD increased rapidly from 0% to 77% (P<0.001), independent of radial access. Although SDD patients were comparable to NSDD patients, SDD was not associated with adverse outcomes (0% mortality, 0% bleeds, and 0.4% acute kidney injury). Patient satisfaction was high with SDD. Propensity score-adjusted costs were $7331 lower/SDD patient (P<0.001), saving an estimated $1.8 million annually. Only 16 patients (6.95%) met the eligibility for SDD by Society for Cardiovascular Angiography and Interventions guidelines, implying our patient-centered approach markedly increased SDD eligibility. CONCLUSIONS: With a patient-centered approach, SDD rapidly increased and was safe in 75% of patients undergoing elective percutaneous coronary intervention, despite patient complexity. Patient satisfaction was high, and hospital costs were lower. Patient-centered decision making to facilitate SDD is an important opportunity to improve the value of percutaneous coronary intervention.

Association of Variation in Contrast Volume With Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention.

Importance: Acute kidney injury (AKI) after percutaneous coronary intervention (PCI) is common, morbid, and costly; increases patients' mortality risk; and can be mitigated by limiting contrast use. Objective: To examine the national variation in AKI incidence and contrast use among US physicians and the variation's association with patients' risk of developing AKI after PCI. Design, Setting, and Participants: This cross-sectional study used the American College of Cardiology National Cardiovascular Data Registry (NCDR) CathPCI Registry to identify in-hospital care for PCI in the United States. Participants included 1 349 612 patients who underwent PCI performed by 5973 physicians in 1338 hospitals between June 1, 2009, and June 30, 2012. Data analysis was performed from July 1, 2014, to August 31, 2016. Main Outcomes and Measures: The primary outcome was AKI, defined according to the Acute Kidney Injury Network criteria as an absolute increase of 0.3 mg/dL or more or a relative increase of 50% or more from preprocedural to peak creatinine. A secondary outcome was the mean contrast volume as reported in the NCDR CathPCI Registry. Physicians who performed more than 50 PCIs per year were the main exposure variable of interest. Hierarchical regression with adjustment for patients' AKI risk was used to identify the variation in AKI rates, the variation in contrast use, and the association of contrast volume with patients' predicted AKI risk. Results: Of the 1 349 612 patients who underwent PCI, the mean (SD) age was 64.9 (12.2) years, 908 318 (67.3%) were men, and 441 294 (32.7%) were women. Acute kidney injury occurred in 94 584 patients (7%). A large variation in AKI rates was observed among individual physicians ranging from 0% to 30% (unadjusted), with a mean adjusted 43% excess likelihood of AKI (median odds ratio, 1.43; 95% CI, 1.41-1.44) for statistically identical patients presenting to 2 random physicians. A large variation in physicians' mean contrast volume, ranging from 79 mL to 487 mL with an intraclass correlation coefficient of 0.23 (interquartile range, 0.21-0.25), was also observed, implying a 23% variation in contrast volume among physicians after adjustment. There was minimal correlation between contrast use and patients' AKI risk (r = -0.054). Sensitivity analysis after excluding complex cases showed that the physician variation in AKI remained unchanged. Conclusions and Relevance: Acute kidney injury rates vary greatly among physicians, who also vary markedly in their use of contrast and do not use substantially less contrast in patients with higher risk for AKI. These findings suggest an important opportunity to reduce AKI by reducing the variation in contrast volumes across physicians and lowering its use in higher-risk patients.

Adhesion promotion via noncovalent interactions in self-healing polymers.

Dimethylnorbornene ester (DNE) is successfully used as a noncovalent adhesion promoter. DNE was confirmed to copolymerize with dicyclopentadiene (DCPD) to yield a copolymer with better adhesion to an EPON 828 epoxy matrix relative to poly(DCPD) alone. The mechanical properties of the copolymer were comparable to that of poly(DCPD) alone. An optimized blend of the monomers was encapsulated using a urea-formaldheyde microencapsulation procedure and the resulting capsules were used for in situ self-healing experiments. Improved healing efficiency was observed for samples containing the DCPD/DNE capsules under conditions in which the monomers were efficiently polymerized.

Robust, double-walled microcapsules for self-healing polymeric materials.

Double-walled polyurethane/poly(urea-formaldehyde) microcapsules (PU/UF) are prepared for use in self-healing materials. This modified encapsulation procedure combines two chemistries to form more robust capsule shell walls in a single operation. Robust capsules are formed by this procedure as long as the aromatic polyisocyanate prepolymer is soluble in the core liquid and the core liquid is compatible with isocyanates. Compared to a standard UF encapsulation, the modified procedure results in capsules with an increase in shell wall thickness from 200 to 675 nm as a function of the amount of PU added to the core liquid. Thermal stability of PU/UF microcapsules prepared with varying amounts of PU is compared to UF microcapsules. Mechanical properties of the PU/UF microcapsules are assessed from single-capsule compression testing.

An evaluation of mesotherapy solutions for inducing lipolysis and treating cellulite.

The aim of this study was to evaluate the lipolytic potential of solutions used in the practice of cosmetic mesotherapy to stimulate lipolysis, cause local fat reduction and reduce the appearance of cellulite. The mesotherapy solutions were tested in a human fat cell assay using the fold induction of glycerol generation as a measure of lipolysis. The following mesotherapy solutions were tested: aminophylline; yohimbine; isoproterenol; melilotus; aminophylline with melilotus; aminophylline with isoproterenol; aminophylline with isoproterenol and yohimbine; aminophylline with isoproterenol and lidocaine; and aminophylline with isoproterenol, yohimbine and lidocaine. Isoproterenol (P<0.002), aminophylline (P<0.00004) and yohimbine (P<0.001) stimulated lipolysis compared to the buffer control. The lipolysis stimulated by melilotus (P<0.01) and isoproterenol (P<0.002) was enhanced by aminophylline (P<0.001 and P<0.001, respectively). The lipolytic stimulation by aminophylline and isoproterenol (P<0.0009), and by aminophylline and isoproterenol with yohimbine (P<0.0007) was inhibited by lidocaine, not significant compared to buffer control for aminophylline and isoproterenol, but aminophylline, isoproterenol and yohimbine still stimulated lipolysis more than control, P<0.05). Isoproterenol, aminophylline, yohimbine and melilotus stimulate lipolysis alone, and lipolysis is further enhanced by combining lipolytic stimulators in mesotherapy solutions. Lidocaine is antilipolytic and should be removed from mesotherapy solutions designed for local fat reduction.

An assay to measure angiogenesis in human fat tissue.

BACKGROUND: Inhibition of angiogenesis reverses rodent obesity. A validated assay in human fat tissue is needed to study the role of angiogenesis in human obesity. METHODS: Human fat tissue fragments from surgery were placed in 96-well plates, embedded in fibrin thrombin clot and overlaid with cell culture media containing 20% fetal bovine serum. After 15 days, the clots were examined by histology and electron microscopy. The effect of taxol, cobalt chloride and a heparin-steroid combination was tested in the fat tissue assay and compared to the validated human placental vein angiogenesis model (HPVAM). RESULTS: Blood vessels initiated growth and elongated from the fat tissue fragments over 15 days. Presence of blood vessels was confirmed with histology and electron microscopy. Taxol at 10(-6) and 10(-7) M completely inhibited angiogenesis, while Taxol 10(-8) and 10(-9) M and the heparin-steroid partially inhibited angiogenesis. The response to taxol and heparin-steroid was similar to that of the HPVAM, a validated angiogenesis assay. Cobalt chloride, a stimulator of vascular endothelial growth factor (VEGF) stimulated angiogenesis initiation at 10(-9) M in fat tissue and the HPVAM, but at 10(-10) M blood vessel growth was stimulated only in the fat assay. CONCLUSION: This angiogenesis assay based on human fat tissue uses three-dimensionally intact human tissue. The vessels are derived from quiescient vessels within the fat. These properties allow the angiogenic switch to be evaluated in an in vitro setting. The angiogenic response of fat tissue is not identical to placental tissue. This assay allows exploration of angiogenesis in fat tissue.

The safety and efficacy of a dietary herbal supplement and gallic acid for weight loss.

The objective of this study was to test the safety and efficacy of NT, a dietary herbal supplement made from rhubarb, ginger, astragulus, red sage, and turmeric, combined with gallic acid (GA) to reduce food intake and cause weight loss. A total of 105 healthy subjects, 18-60 years old with a body mass index of 25-35 kg/m(2) and on no chronic medication, were randomized to a 300 mg/1.2 g NT-GA combination, a 600 mg/2.4 g NT-GA combination, or placebo in three divided doses daily for 24 weeks. Food intake was measured at baseline and 2 weeks, and safety parameters were followed regularly. Pharmacokinetic studies of a 200 mg/800 g NT-GA combination and 800 mg GA alone were performed with and without food. There was no dose-related weight loss or reduction in food intake at the 8-week analysis, and the study was terminated early. Pharmacokinetic studies showed plasma levels of GA did not increase above 10 microM and were not dose-related. The NT-GA at all concentrations was well tolerated, but was ineffective in causing weight loss or in suppressing food intake. Pharmacokinetics suggested that GA plasma levels were limited by oral absorption, and may be the reason for lack of efficacy.

The cost effectiveness of three different measures of breast volume.

BACKGROUND: Several methods including water displacement, casting, the Grossman-Roudner measuring device, photographs, mammograms, ultrasound, and magnetic resonance imaging (MRI) have been proposed for the measurement of breast volume. The most cost-effective method has not been determined. METHODS: This study compared breast volume measurements using the Grossman-Roudner measuring device (a piece of circular plastic with a cut along a radius line), plaster casting, and MRI. The Grossman-Roudner measuring device was formed into a cone around the breast, and the volume was read from a graduated scale on the overlapping edges. The volume of the cast was measured using a butter-sand mixture and water displacement. The volume from the MRI slices was calculated using the ANALYZE bioimaging software. For five women with breast sizes AA, A, B, C, and D, the three volume measures were repeated three times. For a single volume measurement, the cost of the time and materials was 1 US dollar for the Grossman-Roudner cone, 20 US dollars for the cast, and 1,400 US dollars for the MRI. Using the mean and standard deviations of the measurements, a power analysis determined the number of subjects needed to detect a 5% change in volume. The number of subjects was multiplied by the price per test to determine relative cost. RESULTS: As compared with the cost for the Grossman-Roudner cone method, the cost for the volume measurements was 64 to 189 times more using the cast and 373 to 33,500 more using MRI. CONCLUSIONS: The Grossman-Roudner cone was clearly the most cost-effective method for determining breast volume changes in studies testing topical therapies to alter breast size.

Safety of obesity drugs.

The safety of obesity drugs has historically been poor. This and the stigmatisation of obesity in society ensured that a higher standard of safety for obesity drugs must be met. The authors review the safety disasters of obesity drugs that were withdrawn. The authors then review the safety of presently available drugs--benzphetamine, phendimetrazine, diethylpropion, phentermine, sibutramine and orlistat. The safety of rimonabant, a drug with a pending new drug application that has an independent effect on metabolic syndrome, is also reviewed. The authors compare the stage of obesity drug development to that of hypertension in the 1950s. As new and safer drugs with more downstream mechanisms are developed that have independent effects on the cardiovascular risks associated with obesity, third party reimbursement for obesity medicine is likely to improve. This may lead to obesity being treated like hypertension and other chronic diseases with long-term medication. With improved technological tools, the authors believe this process will be more rapid for obesity than it was for hypertension.

Medical and behavioral symptoms as potential medication side effects in adults with developmental disabilities.

The incidence of medical and behavioral symptoms that could occur as side effects of psychotropic medication was assessed in a sample of 30 adults with developmental disabilities. Using a retrospective chart review method, we measured symptoms in six a priori classes of potential side effects over a 2-year period. The majority of side effects involved apparent effects of the psychotropic medications on behavior, mood, or sleep. Different patterns of changes in medication prescription, in relation to recorded side effects, were observed. Overall, there was a significant positive relation between the number of potential side effects recorded and the number of psychotropic medication changes made. Our findings suggest several patterns of side effects associated with psychotropic medication use.

Possible role for the 5-HT1A receptor in the behavioral effects of REM sleep deprivation on free-operant avoidance responding in rat.

RATIONALE: REM sleep deprivation (REMSD) has been shown to increase rates of free-operant avoidance responding. Depletion of 5-hydroxytryptamine (5-HT, serotonin) levels produces similar effects on responding. OBJECTIVE: We studied whether the pharmacological activation of the 5-HT1A receptor would produce effects on avoidance responding similar to REMSD and depleted 5-HT levels. METHODS: Rats were trained to lever press on a free-operant avoidance task. Dose-effect functions were established for 8-OH-DPAT (a 5-HT1A receptor agonist) (0.1-1.0 mg/kg) and WAY 100635 (a 5-HT1A receptor antagonist) (0.1-1.0 mg/kg). Rats were then exposed to REMSD (48 h) or equivalent control conditions, and then administered 8-OH-DPAT (0.6 mg/kg) and/or WAY 100635 (0.025-0.1 mg/kg). RESULTS: Injections of 8-OH-DPAT increased rates of avoidance responding in a dose-dependent manner, while WAY 100635 did not alter responding. The effect of 8-OH-DPAT was antagonized by pre-injection of WAY 100635. REMSD and injections of 8-OH-DPAT increased rates of avoidance responding and the effects of both manipulations were reversed by pre-injection of WAY 100635. CONCLUSIONS: Activation of the 5-HT1A receptor may be a mechanism by which REMSD increases rates of free-operant avoidance responding.

Effects of a reviewer-prompting strategy on timely manuscript reviews.

We studied a reviewer-prompting system designed to improve the timeliness of journal reviews. The prompting system consisted of an e-mail message sent individually to reviewers noting the manuscript number, review due date, and associated social amenities for the timely completion of the task. Our results indicated that the prompting system increased timely reviews.

Differential effects of carbamazepine on negatively versus positively reinforced responding.

To assess its effects on negatively versus positively reinforced operant behavior, carbamazepine (CBZ) or vehicle was acutely administered to rats. Negative reinforcement baselines consisted of a free-operant avoidance task with 5-s shock-shock and 20-s response-shock intervals. Positive reinforcement baselines consisted of responding for food pellets on a variable interval 30-s schedule. Ascending dose-effect functions were established using CBZ for negatively reinforced responding (vehicle, 25, 50, 100 mg/kg ip) and positively reinforced responding (vehicle, 12.5, 25, 50, 100 mg/kg ip). Negatively reinforced responses and avoided shocks were significantly reduced by CBZ injections at 100 mg/kg. Positively reinforced responses and food pellet deliveries were significantly reduced by CBZ injections at 25, 50, and 100 mg/kg. The results show that CBZ has differential, dose-dependent effects on negatively versus positively reinforced responding.

Functional analysis of stereotypical ear covering in a child with autism.

We studied stereotypical ear covering in a child with autism. Results of a descriptive analysis were inconclusive but revealed a correlation between ear covering and another child's screaming. An analogue functional analysis showed that ear covering was emitted only when the screaming was present.