Variation in additional testing and patient outcomes after stress echocardiography or myocardial perfusion imaging, according to accreditation status of testing site.

BACKGROUND: The purpose of the present study was to determine whether patients receiving a stress echocardiogram or myocardial perfusion imaging (MPI) test have differences in subsequent testing and outcomes according to accreditation status of the original testing facility. METHODS AND RESULTS: An all-payer claims dataset from Maine Health Data Organization from 2012 to 2014 was utilized to define two cohorts defined by an initial stress echocardiogram or MPI test. The accreditation status (Intersocietal Accreditation Commission (IAC), American College of Radiology (ACR) or none) of the facility performing the index test was known. Descriptive statistics and multivariate regression were used to examine differences in subsequent diagnostic testing and cardiac outcomes. We observed 4603 index stress echocardiograms and 8449 MPI tests. Multivariate models showed higher odds of subsequent MPI testing and hospitalization for angina if the index test was performed at a non-accredited facility in both the stress echocardiogram cohort and the MPI cohort. We also observed higher odds of percutaneous coronary interventions (PCI) performed (OR 1.68, 95% CI 1.13-2.50), if the initial MPI test was done in a non-accredited facility. CONCLUSION: Cardiac testing completed in non-accredited facilities were associated with higher odds of subsequent MPI testing, hospitalization for angina, and PCI.

First-trimester chorionic bump--Association with fetal aneuploidy in a high-risk population.

PURPOSE: To determine the relationship between the first-trimester chorionic bump and fetal aneuploidy. METHODS: This retrospective cohort study included all singleton pregnancies with chromosomal analysis and sonographic examination performed between 5 0/7 and 13 6/7 weeks from January 1, 2010 through August 15, 2015. Interobserver and intraobserver agreement for identifying a chorionic bump was evaluated by the Kappa statistic. Pregnancies with and without a chorionic bump were compared regarding patient characteristics and fetal karyotypes. RESULTS: Six hundred ninety subjects were included, 16 (2.3%) having a bump. The kappa coefficients for interobserver agreement were 0.88 (95% confidence interval [CI]: 0.71-1.00) and 0.94 (95% CI: 0.82-1.00); those for intraobserver agreement were 0.81 (95% CI: 0.61-1.00) and perfect agreement. One hundred seventeen fetuses (16.9%) were aneuploid, of which five (4.3%) had a bump. The odds of aneuploidy in the presence of a chorionic bump were higher than those in the absence of a chorionic bump, although this difference was not statistically significant (odds ratio [OR] 2.3, 95% CI: 0.8-6.7). In subgroup analyses, odds of aneuploidy were four times higher in the bump group than in the no bump group among those with a sonographically isolated bump (OR 4.5, 95% CI: 1.5-13.5) and 15 times higher among those with an isolated bump and increased first-trimester aneuploidy risk (OR 15.0, 95% CI 2.4-93.3). CONCLUSIONS: Agreement in identifying chorionic bumps is near-perfect. A sonographically nonisolated chorionic bump is not associated with significant additional aneuploidy risk, whereas a sonographically isolated chorionic bump confers a significantly increased likelihood of aneuploidy in high-risk fetuses. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:3-7, 2017.

Biomarkers p16, Human Papillomavirus and p53 Predict Recurrence and Survival in Early Stage Squamous Cell Carcinoma of the Vulva.

OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) develops through 2 distinct molecular pathways, one involving high-risk human papillomavirus (HPV) infection and the other through early p53 suppressor gene mutation. We sought to evaluate the influence of p53 mutation, HPV status, and p16 expression on local recurrence and disease-specific mortality in early stage VSCC. MATERIALS AND METHODS: We performed a retrospective chart review of all patients with stage I VSCC at the Maine Medical Center from 1998 to 2007 (n = 92). Tumor size, depth of invasion, lymphatic/vascular space invasion, and growth pattern were recorded. Paraffin-embedded tissue blocks were stained by immunohistochemistry for p16 and p53; high-risk HPV was detected by polymerase chain reaction assay. Margin distance was determined by a gynecologic pathologist. Survival analyses were conducted to examine predictors of VSCC recurrence and disease-specific mortality. RESULTS: Age, depth of invasion, lymphatic/vascular space invasion, growth pattern, and margin status were not significant predictors of recurrence or disease-specific mortality. Tumor size of greater than 4.0 cm indicated a 4-fold increase in disease-specific mortality but did not significantly increase recurrence. p16-Positive patients were less likely to recur and had no VSCC-related deaths. Human papillomavirus-positive patients were less likely to recur and had no VSCC-related deaths. p53-positive patients were 3 times more likely to recur and nearly 7 times more likely to die from vulvar cancer. CONCLUSIONS: Our findings suggest that HPV and the surrogate biomarker p16 indicate a less aggressive type of vulvar cancer. p53 positivity was associated with poor prognosis and significantly increased both recurrence and disease-specific mortality.

Effect of antifreeze protein I in the freezing solution on in vivo-derived sheep embryos.

This study evaluated the effects of different antifreeze protein type I (AFP I) concentrations added to a slow freezing solution in sheep in vivo-derived embryos. Good-quality embryos were allocated into: AFP-free (CONT); 0.1 µg/mL of AFP I (AFP0.1); or 0.5 µg/mL of AFP I (AFP0.5). After thawing, embryos were in vitro cultured (IVC) for 48 h. At 24 h and 48 h of IVC, dead cells and apoptosis, mitochondrial activity, intracellular reactive oxygen species (ROS), and glutathione (GSH) evaluations were performed. At 24 h, evaluated embryos were submitted to RT-qPCR for metabolism (SIRT2, PRDX1, OCT4, CDX2) and quality (AQP3, CDH1, HSP70, BAX, BCL2) genes. The in vitro survival rate was 56% (22/39) for CONT, 60% (32/53) for AFP0.1, and 53% (23/43) for AFP0.5 (p > 0.05). A tendency (p = 0.09) for a higher blastocyst hatching rate was noted in AFP0.1 (62%) compared to AFP0.5 (33%), and both groups were similar to CONT (50%). An increased (p < 0.05) mitochondrial activity at 24 h was observed in AFP0.1 compared to CONT. No differences (p > 0.05) were observed in oxidative stress homeostasis and viability between treatments. A downregulation (p < 0.05) of CDH1 in AFP0.1 and a downregulation of AQP3 in AFP0.5 were observed in comparison to the other groups. An upregulation (p < 0.05) was detected in HSP70 and BCL2 on AFP0.5 compared to AFP0.1 group. The addition of AFP I in slow freezing solution can benefit cryopreserved sheep in vivo-derived embryos, without affecting embryonic survival.

Identifying therapeutic monoclonal antibodies using target protein collision electrophoresis reflex assay to separate the wheat from the chaff.

Monoclonal gammopathies are characterized by the presence of monoclonal immunoglobulins, also known as M-proteins. Therapeutic monoclonal antibodies (t-mAbs) can interfere in laboratory assays used to monitor the state of disease, such as serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). To establish a correct interpretation of IFE, Target protein-Collision Immunofixation Electrophoresis Reflex Assay (T-CIERA) was developed to identify t-mAbs in IFE. Here we demonstrate that T-CIERA is applicable to a wide variety of t-mAbs for which the target protein is commercially available. Moreover, the shift observed was characteristic for each t-mAb, and T-CIERA enabled the identification of multiple t-mAbs sharing a common target protein. Additionally, the lower limit of detection (LLOD) was determined objectively, and T-CIERA demonstrated an adequate LLOD for all tested t-mAbs. Furthermore, T-CIERA was also successfully applied to serum samples obtained from patients receiving daratumumab, isatuximab, elotuzumab, and durvalumab treatment. In conclusion, T-CIERA is a suitable reflex assay for identifying a wide variety of t-mAbs, including those for which no commercial assay is available to deal with their interference. Moreover, CD38-CIERA could serve as an alternative or complementary test to the commercially available Hydrashift assay kits. T-CIERA would enable laboratories without mass spectrometry equipment and expertise in this area to distinguish between drug and disease to improve clinical response monitoring and diagnosis of monoclonal gammopathies.

The coasting time affects the quality of cumulus-oocyte complexes in superstimulated ewes.

We hypothesized that the coasting time may be beneficial to the quality of cumulus-oocyte complexes recovered from live ewes, as reported in cattle. The present study assessed the effect of coasting times on the quantity and quality of cumulus-oocyte complexes (COCs) in sheep. All ewes were subjected to the "Day 0 protocol", followed by an ovarian stimulation (80 mg of pFSH in three decreasing doses), varying only the coasting time [12 (G12), 36 (G36), or 60 h (G60]. In Experiment 1, data regarding follicular population was assessed. In Experiment 2, the COC quality was checked by their morphology, brilliant cresyl blue (BCB) test, evaluation of chromatin condensation pattern, and oocyte diameter. In Experiment 3, genes related to oocyte developmental competence were evaluated in BCB + COCs. The oocytes in the G60 group had more (P < 0.05) large follicles than the other groups and oocytes with a greater diameter than the G12. Oocyte morphology was similar (P > 0.05) among groups, as well as the BCB + COCs quantity. The G60-oocytes presented a better (P < 0.05) configuration of chromatin condensation compared with the other groups and a greater (P < 0.05) gene expression of BMP15, MATER, ZAR1, and PTGS2 compared with G12, and PTGS2 and HAS2 compared with G36 group. In conclusion, 60 h of coasting time positively affects the quality of COCs recovered after subjecting ewes to the "Day 0 protocol" and ovarian superstimulation. Implementing the appropriate coasting time to a given protocol can positively impact the in vitro embryo production outcomes in sheep.

Urinary stone disease prevalence and associations in cystic fibrosis.

Cystic fibrosis (CF) may predispose patients to urinary stone disease (USD), but reported prevalence of USD in patients with CF in previous small studies is variable. To date, analysis of risk factors for USD within the CF population has been limited. We studied 29,396 patients in the Cystic Fibrosis Foundation Patient Registry to calculate age and sex-stratified prevalence of USD. For adult patients, we examined age and multivariable-adjusted cross-sectional associations between demographic and clinical factors, CFTR mutation class, and prevalent USD. Prevalence of USD was 0.4% (95% CI 0.3-0.5%) under age 18 years, 3.1% (2.7-3.6%) at 18-24 years, 6.4% (5.8-7.1%) at 25-34 years, 7.5% (6.5-8.5%) at 35-44 years, and 6.7% (5.8-7.8%) at 45 years and older. Prevalence for women was higher than men at younger (< 45 years) but not older ages (P value for interaction < 0.0005). Multivariable odds of prevalent USD were significantly increased for severe CFTR mutations, OR 1.53 (1.14-2.06), diabetes, OR 1.24 (1.03-1.50), hypertension, OR 1.58 (1.29-1.93), and chronic macrolide therapy, OR 1.27 (1.07-1.52). BMI was not associated with USD. USD prevalence in CF is similar to that in the general population. With the exception of BMI, known risk factors for USD in the general population also appear to be important for patients with CF. We identified several novel associations in CF patients, including greater prevalence of USD in individuals with severe CFTR mutations and among young women.

Reproductive Seasonality Affects In Vitro Embryo Production Outcomes in Adult Goats.

Reproductive seasonality may have a considerable influence on the efficiency of assisted reproductive technologies in seasonal species. This study evaluated the effect of season on cleavage, blastocyst rates and quality of in vitro produced (IVP) goat embryos. In total, 2348 cumulus-oocyte complexes (COCs) were recovered from slaughterhouse ovaries and subjected to the same IVP system throughout 1.5 years (49 replicates). The odds ratio (OR) among seasons was calculated from values of cleavage and blastocyst rates in each season. Cleavage rate was lower (p < 0.05) in spring (anestrus), in comparison with either autumn (peak of breeding season) or summer, while the winter had intermediate values. Furthermore, lower OR of cleavage was observed in spring. Blastocyst formation rate (from initial number of COCs) was higher (p < 0.05) in autumn (52 ± 2.5%) when compared with the other seasons (combined rates: 40 ± 1.9%). Moreover, its OR was higher (p < 0.05) in autumn compared to all other seasons and impaired in the spring compared to winter (OR: 0.54) and summer (OR: 0.48). Embryo hatchability and blastocyst cell number were similar (p > 0.05) among seasons. In conclusion, the breeding season leads to improved oocyte developmental competence, resulting in higher cleavage and blastocyst yield, whereas embryo quality remained similar throughout the years.

Antifreeze proteins for low-temperature preservation in reproductive medicine: A systematic review over the last three decades.

Antifreeze proteins (AFPs) are synthesized by diverse non-mammalian species, allowing them to survive in severely cold environments. Since the 1990s, the scientific literature reports their use for low-temperature preservation of germplasm. The aim of this systematic review was to compile available scientific evidence regarding the use of AFP for low-temperature preservation of several reproductive specimens. Internet databases were consulted using the terms: "antifreeze protein" OR "AFP" OR "antifreeze glycoprotein" OR "AFGP" OR "ice-binding protein" OR "IBP" OR "thermal hysteresis protein" AND "cryopreservation". From 56 articles, 87 experiments testing AFPs in low-temperature preservation of gametes, embryos or reproductive tissues/cells were fully analyzed and outcomes were annotated. A positive outcome was considered as a statistically significant improvement on any parameter evaluated after low-temperature preservation with AFP, whereas a negative outcome included worsening of any evaluated parameter, in comparison to untreated groups or groups treated with a lower concentration of AFP. The findings indicated that research on the use of AFP as a cryoprotectant for reproductive specimens has increased markedly over the past decade. Some experiments reported both positive and negative results, which depended, on AFP concentration in the preservation media. Variation in the outcomes associated with species was also observed. Among the 66 experiments conducted in mammals, 77.3% resulted in positive, and 28.8% in negative outcomes after the use of AFP. In fishes, positive and negative outcomes were observed in 71.4% and 33.3% of 21 experiments, respectively. Most positive outcomes included preserving cell post-warming survival. The beneficial effect of AFP supports its use in cryobiological approaches used in human and veterinary medicines and animal protein industry. Moreover, combination of different AFP types, or AFP with antioxidants, or even the use of AFP-biosimilar, comprise some promising approaches to be further explored in cryopreservation.

In vitro production of small ruminant embryos: latest improvements and further research.

This review presents the latest advances in and main obstacles to the application of invitro embryo production (IVEP) systems in small ruminants. This biotechnology is an extremely important tool for genetic improvement for livestock and is essential for the establishment of other biotechnologies, such as cloning and transgenesis. At present, the IVEP market is almost non-existent for small ruminants, in contrast with the trends observed in cattle. This is probably related to the lower added value of small ruminants, lower commercial demand and fewer qualified professionals interested in this area. Moreover, there are fewer research groups working on small ruminant IVEP than those working with cattle and pigs. The heterogeneity of oocytes collected from growing follicles in live females or from ovaries collected from abattoirs remains a challenge for IVEP dissemination in goats and sheep. Of note, although the logistics of oocyte collection from live small ruminant females are more complex than in the bovine, in general the IVEP outcomes, in terms of blastocyst production, are similar. We anticipate that after appropriate training and repeatable results, the commercial demand for small ruminant invitro -produced embryos may increase.

New records of interaction between Pseudoxenos (Strepsiptera) and the solitary wasp Pachodynerus grandis in Brazil (Hymenoptera, Vespidae, Eumeninae) with an updated worldwide checklist of eumenine host species of Pseudoxenos.

Interactions between Strepsiptera (Pseudoxenos Saunders, 1872) and solitary wasps (Eumeninae) are recorded for the first time in Brazil for Pachodynerus grandis Willink Roig-Alsina, 1998. An updated worldwide checklist of the host species of Eumeninae for Pseudoxenos is provided.

Embryo development is impaired in goats that are treated for hydrometra and subsequently subjected to superovulation.

BACKGROUND: Reproductive efficiency after hydrometra (HD) treatment is usually unsatisfactory. METHODS: To identify mechanisms involved in low reproductive efficiency of HD-treated goats, pluriparous dairy goats treated for HD (n=10, HD) or with no reproductive disorders (n=11, control: CONT) were induced to oestrus and superovulated. Goats were mated with fertile bucks and seven days after oestrus, non-surgical embryo recovery was performed. Embryos were evaluated and gene expression was performed. RESULTS: There were no differences (P>0.05) in sexual behaviour parameters, superovulation response, mean number of retrieved structures and viable embryos between groups; although embryo recovery rate was higher (P=0.01) in CONT group. Structures in delayed stage (8-16 cells) were more frequent (P<0.05) in HD (29 vs 1 per cent) goats, as well as the percentage of advanced embryos was greater (P<0.05) for CONT (59.3 vs 33.3 per cent) goats. However, the expression of genes related to apoptosis (BAX and Bcl-2), trophectoderm differentiation (CDX2) and pluripotency maintenance (NANOG) was not affected (P>0.05) in embryos that reached the morulae and blastocyst stages. CONCLUSION: Although the HD embryos that developed to morula and blastocyst stages showed no change in the expression of genes related to their quality and implantation capacity, overall, embryo development was impaired in HD-treated goats.

Diagnostic-therapeutic cascade revisited: coronary angiography, coronary artery bypass graft surgery, and percutaneous coronary intervention in the modern era.

BACKGROUND: There is wide geographic variation in the use of coronary revascularization in the United States. Rates are closely related to rates of coronary angiography. We assessed the relationship between coronary angiography and coronary artery revascularization by procedure type (coronary artery bypass graft surgery or percutaneous coronary intervention). METHODS AND RESULTS: Using Part B claims for a 20% sample of the Medicare population, we calculated population-based rates of testing and treatment by region, using events identified in Part B claims as the numerator and the total number of Medicare beneficiaries residing in the area as the denominator and adjusting for regional differences in demographic characteristics with the indirect method. Cardiac catheterization rates varied substantially across regions, from 16 to 77 per 1000 Medicare beneficiaries. The relationship between coronary angiography rates and total coronary revascularization rates was strong (R(2)=0.84). However, there was only a modest association between coronary angiography rates and coronary artery bypass graft surgery rates (R(2)=0.41) with the suggestion of a threshold effect. The association between coronary angiography rates and percutaneous coronary intervention rates was strong (R(2)=0.78) and linear. CONCLUSIONS: The diagnostic-therapeutic cascade for coronary artery disease differs by therapeutic intervention. For coronary artery bypass graft surgery, the relationship is modest, and there appears to be a testing threshold beyond which additional tests do not result in additional surgeries. For percutaneous coronary intervention, the relationship is very tight, and no threshold appears to exist. Given the results of recent studies of medical versus invasive management of stable coronary disease, patients living in high-diagnostic-intensity regions may be getting more treatment than they want or need.

Mortality, morbidity, and cardiac surgery in Injection Drug Use (IDU)-associated versus non-IDU infective endocarditis: The need to expand substance use disorder treatment and harm reduction services.

BACKGROUND: The addiction crisis is widespread, and unsafe injection practices among people who inject drugs (PWID) can lead to infective endocarditis. METHODS: A retrospective analysis of adult patients with definite or possible infective endocarditis admitted to a tertiary care center in Portland, Maine was performed over three-year period. Our primary objective was to examine differences in demographics, health characteristics, and health service utilization between injection drug use (IDU)-associated infective endocarditis and non-IDU infective endocarditis. The association between IDU and mortality, morbidity (defined as emergency department visits within 3 months of discharge), and cardiac surgery was examined. Bivariate and multivariate analyses were performed. A subgroup descriptive analysis of PWID was also performed to better examine substance use disorder (SUD) characteristics, treatment with medication for opioid use disorder (MOUD) and health service utilization. RESULTS: One-hundred and seven patients were included in the study, of which 39.2% (n = 42) had IDU-associated infective endocarditis. PWID were more likely to be homeless, uninsured, and lack a primary care provider. PWID were notably younger and had less documented comorbidities, however had similar in-hospital mortality rates (10% vs. 14%, p = 0.30), ED visits (50% vs. 54%, p = 0.70) and cardiac surgery (33% vs. 26%, p = 0.42) compared to those with non-IDU infective endocarditis. Ninety-day mortality was less among PWID (19.0% vs. 36.9%, p = 0.05). IDU was not associated with morbidity (adjusted odds ratio (AOR) 0.73, 95% CI 0.18-3.36), 90-day mortality (AOR 0.72, 95% CI 0.17-3.01), or cardiac surgery (AOR 0.15, 95% CI 0.03-0.69). Ninety-day mortality among PWID who received MOUD was lower (3% vs 15%, p = 0.45), as were ED visits (10% vs. 41%, p = 0.42) compared to those who did not receive MOUD. CONCLUSIONS: Our results highlight existing differences in health characteristics and social determinants of health in people with IDU-associated versus non-IDU infective endocarditis. PWID had less comorbidities and were significantly younger than those with non-IDU infective endocarditis and yet still had similar rates of cardiac surgery, ED visits, and in-hospital mortality. These findings emphasize the need to deliver comprehensive health services, particularly MOUD and other harm reduction services, to this marginalized population.

Number of Circulating CD 73-Expressing Lymphocytes Correlates With Survival After Cardiac Arrest.

Background Patients resuscitated from cardiac arrest ( CA ) have highly variable neurological, circulatory, and systemic ischemia-reperfusion injuries. After the initial hypoxic-ischemic insult, a cascade of immune and inflammatory responses develops and is often fatal. The role of the immune response in pathophysiological characteristics and recovery is not well understood. We studied immune cell activity and its association with outcomes in a cohort of CA survivors. Methods and Results After informed consent, we collected blood samples at intervals over a week after resuscitation from CA . We examined the expression of CD 39 and CD 73 (alias 5'-nucleotidase), production of tumor necrosis factor-α, generation of reactive oxygen species, and secretion of vascular endothelial growth factor by circulating myeloid and lymphoid cells, in comparison to cells obtained from control subjects before coronary artery bypass grafting surgery. The number of circulating total and CD 73-expressing lymphocytes correlated with survival after CA . Incubation of immune cells, obtained from post- CA subjects, with AMP , a substrate for CD 73, resulted in inhibition of tumor necrosis factor-α production and generation of reactive oxygen species. This effect was blocked by adenosine 5'-(α, ß-methylene) diphosphate, a specific inhibitor of CD 73 and ZM 241385, an A2 adenosine receptor antagonist. We also found that AMP -dependent activation of CD 73 induces production of vascular endothelial growth factor. Conclusions CD 73-expressing lymphocytes mediate cellular protection from inflammation after CA through inhibition of proinflammatory activation of myeloid cells and promotion of vascular endothelial growth factor secretion. The contribution of CD 73 lymphocytes in the regulation of acute inflammation and tissue injury after CA warrants further study.

Frequency of stress testing to document ischemia prior to elective percutaneous coronary intervention.

CONTEXT: Guidelines call for documenting ischemia in patients with stable coronary artery disease prior to elective percutaneous coronary intervention (PCI). OBJECTIVE: To determine the frequency and predictors of stress testing prior to elective PCI in a Medicare population. DESIGN, SETTING, AND PATIENTS: Retrospective, observational cohort study using claims data from a 20% random sample of 2004 Medicare fee-for-service beneficiaries aged 65 years or older who had an elective PCI (N = 23 887). MAIN OUTCOME MEASURES: Percentage of patients who underwent stress testing within 90 days prior to elective PCI; variation in stress testing prior to PCI across 306 hospital referral regions; patient, physician, and hospital characteristics that predicted the appropriate use of stress testing prior to elective PCI. RESULTS: In the United States, 44.5% (n = 10 629) of patients underwent stress testing within the 90 days prior to elective PCI. There was wide regional variation among the hospital referral regions with stress test rates ranging from 22.1% to 70.6% (national mean, 44.5%; interquartile range, 39.0%-50.9%). Female sex (adjusted odds ratio [AOR], 0.91; 95% confidence interval [CI], 0.86-0.97), age of 85 years or older (AOR, 0.83; 95% CI, 0.72-0.95), a history of congestive heart failure (AOR, 0.85; 95% CI, 0.79-0.92), and prior cardiac catheterization (AOR, 0.45; 95% CI, 0.38-0.54) were associated with a decreased likelihood of prior stress testing. A history of chest pain (AOR, 1.28; 95% CI, 1.09-1.54) and black race (AOR, 1.26; 95% CI, 1.09-1.46) increased the likelihood of stress testing prior to PCI. Patients treated by physicians performing 150 or more PCIs per year were less likely to have stress testing prior to PCI (AOR, 0.84; 95% CI, 0.77-0.93). No hospital characteristics were associated with receipt of stress testing. CONCLUSION: The majority of Medicare patients with stable coronary artery disease do not have documentation of ischemia by noninvasive testing prior to elective PCI.

Temporal trends in the utilization of diagnostic testing and treatments for cardiovascular disease in the United States, 1993-2001.

BACKGROUND: Rates of invasive testing and treatment for coronary artery disease have increased over time. Less is known about trends in the utilization of noninvasive cardiac testing for coronary artery disease. The objective of this study was 2-fold: to explore temporal trends in the utilization of noninvasive and invasive cardiac services in relation to changes in the prevalence of cardiac disease, and to examine whether temporal increases have been targeted to potentially underserved populations. METHODS AND RESULTS: We performed an annual cross-sectional population-based study of Medicare patients from 1993 to 2001. We identified stress testing, cardiac catheterization, and revascularization procedures, as well as hospitalizations for acute myocardial infarction, during each year and calculated population-based rates for each using the total fee-for-service Medicare population as the denominator and adjusting for age, gender, and race. We observed marked growth in the utilization rates of cardiac services over time, with relative rates nearly doubling for most services. Acute myocardial infarction hospitalization rates have remained stable over the study period. Although rates of all procedures except coronary artery bypass increased in all subgroups, differences in rates of cardiac testing and treatment between nonblack men and other subgroups persisted over time. CONCLUSIONS: Temporal increases in the use of noninvasive and invasive cardiac services are not explained by changes in disease prevalence and have not succeeded in narrowing preexisting treatment differences by gender and race. Such increases, although conferring benefit for some, may expose others to risk and cost without benefit.

Valproate for agitation in critically ill patients: A retrospective study.

PURPOSE: The purpose was to describe the use of valproate therapy for agitation in critically ill patients, examine its safety, and describe its relationship with agitation and delirium. MATERIALS AND METHODS: This retrospective cohort study evaluated critically ill adults treated with valproate for agitation from December 2012 through February 2015. Information on valproate prescribing practices and safety was collected. Incidence of agitation, delirium, and concomitant psychoactive medication use was compared between valproate day 1 and valproate day 3. Concomitant psychoactive medication use was analyzed using mixed models. RESULTS: Fifty-three patients were evaluated. The median day of valproate therapy initiation was ICU day 7, and it was continued for a median of 7 days. The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of agitation (96% vs 61%, P < .0001) and delirium (68% vs 49%, P = .012) significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models analyses, valproate therapy was associated with reduced fentanyl equivalents (-185 µg/d, P = .0003) and lorazepam equivalents (-2.1 mg/d, P = .0004). Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed adverse effects. CONCLUSIONS: Valproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation.

Should volume standards for cardiovascular surgery focus only on high-risk patients?

BACKGROUND: Payers and policy makers are attempting to concentrate selected cardiovascular procedures in high-volume centers. A recent analysis of coronary artery bypass grafting (CABG), however, suggests that volume-based referral initiatives should focus only on high-risk patients. METHODS AND RESULTS: Using the national Medicare database (1994 to 1999), we studied the operative mortality in patients undergoing 4 cardiovascular procedures (CABG, aortic valve replacement, mitral valve replacement, and elective abdominal aortic aneurysm repair). We defined 2 categories of patient risk: high-risk (patients in the highest 25th percentile of predicted risk on the basis of a logistic regression model) and low-risk (patients in the lowest 75th percentile). We then compared operative mortality in patients undergoing surgery at very-high volume hospitals (VHVH, highest 20th percentile of procedure volume) and very-low volume hospitals (VLVH, lowest 20th percentile of procedure volume). Absolute differences in operative mortality between VLVH and VHVH were somewhat larger in high-risk patients. However, volume-related differences in mortality were also significant for low-risk patients undergoing one of the 4 procedures. In relative terms, the effect of hospital volume was similar in both high- and low-risk patients. For high- and low-risk patients, the relative risk (RR) of mortality between VHVH and VLVH were nearly equal for CABG (RR=0.78 for low-risk patients, RR=0.77 for high risk patients), aortic valve replacement (0.73 versus 0.76), mitral valve replacement (0.73 versus 0.74), and abdominal aortic aneurysm repair (0.51 versus 0.54). CONCLUSIONS: Although the merits of volume-based referral initiatives can be debated on many grounds, there seems to be little rationale for restricting these initiatives to high-risk patients.

Operator volume and outcomes in 12,998 percutaneous coronary interventions. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to determine whether there is a relation between operator volume and outcomes for percutaneous coronary interventions (PCIs). BACKGROUND: A 1993 American College of Cardiology/American Heart Association task force stated that cardiologists should perform > or = 75 procedures/year to maintain competency in PCIs; however, there were limited data available to support this statement. METHODS: Data were collected from 1990 through 1993 on 12,988 PCIs (12,118 consecutive hospital admissions) performed by 31 cardiologists at two hospitals in New Hampshire and two in Maine and one hospital in Massachusetts supporting these procedures. Operators were categorized into terciles based on annualized volume of procedures. Univariate and multivariate regression analyses were used to control for case-mix. Successful outcomes included angiographic success (all lesions attempted dilated to < 50% residual stenosis) and clinical success (at least one lesion dilated to < 50% residual stenosis and no adverse outcomes). In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction (MI) and death. RESULTS: After adjustment for case-mix, higher angiographic (low, middle and high terciles: 84.7%, 86.1% and 90.3%, p-trend 0.006) and clinical success rates (85.8%, 88.0% and 90.7%, p-trend 0.025), with fewer referrals to CABG (4.54%, 3.75% and 2.49%, p-trend <0.001), were seen as operator volume increased. There was a trend toward higher MI rates for high volume operators (2.00%, 1.98% and 2.57%, p-trend 0.06); all terciles had similar in-hospital mortality rates (1.09%, 0.96% and 1.05%, p-trend 0.8). CONCLUSIONS: There is a significant relation between operator volume and outcomes in PCIs. Efforts should be directed toward understanding why high volume operators are more successful and encounter fewer adverse outcomes.