Levonorgestrel vs. Copper Intrauterine Devices for Emergency Contraception.

BACKGROUND: In the United States, more intrauterine device (IUD) users select levonorgestrel IUDs than copper IUDs for long-term contraception. Currently, clinicians offer only copper IUDs for emergency contraception because data are lacking on the efficacy of the levonorgestrel IUD for this purpose. METHODS: This randomized noninferiority trial, in which participants were unaware of the group assignments, was conducted at six clinics in Utah and included women who sought emergency contraception after at least one episode of unprotected intercourse within 5 days before presentation and agreed to placement of an IUD. We randomly assigned participants in a 1:1 ratio to receive a levonorgestrel 52-mg IUD or a copper T380A IUD. The primary outcome was a positive urine pregnancy test 1 month after IUD insertion. When a 1-month urine pregnancy test was unavailable, we used survey and health record data to determine pregnancy status. The prespecified noninferiority margin was 2.5 percentage points. RESULTS: Among the 355 participants randomly assigned to receive levonorgestrel IUDs and 356 assigned to receive copper IUDs, 317 and 321, respectively, received the interventions and provided 1-month outcome data. Of these, 290 in the levonorgestrel group and 300 in the copper IUD group had a 1-month urine pregnancy test. In the modified intention-to-treat and per-protocol analyses, pregnancy rates were 1 in 317 (0.3%; 95% confidence interval [CI], 0.01 to 1.7) in the levonorgestrel group and 0 in 321 (0%; 95% CI, 0 to 1.1) in the copper IUD group; the between-group absolute difference in both analyses was 0.3 percentage points (95% CI, -0.9 to 1.8), consistent with the noninferiority of the levonorgestrel IUD to the copper IUD. Adverse events resulting in participants seeking medical care in the first month after IUD placement occurred in 5.2% of participants in the levonorgestrel IUD group and 4.9% of those in the copper IUD group. CONCLUSIONS: The levonorgestrel IUD was noninferior to the copper IUD for emergency contraception. (Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT02175030.).

Self-reporting of Conflicts of Interest by Ophthalmology Researchers Compared with the Open Payments Database Industry Reports.

PURPOSE: To evaluate the completeness of conflict-of-interest self-reporting by ophthalmology researchers and to assess factors associated with self-reporting. DESIGN: Cross-sectional observational study. PARTICIPANTS: We evaluated articles published between January and June 2017 in Ophthalmology, JAMA Ophthalmology, the American Journal of Ophthalmology, and Investigative Ophthalmology and Visual Science. To assess more accurately the cases in which an author published multiple articles, we defined a unit of analysis, authorship, for which each author of each article is a unique data point. To enable comparison with the Open Payments Database (OPD), we only included United States physician authorships. METHODS: For each authorship, we defined self-reported relationships as the companies listed in the article's conflict-of-interest disclosures. Based on journal policies, we defined OPD-reported relationships as the list of companies that reported payments to the author within 36 months before submission. MAIN OUTCOME MEASURES: For each authorship, we assessed the proportion of OPD-reported relationships that were self-reported. The primary measurement was the proportion of authorships reporting none of their OPD-reported relationships. RESULTS: Of the 660 total authorships (486 unique authors), 413 authorships (63%) reported none of their OPD-reported relationships, 112 (17%) reported some of them, 9 (1%) reported all of them, and 126 (19%) had 0 relationships. The proportion of authorships reporting none of their relationships did not differ significantly between journals that required reporting of all relationships compared with journals that required reporting only of relevant relationships (adjusted percentage, 61.4% vs. 64.3%; P = 0.46). Authorships with more dollars received during the reporting period showed higher rates of self-reporting (P < 0.001). CONCLUSIONS: Even among journals that required complete reporting, self-reporting was low compared with an industry-maintained database of financial relationships. Deficiencies in reporting may undermine confidence in self-reporting and may compromise the transparency that is needed to interpret research results fairly. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Antitachycardia pacing at the His bundle is safer than conventional right ventricular antitachycardia pacing in a canine myocardial ischemic injury model.

INTRODUCTION: Antitachycardia pacing (ATP) is used to terminate ventricular tachycardia (VT) by delivering rapid, low energy pacing to the right ventricle (RV). Unfortunately, ATP is not effective against all VT episodes and can result in adverse outcomes, such as VT acceleration and degeneration into ventricular fibrillation (VF). Improving ATP is therefore desirable. Our objective was to compare the efficacy and safety of ATP delivered at the His bundle to traditional ATP. METHODS: Six dogs were anesthetized and pacing leads were implanted in the RV and His bundle. The left anterior descending artery was occluded for 2 h to create an ischemic injury. In a study 4-7 days later, a 128-electrode sock was placed snugly around the ventricles and VT was induced using rapid pacing. ATP was delivered from either the His bundle or RV lead, then attempted at the other location if unsuccessful. Success rates and instances of VT acceleration and degeneration into VF were calculated. RESULTS: We induced 83 runs of VT and attempted ATP 128 times. RV ATP was successful in 36% of attempts; His ATP was successful in 38% of attempts. RV ATP resulted in significantly more adverse outcomes. RV and His ATP induced VT acceleration in 9% and 3% of trains, respectively, and induced degeneration into VF in 5% and 1% of trains, respectively. CONCLUSION: His bundle ATP is safer, but not significantly more effective, than RV ATP.

Retinopathy of prematurity protection conferred by uteroplacental insufficiency through erythropoietin signaling in an experimental Murine Model.

BACKGROUND: Recent clinical studies suggest that preeclampsia, characterized by uteroplacental insufficiency (UPI) and infant intrauterine growth restriction (IUGR), may be protective against retinopathy of prematurity (ROP) in preterm infants. Experimental models of UPI/IUGR have found an association of erythropoietin (EPO) with less severe oxygen-induced retinopathy (OIR); however, it is unclear if EPO/EPO receptor (EPOR) signaling was involved. We hypothesized that maternal UPI and resultant infant IUGR would protect against features of ROP through EPO/EPOR signaling. METHODS: We compared transgenic mice with hypoactive EPOR signaling (hWtEPOR) to littermate wild-type mice (mWtEpoR) in a novel combined model of IUGR and ROP. Thromboxane A2 (TXA2) was infused into pregnant C57Bl/6J dams to produce UPI/IUGR; postnatal pups and their foster dams were subjected to a murine OIR model. RESULTS: Following hyperoxia, hematocrits were similar between littermate wild-type (mWtEpoR) TXA2/OIR and vehicle/OIR pups. mWtEpoR TXA2/OIR had increased serum EPO, retinal EPO and VEGF, and decreased avascular retinal area (AVA) compared to vehicle/OIR pups. In comparison to the mWtEpoR TXA2/OIR pups, AVA was not reduced in hWtEPOR TXA2/OIR pups. CONCLUSION: Our findings provide biologic evidence that UPI/OIR-induced endogenous EPOR signaling confers protection against hyperoxia-induced vascular damage that may be related to pathophysiology in ROP. IMPACT: Maternal preeclampsia and infant growth restriction confer retinovascular protection against high oxygen-induced damage through endogenous erythropoietin signaling.

Longitudinal analysis of cigar use patterns among US youth and adults, 2013-2019.

BACKGROUND: Cigars are available in a range of pack quantities, which contrasts regulations requiring cigarettes to be sold in packs of 20 or greater. Smaller packages may be associated with increases in initiation while larger packs may lead consumers to smoke more. The purpose of this study was to inform pack quantity regulations by examining whether usual cigar pack quantity purchased was associated with use, initiation, and discontinuation among youth and adults for four cigar types: premium cigars, large cigars, cigarillos, and filtered cigars. METHODS: We analyzed waves 1-5 (2013-2019) of the adult and waves 2-5 (2014-2019) of the youth Population Assessment of Tobacco and Health (PATH) Study. Samples included those responding to the item on pack quantity and providing data at all waves (adults: premium cigars [N = 536], large cigars [N = 1,272], cigarillos [N = 3,504], filtered cigars [N = 1,281]; youth: premium cigars [N = 55], large cigars [N = 217], cigarillos [N = 1514], filtered cigars [N = 266]). Generalized estimating equation models examined the population-averaged effects of pack quantity on cigar use, initiation, and discontinuation. RESULTS: Adult pack quantity was positively associated with the days used per month for premium cigars (b: 0.23, 95% CI: 0.11, 0.34), large cigars (b: 0.17, 95% CI: 0.08, 0.25), cigarillos (b: 0.12, 95% CI: 0.003, 0.24), and filtered cigars (b: 0.07, 95% CI: 0.04, 0.10), and positively associated with amount smoked per day for all cigar types. Youth pack quantity was positively associated with days used per month for premium cigars (b: 0.88, 95% CI: 0.33, 1.43), large cigars (b: 0.79, 95% CI: 0.43, 1.15), and cigarillos (b: 0.17, 95% CI: 0.01, 0.34). Adult initiation was associated with pack quantity for filtered cigars (b: -2.22, 95% CI: -4.29, -0.13), as those who initiated purchased smaller pack quantities compared to those who did not initiate that wave. Pack quantity was not associated with discontinuation for adults or youth. CONCLUSIONS: Cigar use increased as usual pack quantity purchased increased across cigar types for youth and adults. Small increases in pack quantity (e.g., one additional cigar) are likely to result in consuming less than one additional day per month, though larger increases (e.g., 10 additional cigars per pack) may result in greater use.

7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence and Fibrosis of Choroidal Neovascularization via IQGAP1 Phosphorylation-Dependent Signaling.

Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, ß-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells also developed senescence-associated secretory phenotype (SASP) determined by increased IL-1ß, IL-6, and VEGF through mTOR-mediated NF-κB signaling, and reduced barrier integrity that was restored by the mTOR inhibitor, rapamycin. 7KC-induced p21, VEGF, and IL-1ß were inhibited by an inhibitor of protein kinase C. The kinase regulates IQGAP1 serine phosphorylation. Furthermore, after 7KC injection and laser-induced injury, mice with an IQGAP1 serine 1441-point mutation had significantly reduced fibrosis compared to littermate control mice. Our results provide evidence that age-related accumulation of 7KC in drusen mediates senescence and SASP in RPE, and IQGAP1 serine phosphorylation is important in causing fibrosis in AMD.

Increased Incidence of Pseudotumor Cerebri Syndrome Among Users of Tetracycline Antibiotics.

BACKGROUND: To determine whether the use of a tetracycline-class antibiotic is associated with an increased risk of developing pseudotumor cerebri syndrome (PTCS). METHODS: We identified patients in the University of Utah Health system who were prescribed a tetracycline-class antibiotic and determined what percentage of those individuals were subsequently diagnosed with PTCS secondary to tetracycline use. We compared this calculation to the number of patients with PTCS unrelated to tetracycline use. RESULTS: Between 2007 and 2014, a total of 960 patients in the University system between the ages of 12 and 50 were prescribed a tetracycline antibiotic. Among those, 45 were diagnosed with tetracycline-induced PTCS. We estimate the incidence of tetracycline-induced PTCS to be 63.9 per 100,000 person-years. By comparison, the incidence of idiopathic intracranial hypertension (IIH) is estimated to be less than one per 100,000 person-years (Calculated Risk Ratio = 178). CONCLUSIONS: Although a causative link between tetracycline use and pseudotumor cerebri has yet to be firmly established, our study suggests that the incidence of pseudotumor cerebri among tetracycline users is significantly higher than the incidence of IIH in the general population.

Breastfeeding Attitudes and Practices in a Rural Utah Navajo Community.

OBJECTIVES: Despite known health benefits of breastfeeding, the Navajo have low reported frequency of breastfeeding initiation and support. We evaluated breastfeeding frequencies and practices in the predominately Navajo community of rural San Juan County, Utah, to identify factors that affect breastfeeding decisions and duration. METHODS: We performed retrospective chart review for 135 infants aged 0 to 12 months, and surveys of 85 mothers of infants aged 0 to 2 years, and eight primary care providers. We characterized demographic factors using counts/percentages and medians/inter-quartile ranges, and compared mothers who breastfed for 6 months or less versus greater than 6 months. RESULTS: In 96 infants with complete feeding documentation, 86 infants (90%) received some breast milk and 36 infants (38%) were exclusively breastfed at age 2 months. In 67 infants with complete feeding documentation at ≥ 6 months, 22 infants (33%) were exclusively breastfed 6 months. Most mothers knew about breastfeeding benefits. In 56 mothers whose infants were aged ≥ 6 months at the time of the survey, breastfeeding for more than 6 months had been planned by 44 mothers (79%) but performed by only 29 mothers (52%). Mothers who breastfed for > 6 months were more likely to have been influenced by WIC and less likely to have introduced formula at an early age. Barriers to breastfeeding included maternal pain, latch difficulties, and concerns about inadequate milk supply. Primary care providers reported limited confidence in providing breastfeeding support but would support telehealth-driven interventions. CONCLUSIONS FOR PRACTICE: Practical, culturally sensitive interventions, including telehealth and improved provider education, may improve breastfeeding outcomes and community health in this underserved population.

Noninvasive Urine Oxygen Monitoring and the Risk of Acute Kidney Injury in Cardiac Surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiac surgery. An intraoperative monitor of kidney perfusion is needed to identify patients at risk for AKI. The authors created a noninvasive urinary oximeter that provides continuous measurements of urinary oxygen partial pressure and instantaneous urine flow. They hypothesized that intraoperative urinary oxygen partial pressure measurements are feasible with this prototype device and that low urinary oxygen partial pressure during cardiac surgery is associated with the subsequent development of AKI. METHODS: This was a prospective observational pilot study. Continuous urinary oxygen partial pressure and instantaneous urine flow were measured in 91 patients undergoing cardiac surgery using a novel device placed between the urinary catheter and collecting bag. Data were collected throughout the surgery and for 24 h postoperatively. Clinicians were blinded to the intraoperative urinary oxygen partial pressure and instantaneous flow data. Patients were then followed postoperatively, and the incidence of AKI was compared to urinary oxygen partial pressure measurements. RESULTS: Intraoperative urinary oxygen partial pressure measurements were feasible in 86/91 (95%) of patients. When urinary oxygen partial pressure data were filtered for valid urine flows greater than 0.5 ml · kg-1 · h-1, then 70/86 (81%) and 77/86 (90%) of patients in the cardiopulmonary bypass (CPB) and post-CPB periods, respectively, were included in the analysis. Mean urinary oxygen partial pressure in the post-CPB period was significantly lower in patients who subsequently developed AKI than in those who did not (mean difference, 6 mmHg; 95% CI, 0 to 11; P = 0.038). In a multivariable analysis, mean urinary oxygen partial pressure during the post-CPB period remained an independent risk factor for AKI (relative risk, 0.82; 95% CI, 0.71 to 0.95; P = 0.009 for every 10-mmHg increase in mean urinary oxygen partial pressure). CONCLUSIONS: Low urinary oxygen partial pressures after CPB may be associated with the subsequent development of AKI after cardiac surgery.

Patient Willingness to Accept Antibiotic Side Effects to Reduce Surgical Site Infection After Colorectal Surgery.

BACKGROUND: Mechanical bowel preparation with antibiotics is associated with decreased surgical site infections (SSI) after colorectal surgery. However, antibiotics have side effects, such as vomiting. It is unknown how patient willingness to take antibiotics is affected by side effect severity. MATERIALS AND METHODS: This was a single-center study of 86 patients (37 undergoing colorectal surgery) using a modified standard gamble technique. We presented patients with four hypothetical scenarios, holding SSI reduction constant and varying antibiotic side effect severity. Patients reported willingness to take antibiotics using a scale from 0 to 100. Patients also reported the maximum level of side effects they would accept. We examined the association between side effect severity and willingness to take antibiotics with a multivariable mixed-effects regression model and investigated differences in surgical and nonsurgical patients. RESULTS: After adjusting for age, sex, and patient type, willingness scores decreased with increasing side effect severity. No side effects: 92 (CI 86,99), mild: 83 (CI 76,90), moderate: 76 (CI 69,83), and severe: 46 (CI 38,52), P < 0.001. Surgical patients were more willing to take antibiotics at all severity levels compared with nonsurgical patients, P < 0.001. Surgical (57%) and nonsurgical (58%) patients reported that they would accept moderate side effects. Patients with prior SSI (n = 5) would take antibiotics regardless of side effect severity. CONCLUSIONS: Increasing antibiotic side effect severity is associated with decreased willingness to take antibiotics during bowel preparation, despite a reduction in SSI. Adherence may be improved with strategies that increase patient education and decrease side effects during bowel preparation.

Intraoperative Urinary Biomarkers and Acute Kidney Injury After Cardiac Surgery.

OBJECTIVES: To evaluate the association of intraoperative urinary biomarker excretion during cardiac surgery and the subsequent development of acute kidney injury (AKI). DESIGN: Prospective, nonrandomized, observational study. SETTING: Single tertiary-level, university-affiliated hospital. PARTICIPANTS: Ninety patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urinary samples were collected every 30 minutes intraoperatively and then at four, 12, and 24 hours after CPB. Samples were measured for interleukin 18 (IL-18), kidney injury molecule-1 (KIM1), and creatinine concentrations. Urinary biomarker excretion (raw and indexed to creatinine) for four intraoperative and three postoperative points were compared between patients with and those without subsequent AKI defined by increased serum creatinine concentration ≥0.3 mg/dL within the first 48 hours or ≥1.5 times baseline within seven days. Raw and indexed median IL-18 values were similar between AKI groups at all intraoperative points, but became significantly different at 12 hours after CPB. Raw and indexed median KIM1 values were significantly different between AKI groups at multiple intraoperative points and at four and 12 hours after CPB. During intraoperative and postoperative points, patients in the fourth quartile of KIM1 excretion had greater AKI incidence and longer intensive care and hospital lengths of stay than those in the first quartile. Only postoperatively did the differences in these outcomes between the fourth and first quartile of IL-18 excretion occur. CONCLUSIONS: Intraoperative KIM1 but not IL-18 excretion was associated with postoperative development of AKI.

The effect of an electronic medical record intervention on hydroxychloroquine prescribing habits and surveyed providers' opinions of the 2016 American Academy of Ophthalmology guidelines in the rheumatology and dermatology practices of an academic institutionle.

BACKGROUND: Retinal toxicity is a rare adverse event related to the use of hydroxychloroquine (HCQ). To address this, in 2016, the American Academy of Ophthalmology (AAO) issued guidelines recommending that HCQ not exceed 5 mg/kg/day. We analyzed HCQ prescribing habits at our institution, compared to these guidelines, and used surveys to determine the opinions on these guidelines. We then introduced, in a prospective and non-controlled study, a clinical decision support (CDS) tool into the electronic medical record (EMR) to study how this intervention might affect adherence with or opinions on these guidelines. METHODS: Data were collected pre-intervention (June 2017-January 2019) and post-intervention (March 2019-April 2020). In January 2019 we released our CDS tool. Results were analyzed using descriptive statistics for demographic data and Fisher's exact tests for comparisons of proportions between groups. RESULTS: Pre-intervention, we reviewed 1128 rheumatology charts and 282 dermatology charts. 31.0 and 39.7% respectively (32.8% combined) were prescribed HCQ > 5 .0 mg/kg/day. Post-intervention, we reviewed 1161 rheumatology charts and 110 dermatology charts. 23.0 and 25.5% respectively (23.2% combined) were prescribed HCQ > 5.0 mg/kg/day. Post-intervention, 9.6% fewer patients were prescribed HCQ > 5 mg/kg/day (P < .001). Pre-intervention, we compiled 18 rheumatology surveys and 12 dermatology surveys. Post-intervention, we compiled 16 rheumatology surveys and 12 dermatology surveys. Post-intervention, fewer rheumatologists incorrectly described the AAO weight-based guidelines. Combined, there was an overall reduction but not of statistical significance (P = .47). The majority of providers surveyed believed that the CDS tool was useful (72.2%). CONCLUSIONS: At our academic institution, there remains unfamiliarity with and hesitation to comply with the 2016 AAO guidelines. Prescribed doses often exceed what is recommended in these guidelines. A CDS tool can improve adherence with these guidelines and might improve providers' familiarity with these guidelines.

Transient recovery of epicardial and torso ST-segment ischemic signals during cardiac stress tests: A possible physiological mechanism.

BACKGROUND: Acute myocardial ischemia has several characteristic ECG findings, including clinically detectable ST-segment deviations. However, the sensitivity and specificity of diagnosis based on ST-segment changes are low. Furthermore, ST-segment deviations have been shown to be transient and spontaneously recover without any indication the ischemic event has subsided. OBJECTIVE: Assess the transient recovery of ST-segment deviations on remote recording electrodes during a partial occlusion cardiac stress test and compare them to intramyocardial ST-segment deviations. METHODS: We used a previously validated porcine experimental model of acute myocardial ischemia with controllable ischemic load and simultaneous electrical measurements within the heart wall, on the epicardial surface, and on the torso surface. Simulated cardiac stress tests were induced by occluding a coronary artery while simultaneously pacing rapidly or infusing dobutamine to stimulate cardiac function. Postexperimental imaging created anatomical models for data visualization and quantification. Markers of ischemia were identified as deviations in the potentials measured at 40% of the ST-segment. Intramural cardiac conduction speed was also determined using the inverse gradient method. We assessed changes in intramyocardial ischemic volume proportion, conduction speed, clinical presence of ischemia on remote recording arrays, and regional changes to intramyocardial ischemia. We defined the peak deviation response time as the time interval after onset of ischemia at which maximum ST-segment deviation was achieved, and ST-recovery time was the interval when ST deviation returned to below thresholded of ST elevation. RESULTS: In both epicardial and torso recordings, the peak ST-segment deviation response time was 4.9±1.1 min and the ST-recovery time was approximately 7.9±2.5 min, both well before the termination of the ischemic stress. At peak response time, conduction speed was reduced by 50% and returned to near baseline at ST-recovery. The overall ischemic volume proportion initially increased, on average, to 37% at peak response time; however, it recovered to only 30% at the ST-recovery time. By contrast, the subepicardial region of the myocardial wall showed 40% ischemic volume at peak response time and recovered much more strongly to 25% as epicardial ST-segment deviations returned to baseline. CONCLUSION: Our data show that remote ischemic signal recovery correlates with a recovery of the subepicardial myocardium, whereas subendocardial ischemic development persists.

Pharmacological and simulated exercise cardiac stress tests produce different ischemic signatures in high-resolution experimental mapping studies.

OBJECTIVE: Test the hypothesis that exercise and pharmacological cardiac stressors create different electrical ischemic signatures. INTRODUCTION: Current clinical stress tests for detecting ischemia lack sensitivity and specificity. One unexplored source of the poor detection is whether pharmacological stimulation and regulated exercise produce identical cardiac stress. METHODS: We used a porcine model of acute myocardial ischemia in which animals were instrumented with transmural plunge-needle electrodes, an epicardial sock array, and torso arrays to simultaneously measure cardiac electrical signals within the heart wall, the epicardial surface, and the torso surface, respectively. Ischemic stress via simulated exercise and pharmacological stimulation were created with rapid electrical pacing and dobutamine infusion, respectively, and mimicked clinical stress tests of five 3-minute stages. Perfusion to the myocardium was regulated by a hydraulic occluder around the left anterior descending coronary artery. Ischemia was measured as deflections to the ST-segment on ECGs and electrograms. RESULTS: Across eight experiments with 30 (14 simulated exercise and 16 dobutamine) ischemic interventions, the spatial correlations between exercise and pharmacological stress diverged at stage three or four during interventions (p<0.05). We found more detectable ST-segment changes on the epicardial surface during simulated exercise than with dobutamine (p<0.05). The intramyocardial ischemia formed during simulated exercise had larger ST40 potential gradient magnitudes (p<0.05). CONCLUSION: We found significant differences on the epicardium between cardiac stress types using our experimental model, which became more pronounced at the end stages of each test. A possible mechanism for these differences was the larger ST40 potential gradient magnitudes within the myocardium during exercise. The presence of microvascular dysfunction during exercise and its absence during dobutamine stress may explain these differences.

A validated prediction score for having two or more embryos for cryopreservation following freeze-all IVF cycles: an analysis utilizing SART CORS database.

PURPOSE: To develop and validate a prediction score for having 2 or more embryos cryopreserved following an IVF cycle without a fresh transfer such that an embryo selection method may be applicable. We also developed a counseling tool on the probability of not having any embryos following an IVF cycle without a fresh transfer. METHODS: We split the data into a development set and a validation set by region within the USA using a coin flip approach and subsequently performed a logistic regression model to identify factors most predictive of cryopreservation of 2 or more embryos in the development set. This model was validated in the validation set. Subsequently, a clinical prediction score was derived using the model coefficients and the predictive accuracy measured with the concordance (c) statistic. RESULTS: A total of 31,537 potential freeze-all cycles were reported to the Society for Assisted Reproductive Technology in 2014. Of these, 57.87% produced and cryopreserved two or more embryos. We identified that age, AMH, and the number of eggs retrieved were the most significant predictors of having 2 or more embryos cryopreserved with a validated c-statistic of 0.84 (95% CI: 0.83 to 0.85). A clinical prediction score was derived from the model. 28.9% of freeze-all cycles had no embryos created from the IVF cycle despite a cycle start and an egg retrieval. The number of eggs retrieved was the most significant predictor of having no embryos available for a transfer, with a c-statistic of 0.80 when modeled as the only predictor variable. CONCLUSION: We derived counseling tools with acceptable discrimination for use in clinical practice (c-statistics > 0.7). Our study further suggests that the number of eggs retrieved from an IVF cycle is most predictive of having 2 or more embryos cryopreserved and not having any embryos after an IVF cycle, suggesting that clinicians should strive to optimize oocyte yield especially in poor prognosis patients. The probability of having two more embryos cryopreserved in a freeze-all IVF cycle such that an embryo selection method is applicable can be predicted with acceptable precision prior to the IVF cycle and excellent precision following egg retrieval using the prediction score.

County-level Variation in Use of Surgery and Cancer-specific Survival for Stage I-II Pancreatic Adenocarcinoma.

OBJECTIVE: The aim of the study was to describe county-level variation in use of surgery for stage I-II pancreatic ductal adenocarcinoma (PDAC) and the association between county surgery rates and cancer-specific survival (CSS). BACKGROUND: The degree of small geographic area variation in use of surgery for stage I-II PDAC and the association between area surgery rates and CSS remain incompletely defined. METHODS: This is a retrospective cohort study of patients aged 18 to 80 years in the 2007 to 2015 Surveillance, Epidemiology, and End Results database with stage I-II PDAC without contraindications to surgery or refusal. Multilevel models were used to characterize county-level variation in use of surgery and CSS. County-specific risk- and reliability-adjusted surgery rates and CSS rates were calculated. RESULTS: Of 18,100 patients living in 581 counties, 10,944 (60.5%) underwent surgery. Adjusted county-specific surgery rates varied 1.5-fold from 49.9% to 74.6%. Median CSS increased in a graded fashion from 13 months [interquartile range (IQR) 13-14] in counties with surgery rates of 49.9% to 56.9% to 18 months (IQR 17-19) in counties with surgery rates of 68.0% to 74.6%. Results were similar in multivariable analyses. Adjusted county 18-month CSS rates varied 1.6-fold from 32.7% to 53.7%. Adjusted county surgery and 18-month CSS rates were correlated (r = 0.54; P < 0.001) and county surgery rates explained approximately half of county-level variation in CSS. Only 18 (3.1%) counties had adjusted surgery rates of 68.0% to 74.6%, which was associated with the longest CSS. CONCLUSIONS: County-specific rates of surgery varied substantially, and patients living in areas with higher surgery rates lived longer. These data suggest that increasing use of surgery in stage I-II PDAC could lead to improvements in survival.

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

OBJECTIVE: To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. BACKGROUND: Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. METHODS: Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. RESULTS: Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. CONCLUSIONS: Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

Double-Blind Placebo-Controlled Study of Rifaximin and Lactulose Hydrogen Breath Test in Gulf War Veterans with Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) occurs in up to 33% of Gulf War (GW) Veterans. Alterations in gut microflora including small intestinal bacterial overgrowth (SIBO) during deployment may play a role in development of IBS. Rifaximin is a minimally absorbed antibiotic speculated to improve IBS symptoms, in part, by restoring normal gut microflora. The aim of this study was to compare rifaximin to placebo on IBS symptoms and quality of life (QOL) in GW Veterans with IBS without constipation. METHODS: A double-blind, placebo-controlled study was performed. One hundred and twenty-two GW Veterans with IBS (Rome III) from our database and referral to gastroenterology and internal medicine clinics were screened. After a 2-week run-in period, 50 patients were randomized (1:1) to receive either rifaximin 550 gm or placebo twice daily for 2 weeks in a double-blind study. Patients were advised not to change their diet or medications during the study. The symptoms assessed were: (1) stool frequency, (2) stool consistency (Bristol stool scale, 1-7, very hard to watery), (3) urgency (1 = yes/0 = no daily for 7 days), (4) severity of abdominal pain (0-4, none to severe), (5) severity of bloating (1-4, none to severe), and (6) global improvement scale (1-7, substantially worse to substantially improved). These were recorded for 7 consecutive days and then averaged across the 7 days, to generate a continuous variable. The symptom data were compared after 2 weeks of treatment. QOL was assessed using IBS-QOL. The lactulose hydrogen breath test (LHBT) was performed at baseline and after 2 weeks of treatment. RESULTS: Fifty Veterans were randomized to receive treatment; 3 withdrew and 3 were lost to follow-up. Data were analyzed from 44 patients (38 men, 6 women, median age 52, range 33-77 years). Rifaximin was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all P ≥ 0.25) or QOL (all P ≥ 0.26). Normalization of SIBO by LHBT was not different between rifaximin- and placebo-treated Veterans (7 vs. 22%, P = 0. 54). CONCLUSION: Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS.

Opioid Prescribing Patterns After Micrographic Surgery: A Follow-up Retrospective Chart Review.

BACKGROUND: The abuse of opioids has reached epidemic proportions in the United States, and leftover medications are a primary source for nonmedical pain relievers. A past study at the University of Utah showed that micrographic surgeons were likely overprescribing opioids, with 35% of patients receiving a postoperative prescription. OBJECTIVE: To examine the current opioid prescribing habits of the micrographic surgeons at the University of Utah compared with those in 2010. METHODS: Retrospective chart review of the patient records of 4 micrographic surgeons between February and May 2017. RESULTS: Four hundred patient visits were reviewed. An opioid prescription was provided after 12% of encounters, 23% lower than in 2010 (p = .004). Younger patient age, increased number of stages and defect size, repair of the defect, and particular surgeons predicted opioid prescription. CONCLUSION: The percentage of patients who received an opioid prescription after undergoing micrographic surgery at the University of Utah decreased from 35% in 2010 to 12% in 2017. Reports of the minimal need of opioids after micrographic surgery, the authors' past study showing an institutional tendency to overprescribe, and reports of the national opioid epidemic likely all contributed to the decrease in opioid prescriptions at the authors' institution.

Interruptions and Delivery of Care in the Intensive Care Unit.

OBJECTIVE: This study samples interruption frequency in intensive care unit (ICU) settings to assess the relationship between interruptions and common patient hazards. BACKGROUND: Task interruptions are accident contributors in numerous industries. Recently, studies on health care interruptions and their impact on patient hazards have received attention. METHOD: Seven ICUs in four hospitals participated in a 24-month study. Experienced ICU nurses directly observed nursing tasks, interruptions, and patient hazards (delays in care, breaks in device task protocols, and patient safety hazards). RESULTS: During 1,148 hours of observation, 175 nurses performed 74,733 nursing tasks. Interruptions occurred at a rate of 4.95 per hour, and 8.4% of tasks were interrupted. Interruptions originated mostly from humans (65.9%), alarms (24.1%), and others (10%). A total of 774 patient hazards were observed, with a hazard occurring on average every 89 minutes. Relative to noninterrupted tasks, device alarm interrupted nonstructured tasks were associated with increased rates of delays in care and safety hazards (rate ratio [RR] = 3.19). In contrast, rate of delays in care and safety hazards did not increase during human interrupted tasks (RR = 1.13). Rates of protocol nonadherence varied by device type and were highest during artificial airway, medication administration, chest tube, and supplemental oxygen management. CONCLUSION: Interruptions in the ICU are frequent and contribute to patient hazards, especially when caused by device alarms during nonstructured tasks. Nonadherence to protocols is common and contributed to patient hazards. APPLICATION: The findings suggest a need for improvement in task and device design to reduce patient hazards.