"Real-World" Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States.

OBJECTIVES: The 30-day clinical outcomes with prasugrel or ticagrelor were compared using a US payer database in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Prasugrel and ticagrelor demonstrated superior efficacy with increased non-coronary artery bypass graft major bleeding compared with clopidogrel in randomized clinical trials. No direct randomized or observational studies have compared clinical outcomes between prasugrel and ticagrelor. METHODS: Patients hospitalized for ACS-PCI between August 1, 2011 and April 30, 2013 and prescribed prasugrel or ticagrelor were selected. Drug treatment cohorts were propensity matched based upon demographic and clinical characteristics. The primary objective compared 30-day net adverse clinical events (NACE) in prasugrel- and ticagrelor-treated patients using a prespecified 20% noninferiority margin. Secondary objectives included comparisons of major adverse cardiovascular events (MACE) and major bleeding. RESULTS: Data were available for 16,098 patients (prasugrel, n = 13,134; ticagrelor, n = 2,964). In unmatched cohorts, prasugrel-treated patients were younger with fewer comorbidities than ticagrelor-treated patients, and 30-day NACE rates were 5.6 and 9.3%, respectively (P < 0.001). Following propensity matching, NACE was noninferior (P < 0.001) and 22% lower in prasugrel-treated than in ticagrelor-treated patients (RR, 0.78; 95% CI, 0.64-0.94). A 30-day adjusted MACE (RR, 0.80; 95% CI, 0.64-0.98) and major bleeding (RR, 0.65; 95% CI, 0.45-0.95) were also lower in prasugrel-treated patients compared with ticagrelor-treated patients. CONCLUSIONS: In this "real-world," retrospective, observational study, physicians appear to preferentially use prasugrel in younger patients with lower risk of bleeding or comorbidities compared with ticagrelor. Following adjustment, clinical outcomes associated with prasugrel use appear as good, if not better, than those associated with ticagrelor in ACS-PCI patients. © 2015 Wiley Periodicals, Inc.

Persistent organochlorines in 13 shark species from offshore and coastal waters of Korea: Species-specific accumulation and contributing factors.

Data on persistent organochlorines (OCs) in sharks are scarce. Concentrations of OCs such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were determined in the muscle tissue of 13 shark species (n=105) collected from offshore (Indian and Pacific Oceans) and coastal waters of Korea, to investigate species-specific accumulation of OCs and to assess the potential health risks associated with consumption of shark meat. Overall OC concentrations were highly variable not only among species but also within the same species of shark. The concentrations of PCBs, DDTs, chlordanes, hexachlorobenzene, and heptachlor in all shark species ranged from

Management of cystic or predominantly cystic thyroid nodules: role of simple aspiration of internal fluid.

PURPOSE: The purpose of this study is to evaluate the efficacy of simple aspiration of cystic thyroid nodules by comparing with control groups to exclude the occurrence of spontaneous regression by the definition of current guidelines of American Thyroid Association. MATERIALS AND METHODS: 217 nodules from 210 patients with cystic thyroid nodules (cystic portion >50%) were included. Nodules were classified into three groups as follows: Group 1, observation only; Group 2, fine needle aspiration (FNA) without aspiration of internal fluid; and Group 3, FNA after aspiration of internal fluid. Significant nodule size change was defined as a difference in the largest diameter of 20%, as seen on the last follow-up ultrasound (US) compared to the initial US. RESULTS: Demographic characteristics did not show significant differences among the three groups except for the patient age (p = 0.039). Mean nodule size significantly decreased only in group 3 (p = 0.005). Significant nodule size reductions were observed in 22.0% (13/59) in group 1, 25.7% (28/109) in group 2, and 40.8% (20/49) in group 3, respectively. CONCLUSIONS: Aspiration of internal fluid should be considered as the first-line procedure for both the diagnosis and treatment of cystic or predominantly cystic thyroid nodules.

Evaluation of phytoplankton community composition in the eutrophic Masan Bay by HPLC pigment analysis.

To assess the spatiotemporal changes in phytoplankton community composition in relation to the environment of Masan Bay, a semi-enclosed bay on the southern coast of Korea, photosynthetic pigments and environmental variables were analyzed in seawater, every month between March and November 2010. The level of dissolved inorganic nutrients was highest between July and September when the freshwater influx was at its peak, whereas chlorophyll a level was highest in April and August. Phosphate concentration was low in April (average: 0.22 +/- 0.17 microM), indicating the role of phosphate as a growth-limiting factor for phytoplankton. The results of pigment analysis indicate that dinoflagellate blooms occurred under favorable conditions, where competition with diatoms occurred. Fucoxanthin- and chlorophyll b-containing phytoplankton dominated the surface layer of Masan Bay from July to September. The composition of phytoplankton community in Masan Bay changed dramatically each month according to variations in the amount and composition of nutrients introduced through surface runoff.

Infant exposure to polybrominated diphenyl ethers (PBDEs) via consumption of homemade baby food in Korea.

Limited data are available on the residue levels of polybrominated diphenyl ethers (PBDEs) in baby food. In this study, 24 PBDE congeners were determined in 147 homemade baby food samples collected from 97 households for 6-, 9-, 12-, 15-, and from 24 to 27-month-old infant groups during the period of 2012-2013. The concentrations of total PBDEs (ΣPBDE) ranged from 24.5 to 6000 (mean: 263) pg/g fresh weight, higher than those found in commercial formulae from the United States. The predominant congeners were BDEs 209 and 47, accounting for 92% of the ΣPBDE concentrations, reflected by high deca-BDE consumption in Korea. The residue levels and detection rates of BDE 47 in the baby food samples showed a gradual increasing trend with an increase in infant ages, due to changes in the food ingredients from hypoallergenic to greasy. The daily intakes of BDEs 47 and 209 via baby food consumption ranged from 0.04 to 0.58, 0.80 to 20.3, and 1.06 to 22.3 ng/kg body weight/day for 6-, 9-, 12-, 15-, and 24-27-month-old infant groups, respectively; these intakes were lower than the oral reference doses proposed by the US EPA. Together with three exposure sources, baby food, breast milk and dust ingestion for 6-month-old infants, the daily intake of ΣPBDE was 25.5 ng/kg body weight/day, which was similar to the intake via baby food consumption only for over 24-month-old infants in our study. This indicates that baby food is an important exposure pathway of PBDEs for over 24-month-old infants. This is the first study regarding the occurrence and exposure assessment of PBDEs via homemade baby food.

Algal photosynthetic responses to toxic metals and herbicides assessed by chlorophyll a fluorescence.

Chlorophyll a fluorescence is established as a rapid, non-intrusive technique to monitor photosynthetic performance of plants and algae, as well as to analyze their protective responses. Apart from its utility in determining the physiological status of photosynthesizers in the natural environment, chlorophyll a fluorescence-based methods are applied in ecophysiological and toxicological studies to examine the effect of environmental changes and pollutants on plants and algae (microalgae and seaweeds). Pollutants or environmental changes cause alteration of the photosynthetic capacity which could be evaluated by fluorescence kinetics. Hence, evaluating key fluorescence parameters and assessing photosynthetic performances would provide an insight regarding the probable causes of changes in photosynthetic performances. This technique quintessentially provides non-invasive determination of changes in the photosynthetic apparatus prior to the appearance of visible damage. It is reliable, economically feasible, time-saving, highly sensitive, versatile, accurate, non-invasive and portable; thereby comprising an excellent alternative for detecting pollution. The present review demonstrates the applicability of chlorophyll a fluorescence in determining photochemical responses of algae exposed to environmental toxicants (such as toxic metals and herbicides).

Seeing the whole elephant: integrated advanced data analytics in support of RWE for the development and use of innovative pharmaceuticals.

INTRODUCTION: The 21st century has brought about significant technological advancement, allowing the collection of new types of data from the real world on an unprecedented scale. The healthcare industry will benefit immensely from this abundance of patient data from electronic health records (EHR), patient-reported outcomes (PROs), laboratory, demographic, social media, digital, and even climate data. AREAS COVERED: While conventional statistical methods still play a significant role in supporting the drug lifecycle, machine learning (ML) and artificial intelligence (AI) are assuming a more prominent role in the analysis of this 'big data.' Moving forward, conventional statistics and AI/ML will work together to support descriptive, diagnostic, and even predictive analytics to further revolutionize drug discovery and development, regulatory approvals, and payer acceptance. In addition, counterfactual prescriptive analytics, such as causal inference analysis using real-world data (RWD) to generate insights that have cause-and-effect conclusions, will gain momentum as a methodology that can stand up against the rigor of regulatory review. EXPERT OPINION: Our real-world evidence/health economics and outcomes research (RWE/HEOR) field has evolved in ways that require us to integrate all the methods and data into a single framework that guides a holistic analytic approach and decision-making.

A cost-effectiveness analysis of intrauterine spacers used to prevent the formation of intrauterine adhesions following endometrial cavity surgery.

AIM: To assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery. MATERIALS AND METHODS: A decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results. RESULTS: In this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan. LIMITATIONS: There are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided. CONCLUSION: This analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

Every year, women in the United States (US) undergo surgery to treat intrauterine abnormalities to maintain or improve the uterus' ability to support fetal development and result in a term delivery. Despite the benefits of these procedures, damage caused to the endometrium (uterine lining) is associated with a risk of adherence of the endometrial cavity surfaces with scar tissue known as intrauterine adhesions (IUAs).Damage to the endometrium and the resulting IUAs may be associated with infertility, light or absent menstruation, pregnancy loss, and other pregnancy-related complications. Treating these conditions within the US healthcare system consumes resources and adds costs for healthcare payers (public and private insurance providers).To facilitate endometrial repair and to reduce or prevent IUAs, researchers have developed materials to place within the endometrial cavity following surgery to separate the endometrial surfaces during the early healing period. These intrauterine "spacers" are intended to improve patients' subsequent clinical outcomes and save money for healthcare payers. It is unknown whether these improved clinical outcomes offset the cost of the routine use of spacers following "at-risk" procedures that involve the endometrial cavity.We developed a model designed to determine the cost-effectiveness of an intrauterine spacer by quantifying improvements in clinical outcomes and the resultant cost savings for patients undergoing uterine surgeries with or without spacers. Our model predicted that routinely using such spacers following at-risk procedures would improve patient outcomes and reduce costs to US payers.

Administration burden associated with recombinant human growth hormone treatment: perspectives of patients and caregivers.

Patients treated with recombinant human growth hormone (rhGH) for growth hormone disorders follow a challenging treatment schedule. This study assessed patient and caregiver experiences with rhGH therapy treatment regimens. Patients 13 years or older with growth hormone deficiency and caregivers completed Web-based surveys. A total of 61 patients and 239 caregivers participated. Storage of rhGH was considered burdensome by more than a third. More than 51% considered storage "somewhat more" to "much more of a burden" relative to the burden while not traveling. "Away from home or traveling" was the most frequently endorsed reason for missing a dose. rhGH treatment while traveling is challenging because of rhGH storage burden.

A stable isotopic approach for quantifying aquaculture-derived organic matter deposition dynamics in the sediment of a coastal fish farm.

The stable carbon and nitrogen isotopic compositions (δ13C and δ15N) of sedimentary organic matter (OM) in fish farms (FFs) were investigated to quantify the aquaculture-derived OM deposition dynamics in the sediment. The dual isotopic compositions of mixed OMs in surface sediments at FFs differed significantly (p < 0.05) from those at reference sites, indicating an increased deposition of fish feces or uneaten feed in the sediments. Furthermore, OM source apportionments revealed that the quantitative contribution of fish feces (23.3 mg g-1 dw) during farming activities was significantly higher than that of other natural OM sources (C3 plants and phytoplankton). After the disassembly of fish cages, the deposited fish feces may be preferentially degraded through processes that require a large amount of oxygen consumption (<0.1 kg C m-2 yr-1). Our isotopic approach may be helpful for assessing the impact of FF wastes and for taking measures to minimize environmental deterioration.

Significant contribution of coastal fish-farm activities to the inventory of trace elements in coastal waters: Traced by ammonia and rare earth elements.

In this study, we investigated the influence of fish-farm activities on the inventory of trace elements (Mn, Fe, Co, Ni, and Cu) in the coastal waters off the fish-farm plants on Jeju Island, Korea. NH4+ and rare earth elements (REEs) were used as tracers to examine the production and removal processes. Relatively higher concentrations of trace elements were observed in the coastal waters and significantly correlated with NH4+. Our results suggest that the excess dissolved trace elements in the coastal waters could be mainly produced inside fish farms, together with the production of NH4+ and light-REEs (La to Nd). Although dissolved trace elements were found to be partially scavenged onto particles in the fish-farm rearing waters, indicated by the significant removal of particle-reactive Ce, these particles would be eventually discharged into the coastal ocean and release the dissolved trace elements back into the water columns.

Estuarine dam water discharge enhances summertime primary productivity near the southwestern Korean coast.

The gate opening of estuarine dams discharge a large amount of freshwater into coastal zones during the summer monsoon in northeast Asia. We investigated seasonal and spatial variations in primary productivity (PP) and community structures of phytoplankton on a downstream macrotidal flat and examined the dam discharge effects. Our harmonic analysis of the PP revealed a clear seasonality with a unimodal peak in summer, possibly driven by high ammonium loading through internal recycling. External nitrate supply from the dam-water discharge promoted PP during July-August, generating conspicuous blooms near the discharging site. Phytoplankton community was characterized by a predominance of diatoms all year round and seasonal dominances from dinoflagellates, cryptophytes, and prasinophytes in spring to chlorophytes in summer, reflecting spatiotemporal patterns in ammonium and nitrate supply. Our findings provide new insights into the summer phytoplankton bloom linked to monsoonal rainfall in the shallow coastal seas along the Northeast Asian coast.

Extended Multivariate Generalizability Theory With Complex Design Structures.

This article extends multivariate generalizability theory (MGT) to tests with different random-effects designs for each level of a fixed facet. There are numerous situations in which the design of a test and the resulting data structure are not definable by a single design. One example is mixed-format tests that are composed of multiple-choice and free-response items, with the latter involving variability attributable to both items and raters. In this case, two distinct designs are needed to fully characterize the design and capture potential sources of error associated with each item format. Another example involves tests containing both testlets and one or more stand-alone sets of items. Testlet effects need to be taken into account for the testlet-based items, but not the stand-alone sets of items. This article presents an extension of MGT that faithfully models such complex test designs, along with two real-data examples. Among other things, these examples illustrate that estimates of error variance, error-tolerance ratios, and reliability-like coefficients can be biased if there is a mismatch between the user-specified universe of generalization and the complex nature of the test.

Shifts in benthic bacterial communities associated with farming stages and a microbiological proxy for assessing sulfidic sediment conditions at fish farms.

To assess the aquaculture-induced sediment conditions associated with sulfur cycles, shifts in bacterial communities across farming stages were investigated. The sulfate reduction rate (SRR), and concentrations of acid volatile sulfide (AVS) and H2S were significantly higher at the mid- and post-farming stages than at the early stage, indicating that the aquaculture effects persist even after harvest. Incomplete organic carbon-oxidizing sulfate-reducing bacteria (IO-SRB) affiliated with Desulfobulbaceae, and gammaproteobacterial sulfur oxidizing bacteria (SOB) (Thiohalobacter, Thioprofundum, and Thiohalomonas) were dominant during the early stage, whereas fermenting bacteria (Bacteroidetes and Firmicutes) and complete oxidizing SRB (CO-SRB) belonging to Desulfobacteraceae, and epsilonproteobacterial SOB (Sulfurovum) dominated during the mid- and post-stages. The shift in SRB and SOB communities well reflected the anoxic and sulfidic conditions of farm sediment. Especially, the Sulfurovum-like SOB correlated highly and positively with H2S, AVS, and SRR, suggesting that they could be relevant microbiological proxies to assess sulfidic conditions in farm sediment.

Spatial variability of water quality and sedimentary organic matter during winter season in coastal aquaculture zone of Korea.

We investigated the composition, source, and reactivity of sedimentary organic matter (OM) present in aquaculture systems along the Korean coast. A multi-isotopic approach was applied to 216 surface sediments from five sections: western (W)-1, W-2, southern (S)-1, S-2, and eastern (E)-1 sections. The 15N-enriched total nitrogen signatures in the surface sediments of the W-1 section may indicate that a substantial fraction of sedimentary OM has anthropogenic origins exported through the Han River. Simultaneously, the deposition of allochthonous OM is predominant in the S sections (Jinhae and Masan Bays). The 34S-depleted patterns at the S-2 section may indicate that sulfate reduction occurring at the sedimentary boundary contributes to active OM decomposition, depending on the increased sedimentation of the aquaculture-derived OM. Our results highlight that isotopic-based source tracking near aquaculture systems provide important information for identifying anthropogenic contamination in coastal marine sediments and for improving environmental management.

Imaging features of benign solid testicular and paratesticular lesions.

OBJECTIVE: The presence of an intratesticular solid lesion is usually highly suspicious for malignancy. Conversely, most extratesticular solid lesions including paratesticular lesions are benign. The characteristic imaging features of malignant solid testicular lesions are well known, but various unusual causes and imaging features of benign solid testicular lesions can be particularly misleading. Therefore, a careful assessment of solid testicular and paratesticular lesions is warranted. The purpose of this article is to present the clinical and imaging features of the spectrum of benign solid testicular and paratesticular lesions. METHODS: We demonstrate a variety of benign solid testicular and paratesticular lesions and correlate them with pathologic results. RESULTS: Specific the clinical and imaging features of the spectrum of benign solid testicular and paratesticular lesions have been described. CONCLUSIONS: Familiarity with the clinical setting and imaging features of benign solid testicular and paratesticular lesions should facilitate prompt, accurate diagnosis and treatment.

Interval estimation procedures for true scores of a test composed of polytomous items: An application of the multinomial error model.

When a person takes alternative forms of the same test across replications of the testing procedure, the test taker's observed scores on the alternative forms are rarely identical. In educational and psychological measurement, inconsistencies in a test taker's scores that are irrelevant to the construct being measured are attributed to errors of measurement. Typically, errors of measurement are summarized as the standard deviation of a test taker's observed scores over replication of the same testing procedure. Assuming that errors of measurement follow a multinomial distribution (i.e., multinomial error model), the main goal of this study was to propose two interval estimation procedures, which are referred to as the score-like and Perks procedures, for true scores of a test with polytomous items. The performance of the score-like and Perks procedures was compared with that of two normal approximation procedures under the multinomial error model and a procedure based on item response theory (IRT) through simulation. In general, the score-like and Perks procedures outperformed the other three procedures when data were generated under the multinomial error theory framework and showed reasonable results when data were generated under the IRT framework. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Quality of Life in Primary Open-Angle Glaucoma and Cataract: An Analysis of VFQ-25 and OSDI From the iStent inject® Pivotal Trial.

OBJECTIVE: To assess quality of life (QOL) as measured by patient-reported outcomes (PRO) within the iStent inject® pivotal trial. DESIGN: Randomized controlled trial analysis of secondary outcomes. METHODS: The Vision Function Questionnaire (VFQ-25) and Ocular Surface Disease Index (OSDI) questionnaire were administered at baseline and at months 1, 6, 12, and 24. PRO responders were defined as patients reaching improvement based on minimally important differences. RESULTS: A total of 505 patients were randomized (386 iStent inject® [Glaukos], 119 surgery alone). The iStent inject® group exhibited a greater percentage of PRO responders across all follow-up visits over 24 months, averaging 58.0% vs 45.8%; P < .05 for VFQ-25 composite scores and 56.7% vs 48.9%; P < .05 for OSDI composite scores. Odds of being a responder in the iStent inject® group was 60% (P < .05) higher for the VFQ-25 and 32% (P > .05) higher for the ODSI. Driving (49.0% vs 28.8%; P < .05), ocular pain (59.3% vs 47.2%; P < .05), and general vision (71.8% vs 60.0%; P < .05) were the VFQ-25 subscales responsible for differences between treatment groups. At month 24, 76.5% of VFQ-25 responders and 62.5% of nonresponders were medication free regardless of treatment group (P < .05). CONCLUSIONS: Exploratory analysis suggests that by reducing medication dependence, implantation with the micro-scale iStent inject® device with cataract surgery may improve QOL vs cataract surgery alone over 24 months, with improvements influenced by ocular symptoms and vision-related activities.

Influence of intensive net cage farming on hydrodynamic and geochemical environmental conditions and the mass mortality of abalone in South Korea.

The abalone aquaculture industry in South Korea has grown rapidly since the 2000s. In this study, we investigated the sedimentary pollution at four major abalone farms responsible for ~60% of all South Korean abalone produced. We also surveyed the current statuses of cage facilities, abalone mass mortality, and current velocities within and outside farm cages. The concentrations of total organic carbon in the study area were 7.92 ± 2.09 mg g-1, indicating a mild level of sedimentary pollution. We observed higher mortality rates in rectangular-shaped shelter cages than in triangular shelters. With increases in the number and size of abalone farming facilities, current velocities inside the cages declined by an average of 45% relative to those outside the cages, leading to poor habitat conditions for farmed abalone. Our results provide insights into the current status of the benthic environments and major causes of mass mortality in the abalone farms of South Korea.

Spatiotemporal change in coastal waters caused by land-based fish farm wastewater-borne nutrients: Results from Jeju Island, Korea.

We investigated spatiotemporal distributions of dissolved inorganic nutrients and organic carbon (DOC) and nitrogen (DON) in coastal waters and land-based fish farm wastewater to determine effects of wastewater on seawater of Jeju Island, Korea. The nutrient concentrations in seawater were lower than in wastewater with negative correlations against salinity, indicating a terrestrial source. Wastewater-derived DOC and DON were transported offshore while wastewater-derived inorganic nutrients were effectively removed, likely via biological production, and this was closely linked to decline in N:P ratios. The correlations between DOC, DON, and colored dissolved organic matter suggest that organic matters likely originate from the fish farm wastewater. Quantitatively, the estimated wastewater-derived DOC flux was equivalent to that through submarine groundwater, which is a significant water source on the island. Our results will be able to trace contaminant sources and support assessments of seawater quality for appropriate regulation of fish farm wastewater discharge into coastal zones.