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Objective: Patients with glioblastoma (GBM) often undergo surgery to prolong survival. However, the use of surgery, and more specifically achieving gross total resection (GTR), in patients >80 years old has yet to be fully assessed. Using the Surveillance, Epidemiology, and End Results (SEER) database, we aim to assess the efficacy of surgical resection, radiotherapy (RT) and chemotherapy (CT) on overall survival (OS) in very elderly GBM patients compared to elderly counterparts (age 65-79 years)., Methods: The SEER database was queried for all patients >65 years old with GBM (2000-2020). Patients not undergoing surgery or biopsy were excluded. Patients were stratified by age, and demographic relationships were assessed with chi-squared testing for categorical variables. Bivariable models were created using Kaplan-Meier survival estimates. All significant variables from bivariable analysis were included on multivariable Cox survival regression models to determine independent associations between clinical variables and OS., Results: A total of 27,090 operative GBM patients were identified; 1868 patients (15.92 %) were very elderly and 10,092 patients (84.38 %) were elderly. Very elderly patients were less likely to undergo GTR (28 % vs 35 %, p<0.001), RT (59 % vs 78 %, p<0.001) and CT (40 % vs 66 %, p<0.001). In multivariable Cox regression analysis, very elderly patients who achieved GTR (HR=.696, p<0.001), received RT (HR=0.583, p<0.001) and underwent CT (HR=0.4197, p<0.001) had significantly improved OS compared to very elderly patients that did not undergo these treatment options., Conclusion: Currently, very elderly GBM patients undergo lower rates of aggressive surgery, RT and CT. However, very elderly patients that undergo surgery, RT and CT may have a survival advantage. These treatments should be considered as potential options for this patient population., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To explore the goals, barriers, and facilitators set by caregivers of preschool-aged children to improve food parenting practices and household food environments., Design: Secondary qualitative analysis of collaborative goal sheets completed during in-home and telephone visits as part of a home-based pilot intervention., Participants: Thirty-three Hispanic/Latinx caregivers, predominantly of low income., Phenomenon of Interest: Patterns in goal content and anticipated barriers and facilitators., Analysis: Thematic analysis of goal sheets with a mixed inductive-deductive approach., Results: Almost half of the goals were to support a healthy environment (40.7%) by increasing the availability of healthy foods through food shopping and meal planning. Other goals were to increase structure (33.7%) by establishing food-related routines and decreasing distractions. Goals related to autonomy support (25.4%) included involving their children (eg, cooking together). Caregivers' perceived barriers encompass individual (eg, stress, lack of time), interpersonal (eg, other family members' eating behaviors), and environmental-level (eg, food availability) factors. Caregivers only identified facilitators at the individual and interpersonal levels (eg, motivation)., Conclusions and Implications: Understanding goals, barriers, and facilitators can be used to tailor key messages to improve food parenting practices and children's diets. Future interventions can target broader environmental barriers while increasing awareness of individual, interpersonal, and environmental-level facilitators., (Copyright © 2024 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Background: Energy density (ED) and the variety of foods are 2 factors that may have a combined effect on preschool-aged children's ability to regulate food intake. However, little is known about the variety of foods consumed within different ED categories by children in the United States., Objective: Therefore, we explored the variety of high ED (HED, 4-9 kcal/g) and very low ED (VLED, <0.6 kcal/g) foods consumed by a nationally representative sample of children aged 2-5 y in the United States and the relationship between variety with food intake, diet quality, and weight status., Methods: ED, variety, and diet quality were assessed using two 24-h dietary recalls collected as part of the National Health And Nutrition Examination Survey 2011-2018 cycles (n = 1682). We assessed associations between HED and VLED varieties with energy intake, volume of food, diet quality, and weight status using multivariable linear and logistic regressions., Results: The HED variety was positively associated with energy intake (P < 0.0001). The VLED variety was positively associated with the volume of food (P < 0.0001) and diet quality (P < 0.0001). VLED was negatively associated with the odds of having obesity in minimally adjusted models [odds ratio (OR): 0.62; 95% confidence interval (CI): 0.31, 0.87]; however, the relationship was not significant in fully adjusted models. Patterns of variety intake were differently associated with energy, volume, and diet quality. Children consuming the high VLED variety and the low HED variety had lower odds of obesity [OR: 0.43; 95% CI: 0.21, 0.90]; however, this pattern was rare (10%)., Conclusions: These findings suggest that the variety of HED foods is associated with higher average energy intake per day, and the variety of VLED foods is associated with a higher volume of food consumed per day and diet quality in a nationally representative sample of preschool-aged children., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Throughout the last decades, mRNA vaccines have been developed as a cancer immunotherapeutic and the technology recently gained momentum during the COVID-19 pandemic. Recent promising results obtained from clinical trials investigating lipid-based mRNA vaccines in cancer therapy further highlighted the potential of this therapy. Interestingly, while the technologies being used in authorized mRNA vaccines for the prevention of COVID-19 are relatively similar, mRNA vaccines in clinical development for cancer vaccination show marked differences in mRNA modification, lipid carrier, and administration route. In this review, we describe findings on how these factors can impact the potency of mRNA vaccines in cancer therapy and provide insights into the complex interplay between them. We discuss how lipid carrier composition can affect passive targeting to immune cells to improve the efficacy and safety of mRNA vaccines. Finally, we summarize strategies that are established or still being explored to improve the efficacy of mRNA cancer vaccines and include next-generation vaccines that are on the horizon in clinical development., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.V., I.L., and S.D.S. are contributors to patent applications no. WO2020058239A1; Therapeutic nanoparticles and methods of use thereof, and no. EP22170845.6; Vaccine Compositions against Listeria Infection. K.W.H. has a financial interest and is a director of Myeloid Enhancement Therapeutics Inc. P.R.C. has a financial interest in Acuitas Therapeutics and NanoVation Therapeutics as well as being Chair of NanoVation Therapeutics., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Suicidal ideation and suicidal behavior (SI/SB) are prevalent among adolescents. Treatment of SI/SB in adolescents relies on their disclosure, yet there is limited research on adolescent SI/SB disclosure experiences. Understanding who they disclose to and how they experience their parents' responses to their disclosures is important, as parents are often involved in adolescent mental health treatment., Methods: The present study characterized adolescent SI/SB disclosures in a sample of psychiatrically hospitalized adolescents, examining to whom they disclosed SI/SB, perceived parental responses to SI/SB disclosures, and what they would prefer their parents did differently in response to SI/SB disclosures., Results: Results indicate that over 50% of youth disclosed their SI/SB directly to their parent and approximately 15%-20% of youth did not disclose their SI/SB to anyone prior to psychiatric hospitalization. Perceived parental responses to disclosures varied, including both validating and invalidating responses., Discussion: Findings have important implications for supporting parents and adolescents in discussing SI/SB., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Ultrasound is the hallmark imaging modality traditionally used by obstetricians for fetal diagnosis and surveillance. The COVID-19 pandemic highlighted the role of point of care ultrasound for expeditious assessment of the maternal cardiopulmonary status. The familiarity of obstetricians with ultrasound, coupled with the availability of ultrasound equipment without the need to transport the patient, make point of care ultrasound particularly valuable in the labor and delivery unit. The rising contribution of cardiopulmonary disorders to maternal morbidity and mortality carves out many potential applications for point of care ultrasound during labor and delivery. Obstetricians have access to the technology and the skills to obtain the basic views required to assess for the presence of pulmonary edema, ventricular dysfunction, or intra-abdominal free fluid. Point of care ultrasound can be used routinely for the evaluation of pulmonary complaints or in the assessment of hypotension and may play an essential role in the diagnosis and management of life-threatening emergencies such as shock, an amniotic fluid embolism, or cardiac arrest. We reviewed the currently established point of care ultrasound protocols for the evaluation of cardiopulmonary complaints through the lens of the obstetrician. We call on educators and academic leaders to incorporate maternal point of care ultrasound teachings into existing curricula. Point of care ultrasound is of enormous value for providers with limited access to diagnostic imaging or subspecialty providers. With the growing complexity of the obstetrical population, acquiring the clinical skills to meet these evolving needs is a requisite step in the ongoing efforts to reduce maternal morbidity and mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The socioemotional climate when feeding is a focus in childhood obesity prevention efforts. However, little is known about why caregivers create nonsupportive or supportive climates. This cross-sectional study used a Self-Determination Theory perspective to identify factors associated with the socioemotional climate when feeding in ethnically diverse families with low income., Methods: Caregivers of children aged 2-5 years (n = 66) completed the Parent Socioemotional Context of Feeding Questionnaire, the Basic Psychological Need (BPN) Satisfaction and Frustration Scale, and demographic surveys at baseline. Multivariable regressions assessed the association between BPN satisfaction/frustration with autonomy-supportive, structured, controlling, and chaotic feeding climates., Results: Participants were predominately Hispanic/Latinx (86.6%), women (92.5%), and born outside the US (60%). Their BPN frustration was positively associated with controlling (β = 0.96; SE = 0.26; P = 0.001) and chaotic (β = 0.79; SE = 0.27; P = 0.01) feeding., Conclusions and Implications: This analysis suggests that BPN frustration is associated with controlling and chaotic feeding and may be important to consider when encouraging responsive feeding., (Copyright © 2023 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Objective: Pineoblastomas (PBLs) are rare high-grade tumors treated variably with surgery and/or radiation. The role of surgical extent of resection and radiotherapy (RT) in adult PBL remains unclear. We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess these variables' effects on overall survival (OS) in adult PBL., Methods: The SEER (1975-2016) database was queried for adult patients with diagnosis of PBL (ICD-0-3: 9362/3). Variables extracted included age, sex, race, geographical region, extent of tumor resection, RT, chemotherapy (CT), and OS data. Comparisons were performed with the χ 2 test for categorical variables, Cox proportional hazards models to assess the association of clinical variables on OS, and Kaplan-Meier curves were generated., Results: A total of 201 patients with PBL were identified with mean age 40.0 years (interquartile range 27.0-51.0) and most patients being male (53%) and Caucasian (77%). 101 (50%) patients received RT, and gross total resection was achieved in 83 (41%). Age stratification by decade revealed statistically significant poorer OS in patients aged ≥70 years. In bivariate analysis, RT with or without surgery was associated with improved 5-year OS compared with no RT (77.3% vs. 63.2%, P = 0.020). In multivariate analysis, age was a poor prognostic factor for OS (P < 0.001) and RT did appear to improve survival (P = 0.020). Extent of surgical resection was not significantly associated with improved survival., Conclusions: In adult patients with PBL, RT may offer an OS benefit irrespective of surgery or extent of surgical resection. Patients ≥70 years of age are associated with poorer OS., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: FFR CT assesses the functional significance of lesions seen on CTCA, and may be a more efficient approach to chest pain evaluation. The FORECAST randomized trial found no significant difference in costs within the UK National Health Service, but implications for US costs are unknown. The purpose of this study was to compare costs in the FORECAST trial based on US healthcare cost weights, and to evaluate factors affecting costs., Methods: Patients with stable chest pain were randomized either to the experimental strategy (CTCA with selective FFR CT ), or to standard clinical pathways. Pre-randomization, the treating clinician declared the planned initial test. The primary outcome was nine-month cardiovascular care costs., Results: Planned initial tests were CTCA in 912 patients (65%), stress testing in 393 (28%), and invasive angiography in 94 (7%). Mean US costs did not differ overall between the experimental strategy and standard care (cost difference +7% (+$324), CI -12% to +26%, p ​= ​0.49). Costs were 4% lower with the experimental strategy in the planned invasive angiography stratum (p for interaction ​= ​0.66). Baseline factors independently associated with costs were older age (+43%), male sex (+55%), diabetes (+37%), hypertension (+61%), hyperlipidemia (+94%), prior angina (+24%), and planned invasive angiography (+160%). Post-randomization cost drivers were coronary revascularization (+348%), invasive angiography (267%), and number of tests (+35%)., Conclusions: Initial evaluation of chest pain using CTCA with FFR CT had similar US costs as standard care pathways. Costs were increased by baseline coronary risk factors and planned invasive angiography, and post-randomization invasive procedures and the number of tests. Registration at ClinicalTrials.gov (NCT03187639)., Competing Interests: Declaration of competing interest MAH reports a research grant for FORECAST from HeartFLow. KF has received fees and/or travel expenses from Servier, AstraZeneca, Celixir, Taurx, UCB and Broadview Ventures. He was a Director of Vesalius Trials Ltd. GM reports grants from HeartFlow & Bayer, and support by a NIHR Research Professorship (2017-08-ST2-007). CB is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GSK, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health. CB receives research funding from the British Heart Foundation (RE/18/6134217). PSD reports a grant from HeartFlow. NC reports unrestricted research grants from HeartFlow, Boston Scientific, Beckmann Coulter; consultancy/speaker fees from Abbott, HeartFlow, Boston Scientific, Phillips; travel sponsorship from Haemonetics, Abbott, Medtronic, Biosensors, and Edwards. All other authors report no relationships with industry., (Copyright © 2022 Society of Cardiovascular Computed Tomography. All rights reserved.)

Aims: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry., Methods and Results: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy., Conclusions: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.', Clinical Trial Registration: http://www., Clinicaltrials: gov identifier: NCT01991795., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: A patient's health information is generally fragmented across silos because it follows how care is delivered: multiple providers in multiple settings. Though it is technically feasible to reunite data for analysis in a manner that underpins a rapid learning healthcare system, privacy concerns and regulatory barriers limit data centralization for this purpose., Objectives: Machine learning can be conducted in a federated manner on patient datasets with the same set of variables but separated across storage. But federated learning cannot handle the situation where different data types for a given patient are separated vertically across different organizations and when patient ID matching across different institutions is difficult. We call methods that enable machine learning model training on data separated by two or more dimensions "confederated machine learning", which we aim to develop in this study., Methods: We propose and evaluate confederated learning for training machine learning models to stratify the risk of several diseases among silos when data are horizontally separated by individual, vertically separated by data type, and separated by identity without patient ID matching. The confederated learning method can be intuitively understood as a distributed learning method with representation learning, generative model, imputation method and data augmentation elements., Results: Our confederated learning method achieves AUCROC (Area Under The Curve Receiver Operating Characteristics) of 0.787 for diabetes prediction, 0.718 for psychological disorders prediction, and 0.698 for Ischemic heart disease prediction using nationwide health insurance claims., Conclusion: Our proposed confederated learning method successfully trained machine learning models on health insurance data separated by two or more dimensions., Competing Interests: Declaration of Competing Interest Author Dr Kathe Fox previously worked at Aetna which is now part of CVS health. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Acute kidney injury (AKI) occurs in one-fourth of children and young adults admitted to pediatric intensive care unit (PICU). Severe AKI (sAKI; Kidney Disease: Improving Global Outcomes stage 2 or 3) is associated with morbidity and mortality. An AKI risk stratification system, the Renal Angina Index (RAI) calculated at 12 hours of admission, exhibits excellent performance to rule out sAKI at 72 hours of admission. We found that integration of urine neutrophil gelatinase-associated lipocalin (NGAL) with RAI improves prediction of sAKI. We now report the first-year results after implementation of our prospective automated RAI-NGAL clinical decision support (CDS) program., Methods: Patients 3 months to 25 years of age were eligible. Admission order sets have a conditional order for urine NGAL released when a 12-hour RAI ≥8. The primary outcome was sAKI any time at days 2 to 4 of admission. We assessed performance of the RAI and RAI+/NGAL to predict the primary outcome., Results: A total of 1427 unique patients accounted for 1575 admissions. In 147 admissions, RAI was ≥8. RAI <8 had negative predictive value (NPV) of 0.98 (95% CI 0.97-0.99); RAI ≥ 8 had positive predictive value (PPV) of 0.37 (95% CI 0.30-0.46) to predict days 2 to 4 sAKI (area under the receiver operating characteristic curve [AUC-ROC] 0.88 [95% CI 0.84-0.92]). Of 147 RAI+ patients, 89 had NGAL available. RAI/NGAL combination improved PPV (0.64, 95% CI 0.50-0.79) without decrement in NPV (0.98, 95% CI 0.97-0.98)., Conclusion: AKI biomarker assessment directed by risk stratification improves prediction of sAKI in critically ill children and young adults. This CDS process has potential to enrich the population for interventional study, although improvement to adherence to CDS is needed., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Background: Treating patients with glioblastoma (GBM) requires extensive medical infrastructure. Individualized risk assessment for extended length of stay (LOS), nonroutine discharge disposition, and increased total hospital charges is critical to optimize delivery of care. Our study sought to develop predictive models identifying independent risk factors for these outcomes., Methods: We retrospectively reviewed patients undergoing GBM resection at our institution between January 2017 and September 2020. Extended LOS and elevated hospital charges were defined as values in the upper quartile of the cohort. Nonroutine discharge was defined as any disposition other than to home. Multivariate models for each outcome included covariates demonstrating P ≤ 0.10 on bivariate analysis., Results: We identified 265 patients undergoing GBM resection, with an average age of 58.2 years. 24.5% of patients experienced extended LOS, 22.6% underwent nonroutine discharge, and 24.9% incurred elevated total hospital charges. Decreasing Karnofsky Performance Status (KPS) (P = 0.004), increasing modified 5-factor frailty (mFI-5) index (P = 0.012), lower surgeon experience (P = 0.005), emergent surgery (P < 0.0001), and larger tumor volume (P < 0.0001) predicted extended LOS. Independent predictors of nonroutine discharge included older age (P = 0.02), decreasing KPS (P < 0.0001), and emergent surgery (P = 0.048). Nonprivate insurance (P = 0.011), decreasing KPS (P = 0.029), emergent surgery (P < 0.0001), and larger tumor volume (P = 0.004) predicted elevated hospital charges. These models were incorporated into an open-access online calculator (https://neurooncsurgery3.shinyapps.io/gbm&#95;calculator/)., Conclusions: Several factors were independent predictors for at least 1 high-value care outcome, with lower KPS and emergent admission associated with each outcome. These models and our calculator may help clinicians provide individualized postoperative risk assessment to glioblastoma patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of this study was to examine trait, state, and temporal instability measures of self-critical and self-punishment cognitions to evaluate their respective roles in nonsuicidal self-injury (NSSI). Participants were university students with a history of NSSI (n = 64) and those with no history of NSSI (n = 59). At baseline, participants completed measures assessing history of NSSI behavior, as well as trait measures of self-criticism and self-punishment. After completion of baseline procedures, participants subsequently participated in a 10-day ecological momentary assessment protocol in which self-critical and self-punishment cognitions were assessed in real time three times daily. Employing bivariate and multivariate frameworks, our results demonstrate that both trait and state levels of self-critical and self-punishment cognitions robustly differentiate between young adults with and without a lifetime history of NSSI. The present results also confirm that the temporal instability of these cognitive states also meaningfully differentiate between groups, such that those who exhibit greater fluctuations in these cognitive states are more likely to have a history of NSSI. The current findings suggest that trait, state, and temporal instability of negative self-focused cognitions may be vulnerability factors for engagement in NSSI., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI., Methods: We did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21-85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89)., Findings: From Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to receive either trimetazidine (n=2998) or placebo (n=3009). After a median follow-up of 47·5 months (IQR 42·3-53·3), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23·3%] patients) and the placebo group (714 [23·7%]; hazard ratio 0·98 [95% CI 0·88-1·09], p=0·73). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. Similar results were obtained when patients were categorised according to whether they had an elective or urgent PCI. 1219 (40·9%) of 2983 patients in the trimetazidine group and 1230 (41·1%) of 2990 patients in the placebo group had serious treatment-emergent adverse events. Frequencies of adverse events of interest were similar between the groups., Interpretation: Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. However, the long-term prescription of this treatment does not appear to be associated with any statistically significant safety concerns in the population studied., Funding: Servier., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Fractional flow reserve measurement based on computed tomography (FFR CT ) is a novel, well validated, non-invasive method for determining the presence and extent of coronary artery disease (CAD) combined with a physiological assessment of vessel-specific ischemia in patients with chest pain. Previous studies indicate that FFR CT reduces the uptake of invasive angiography that shows no significant CAD, without compromising patient safety. The clinical effectiveness and economic impact of using FFR CT instead of other tests in the initial evaluation of patients with stable chest pain has not been tested in a randomized trial., Methods: The FORECAST trial will randomise 1400 patients with stable chest pain to receive either FFR CT or routine clinical assessment as directed by the National Institute for Health and Care Excellence (NICE) CG95 guideline for Chest Pain of Recent Onset. The primary endpoint will be resource utilisation over the subsequent nine months, including non-invasive cardiac investigations, invasive coronary angiography, coronary revascularization, hospitalization for cardiac events, and the use of cardiac medications. Key pre-specified secondary endpoints will be major adverse cardiac events, angina severity, quality of life, patient satisfaction, time to definitive management plan, time to completion of initial evaluation, number of hospital attendances, and working days lost in patients who are in employment., Conclusion: The FORECAST randomized trial will assess the clinical and economic outcomes of using FFR CT as the primary test to evaluate patients presenting with stable chest pain., Competing Interests: Declaration of competing interest Michael Mahmoudi & Zoe Nicholas have no conflicts of interests. Nick Curzen has received unrestricted research grants from HeartFlow, Haemonetics and Boston Scientific; speaker fees/honoraria from Abbott Vascular, HeartFlow, Haemonetics and Boston Scientific; travel sponsorship from HeartFlow, Haemonetics; Biosensors; Abbott Vascular, Medtronic & Boston Scientific. Mark Hlatky has received research grants from HeartFlow. Colin Berry is employed by the University of Glasgow, which holds consultancy and research agreements with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Menarini Pharmaceuticals, Philips and Siemens Healthcare. These companies had no involvement in the current research or the manuscript., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Commercial hernia mesh is commonly made from polypropylene (PP), due to its inertness, biocompatibility, physical properties, ease of processing and versatility for conversion into flexible shape. However, reportedly hernia mesh prepared from PP experienced issues such as diminished long-term strength, foreign body rejection, lack of biocompatibility and high adhesion to the abdomen wall. Infiltration of the mesh by soft tissue (called remodeling) results in an integration of mesh into the body, leading to a rapid reduction in mesh mechanical properties and potential infection. Here, this study addresses these issues through the incorporation of nanodiamond (ND) into PP filament and coating on the surface of plasma-treated PP-ND mesh. The results show that the dynamic modulus of the PP-ND mesh increased significantly, without compromising its flexibility. Coating PP-ND mesh with hydroxylated ND led to a reduction in nonspecific protein adsorption onto the surface of nanocomposite, which is an important characteristic for hernia mesh to prevent foreign body reaction, attachment of mesh to the abdominal wall and nearby organs. In-vitro study with mammalian cells shows that coated PP-ND mesh with functionalized ND exhibits a significant increase in the number of adhered cells with more elongated morphology in comparison with other PP meshes, due to the better hydrophilicity. Therefore, the ND coated nanocomposite mesh can be a promising candidate for hernia repair in the future; however, more investigation is required., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

For decades, scientists have collected genomic information from Indigenous peoples and their ancestors with the goal of elucidating human migration events, understanding ancestral origins, and identifying ancestral variants contributing to disease. However, such studies may not have offered much benefit to the Indigenous groups who contributed DNA, and many have instead perpetuated stereotypes and other harms. With recent advances in genomic technology facilitating the study of both ancient and present-day DNA, researchers and Indigenous communities have new opportunities to begin collaboratively addressing important questions about human health and history. Yet, while there are increased efforts to ethically engage Indigenous communities, more work is still needed as the discipline struggles to absolve itself of the racialized science and extractive biocolonialism that defined its past., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Pregnancy-related deaths in the United States are increasing. Medical, social, economic, and cultural issues have all been implicated in this trend, but few data exist to differentiate the relative contributions of these various factors., Objective: The objective of the study was to examine trends in US pregnancy-related mortality by place of death and maternal race and age. We hypothesized that such an analysis may allow some distinction between deaths related to medical performance and those more closely related to social, cultural, or environmental issues., Study Design: We conducted a retrospective, cross-sectional study for the years 2003-2016 using multiple cause-of-death mortality data provided by the Centers for Disease Control and Natality Data provided by National Vital Statistics System of the National Center for Health Statistics. Temporal trends analyses for the place of death, race/ethnicity, and age at the time of death were performed using joinpoint regression over the study period., Results: Approximately one third of pregnancy-related deaths occurred outside a medical facility. The fraction of maternal deaths occurring in inpatient facilities fell by 20% over the study period, from 53% to 44% of all maternal deaths (P < .0001). Maternal deaths in an outpatient facility or emergency room demonstrated a similar decline (24%) in relative frequency (P < .0001). In contrast, there was a significant increase in the relative frequency of maternal mortality in other settings, particularly within the descendant's home, with a doubling over this time period. However, overall pregnancy-related deaths continued to increase in all settings. These increases were particularly striking in non-Hispanic black and white women and among women in the youngest and oldest age groups., Conclusion: Against a background of rising US pregnancy-related mortality, stratification of such deaths by place of death and maternal age and race highlights both the need for ongoing improvements in the quality of medical care and the potential contribution of events occurring outside a medical facility to the overall morality ratio. Current trends in pregnancy-related mortality in the United States are, in part, driven by social, cultural, and financial issues beyond the direct control of the medical community., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Income inequality has been associated with worse oral health outcomes and reduced dental care use. It is unknown whether income inequality may motivate people to seek orthodontic treatment., Methods: This was a logistic mixed-effects model of deidentified claims from a private insurer in the United States with enrolled members having at least 1 orthodontic visit in the calendar year as the dependent variable. Total number of dental visits, age, and sex were individual-level covariates. Median household income, Gini coefficient, female population proportion, number of practicing dentists and orthodontists, population size, and population density were zip code-level covariates., Results: A total of 1,860,709 people had at least 1 orthodontic claim. Adjusting for population demographics, the Gini index was significantly positively associated with orthodontic use for children but not for adults (odds ratio, 1.69 for children; P < .0001). Being female was the strongest predictor of orthodontic use for adults and was a significant predictor of use for children (odds ratio, 1.50 and 1.45, respectively; P < .0001)., Conclusions: The Gini index is associated with orthodontic use in children in a privately insured population. Individual characteristics are more predictive of orthodontic use among privately insured adults., Practical Implications: Demographic and economic traits of communities can affect oral health care use; effects on orthodontic use may be more dramatic than on other forms of oral health care., (Copyright © 2020. Published by Elsevier Inc.)

In October 2018, Colorado Parks and Wildlife seized an animal believed to be an illegally possessed bobcat. The owner claimed the animal was a bobcat/domestic cat hybrid, exempted from license requirements. Burden of proof lay with CPW to determine the lineage of the animal. Commercial microsatellite arrays and DNA barcoding have not been developed for identification of bobcat/domestic cat hybrids, and limited time and resources prevented development of such tests for this application. Instead, we targeted endogenous feline leukemia virus (enFeLV) to quickly and inexpensively demonstrate the absence of domestic cat DNA in the contested animal. Using this assay, we were able to confirm that the contested animal lacked enFeLV, and therefore was not a domestic cat hybrid., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction., Background: Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined., Methods: In a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumab alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy-related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to <50%., Results: Over a median of 2.1 years (interquartile range [IQR]: 1.3 to 4.2 years), participants treated with doxorubicin or doxorubicin followed by trastuzumab demonstrated a persistent worsening in diastolic function, with reductions in the E/A ratio, lateral and septal e' velocities, and increases in E/e' (p < 0.01). These changes were not observed with trastuzumab alone. Incident abnormal diastolic function grade occurred in 60% at 1 year, 70% by 2 years, and 80% by 3 years. Abnormal diastolic function grade was associated with a subsequent decrease in LVEF (-2.1%; 95% confidence intervals [CI]: -3.1 to -1.2; p < 0.001) and worsening in longitudinal strain (0.6%; 95% CI: 0.1 to 1.1; p = 0.013) over time. Changes in E/e' ratio were modestly associated with worsening longitudinal strain (0.1%; 95% CI: 0.0 to 0.2; p = 0.022)., Conclusions: A modest, persistent worsening of diastolic function is observed with contemporary breast cancer therapy. Abnormal and worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Maternal diabetes is a known teratogen that can cause a wide spectrum of birth defects, collectively referred to as diabetic embryopathy (DE). However, the pathogenic mechanisms underlying DE remain uncertain and there are no definitive tests to establish the diagnosis. Here, we explore the potential of DNA methylation as a diagnostic biomarker for DE and to inform disease pathogenesis., Methods: Bisulfite sequencing was used to identify gene regions with differential methylation between DE neonates and healthy infants born with or without prenatal exposure to maternal diabetes, and to investigate the role of allele-specific methylation at implicated sites., Results: We identified a methylation signature consisting of 237 differentially methylated loci that distinguished infants with DE from control infants. These loci were found proximal to genes associated with Mendelian syndromes that overlap the DE phenotype (e.g., CACNA1C, TRIO, ANKRD11) or genes known to influence embryonic development (e.g., BRAX1, RASA3). Further, we identified allele-specific methylation (ASM) at 11 of these loci, within which 61.5% of ASM single-nucleotide variants are known expression quantitative trait loci (eQTLs)., Conclusions: Our study suggests a role for aberrant DNA methylation and cis-sequence variation in the pathogenesis of DE and highlights the diagnostic potential of DNA methylation for teratogenic birth defects.

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor., Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population)., Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction =0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction =0·012. Benefit was present irrespective of time from most recent PCI., Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk., Funding: AstraZeneca., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To determine barriers, motivators, and perspectives regarding plate waste reduction of early adolescents., Design: Trained interviewers conducted audio-recorded individual interviews with adolescents., Setting: Elementary schools implementing the National School Lunch Program in Hawai'i, Montana, and Virginia., Participants: Early adolescents (n = 47, aged 9-13 years) from families receiving or eligible to receive Supplemental Nutrition Assistance Program benefits were recruited to participate., Phenomenon of Interest: Factors influencing plate waste among adolescents and potential plate waste reduction strategies., Analysis: Coders analyzed content and thematic data to identify code categories and themes., Results: Main barriers to reducing school lunch plate waste were unsupportive school policy, undesirable food quality, satiation, and social influences. Key motivators to reducing school lunch plate waste were supportive school policy, including allowing students to share food with peers and save food to eat later; and social influences. Participants found it acceptable to throw away disliked food and unacceptable to throw away wanted food; they perceived that their peers did not care whether food was thrown away; and they thought their parents disliked wasting food., Conclusion and Implications: Results suggest that several factors might allow for minimization of school lunch plate waste in the National School Lunch Program, including improvements in food quality, food policy, and social influences. Under these important themes, strategies to employ may include improving food preparation and taste, allocating more time for students to finish lunch, allowing students to self-select food lunch items, and permitting them to share and save their leftover food., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We describe preparation, characterization and cytocompatibility of nanodiamond (ND) dispersed in poly (ε-caprolactone) (PCL) based nanofibrous scaffold. The results show that this unique scaffold potentially provides essential properties for wound healing by enhancing proliferation of epithelial cells, in addition to restricting the microbial activities. Electrospinning technique was used to fabricate and develop PCL-NDs nanocomposite scaffold. The developed nanocomposites were characterized for morphology, thermal, surface and biological properties. The incorporation of ND into the PCL matrix resulted in better moisture management and higher thermal stability. Transmission electron microscopy images and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy showed existence of ND particles on the surface of the nanofibers. The aggregation of ND particles increased with the increase in their concentration in nanofiber. The developed scaffolds showed no cytotoxicity and, due to improved hydrophilicity, better cellular activities with Chinese hamster ovarian (CHO) cells, 43%, 38% and 22% more cell proliferation for PCL-5% ND for 1, 3- and 7-days incubations in compare with PCL. Furthermore, Staphylococcus aureus (S. aureus) showed significantly less affinity to the scaffold surface with the increase in ND concentration, ~56% less for PCL-5% ND in compare with PCL, indicating that such ND dispersed nanofibrous scaffold maybe asuitable choice for complex wound management., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: The cornerstone of the treatment of patients affected by stable angina is based on drugs administration classified as first (beta-blockers, calcium channel blockers, short acting nitrates) or second line treatment (long-acting nitrates, ivabradine, nicorandil, ranolazine and trimetazidine). However, few data on comparison between different classes of drugs justify that one class of drugs is superior to another., Methods: We performed a systematic review of the literature following PRISMA guidelines., Inclusion Criteria: i) paper published in English; ii) diagnosis of stable coronary disease; iii) randomized clinical trial; iv) comparison of two anti-angina drugs; v) a sample size >100 patients; vi) a follow-up lasting at least 2 weeks; vii) paper published after 1999, when a meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina of Heidenreich et al. was published., Outcome: to establish whether the categorization in first and second line antianginal treatment is scientifically supported., Results: Eleven trials fulfilled inclusion criteria. The results show that there is a paucity of data comparing the efficacy of antianginal agents. The little data available show that there are not compounds superior to others in terms of improvement in exercise test duration, frequency of anginal attacks, need for sub-lingual nitroglycerin., Conclusion: The categorization of antianginal drug in first and second line is not confirmed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Preventing blood loss at the time of a cesarean delivery during a scheduled, nonemergent cesarean hysterectomy for placenta percreta may reduce the need for crystalloid and blood product transfusion. Commonly a classical hysterotomy is created and this can result in as much as a 500-800 mL blood loss before the hysterotomy is closed. Our technique involves placement of 4 full-thickness interrupted sutures in a box pattern to create an unperfused area of upper uterine segment. Diathermy is used to open the uterus to the membranes in the center of the "box" without blood loss. A finger is then inserted between the membranes and uterus to create a space into which 1 side of an 80-mm linear cutting stapler is introduced. The other side of the stapler is then attached and clamped closed, and the stapler is activated. Forward motion of the lever lays down 2 rows of staples, and backward movement of the lever divides the uterine muscle between the 2 staple lines. The stapler is removed and reloaded and reintroduced 1 or 2 times as needed to create an avascular hysterotomy large enough to atraumatically deliver the baby. The membranes are then opened and the baby is delivered. Following this the umbilical cord is clamped and cut without any attempt to remove the placenta, replaced in the uterine cavity, and the hysterotomy is closed with a running locked suture that incorporates the membrane edges. The hysterectomy then proceeds. In most cases there is minimal blood loss (usually <20 mL) from the cesarean delivery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: Bighorn sheep (Ovis canadensis) routinely experience violent impacts to the head as part of intraspecific fighting. Dynamic 3D finite element models of the skull and horns of a male bighorn sheep were developed to gain an understanding of the roles that the horn and bone materials and structure play in absorbing the impact that occurs during ramming. The geometry and volume mesh of the model were derived from CT scan images. The models included the horn, bony horn core, and bone of the skull. The horn core fills a portion of the hollow horn and consists of a thin cortical bone shell filled with foam-like trabecular bone. Two modified models were also created: one with the distal half of the horn length removed to assess the effects of the tapered spiral geometry of the horn, and one with the internal trabecular bone material of the horn core removed. The trabecular bone material stored three times more strain energy during impact than the horn material in the intact model. Removing half of the horn length had the effect of increasing translational accelerations in the brain cavity by 49%. Removing the trabecular bone in the horn core resulted in a 442% increase in rotational accelerations within the brain cavity. These findings support the investigation of novel bioinspired materials and designs that could be used in mitigating brain injuries and in other applications involving high-impact collisions., Statement of Significance: Bighorn sheep routinely experience violent impacts to the head and horns without apparent negative consequences to the brain or horns. A portion of the horn is filled with a thin cortical bone shell containing foam-like trabecular bone. We developed novel dynamic finite element models of the skull and horns of bighorn sheep to gain an understanding of the roles that the horn and bone materials play in absorbing the impact that occurs during ramming. The study revealed that both horn and bone materials and the structures made from these materials (i.e., tapered spiral horns and foam-like trabecular bone struts) are important for absorbing impact energy and reducing brain cavity accelerations., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study sought to determine the relationships between echocardiography-derived measures of myocardial mechanics and cancer therapeutics-related cardiac dysfunction (CTRCD)., Background: Doxorubicin and trastuzumab are highly effective breast cancer therapies, but have a substantial risk of CTRCD. There is a critical need for the early detection of patients at increased risk of toxicity., Methods: We performed a prospective, longitudinal cohort study of breast cancer participants undergoing doxorubicin and/or trastuzumab therapy. Echocardiography was performed prior to therapy initiation (baseline) and at standardized follow-up intervals during and after completion of therapy. Ejection fraction (EF), strain, strain rate, and ventricular-arterial coupling (effective arterial elastance [Ea]/end-systolic elastance [Ees sb ]) were quantitated. CTRCD was defined as a ≥10% reduction in EF from baseline to <50%. Multivariable logistic regression models were used to determine the associations between baseline levels and changes from baseline in echocardiographic measures and CTRCD. Receiver-operating characteristic curves were used to evaluate the predictive ability of these measures., Results: In total, 135 participants contributed 517 echocardiograms to the analysis. Over a median follow-up time of 1.9 years (interquartile range: 0.9 to 2.4 years), 21 participants (15%) developed CTRCD. In adjusted models, baseline levels and changes in Ea/Ees sb , circumferential strain, and circumferential strain rate were associated with 21% to 38% increased odds of CTRCD (p < 0.001). Changes in longitudinal strain (p = 0.037), radial strain (p = 0.015), and radial strain rate (p = 0.006) were also associated with CTRCD. Ea/Ees sb (area under the curve: 0.703; 95% confidence interval: 0.583 to 0.807) and circumferential strain (area under the curve: 0.655; 95% confidence interval: 0.517 to 0.767) demonstrated the greatest predictive utility. Sensitivity analyses using an alternative CTRCD definition did not impact our results., Conclusions: Over an extended follow-up time, ventricular-arterial coupling and circumferential strain were strongly predictive of CTRCD. Our findings suggest a noninvasive strategy to identify high-risk patients prior to, during, and after cardiotoxic cancer therapy., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Diamond has shown great potential in different biomedical applications, but the effects of sterilization on its properties have not been investigated. Here, we studied the influence of five sterilization techniques (solvent cleaning, oxygen plasma, UV irradiation, autoclave and hydrogen peroxide) on nitrogen-included ultrananocrystalline diamond. The chemical modification of the diamond surface was evaluated using X-ray photoelectron spectroscopy and water contact angle measurements. Different degrees of surface oxidation and selective sp(2) bonded carbon etching were found following all sterilization techniques, resulting in an increase of hydrophilicity. Higher viabilities of in vitro mouse 3T3 fibroblasts and rat cortical neuron cells were observed on oxygen plasma, autoclave and hydrogen peroxide sterilized diamond, which correlated with their higher hydrophilicity. By examination of apatite formation in simulated body fluid, in vivo bioactivity was predicted to be best on those surfaces which have been oxygen plasma treated and lowest on those which have been exposed to UV irradiation. The charge injection properties were also altered by the sterilization process and there appears to be a correlation between these changes and the degree of oxygen termination of the surface. We find that the modification brought by autoclave, oxygen plasma and hydrogen peroxide were most consistent with the use of N-UNCD in biological applications as compared to samples sterilized by solvent cleaning or UV exposure or indeed non-sterilized. A two-step process of sterilization by hydrogen peroxide following oxygen plasma treatment was then suggested. However, the final choice of sterilization technique will depend on the intended end application., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Angiotensin-converting-enzyme inhibition reduces the risk of cardiovascular events at a group level. Presumably, the absolute effect of treatment varies between individuals. We sought to develop multivariable prediction scores to estimate individual treatment effect of perindopril in patients with stable coronary artery disease (sCAD)., Methods: In EUROPA trial participants, we estimated the individual patient 5-year absolute risk reduction (ARR) of major adverse cardiovascular events(MACE) by perindopril. Predictions were based on a new Coxproportional-hazards model with clinical characteristics and an external risk score in combination with the observed relative risk reduction. Second, a genetic profile modifying the relative efficacy of perindopril was added. The individual patient ARR was defined as the difference in MACE risk with and without treatment. The group level impact of selectively treating patients with the largest predicted treatment effect was evaluated using net benefit analysis., Results: The risk score combining clinical and genetic characteristics estimated the 5-year absolute treatment effect to be absent or adverse in 27% of patients. On the other hand, the risk score estimated a small 5-year ARR of ≤2% (NNT5≥50) in 20% of patients, a modest ARR of 2-4% (NNT5 25-50) in 26%, and a large ARR of ≥4% (NNT5≤25) in 28%. The external risk score yielded similar predictions. Selective prediction-based treatment resulted in higher net benefit compared to treat everyone at any treatment threshold., Conclusion: A prediction score combining clinical characteristics and genetic information can quantify the ARR of MACE by perindopril for individual patients with sCAD and may be used to guide treatment decisions., Trial Registration Number: ISRCTN37166280., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)