Predicting major complications in patients undergoing laparoscopic and open hysterectomy for benign indications

BACKGROUND: Hysterectomy, the most common gynecological operation, requires surgeons to counsel women about their operative risks. We aimed to develop and validate multivariable logistic regression models to predict major complications of laparoscopic or abdominal hysterectomy for benign conditions. METHODS: We obtained routinely collected health administrative data from the English National Health Service (NHS) from 2011 to 2018. We defined major complications based on core outcomes for postoperative complications including ureteric, gastrointestinal and vascular injury, and wound complications. We specified 11 predictors a priori. We used internal–external cross-validation to evaluate discrimination and calibration across 7 NHS regions in the development cohort. We validated the final models using data from an additional NHS region. RESULTS: We found that major complications occurred in 4.4% (3037/68 599) of laparoscopic and 4.9% (6201/125 971) of abdominal hysterectomies. Our models showed consistent discrimination in the development cohort (laparoscopic, C-statistic 0.61, 95% confidence interval [CI] 0.60 to 0.62; abdominal, C-statistic 0.67, 95% CI 0.64 to 0.70) and similar or better discrimination in the validation cohort (laparoscopic, C-statistic 0.67, 95% CI 0.65 to 0.69; abdominal, C-statistic 0.67, 95% CI 0.65 to 0.69). Adhesions were most predictive of complications in both models (laparoscopic, odds ratio [OR] 1.92, 95% CI 1.73 to 2.13; abdominal, OR 2.46, 95% CI 2.27 to 2.66). Other factors predictive of complications included adenomyosis in the laparoscopic model, and Asian ethnicity and diabetes in the abdominal model. Protective factors included age and diagnoses of menstrual disorders or benign adnexal mass in both models and diagnosis of fibroids in the abdominal model. INTERPRETATION: Personalized risk estimates from these models, which showed moderate discrimination, can inform clinical decision-making for people with benign conditions who may require hysterectomy

Predicting Subclinical Atherosclerosis in Low-Risk Individuals Ideal Cardiovascular Health Score and Fuster-BEWAT Score

BACKGROUND The ideal cardiovascular health score (ICHS) is recommended for use in primary prevention. Simpler tools not requiring laboratory tests, such as the Fuster-BEWAT (blood pressure [B], exercise [E], weight [W], alimentation [A], and tobacco [T]) score (FBS), are also available. OBJECTIVES The purpose of this study was to compare the effectiveness of ICHS and FBS in predicting the presence and extent of subclinical atherosclerosis. METHODS A total of 3,983 participants 40 to 54 years of age were enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) cohort. Subclinical atherosclerosis was measured in right and left carotids, abdominal aorta, right and left iliofemoral arteries, and coronary arteries. Subjects were classified as having poor, intermediate, or ideal cardiovascular health based on the number of favorable ICHS or FBS. RESULTS With poor ICHS and FBS as references, individuals with ideal ICHS and FBS showed lower adjusted odds of having atherosclerotic plaques (ICHS odds ratio [OR]: 0.41; 95\% confidence interval [CI]: 0.31 to 0.55 vs. FBS OR: 0.49; 95\% CI: 0.36 to 0.66), coronary artery calcium (CACS) >= 1 (CACS OR: 0.41; 95\% CI: 0.28 to 0.60 vs. CACS OR: 0.53; 95\% CI: 0.38 to 0.74), higher number of affected territories (OR: 0.32; 95\% CI: 0.26 to 0.41 vs. OR: 0.39; 95\% CI: 0.31 to 0.50), and higher CACS level (OR: 0.40; 95\% CI: 0.28 to 0.58 vs. OR: 0.52; 95\% CI: 0.38 to 0.72). Similar levels of significantly discriminating accuracy were found for ICHS and FBS with respect to the presence of plaques (C-statistic: 0.694; 95\% CI: 0.678 to 0.711 vs. 0.692; 95\% CI: 0.676 to 0.709, respectively) and for CACS >= 1 (C-statistic: 0.782; 95\% CI: 0.765 to 0.800 vs. 0.780; 95\% CI: 0.762 to 0.798, respectively). CONCLUSIONS Both scores predict the presence and extent of subclinical atherosclerosis with similar accuracy, highlighting the value of the FBS as a simpler and more affordable score for evaluating the risk of subclinical disease. (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.The PESA study was co-funded by Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Banco Santander. Funding was also provided by Institute of Health Carlos III (PI15/02019) and European Regional Development Fund. CNIC is supported by the Ministry of Economy, Industry and Competitiveness and Pro CNIC Foundation; and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work is part of a project that received funding from the European Union Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant 707642 and American Heart Association grant 14SFRN20490315. Dr. Bueno has received research funding from Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; is a consultant for Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speakers fees and travel and attendance support from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Ferrer, Novartis, Servier, and Medscape. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Matthew Budoff, MD, served as Guest Editor for this paper.S

Does Socioeconomic Status Influence the Risk of Subclinical Atherosclerosis?: A Mediation Model

BACKGROUND: Socioeconomic status (SES)-education, income level, and occupation-is associated with cardiovascular risk. OBJECTIVES: This study aimed to investigate the association between SES and subclinical atherosclerosis and the potential mechanisms involved. METHODS: SES, lifestyle habits (smoking, dietary patterns, physical activity, and hours of sleep), traditional risk factors, and subclinical atherosclerosis extent were prospectively assessed in 4,025 individuals aged 40 to 54 years without known cardiovascular disease enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) study. After factors associated with atherosclerosis were identified, a multiple mediation model was created to quantify the effect of SES on subclinical atherosclerosis as explained by lifestyle behaviors. RESULTS: Although education level was significantly associated with the presence of atherosclerosis, no differences were found according to income level in this population. Participants with lower education presented with a higher risk of generalized atherosclerosis than those with higher education (odds ratio: 1.46; 95% confidence interval: 1.15 to 1.85; p = 0.002). Lifestyle behaviors associated with both education level and atherosclerosis extent were: smoking status, number of cigarettes/day, and dietary pattern, which explained 70.5% of the effect of SES on atherosclerosis. Of these, tobacco habit (smoking status 35% and number of cigarettes/day 32%) accounted for most of the explained differences between groups, whereas dietary pattern did not remain a significant mediator in the multiple mediation model. CONCLUSIONS: Despite the relative economic homogeneity of the cohort, lower education level is associated with increased subclinical atherosclerosis, mainly mediated by the higher and more frequent tobacco consumption. Smoking cessation programs are still needed, particularly in populations with lower education level.The PESA study is cofunded equally by the Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; and Banco Santander, Madrid, Spain. The study also receives funding from the Institute of Health Carlos III (PI15/02019) and the European Regional Development Fund. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No707642; and from the American Heart Association under grantnumber14SFRN20490315. Dr. Bueno has received research funding from the Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; has received consulting fees from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speaking fees or support for attending scientific meetings from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Ferrer, Novartis, Servier, and MEDSCAPE-the heart.org.S

Entropy calculation for a toy black hole

In this note we carry out the counting of states for a black hole in loop quantum gravity, however assuming an equidistant area spectrum. We find that this toy-model is exactly solvable, and we show that its behavior is very similar to that of the correct model. Thus this toy-model can be used as a nice and simplifying `laboratory' for questions about the full theory.Comment: 18 pages, 4 figures. v2: Corrected mistake in bibliography, added appendix with further result

Oxidized LDL Is Associated With Metabolic Syndrome Traits Independently of Central Obesity and Insulin Resistance

This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baseline data from 3,987 subjects without diabetes in the Progression of Early Subclinical Atherosclerosis (PESA) Study. For the second, third, and fourth ox-LDL quartiles versus the first, the odds ratios (95% CI) for MS were 0.84 (0.52, 1.36), 1.47 (0.95, 2.32), and 2.57 (1.66, 4.04) (P < 0.001 for trend) once adjusted for age, sex, smoking, LDL-cholesterol, BMI, waist circumference, and HOMA-insulin resistance (HOMA-IR). Results showing the same trend were found for all MS components except glucose concentration. Ox-LDL mediated 13.9% of the association of waist circumference with triglycerides and only 1-3% of the association with HDL-cholesterol, blood pressure, and insulin concentration. HOMA-IR did not mediate the association between ox-LDL and MS components. This study found higher ox-LDL concentrations were associated with MS and its components independently of central obesity and insulin resistance. Ox-LDL may reflect core mechanisms through which MS components develop and progress in parallel with insulin resistance and could be a clinically relevant predictor of MS development.Y.H.-R. received support from Republic of Peru and the Inter-American Development Bank through FINCyT Science and Technology Program Scholarships No. 088-FINCyT-BDE-2014 under agreement 1663/OC-PE. M.L. received partial support from the Institute de Salud Carlos III, cofunded by the European Regional Development Fund/European Social Fund, "Investing in Your Future" grants PI10/00021 and PI14/00009. The PESA study is supported by a noncompetitive unrestricted grant shared between the CNIC and Santander Bank. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

Subclinical Atherosclerosis Burden by 3D Ultrasound in Mid-Life: The PESA Study

BACKGROUND: Detection of subclinical atherosclerosis improves risk prediction beyond cardiovascular risk factors (CVRFs) and risk scores, but quantification of plaque burden may improve it further. Novel 3-dimensional vascular ultrasound (3DVUS) provides accurate volumetric quantification of plaque burden. OBJECTIVES: The authors evaluated associations between 3DVUS-based plaque burden and CVRFs and explored potential added value over simple plaque detection. METHODS: The authors included 3,860 (92.2%) PESA (Progression of Early Subclinical Atherosclerosis) study participants (age 45.8 ± 4.3 years; 63% men). Bilateral carotid and femoral territories were explored by 3DVUS to determine the number of plaques and territories affected, and to quantify global plaque burden defined as the sum of all plaque volumes. Linear regression and proportional odds models were used to evaluate associations of plaque burden with CVRFs and estimated 10-year cardiovascular risk. RESULTS: Plaque burden was higher in men (63.4 mm3 [interquartile range (IQR): 23.8 to 144.8 mm3] vs. 25.7 mm3 [IQR: 11.5 to 61.6 mm3] in women; p < 0.001), in the femoral territory (64 mm3 [IQR: 27.6 to 140.5 mm3] vs. 23.1 mm3 [IQR: 9.9 to 48.7 mm3] in the carotid territory; p < 0.001), and with increasing age (p < 0.001). Age, sex, smoking, and dyslipidemia were more strongly associated with femoral than with carotid disease burden, whereas hypertension and diabetes showed no territorial differences. Plaque burden was directly associated with estimated cardiovascular risk independently of the number of plaques or territories affected (p < 0.01). CONCLUSIONS: 3DVUS quantifies higher plaque burden in men, in the femoral territory, and with increasing age during midlife. Plaque burden correlates strongly with CVRFs, especially at the femoral level, and reflects estimated cardiovascular risk more closely than plaque detection alone. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318).The PESA study is cofunded equally by the Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain, and Banco Santander, Madrid, Spain. The study also receives funding from the Institute of Health Carlos III (PI15/02019) and the European Regional Development Fund (ERDF). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MINECO) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Dr. Sanchez-Gonzalez is an employee of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Stephen J. Nicholls, MD, served as Guest Editor for this paperS

Development, validation and clinical utility of a risk prediction model for adverse pregnancy outcomes in women with gestational diabetes:The PeRSonal GDM model

BACKGROUND: The ability to calculate the absolute risk of adverse pregnancy outcomes for an individual woman with gestational diabetes mellitus (GDM) would allow preventative and therapeutic interventions to be delivered to women at high-risk, sparing women at low-risk from unnecessary care. We aimed to develop, validate and evaluate the clinical utility of a prediction model for adverse pregnancy outcomes in women with GDM. METHODS: A prediction model development and validation study was conducted on data from a observational cohort. Participants included all women with GDM from three metropolitan tertiary teaching hospitals in Melbourne, Australia. The development cohort comprised those who delivered between 1 July 2017 to 30 June 2018 and the validation cohort those who delivered between 1 July 2018 to 31 December 2018. The main outcome was a composite of critically important maternal and perinatal complications (hypertensive disorders of pregnancy, large-for-gestational age neonate, neonatal hypoglycaemia requiring intravenous therapy, shoulder dystocia, perinatal death, neonatal bone fracture and nerve palsy). Model performance was measured in terms of discrimination and calibration and clinical utility evaluated using decision curve analysis. FINDINGS: The final PeRSonal (Prediction for Risk Stratified care for women with GDM) model included body mass index, maternal age, fasting and 1-hour glucose values (75-g oral glucose tolerance test), gestational age at GDM diagnosis, Southern and Central Asian ethnicity, East Asian ethnicity, nulliparity, past delivery of an large-for-gestational age neonate, past pre-eclampsia, GWG until GDM diagnosis, and family history of diabetes. The composite adverse pregnancy outcome occurred in 27% (476/1747) of women in the development (1747 women) and in 26% (244/955) in the validation (955 women) cohorts. The model showed excellent calibration with slope of 0.99 (95% CI 0.75 to 1.23) and acceptable discrimination (c-statistic 0.68; 95% CI 0.64 to 0.72) when temporally validated. Decision curve analysis demonstrated that the model was useful across a range of predicted probability thresholds between 0.15 and 0.85 for adverse pregnancy outcomes compared to the alternatives of managing all women with GDM as if they will or will not have an adverse pregnancy outcome. INTERPRETATION: The PeRSonal GDM model comprising of routinely available clinical data shows compelling performance, is transportable across time, and has clinical utility across a range of predicted probabilities. Further external validation of the model to a more disparate population is now needed to assess the generalisability to different centres, community based care and low resource settings, other healthcare systems and to different GDM diagnostic criteria. FUNDING: This work is supported by the Mothers and Gestational Diabetes in Australia 2 NHMRC funded project #1170847

Assessment of goods and services, vulnerability, and conservation status of European seabed biotopes: a stepping stone towards ecosystem-based marine spatial management

The goal of ecosystem-based marine spatial management is to maintain marine ecosystems in a healthy, productive and resilient condition; hence, they can sustainably provide the needed goods and services for human welfare. However, the increasing pressures upon the marine realm threaten marine ecosystems, especially seabed biotopes, and thus a well-planned approach of managing use of marine space is essential to achieve sustainability. The relative value of seabed biotopes, evaluated on the basis of goods and services, is an important starting point for the spatial management of marine areas. Herein, 56 types of European seabed biotopes and their related goods, services, sensitivity issues, and conservation status were compiled, the latter referring to management and protection tools which currently apply for these biotopes at European or international level. Fishing activities, especially by benthic trawls, and marine pollution are the main threats to European seabed biotopes. Increased seawater turbidity, dredged sediment disposal, coastal constructions, biological invasions, mining, extraction of raw materials, shipping-related activities, tourism, hydrocarbon exploration, and even some practices of scientific research, also exert substantial pressure. Although some first steps have been taken to protect the European sea beds through international agreements and European and national legislation, a finer scale of classification and assessment of marine biotopes is considered crucial in shaping sound priorities and management guidelines towards the effective conservation and sustainability of European marine resources