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Abstract. Background: Coronavirus disease 2019 (COVID-19) threatens people's physical and mental health, globally, and it may even trigger suicide ideation and suicidal behavior. Aims: We aimed to examine the impact of COVID-19 on suicide risk by sampling Chinese Weibo users and analyzing their social media messages. Method: We predicted the probability of suicide (including hopelessness, suicidal ideation, negative self-evaluation, and hostility) of Weibo users in order to assess the changes in suicide probability at different times. Repeated-measures ANOVA was performed to examine the differences in suicide probability in different regions during different periods. Results: There was no significant difference in suicide probability between profoundly infected areas (PIAs) and less infected areas (LIAs) before the outbreak of COVID-19. LIAs had an increase in hopelessness during the COVID-19 growth period, while hopelessness and hostility in PIA increased during the COVID-19 decline period, indicating potential suicide probability. Limitations: Results should be interpreted with caution, and cross-cultural research may be considered in the future. Conclusion: COVID-19 has a dynamic impact on suicide probability. Using data from online social networks may help to understand the impact pattern of COVID-19 on people's suicide probability.

Background. Up to now, an accurate nomogram to predict the lung metastasis probability in Ewing sarcoma (ES) at initial diagnosis is lacking. Our objective was to construct and validate a nomogram for the prediction of lung metastasis in ES patients. Methods. A total of 1157 patients with ES from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. The predictors of lung metastasis were identified via the least absolute shrinkage and selection operator (LASSO) and multivariate logistic analysis. The discrimination and calibration of the nomogram were validated by receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was used to evaluate the clinical usefulness and net benefits of the prediction model. Results. Factors including age, tumor size, primary site, tumor extension, and other site metastasis were identified as the ultimate predictors for the nomogram. The calibration curves for the training and validation cohorts both revealed good agreement, and the Hosmer&ndash, Lemeshow test identified that the model was well fitted (p &gt, 0.05). In addition, the area under the ROC curve (AUC) values in the training and validation cohorts were 0.732 (95% confidence interval, CI: 0.607&ndash, 0.808) and 0.741 (95% CI: 0.602&ndash, 0.856), respectively, indicating good predictive discrimination. The DCA showed that when the predictive metastasis probability was between 1% and 90%, the nomogram could provide clinical usefulness and net benefit. Conclusion. The nomogram constructed and validated by us could provide a convenient and effective tool for clinicians that can improve prediction of the probability of lung metastasis in patients with ES at initial diagnosis.

Aim To determine the long-term probability of remission without antiepileptic treatment of common epileptic syndromes and of children without a specific syndromic diagnosis. Patients and methods All children less than 14 years old with 2 or more unprovoked seizures seen at our hospital between June 1, 1994, and March 1, 2011 (n = 680), were included and prospectively followed up until August 15, 2020. Syndromic diagnosis was made retrospectively but blinded to subsequent evolution, employing the data available at 6 months after diagnosis and under predefined operational criteria. Results The Kaplan-Meier estimate of the probability of achieving a remission period of at least 5 years, with neither seizures nor antiepileptic treatment at 14 years was 97% for well-defined childhood epilepsy with centrotemporal spikes, 82% for uncertain childhood epilepsy with centrotemporal spikes, 85% for well-defined Panayiotopoulos syndrome, 88% for uncertain Panayiotopoulos syndrome, 93% for nonfamilial self-limited infantile epilepsy, 100% for familial self-limited infantile epilepsy, 86% for absence epilepsy, 6% for juvenile myoclonic epilepsy, 71% for cryptogenic West syndrome, 72% for patients with no associated neurologic deficits and no specific syndromic diagnosis, 65% for symptomatic West syndrome, and 40% for patients with associated neurologic deficits and no specific syndromic diagnosis. Conclusions The study results highlight the long-term outcomes of the main epileptic syndromes and also of the patients with no syndromic diagnosis.

The geographical overlaps of malaria parasites and Salmonella spp. can lead to co-infection of these two pathogens, especially in the tropics where malaria is endemic. Moreover, few literatures suggested that malaria infection was associated with Salmonella bacteremia. Therefore, this study quantified pooled prevalence of typhoidal/non-typhoidal Salmonella (NTS) and probability of typhoidal/NTS and malaria co-infection among febrile patients. The systematic review protocol was registered at PROSPERO (CRD42021252322). Studies on co-infection of typhoidal/NTS and malaria were searched in PubMed, Scopus, and Web of Science. The risk of bias of the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. Meta-analyses on the following criteria were performed: (1) pooled prevalence of typhoidal/NTS and malaria co-infection among febrile patients, (2) pooled prevalence of typhoidal/NTS among malaria patients, (3) pooled prevalence of malaria infections among patients with Salmonella spp. infection, and (4) probability of typhoidal/NTS and malaria co-infection among febrile patients. Additionally, the case fatality rate and mean difference of malarial parasitemia between typhoidal/NTS and malaria co-infection and Plasmodium monoinfection were also determined. The subgroup analyses of typhoidal/NTS, regions (Africa and Asia), countries, time (publication year), characteristics of participants, and diagnostic tests for identifying Salmonella spp. were also conducted. A sensitivity test was performed to determine the robustness of the study outcomes. Publication bias among the included studies was evaluated using the funnel plot and Egger’s test. All analyses were performed using Stata version 15 (StataCorp LLC, Texas, USA) with a p-value 2, 99.4%; 2971/17,720 cases) and 1% (95% CI 1–1%; I2, 89.9%; 252/29,081 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of typhoidal/NTS infection among patients with malaria were 31% (95% CI 23–39%; I2, 99.5%; 3202/19,208 cases) and 3% (95% CI 2–3%; I2, 86.8%; 407/40,426 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of malaria infection among patients with typhoidal/NTS were 17% (95% CI 6–29%; I2, 33.3%; 13/75 cases) and 43% (95% CI 32–53%; I2, 89.1%; 287/736 cases), respectively. Malaria infection was associated with typhoidal/NTS in children aged 2, 73.9%; 3188/43,212 cases). The case fatality rate in patients with malaria and NTS co-infections was 16% (95% CI 9–24%; I2, 89.1%; 18/103 cases). From the view of the present study, the inappropriate use of the Widal test for Salmonella spp. diagnosis can overestimate the prevalence of typhoidal/NTS and malaria co-infections. Malaria infection associated with typhoidal/NTS in children and the high case fatality rates among few patients with co-infections were highlighted. Future prospective longitudinal studies using the appropriate and confirmatory dsiagnosis for Salmonella spp. infections are highly recommended to ensure the real prevalence of co-infection and highlight the outcome of co-infection for providing adequate treatment in febrile patients who live in areas where malaria is endemic, such as tropical Africa and India.

The analysis of the influence of predictors on the probability of retinal detachment in children of the Minsk region was carried out on the basis of a study of the medical records of 660 children's patients treated at the Health care Institutions "4th Children's City Clinical Hospital" and “Minsk Regional Children's Clinical Hospital” for the period 2009–2019. Of these, 313 patients were older than 1 year with an established diagnosis of retinal detachment, 107 children under the age of 1 year, 240 children older than 1 year without retinal detachment at the time of treatment and the presence of predictors of its development (comparison group). To assess the influence of factors, a methodology based on the calculation of the odds ratio was used. The most significant risk factors were assigned a score equivalent from one to four, which allowed quantifying the probability of retinal detachment and identifying risk groups depending on the total score. The use of the proposed method allowed the children of the comparison group to identify changes in the vitreoretinal interface, which required primary laser preventive treatment in 46.7% of cases (113 eyes) during the three-year follow-up period, in 45.4% of children (109 eyes) it was limited only to dynamic observation without treatment. In 95.0% of children in the comparison group, it was possible to prevent the development of retinal detachment.

BACKGROUND A decrease in glutathione (GSH) levels is considered one of the earliest biochemical changes in Parkinson's disease (PD). OBJECTIVE The authors explored the potential role of plasma GSH as a risk/susceptibility biomarker for prodromal PD (pPD) by examining its longitudinal associations with pPD probability trajectories. METHODS A total of 405 community-dwelling participants (median age [interquartile range] = 73.2 [7.41] years) without clinical features of parkinsonism were followed for a mean (standard deviation) of 3.0 (0.9) years. RESULTS A 1 μmol/L increase in plasma GSH was associated with 0.4% (95% confidence interval [CI], 0.1%-0.7%; P = 0.017) less increase in pPD probability for 1 year of follow-up. Compared with participants in the lowest GSH tertile, participants in the highest GSH tertile had a 12.9% (95% CI, 22.4%-2.2%; P = 0.020) slower rate of increase of pPD probability for 1 year of follow-up. CONCLUSION Plasma GSH was associated with pPD probability trajectories; therefore, it might assist in the identification of individuals who are likely to reach the threshold for pPD diagnosis more rapidly. © 2021 International Parkinson and Movement Disorder Society.

As a reaction to the pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a multitude of clinical trials for the treatment of SARS‐CoV‐2 or the resulting corona disease 2019 (COVID‐19) are globally at various stages from planning to completion. Although some attempts were made to standardize study designs, this was hindered by the ferocity of the pandemic and the need to set up clinical trials quickly. We take the view that a successful treatment of COVID‐19 patients (i) increases the probability of a recovery or improvement within a certain time interval, say 28 days; (ii) aims to expedite favorable events within this time frame; and (iii) does not increase mortality over this time period. On this background, we discuss the choice of endpoint and its analysis. Furthermore, we consider consequences of this choice for other design aspects including sample size and power and provide some guidance on the application of adaptive designs in this particular context.

Background The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function. Methods Baseline renal function was categorized as normal renal function (creatinine clearance 80–130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit. Results A > 99% and > 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [− 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; − 2.6 [− 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; − 2.1 [− 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [− 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [− 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [− 8.7 to 19.0]). Conclusions C/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

PURPOSE: To determine the influence of different genotypes of Ala307Thr and Asn680Ser FSHr polymorphisms on controlled ovarian stimulation (COS) outcome and pregnancy. METHODS: This study collected blood and physiological and clinical parameters of 517 Caucasian patients (Statistical power ≥ 80%) that underwent COS treatment. Genotypes of Ala307Thr and Asn680Ser polymorphisms were determined using PCR amplification followed by Bsu36I and BsrI digestion, respectively. RESULTS: Ala307Ala and Ser680Ser genotypes associated to worse parameters of COS outcome (preovulatory follicles P = 0.05, in both), justifying their lower pregnancy rate than Non-Ala307Ala, P = 0.01 and Non-Ser680Ser, P = 0.004, respectively or together, (P = 0.003). Within the Non-Ala307Ala group, Thr307Thr genotype showed higher number of fertilized oocytes (P = 0.04) and embryos (P = 0.01) than Non-Thr307Thr, but no influence on pregnancy rate. Ala307Ala and Ser680Ser patients doubled probability of non-pregnancy than Non-Ala307Ala (odds ratio = 2.0) and Non-Ser680Ser (odds ratio = 2.11), respectively. Ala307Ala and Ser680Ser genotypes tend to appear together (P < 0.0001), which increases the probability of non-pregnancy. CONCLUSIONS: Ala307Ala and Ser680Ser genotypes of 307 and 680 FSHr polymorphisms associate to worse COS outcome than its respective Non-Ala307Ala and Non-Ser680Ser. Within the Non-Ala307Ala genotypes, Thr307Thr, although shows higher Fertilized Oocytes and Embryos, do not influence on pregnancy rate. Ala307Ala and Ser680Ser genotypes double the probability of Non-Pregnancy than their respective Non-Ala307Ala and Non-Ser680Ser genotypes. Furthermore, the strong tendency of these genotypes to appear together worsens the probability of pregnancy in these patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02276-0.

Summary Colorectal cancer is a heterogeneous disease with diverse prognoses between left-sided and right-sided patients; therefore, it is necessary to precisely evaluate the survival probability of side-specific colorectal cancer patients. Here, we collected multi-omics data from The Cancer Genome Atlas program, including gene expression, DNA methylation and microRNA expression. Specificity measure and robust likelihood-based survival analysis were used to identify 6 left-sided and 28 right-sided prognostic biomarkers. Compared to the performance of clinical prognostic models, the addition of these biomarkers could significantly improve the discriminatory ability and calibration in predicting side-specific 5-year survival for colorectal cancer. Additional dataset derived from Gene Expression Omnibus was used to validate the prognostic value of side-specific genes. Finally, we constructed colorectal cancer side-specific molecular database (CoSMeD), a user-friendly interface for estimating side-specific colorectal cancer 5-year survival probability, which can lay the basis for personalized management of left-sided and right-sided colorectal cancer patients. Availability and implementation CoSMeD is freely available at https://mulongdu.shinyapps.io/cosmed. Supplementary information Supplementary data are available at Bioinformatics online.

Contains fulltext : 244552.pdf (Publisher’s version ) (Open Access) BACKGROUND: Histology restricted genetic predisposition testing of ovarian carcinoma patients is a topic of debate as the prevalence of BRCA1/2 pathogenic variants (PVs) in various histological subtypes is ambiguous. Our primary aim was to investigate the proportion of germline BRCA1/2 PVs per histological subtype. Additionally, we evaluated (i) proportion of somatic BRCA1/2 PVs and (ii) proportion of germline PVs in other ovarian carcinoma risk genes. METHODS: PubMed, EMBASE and Web of Science were systematically searched and we included all studies reporting germline BRCA1/2 PVs per histological subtype. Pooled proportions were calculated using a random-effects meta-analysis model. Subsets of studies were used for secondary analyses. RESULTS: Twenty-eight studies were identified. The overall estimated proportion of germline BRCA1/2 PVs was 16.8% (95% CI 14.6 to 19.2). Presence differed substantially among patients with varying histological subtypes of OC; proportions being highest in high-grade serous (22.2%, 95% CI 19.6 to 25.0) and lowest in clear cell (3.0%, 95% CI 1.6 to 5.6) and mucinous (2.5%, 95% CI 0.6 to 9.6) carcinomas. Somatic BRCA1/2 PVs were present with total estimated proportion of 6.0% (95% CI 5.0 to 7.3), based on a smaller subset of studies. Germline PVs in BRIP1, RAD51C, RAD51D, PALB2, and ATM were present in approximately 3%, based on a subset of nine studies. CONCLUSION: Germline BRCA1/2 PVs are most frequently identified in high-grade serous ovarian carcinoma patients, but are also detected in patients having ovarian carcinomas of other histological subtypes. Limiting genetic predisposition testing to high-grade serous ovarian carcinoma patients will likely be insufficient to identify all patients with a germline PV.

Purpose: Osteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no normal tissue complication probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORNI-IV) and grade IV (ORNIV) after RT (+/- chemotherapy) in patients with HNC.Methods and Materials: Included patients with HNC were treated with (chemo-)RT between 2005 and 2015. Mandible bone radiation dose-volume parameters and clinical variables (ie, age, sex, tumor site, pre-RT dental extractions, chemotherapy history, postoperative RT, and smoking status) were considered as potential predictors. The patient cohort was randomly divided into a training (70%) and independent test (30%) cohort. Bootstrapped forward variable selection was performed in the training cohort to select the predictors for the NTCP models. Final NTCP model(s) were validated on the holdback test subset.Results: Of 1259 included patients with HNC, 13.7% (n = 173 patients) developed any grade ORN (ORNI-IV primary endpoint) and 5% (n = 65) ORNIV (secondary endpoint). All dose and volume parameters of the mandible bone were significantly associated with the development of ORN in univariable models. Multivariable analyses identified D30% and pre-RT dental extraction as independent predictors for both ORNI-IV and ORNIV best-performing NTCP models with an area under the curve (AUC) of 0.78 (AUCvalidation = 0.75 [0.69-0.82]) and 0.81 (AUCvalidation = 0.82 [0.74-0.89]), respectively.Conclusions: This study presented NTCP models based on mandible bone D30% and pre-RT dental extraction that predict ORNI-IV and ORNIV (ie, needing invasive surgical intervention) after HNC RT. Our results suggest that less than 30% of the mandible should receive a dose of 35 Gy or more for an ORNI-IV risk lower than 5%. These NTCP models can improve ORN prevention and management by identifying patients at risk of ORN. (C) 2021 The Author(s). Published by Elsevier Inc.

Introduction: Stereotactic ablative radiotherapy (SABR) can achieve good local control for metastatic adrenal lesions. Magnetic resonance (MR)-guidance with daily on-table plan adaptation can augment the delivery of SABR with greater dose certainty. The goal of this study was to quantify the potential clinical benefit MR-guided daily-adaptive adrenal SABR using the normal tissue complication probability (NTCP) framework. Methods: Patients treated with adrenal MR-guided SABR at a single institution were retrospectively reviewed. Lyman-Kutcher-Burman NTCP models were used to calculate the NTCP of upper abdominal organs-at-risk (OARs) at simulation and both before and after daily on-table plan adaptation. Differences in OAR NTCPs were assessed using signed-rank tests. Potential predictors of the benefits of adaptation were assessed by linear regression. Results: Fifty-two adrenal MR-guided SABR courses were analyzed. The baseline simulation plan underestimated the absolute stomach NTCP by 10.0% on average (95% confidence interval: 4.7–15.2%, p < 0.001). Daily on-table adaptation lowered absolute NTCP by 8.7% (4.2–13.2%, p < 0.001). The most significant predictor of the benefits of adaptation was lesion laterality (p = 0.018), with left-sided lesions benefitting more (13.3% [6.3–20.4%], p < 0.001) than right-sided lesions (2.1% [−1.6–5.7%], p = 0.25). Sensitivity analyses did not change the statistical significance of the findings. Conclusion: NTCP analysis revealed that patients with left adrenal tumors were more likely to benefit from MR-guided daily on-table adaptive SABR using current dose/fractionation regimens due to reductions in predicted gastric toxicity. Right-sided adrenal lesions may be considered for dose escalation due to low predicted NTCP.

STUDY QUESTION Does the probability of a live birth after fresh IVF/ICSI cycles with autologous oocytes differ in early onset female cancer survivors compared to their siblings? SUMMARY ANSWER The probability of a live birth was similar in female cancer survivors and siblings after four fresh IVF/ICSI cycles. WHAT IS KNOWN ALREADY Fertility preservation strategies are rapidly being developed to help female cancer patients who wish to have children later. However, there are only a few studies available on fertility treatments and following live births in female cancer survivors before fertility preservation strategies became available. In one of them, the probability of a live birth was reduced after assisted reproductive technology with autologous oocytes in cancer survivors compared to siblings. STUDY DESIGN, SIZE, DURATION In this retrospective, register-based study, data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8944 female cancer survivors (diagnosed with cancer between 1953 and 2012 at the age of 0–40 years) and 9848 female siblings of survivors eligible for IVF/ICSI treatments between January 1993 and December 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Fresh IVF/ICSI cycles and following live birth rates (LBRs) within 22–48 weeks in cancer survivors and siblings at the age of 20–41 years were identified. A binomial regression model with log-link function was used to calculate risk ratio (RR) for live births after fresh IVF/ICSI cycles in survivors compared to siblings, adjusting for attained age and calendar time. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for an IVF/ICSI treatment, as well as overall live births, including both pregnancies after fertility treatments and spontaneous pregnancies, in survivors compared to siblings. MAIN RESULTS AND THE ROLE OF CHANCE We observed an overall decreased LBR, irrespective of IVF/ICSI treatments, in cancer survivors compared to siblings (IRR 0.68, 95% CI 0.64–0.71). All in all, 179 (2.0%) survivors and 230 (2.3%) siblings were prescribed fertility drugs for IVF/ICSI treatments (IRR 0.72, 95% CI 0.62–0.84). For the first fresh IVF/ICSI cycle, the LBR was 17.2% among survivors and 15.7% among siblings (RR 1.13, 95% CI 0.72–1.87). The mean LBR after four fresh IVF/ICSI cycles was not statistically different in survivors compared to siblings. LIMITATIONS, REASONS FOR CAUTION In this study, only IVF/ICSI treatments with autologous oocytes were included. The probability of a live birth after a frozen embryo transfer or oocyte donation could not be evaluated in this study. Information on miscarriages, extrauterine pregnancies or termination of pregnancies was not available. WIDER IMPLICATIONS OF THE FINDINGS For those early onset cancer survivors, who received IVF/ICSI treatments, the probability of live birth was not different from siblings who received IVF/ICSI treatments. However, an overall decreased LBR, irrespective of IVF/ICSI treatments, was observed in cancer survivors compared to siblings, indicating that cancer survivors receiving IVF/ICSI treatments in our study consisted of a selected group with at least a moderate ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by a grant from the Cancer Foundation (Finland) (grant number 130079) and by a grant from LähiTapiola. The authors have no potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

The survival of completely buried victims in an avalanche mainly depends on burial duration. Knowledge is limited about survival probability after 60 min of complete burial. We aimed to study the survival probability and prehospital characteristics of avalanche victims with long burial durations. We retrospectively included all completely buried avalanche victims with a burial duration of ≥60 min between 1997 and 2018 in Switzerland. Data were extracted from the registry of the Swiss Institute for Snow and Avalanche Research and the prehospital medical records of the physician-staffed helicopter emergency medical services. Avalanche victims buried for ≥24 h or with an unknown survival status were excluded. Survival probability was estimated by using the non-parametric Ayer-Turnbull method and logistic regression. The primary outcome was survival probability. We identified 140 avalanche victims with a burial duration of ≥60 min, of whom 27 (19%) survived. Survival probability shows a slight decrease with increasing burial duration (23% after 60 min, to

Objectives To elaborate an ECG-based nomogram estimating the probability to detect cardiac involvement by cardiac magnetic resonance (CMR) in Fabry Disease (FD). Methods 119 FD patients and 26 healthy controls underwent ECG and CMR. Test (n = 88, 60%) and validation cohorts (n = 57, 40%) were randomly derived. Cardiac involvement was defined as the presence of low myocardial T1 value, a CMR-surrogate of myocardial glycosphingolipid storage. ECG changes associated with low T1 value were identified in the test cohort, included in the nomogram and then tested in the validation cohort. Results Sokolow-Lyon index (AUC = 0.769), ratio between P-wave and PR-segment durations (Pwave/PRsegment) (AUC = 0.778), QRS duration (AUC = 0.703), QT (AUC = 0.769) duration were independently associated with the presence of low T1 on CMR at multivariate analysis. An ECG-based nomogram including these four parameters was accurate in identifying patients with CMR evidence of glycosphingolipid storage (c-index of the derived-nomogram = 0.90 in the test group; 0.81 in the validation group). Conclusion We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.

Aim: The purpose of the study is the development and evaluation of the informativeness of the author’s 3D nephrometric score application to predict the probability of intraoperative and postoperative complications in kidney operations. Material and methods: The study includes 264 patients who underwent surgical treatment of renal tumors, before that CT and 3D modeling were carried out. All patients underwent an analysis of the surgical intervention complexity on the C-index, PADUA, R.E.N.A.L., and developed 3D nephrometric score. To determine the set of variables that allow to classify patients, the method of discriminant analysis was used to predict the nature, volume of blood loss, duration of ischemia, and the number of complications. The sensitivity and specificity of the predictors were estimated with the help of ROC analysis. Results: Indicators have been established to classify patients according to the probability of complications, the amount of blood loss and the duration of ischemia during surgery for kidney cancer. We have created linear models that predict the development of bleeding during surgery, the volume of blood loss of more than 200 ml and the duration of ischemia more than 20 min, as well as the likelihood of complications using discriminant functions. The proposed author’s nephrometric score exceeds the capabilities of C-index, PADUA, R.E.N.A.L in many ways in blood loss and time of ischemia predicting, which allows us to recommend it for the assessment of resectability in kidney operations.

BACKGROUND AND PURPOSE: Several modifiable lifestyle factors have been associated with the onset and health outcomes of multiple sclerosis (MS), including clinically significant fatigue. A combined lifestyle score approach represents one method of assessing their relationship with clinical outcomes. The aim was to examine the association of two lifestyle scores with clinically significant fatigue and change thereof over 2.5 years' follow-up using inverse probability treatment weighting (IPTW). METHODS: Data on sociodemographic, lifestyle, and clinical characteristics surveyed from an international cohort of people with MS at baseline and at 2.5-year follow-up were used. Fatigue was defined by the Fatigue Severity Scale (FSS >5) and healthy lifestyle by the Healthy Lifestyle Index Score (HLIS) and the Smoking, Nutrition, Alcohol Consumption and Physical Activity (SNAP) score. Analyses were by IPTW accounting for age, sex, MS type, disability, treated comorbidity number, immunomodulatory medication use, prescription antifatigue medication use, and ongoing relapse symptoms. RESULTS: In total, 1268 participants completed the FSS at both time points; approximately 62% had fatigue. Using doubly robust IPTW, high (>11/20) HLIS (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.81-0.98) and high (>3/5) SNAP (OR 0.82, 95% CI 0.73-0.90) were each associated with lower risk of fatigue at follow-up. Evaluating change in fatigue, a higher SNAP score was associated with a lower risk of fatigue (OR 0.89, 95% CI 0.80-0.97) but the score for HLIS did not reach statistical significance (OR 0.93, 95% CI 0.85-1.01). CONCLUSION: These results suggest a robust role for key lifestyle factors in preventing clinically significant fatigue and may represent a place for lifestyle modification in improving clinical outcomes in MS.

OBJECTIVE Decisions in glioblastoma surgery are often guided by presumed eloquence of the tumor location. The authors introduce the “expected residual tumor volume” (eRV) and the “expected resectability index” (eRI) based on previous decisions aggregated in resection probability maps. The diagnostic accuracy of eRV and eRI to predict biopsy decisions, resectability, functional outcome, and survival was determined. METHODS Consecutive patients with first-time glioblastoma surgery in 2012–2013 were included from 12 hospitals. The eRV was calculated from the preoperative MR images of each patient using a resection probability map, and the eRI was derived from the tumor volume. As reference, Sawaya’s tumor location eloquence grades (EGs) were classified. Resectability was measured as observed extent of resection (EOR) and residual volume, and functional outcome as change in Karnofsky Performance Scale score. Receiver operating characteristic curves and multivariable logistic regression were applied. RESULTS Of 915 patients, 674 (74%) underwent a resection with a median EOR of 97%, functional improvement in 71 (8%), functional decline in 78 (9%), and median survival of 12.8 months. The eRI and eRV identified biopsies and EORs of at least 80%, 90%, or 98% better than EG. The eRV and eRI predicted observed residual volumes under 10, 5, and 1 ml better than EG. The eRV, eRI, and EG had low diagnostic accuracy for functional outcome changes. Higher eRV and lower eRI were strongly associated with shorter survival, independent of known prognostic factors. CONCLUSIONS The eRV and eRI predict biopsy decisions, resectability, and survival better than eloquence grading and may be useful preoperative indices to support surgical decisions.

A goal of rehabilitation after stroke is to promote pre-stroke levels of arm use for every day, frequently bimanual, functional activities. We reasoned that, after a stroke, the choice to use one or both hands for bimanual tasks might depend not only on residual motor capacity, but also the specialized demands imposed by the task on the paretic hand. To capture spontaneous, task-specific choices, we covertly observed 50 pre-stroke right-handed chronic stroke survivors (25 each of left, LHD, and right-hemisphere damage, RHD) and 11 age-similar control adults and recorded their hand use strategies for two pairs of bimanual tasks with distinct demands: one with greater precision requirements (photo-album tasks), and another with greater stabilization requirements (letter-envelope tasks). The primary outcome was the choice to use one or both hands. Logistic regression was used to test the two hypotheses that the probability of choosing a bimanual strategy would be greater in those with less severe motor impairment and also in those with LHD. When collapsed across the four tasks, we found support for these hypotheses. Notably, however, the influence of these factors on bimanual choice varied based on task demands. For the photo–album pair, the probability of a bimanual strategy was greater for those with LHD compared to RHD, regardless of the degree of motor impairment. For the letter–envelope pair, we found a significant interaction between impairment and side of lesion in determining the likelihood of choosing both hands. Therefore, the manner in which side of lesion moderates the effect of impairment on hand use depends on the task.

Objective To explore the risk probability and main influencing factors of stroke in followed-up hypertension patients through the analysis of long-term followed-up cohort data. Methods The method of followed-up observation cohort was used to collect the information of 168,417 followed-up hypertension patients from 2002 to 2020 in Jiading District in Shanghai. Kaplan–Meier method was used to analyze the risk probability of stroke complications in long-term followed-up HTN patients, and the influencing factors were analyzed by Cox proportional risk model. Results Among 168,417 followed-up hypertension patients, 11,143 cases had suffered stroke, and the cumulative incidence rate of stroke was 6.62% (male was 6.87%, female was 6.37%). With the extension of the hypertension years, the cumulative risk probability of stroke in HTN patients would continue to increase and the interval was not equidistant. The total cumulative risk probability of stroke in HTN patients was 78.9% (male was 91.0%, female was 70.7%). During the period of hypertension, the risk occurring probability of stroke was not fixed, but fluctuating. There were 4 onset peaks, which were in 8 years (probability was 4.2%), 15 years (probability was 14.0%), 22 years (probability was 6.0%) and 26 years (probability was 13.9%). The highest risk probability of male patients was in 26 years (probability was 23.1%), and the second peak was in 15 years (probability was 15.6%). The highest risk probability of female patients was in 15 years (probability was 12.9%), and the second peak was in 26 years (probability was 8.7%). The risk probability of different gender, BP grade and BMI was different, the male were at higher risk than the female, stage 3 HTN was higher than stage 2 and stage 1 HTN, obese people and underweight people were at higher risk than those who have normal weight. The main factors closely related to the occurrence of stroke complications were age (RR = 2.917, p p p p Conclusion The risk probability of stroke among hypertension patients was high in followed-up hypertension patients (total 78.9%, male 91.0%, female 70.7%), and would continue to increase disproportionately during period of hypertension (4 different onset peaks). With the persistence of hypertension, the risk probability of stroke would increase continuously. Multivariate Cox regression analysis showed that male patients, patients with HBP, abnormal BMI and positive family history were main factors closely related to the occurrence of stroke complications.

Choking/strangulation during sex is prevalent among young adults in the United States. We examined associations between having ever been choked and participants' current mental health symptoms (e.g., feeling depressed, anxious, sad, lonely) in the prior 30 days and in the prior year. Participants were 4352 randomly sampled undergraduates who completed a confidential online survey and reported lifetime partnered sexual activity. 33.6% of women and 6.0% of men reported having been choked more than five times. After adjusting for demographic characteristics, having been choked remained significantly associated with all four mental health outcomes, except for overwhelming anxiety among men.

The high-probability (high-p) instructional sequence typically consists of the delivery of a series of high-p instructions immediately followed by the delivery of a low-probability (low-p) instruction and is a commonly used procedure to increase compliance among children with intellectual disabilities. In the current study, we used withdrawal designs to evaluate the use of the high-p sequence to increase compliance with a series of 2 or 3 low-p instructions among 3 children with autism. The sequence was moderately effective in increasing compliance with all low-p instructions for 2 participants. Compliance exhibited by the 3rd participant, for whom the high-p sequence was ineffective, increased when differential reinforcement was delivered. We discuss the utility of the high-p sequence to increase compliance with multiple instructions and the putative mechanisms responsible for the effects of the sequence.

Background: Several studies have reported that abdominal fat and muscle changes occur in diabetic patients. However, there are few studies about such changes among prediabetic patients. In this study, we evaluated the differences in abdominal fat and muscles based on abdominopelvic computed tomography in prediabetic and diabetic subjects compared to normal subjects.Methods: We performed a cross-sectional study using health examination data from March 2014 to June 2019 at Ulsan University Hospital and classified subjects into normal, prediabetic, and diabetic groups. We analyzed the body mass index corrected area of intra-abdominal components among the three groups using inverse probability treatment weighting (IPTW) analysis.Results: Overall, 8,030 subjects were enrolled; 5,137 (64.0%), 2,364 (29.4%), and 529 (6.6%) subjects were included in the normal, prediabetic, and diabetic groups, respectively. After IPTW adjustment of baseline characteristics, there were significant differences in log visceral adipose tissue index (VATI; 1.22±0.64 cm2/[kg/m2] vs. 1.30±0.63 cm2/[kg/m2] vs. 1.47±0.64 cm2/[kg/m2], P

Prior research has described women's experiences with exercise-induced orgasm (EIO). However, little is known about men's experiences with EIO, the population prevalence of EIO, or the association of EIO with other kinds of orgasm. Using U.S. probability survey data, the objectives of the present research were to: (1) describe the lifetime prevalence of exercise-induced orgasm (EIO) and sleep orgasm; (2) assess respondents' age at first experience of EIO as well as the type of exercise connected with their first EIO; (3) examine associations between lifetime EIO experience and orgasm at respondents' most recent partnered sexual event; and (4) examine associations between lifetime EIO experience and sleep orgasms. Data were from the 2014 National Survey of Sexual Health and Behavior (1012 men and 1083 women, ages 14 years and older). About 9% of respondents reported having ever experienced exercise-induced orgasm. More men than women reported having experienced orgasm during sleep at least once in their lifetime (66.3% men, 41.8% women). The mean age for women's first EIO was significantly older than men (22.8 years women, 16.8 years men). Respondents described a wide range of exercises as associated with their first EIO (i.e., climbing ropes, abdominal exercise, yoga). Lifetime EIO experience was associated with lifetime sleep orgasms but not with event-level orgasm during partnered sex. Implications related to understanding orgasm and recommendations for clinicians and sex educators are discussed.

PURPOSE: Stereotactic body radiation therapy (SBRT) has emerged as a viable reirradiation strategy for locally recurrent previously-irradiated head and neck cancer. Doses in the literature have varied, which challenges clinical application of SBRT as well as clinical trial design. MATERIAL & METHODS: A working group was formed through the American Association of Physicists in Medicine to study tumor control probabilities for SBRT in head and neck cancer. We herein present a systematic review of the available literature addressing the dose/volume data for tumor control probability with SBRT in patients with locally recurrent previously-irradiated head and neck cancer. Dose-response models are generated that present tumor control probability as a function of dose. RESULTS: Data from more than 300 cases in 8 publications suggest that there is a dose-response relationship, with superior local control and possibly improved overall survival for doses of 35 to 45 Gy (in 5 fractions) compared with

Background D-dimer levels below a well-defined cut-off level enable to safely rule out VTE in patients with a low or intermediate pre-test probability (PTP), as the test negative predictive value (NPV) was high. As ageing is associated with increased D-dimer levels, the question was raised of the usefulness of their measurement to rule out VTE in elderly patients. Various attempts were made in the recent years to address that issue, particularly the use of age-adjusted cut-off values calculated by multiplying the patient's age by 10, in patients aged over 50. Aim of that study The aim of the study was to validate such a strategy, and to evaluate its economic impact in unselected outpatients referred to the emergency departments of 5 French centres (2 university hospitals, and 3 general hospitals). Patients, Materials and Methods After exclusion of those on anticoagulant treatment at the time of the diagnosis (n=23), a total of 1255 consecutive patients with a non-high PTP of VTE were included in the study. The same standardized procedure was used in the 5 centres, i.e. D-dimer measurement in patients with a non-high PTP, and imaging techniques (usually computed pulmonary angiography in case of suspected PE and Doppler ultrasonography in case of suspected DVT) only when D-dimer was above the cut-off level. D-dimer was evaluated using the same latex-based fully automated assay (HemosIL D-dimer HS500 assay, Instrumentation Laboratory). Test results were expressed in ng/mL fibrinogen equivalent units (FEU), and the traditional cut-off level for VTE exclusion was 500 ng/mL. Results VTE was diagnosed in 105 patients of the 1255 included patients (8.4%): 88 patients were diagnosed out of the 1082 patients referred for suspected PE and 27 out the 173 referred for suspected DVT. D-dimer levels were above 500 ng/mL in all patients with VTE and in 521 of the 1150 patients without VTE (45.3%). The test NPV was 100% as well as its sensitivity. If the overall test specificity was 54.7%, it significantly decreased in an age-dependent manner over 70 years, related to a high percentage of increased D-dimer levels in elderly patients, particularly in those above 80 years. Using age-adjusted cut-off levels, calculated by multiplying the patient's age by 10, induced a significantly improvement in test specificity, particularly in very old patients with an overall NPV=60.2% vs. 54.7% using the fixed cut-off value. The overall NPV remained high (99.9%), even if a 78 y-old female with a low PTP of PE would have been misdiagnosed as her D-dimer level (540 ng/mL) was above 500 ng/mL but below the age-adjusted cut-off value. Such an improvement in test performance was found both in patients with suspected PE and DVT (Table). As this increase in test specificity would have led to exclude VTE in a higher percentage of patients in the studied population, we evaluated the cost-effectiveness of that strategy, taking into account the local cost of D-dimer testing, angiography and Doppler US (16.20, 58.72, and 75.60 Euros respectively). In the case of suspected PE, the economic impact of the proposed diagnosis strategy was a decreased of 6.9% of total costs (45,023.4 vs. 48,356.4 Euros). In the case of DVT, the overall saving was 5.1% (9,909 vs. 10,438.2 Euros). If such an analysis was used in the US, where angiography and Doppler US were more expensive (648 and 226 US$ respectively), and D-dimer less costly (14 US$), the cost savings would have been even higher (-11.0% for PE, and -6.3% for DVT). Conclusions The use age-adjusted cut-off levels for D-dimer, in patients aged over 50 years old, leaded to a significant increase in the test specificity, but correlatively to slightly decreased NPV and sensitivity, as some patients with D-dimer levels above 500 ng/mL but below the age-adjusted cut-off value could be misdiagnosed. However such a strategy was found to be safe in our studied populations, as the NPV remained high (99.9%), and cost-effective. Table Table. Disclosures No relevant conflicts of interest to declare.

We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose–volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance–covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child–Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74–0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.

Purpose The extent of lymphadenectomy and clinical features influence the risk of occult nodes in node-negative prostate cancer. We derived a simple estimation model for the negative predictive value (npv) of histopathologically node-negative prostate cancer patients (pN0) to guide adjuvant treatment. Methods Approximations of sensitivities in detecting lymph node metastasis from current publications depending on the number of removed lymph nodes were used for a theoretical deduction of a simplified formulation of npv assuming a false node positivity of 0. Results A theoretical formula of npv = p(N0IpN0) = (100 − prevalence) / (100 − sensitivity × prevalence) was calculated (sensitivity and preoperative prevalence in %). Depending on the number of removed lymph nodes (nLN), the sensitivity of pN0-staged prostate cancer was derived for three sensitivity levels accordingly: sensitivity = f(nLN) = 9 × nLN /100 for 0 ≤ nLN ≤ 8 and f(nLN) = (nLN + 70) /100 for 9 ≤ nLN ≤ 29 and f(nLN) = 1 for nLN ≥ 30. Conclusion We developed a theoretical formula for estimation of the npv in pN0-staged prostate cancer patients. It is a sine qua non to use the formula in a clinically experienced context before deciding to electively irradiate pelvic lymph nodes or to intensify adjuvant systemic treatment.

To evaluate the optimal timing of neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). Data from a retrospective cohort study conducted by the Japanese CDH Study Group between 2011 and 2018 were divided into two groups according to delivery timing: 36–37 and 38–41 weeks of gestation (wg). Death before 90 days as the primary outcome and the duration of hospitalization, oxygen therapy and tube feeding at discharge as the secondary outcomes were analyzed with generalized linear model applying inverse probability of treatment weighting method. We also performed layered analysis according to stomach position. Among 493 neonates with prenatally diagnosed, isolated and left CDH, 237 were born at 38–41wg. The duration of hospitalization was significantly shorter in those born at 38–41wg, especially among those with stomach malposition, and the other outcomes showed no difference. Delivery at 38–41wg could be beneficial for those with high grade stomach position.

Venous thromboembolism is a significant clinical entity that includes two associated medical disorders: deep vein thrombosis and pulmonary embolism. The goal of this article is to describe the optimal approach to evaluating venous thromboembolism including pretest probability clinical decision rules and appropriate testing to ensure an accurate diagnosis.

Background: Cardiopulmonary resuscitation (CPR) is occurring more frequently at community hospitals but most patients undergoing CPR do not survive to discharge. Tools to predict CPR survival can be improved by the identification of high-yield clinical indicators.Objective: To identify variables associated with survival to discharge following in-hospital cardiac arrest.Methods: Retrospective cohort study of 463,530 hospital admissions from the Nationwide Inpatient Sample (2012–2016). The analysis includes adults (age ≥50) who underwent in-hospital CPR at US community hospitals.Results: Overall survival to discharge was 29.8% (95% CI: 29.5–30.1%). Age was the strongest predictor of survival and had greater prognostic value than the Charlson comorbidity index. Obesity was associated with improved survival (35.9%, 95% CI: 35.1–36.7%), whereas underweight patients had decreased survival (24.0%, 95% CI: 22.2–25.7%). Acute indicators of poor survival included hyperkalemia, hypercalcemia, and sepsis. We generated an ABCD index based upon four high-yield variables (age, body habitus, comorbidity, day of hospital admission). An ABCD score of 2 or less was a sensitive but non-specific predictor of post-CPR survival (96.8% sensitivity, 95% CI: 96.6–97.0), and those with extreme scores differed 3.8-fold with respect to post-CPR survival probability (46.0% versus 12.1%).Conclusion: Age is the strongest predictor of post-CPR survival, but body habitus is also an important indicator that may currently be underutilized. Our results support improved post-CPR survival of obese patients, consistent with an ‘obesity paradox’. The ABCD score provides an efficient means of risk-stratifying patients and can be calculated in less than 1 minute.

ObjectivesThe differences of efficacy between each Janus kinase (JAK) inhibitors have not been clarified in the patients with rheumatoid arthritis (RA) in clinical practice. Here, we compared the efficacy between tofacitinib (TOFA) and baricitinib (BARI) in clinical practice.MethodsThe efficacy of TOFA (n=156) in patients with RA was compared with BARI (n=138). Selection bias was reduced to a minimum using propensity score-based inverse probability of treatment weighting (IPTW). The Clinical Disease Activity Index (CDAI) trajectory for patients who started TOFA or BARI was analysed using growth mixture modelling (GMM).ResultsNo significant difference was observed in patient characteristics between the TOFA and BARI groups in after adjustment by propensity score-based IPTW. The BARI group had a significantly higher rate of CDAI remission at week 24 after the introduction of JAK inhibitors than the TOFA group. The treatment-resistant group defined by GMM, comprising patients who did not achieve low disease activity at week 24, was more likely to include those who had received many biological disease-modifying antirheumatic drugs (bDMARDs) before the introduction of JAK inhibitors and those who received TOFA. Among patients with RA who received TOFA, those who had received ≥4 bDMARDs before the introduction of TOFA were more likely to be classified into the treatment-resistant group.ConclusionsBARI showed a similar safety profile and better clinical outcome when compared with TOFA after reduction to a minimum of selection bias. However, these were observed in a small population. Accordingly, further investigation is required in an accurately powered head-to-head trial.

To identify which positive prognostic parameters contribute to successful treatment outcomes and the probability of pregnancy by analyzing the results of infertile couples underwent ovulation stimulation (OS) and intra-uterine insemination (IUI) in our clinic.Five hundred and nineteen couples who underwent OS-IUI treatment because of a mild-moderate male factor, unexplained infertility, or anovulation were retrospectively analyzed. The data collected included patient demographics, cycle characteristic, sperm parameters and pregnancy rates. The main outcome measure was pregnancy rate (PR).Our overall PR was 17.72% (n = 92). In women who did not achieve pregnancy, age, BMI and duration of infertility were significantly higher (P 0.001, P 0.001 and P = 0.03, respectively). The IUI indications of higher PR were unexplained infertility (P = 0.018) and primary infertility (P = 0.003). AFC was significantly lower and the total dosage of gonadotropins was significantly higher in women who did not achieve pregnancy (P = 0.001 and P = 0.017, respectively). The number of progressive motile spermatozoa inseminated and the morphology were significantly higher in women who did not achieve pregnancy (P = 0.056 and P = 0.001, respectively). Female age ≤ 30 (OR = 0.87; 95% CI: 0.81-0.95; P 0.01), BMI ≤23.3 kg/mYounger women, especially those with unexplained infertility, primary infertility, shorter duration of infertility, normal ovarian reserve, higher motile spermatozoa inseminated and sperm morphology, could benefit from OS-IUI.

Background The aim of this study was to compute the event rate of patients with breast cancer (BC) using Bayesian network (BN) structure. Method Data for 1,154 patients newly diagnosed with BC were recruited in this study during 2007 and 2016 in Iran. The database was linked to the regional death registration system and active follow-up was performed by referring to hospital information system or calling the patients. BN structure with inverse probability of censoring weighting (IPCW) approach was used to assess the relationship between event rate and underlying risk factors. Results The median (25th, 75th percentiles) of patients’ survival time was 46.8 (32.6, 69.3) months. There were 217 (18.8%) deaths from BC by the end of the study. The optimal BN structure (Akaike Information Criteria = −8743.66 and Bayesian Information Criteria = −8790.80) indicated that being male (conditional probability [CP] = 0.316), age >50 (CP = 0.215), higher grades (CP = 0.301) and lower survival times (CP = 0.566) had higher event rate. Also lobular carcinoma (CP = 0.157) and ductal carcinoma (CP = 0.178) type of morphology had lower event rate while other types (CP = 0.316) had higher. Conclusions The BN structure in which time was as a mediator of predictors-event relationship could be presented as the optimal tool to compute the event rate of BC. The findings could be used to identify the high risk patients and recommend for health policy making, prevention and planning for decrease the mortality in patients with BC.

This study proposes phenomenological models for total normal tissue complication probability (TNTCP) and NTCP0. NTCP0 is a new acronym for reformulating the current complication-free cure (P+) and uncomplicated tumor control probability (UTCP) concepts, and TNTCP will reformulate the current NTCP involving multiple organs at risks. The current probabilistic concepts are incoherently formulated with mathematical operations of tumor control probability (TCP) and normal tissue complication probability (NTCP) that are associated with different stochastic processes and random variables. NTCP0 is equal to NTCP

Background Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, clearly distinguishing benign from malignant lung nodules at an early stage is of great significance. However, determining the kind of lung nodule which is more prone to lung cancer remains a problem worldwide. Methods A total of 480 patients with pulmonary nodule data were collected from Shandong, China. We assessed the clinical characteristics and computed tomography (CT) imaging features among pulmonary nodules in patients who had undergone video‐assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018. Preliminary selection of features was based on a statistical analysis using SPSS. We used WEKA to assess the machine learning models using its multiple algorithms and selected the best decision tree model using its optimization algorithm. Results The combination of decision tree and logistics regression optimized the decision tree without affecting its AUC. The decision tree structure showed that lobulation was the most important feature, followed by spiculation, vessel convergence sign, nodule type, satellite nodule, nodule size and age of patient. Conclusions Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population., Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, it is of great significance to clearly distinguish between benign and malignant lung nodules at early stages. However, what kind of lung nodules are more prone to lung cancer is still a worldwide problem. In this study, 458 cases with pulmonary nodules data were collected from Shandong, China. We assessed the clinical characteristics and low‐dose computed tomography (LDCT) imaging features among pulmonary nodules in patients who had undergone video‐assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018 to determine the machine learning models using multiple algorithms and select the best decision tree model. Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population.

Purpose Predictive models in spine surgery are of use in shared decision-making. This study sought to develop multivariable models to predict the probability of general and surgical perioperative complications of spinal surgery for lumbar degenerative diseases. Methods Data came from EUROSPINE's Spine Tango Registry (1.2012–12.2017). Separate prediction models were built for surgical and general complications. Potential predictors included age, gender, previous spine surgery, additional pathology, BMI, smoking status, morbidity, prophylaxis, technology used, and the modified Mirza invasiveness index score. Complete case multiple logistic regression was used. Discrimination was assessed using area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI). Plots were used to assess the calibration of the models. Results Overall, 23′714/68′111 patients (54.6%) were available for complete case analysis: 763 (3.2%) had a general complication, with ASA score being strongly predictive (ASA-2 OR 1.6, 95% CI 1.20–2.12; ASA-3 OR 2.98, 95% CI 2.19–4.07; ASA-4 OR 5.62, 95% CI 3.04–10.41), while 2534 (10.7%) had a surgical complication, with previous surgery at the same level being an important predictor (OR 1.9, 95%CI 1.71–2.12). Respectively, model AUCs were 0.74 (95% CI, 0.72–0.76) and 0.64 (95% CI, 0.62–0.65), and calibration was good up to predicted probabilities of 0.30 and 0.25, respectively. Conclusion We developed two models to predict complications associated with spinal surgery. Surgical complications were predicted with less discriminative ability than general complications. Reoperation at the same level was strongly predictive of surgical complications and a higher ASA score, of general complications. A web-based prediction tool was developed at https://sst.webauthor.com/go/fx/run.cfm?fx=SSTCalculator.

Objective:. This study conducted inverse probability of treatment weighting (IPTW) survival analysis to examine survival in pancreatic adenocarcinoma patients. Methods:. In this population-based study, data from the Surveillance, Epidemiology, and End Results program of the United States were analyzed to identify patients diagnosed with adenocarcinoma of the pancreas 2004 to 2014. Differences in survival rates were examined among patients who underwent pancreatectomy alone, radiotherapy alone, and those who had pancreatectomy plus adjuvant radiotherapy. Kaplan–Meier estimates and Cox proportional hazards models with the IPTW were performed to determine the effect of different treatments on overall and cancer-specific survival. This study was approved by the Ethics Review Board of Weifang Medical University. Results:. A total of 8191 patients were included, with 3409 taking pancreatectomy only, 2865 taking radiotherapy only, and 1917 taking pancreatectomy plus adjuvant radiotherapy. Patients who received surgery plus adjuvant radiotherapy had statistically a higher survival rate than those who received the other 2 treatments. Survival analysis with the IPTW for the 3 different groups showed that the difference in median overall survival time among these patient groups was significant. Conclusion:. Using IPTW survival analysis, the present study shows that surgery with adjuvant radiotherapy is significantly associated with improved overall and cancer-specific survival among patients with pancreatic adenocarcinoma.

Background: Kainic acid (KA)-induced seizures may be a valuable tool in the assessment of anti-epileptic drug efficacy in complex partial seizures. This study investigated the effects of KA on ATP-sensitive K+ (KATP) channels opening probability (NPo), which plays a crucial role in neuronal activities. Methods: For the optimisation and validation protocol, β-cells were plated onto 35 mm plastic petri dishes and maintained in RPMI-1640 media supplemented with 10 mM glucose, 10% FCS and 25 mM of N-2-hydroxyethylpiperazine-N-ethanesulfonic acid (HEPES). The treatment effects of 10 mM glucose and 30 μM fluoxetine on KATP channels NPo of β–cells were assessed via cell-attached patch-clamp recordings. For hippocampus cell experiments, hippocampi were harvested from day 17 of maternal Lister-hooded rat foetus, and then transferred to a Ca2+ and Mg2+-free HEPES-buffered Hank’s salt solution (HHSS). The dissociated cells were cultured and plated onto a 25 mm round cover glasses coated with poly-d-lysine (0.1 mg/mL) in a petri dish. The KATP channels NPo of hippocampus cells when perfused with 1 mM and 10 mM of KA were determined. Results: NPo of β-cells showed significant decreasing patterns (P < 0.001) when treated with 10 mM glucose 0.048 (0.027) as well as 30 μM fluoxetine 0.190 (0.141) as compared to basal counterpart. In hippocampus cell experiment, a significant increase (P < 0.001) in mean NPo 2.148 (0.175) of neurons when applied with 1 mM of KA as compared to basal was observed. Conclusion: The two concentrations of KA used in the study exerted contrasting effects toward the mean of NPo. It is hypothesised that KA at lower concentration (1 mM) opens more KATP channels, leading to hyperpolarisation of the neurons, which may prevent neuronal hyper excitability. No effect was shown in 10 mM KA treatment, suggesting that only lower than 10 mM KA produced significant changes in KATP channels. This implies further validation of KA concentration to be used in the future.

Using data from an undergraduate probability sample, we aimed to: (1) describe the prevalence and demographic characteristics of students who reported having engaged in rough sex with their current partner; (2) assess which sexual behaviors students consider to be rough sex; (3) describe the frequency with which participants report engaging in rough sex as well as their reports of initiating and liking rough sex, in relation to gender and sexual identity; and (4) examine predictors of rough sex frequency. Participants were 4998 students randomly sampled from a large Midwestern university who completed a confidential Internet-based survey (2453 women, 2445 men, 41 gender non-binary, 36 transgender or other gender non-conforming identities). Within these, 1795 individuals who reported a romantic/sexual partner of at least 3 months responded to questions about engaging, liking, and initiating rough sex. The most common behaviors participants considered to be rough sex were choking, hair pulling, and spanking. Transgender and gender non-binary students more often endorsed behaviors as rough sex. Also, rough sex was conceptualized as multidimensional, with one cluster being more consistent with earlier conceptualizations of rough sex (e.g., hair pulling, spanking) and the second cluster including behaviors such as choking, slapping, punching, and making someone have sex. About 80% of those with a current sexual or romantic partner engaged in rough sex with them and most who engaged it liked it. Bisexual women reported greater rough sex frequency and enjoyment (54.1% indicated enjoying it "very much"). Implications for sexuality research and education are discussed.

Background The benefits and necessity of revascularization for asymptomatic carotid stenosis remains under debate. This study aimed to determine the more durable and beneficial alternative between carotid revascularization and optimal medical treatment (OMT) alone for asymptomatic carotid stenosis. Methods We performed a retrospective analysis of patients with asymptomatic severe carotid stenosis at a tertiary institution between 1994 and 2017. We compared revascularization (carotid endarterectomy [CEA] and carotid artery stenting [CAS]) with OMT alone by using inverse-probability-of-treatment weighting with propensity scores to account for selection bias. The primary end point was a composite of any stroke, myocardial infarction, and death within 30 days, plus ipsilateral stroke thereafter. Results A total of 1089 patients were included in the analysis (56% CEA, 25% CAS, 19% OMT alone). Patients who underwent CAS consistently showed greater risk regarding the primary composite end point compared with those who received OMT alone (hazard radio [HR] 3.32, 95% confidence interval 1.014–10.868; P = 0.047), but the CEA group showed no significant difference (HR 1.19, 95% confidence interval 0.385–4.584; P = 0.761). The CAS group had the greatest rates of any stroke within 30 days (4.0%, P = 0.0006) and ipsilateral stroke thereafter (3.68%, P = 0.0009). There was no death within 30 days. In the long-term outcomes, neither CEA nor CAS showed significant differences in HR compared with OMT alone. Conclusions Our study suggests that for stroke prevention in asymptomatic severe carotid stenosis, CAS might be inferior to the other 2 options regarding early outcomes. However, further investigation is required regarding the efficacy and durability of OMT alone.

OBJECTIVES: Inpatient alcohol withdrawal syndrome (AWS) is common and early treatment improves outcomes, but no prior study has used electronic health record (EHR) data, available at admission, to predict the probability of inpatient AWS. This study estimated the probability of inpatient AWS using prior-year EHR data, hypothesizing that documented alcohol use disorder (AUD) and AWS would be strongly associated with inpatient AWS while exploring associations with other patient characteristics. METHODS: The study investigated patients hospitalized ≥24 hours on medical services in the Veterans Health Administration during 2013 using EHR data extracted from the Veterans Health Administration Corporate Data Warehouse. ICD-9-CM diagnosis code, demographic, and healthcare utilization data documented in the year before admission defined prior-year AUD, AWS, and other factors associated with inpatient AWS. The primary outcome, inpatient AWS, was defined by inpatient ICD-9-CM codes. RESULTS: The unadjusted probability of AWS was 5.0% (95% CI 4.5%–5.4%) among 209,151 medical inpatients overall, 26.4% (95% CI 24.4%–28.4%) among those with prior-year AUD, and 62.5% (95% CI 35.2%–39.7%) among those with prior-year AWS. Of those with AWS, 86% had documented prior-year AUD and/or AWS. Other patient characteristics associated with increased probability of inpatient AWS (P < 0.001) were: male sex, single relationship status, homelessness, seizure, and cirrhosis. CONCLUSIONS: Although inpatient providers often use history to predict AWS, this is the first study in hospitalized patients to inform and validate this practice, showing that prior-year diagnosis of AUD and/or AWS in particular, can identify the majority of inpatients who should be monitored for AWS.

Introduction Low socioeconomic status has been associated with worse outcome after cardiac arrest. This study aims to investigate if patients´ income influences the probability to receive early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients. Methods In this nationwide retrospective observational study, 3906 OHCA patients admitted alive and registered in the Swedish Registry for Cardiopulmonary Resuscitation were included. Individual data on income and educational level, prehospital parameters, coronary angiography results and comorbidity were linked from SWEDEHEART and other national registers. Results Patients were divided into quarters depending on their income level. In the unadjusted model there was a strong correlation between income level and rate of early coronary angiography where 35.5% of patients in the highest income quarters received early angiography compared to 15.4% in the lowest income quarters. When adjusting for educational level, sex, age, comorbidity and hospital type, there were still higher chance of receiving early coronary angiography with increasing income, OR 1.31 (CI 1.01–1.68) and 1.67 (CI 1.29–2.16) for the two highest income quarters respectively compared to the lowest income quarter. When adding potential mediators to the model (first recorded ECG rhythm by the EMS, location, response time, bystander cardiopulmonary resuscitation and if the arrest was witnessed) no difference in early angiography related to income level where found. The main mediator was first recorded ECG rhythm. Conclusion Income level is associated with the probability to undergo early coronary angiography in OHCA patients. This association seems to be mediated by the initial ECG rhythm.

Study design This is a multicenter retrospective review of 257 surgically treated consecutive ASD patients who had a minimum of five fused segments, completed a 2-year follow-up (53 ± 19 yrs, females: 236 [92%]). Objective This study aimed to validate the predictive probability of the GAP score in an Asian ASD patient cohort. Summary of background data The GAP score is a recently established risk stratification model for MF following ASD surgery. However, the predictive ability of the GAP score is not well studied. This study aimed to validate the predictive probability of the GAP score in an Asian ASD patient cohort. Methods Comparisons of the immediate postoperative GAP scores between MF the and MF-free groups were performed. We evaluated the discriminative ability of the GAP score based on the area under the receiver operating characteristic curve (AUROC). The Cuzick test was performed to determine whether there is a trend between the GAP score and the incidence of MF or revision surgery. Univariate logistic regression analyses were performed to explore the associations between the GAP score and the incidence of MF or revision surgery. Results No difference was observed in the GAP score between the MF and MF-free groups (MF vs. MF-free; GAP: 5.9 ± 3.3 vs. 5.2 ± 2.7, P = 0.07). The Cuzick analysis showed no trend between the GAP score and the risk for MF or revision surgery. Likewise, the MF rate was not correlated with the GAP score, as shown by the ROC curve (AUC of 0.56 [95% CI 0.48-0.63], P = 0.124). Univariate logistic regression confirmed no associations between the GAP score and the incidence of MF or revision surgery (MF; moderately disproportioned [MD]: OR: 0.6 [95% CI: 0.3-1.2], P = 0.17, severely disproportioned [SD]: OR: 1.2 [95% CI: 0.6-2.3], P = 0.69, revision surgery; MD: OR: 0.8 [95% CI: 0.2-2.8], P = 0.71, SD: OR: 1.2 [95% CI: 0.9-8.7], P = 0.08). Conclusion In this multicenter study, in an Asian ASD patient cohort, the GAP score was not associated with the incidence of MF or revision surgery. Additional studies on the predictive ability of the GAP score in different patient cohorts are warranted.Level of Evidence: 3.

Objective To determine if clinicopathologic (CP) factors could identify patients at "very low" and/or "very high" pretest probability of a high Oncotype DX (ODX) score. Methods A retrospective analysis of all patients that had ODX testing 2008-2018 at a single institution. Results Of 215 patients, all 16 (7.4%) with "all high" risk CP factors had high ODX scores, and all 45 (20.9%) over age 50 with "all low" risk CP factors had ODX recommendations for no chemotherapy. Conclusions Oncotype DX results did not change chemotherapy recommendations in those with "very low" or "very high" pretest probability of high ODX scores.

According to our experience the 12-lead electrocardiogram (ECG) may be used to estimate the pretest probability of acute pulmonary embolism (acPE). To this end, we devised a novel ECG score (nECGs) composed of 5 known ECG criteria, best characterizing the key pathogenetic steps of acPE. A retrospective derivation cohort including 136 patients with acPE and a prospective validation cohort including 149 consecutive patients were used to devise and validate the nECGs. The latter cohort consisted of 76 patients with acPE and 73 controls presenting with characteristic symptoms of acPE, in whom the work-up ruled out acPE. We compared the diagnostic value of our nECGs with those of another ECG score (Daniel-ECG-score) and of the best prediction rules (3 Wells score and 2 Geneva score variants). The sensitivity (98.7%), negative predictive value (98%), test accuracy (84.4%) and the negative likelihood ratio (LR) (0.019) of the nECGs were superior to those of all other investigated methods. There was no between-groups difference in the positive LR. The specificity (69%) of the nECGs was inferior to those of the Daniel-ECG-score and Wells scores and did not differ or was superior to those of the Geneva score variants. The positive predictive value (77.3%) of the nECGs was superior to those of the 2 Geneva scores and did not differ from those of the other methods. In conclusion, the nECGs due to its superior sensitivity, negative predictive value, test accuracy, and negative LR estimated the pretest probability of acPE better than the Daniel-ECG-score and the prediction rules.

Background and purpose: Proton therapy (PT) is currently being studied to improve normal tissue (NT) sparing beyond what can be achieved with conventional photon-based therapy. Compared to photons, PT dose distributions have a reduced NT low-to-intermediate ‘dose bath’ and a different biological effectiveness, questioning the applicability of photon-based NT complication probability (NTCP) models to PT. The aim of this study was to assess the applicability of photon-based NTCP models to rectum morbidity outcomes following PT. Materials and methods: Treatment planning and morbidity data from 1151 prostate cancer patients treated with passive scattering PT and from 159 patients treated with conventional 3D conformal four-field photon therapy were analysed. Prospectively scored gastrointestinal morbidities (grade >=2) were analysed, with a total of 184 events (protons; medical and procedural) and 12 events (photons; procedural only), respectively. Rectal dose volume histograms were extracted for all patients in both cohorts and used as input to two different NTCP models, with up to six different published photon-based parameter sets. Results: Photon-based rectal NTCP models either over- or underestimated the clinically observed gastrointestinal morbidity when used on the proton cohort, depending on the choice of endpoint (p < 0.05 for all parameter sets, for both morbidity classifications). Four of the six photon-based NTCP models showed a good fit to the photon outcome data (p > 0.05). Conclusion: There were large differences in morbidity predictions between cohorts and modalities, indicating that the validity of NTCP models and parameters across institutions and treatment modalities should be carefully investigated prior to clinical application.

Late-onset toxicities often occur in phase I trials investigating novel immunotherapy and molecular targeted therapies. For trials with cohort based designs (such as modified toxicity probability interval, Bayesian optimal interval, and i3+3), patients are often turned away since the current cohort are still being followed without definite dose-limiting toxicities, which results in prolonged trial duration and waste of patient resources. In this paper, we incorporate a probability-of-decision framework into the i3+3 design and allow real-time dosing inference when the next patient becomes available. Both follow-up time for the pending patients and time to dose-limiting toxicities for the observed patients are used in calculating the posterior probability of each possible dosing decision. An intensive simulation study is conducted to evaluate the operating characteristics of the newly proposed probability-of-decision-i3+3 design under various dosing scenarios and patient accrual settings. Results show that the probability-of-decision-i3+3 design achieves comparable safety and reliability performances but much shorter trial duration compared to the complete designs.