Pitfalls and potentials in simulation studies: Questionable research practices in comparative simulation studies allow for spurious claims of superiority of any method.

Comparative simulation studies are workhorse tools for benchmarking statistical methods. As with other empirical studies, the success of simulation studies hinges on the quality of their design, execution, and reporting. If not conducted carefully and transparently, their conclusions may be misleading. In this paper, we discuss various questionable research practices, which may impact the validity of simulation studies, some of which cannot be detected or prevented by the current publication process in statistics journals. To illustrate our point, we invent a novel prediction method with no expected performance gain and benchmark it in a preregistered comparative simulation study. We show how easy it is to make the method appear superior over well-established competitor methods if questionable research practices are employed. Finally, we provide concrete suggestions for researchers, reviewers, and other academic stakeholders for improving the methodological quality of comparative simulation studies, such as preregistering simulation protocols, incentivizing neutral simulation studies, and code and data sharing.

Prognostic models for predicting clinical disease progression, worsening and activity in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects millions of people worldwide. The disease course varies greatly across individuals and many disease-modifying treatments with different safety and efficacy profiles have been developed recently. Prognostic models evaluated and shown to be valid in different settings have the potential to support people with MS and their physicians during the decision-making process for treatment or disease/life management, allow stratified and more precise interpretation of interventional trials, and provide insights into disease mechanisms. Many researchers have turned to prognostic models to help predict clinical outcomes in people with MS; however, to our knowledge, no widely accepted prognostic model for MS is being used in clinical practice yet. OBJECTIVES: To identify and summarise multivariable prognostic models, and their validation studies for quantifying the risk of clinical disease progression, worsening, and activity in adults with MS. SEARCH METHODS: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews from January 1996 until July 2021. We also screened the reference lists of included studies and relevant reviews, and references citing the included studies. SELECTION CRITERIA: We included all statistically developed multivariable prognostic models aiming to predict clinical disease progression, worsening, and activity, as measured by disability, relapse, conversion to definite MS, conversion to progressive MS, or a composite of these in adult individuals with MS. We also included any studies evaluating the performance of (i.e. validating) these models. There were no restrictions based on language, data source, timing of prognostication, or timing of outcome. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently screened titles/abstracts and full texts, extracted data using a piloted form based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS), assessed risk of bias using the Prediction Model Risk Of Bias Assessment Tool (PROBAST), and assessed reporting deficiencies based on the checklist items in Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD). The characteristics of the included models and their validations are described narratively. We planned to meta-analyse the discrimination and calibration of models with at least three external validations outside the model development study but no model met this criterion. We summarised between-study heterogeneity narratively but again could not perform the planned meta-regression. MAIN RESULTS: We included 57 studies, from which we identified 75 model developments, 15 external validations corresponding to only 12 (16%) of the models, and six author-reported validations. Only two models were externally validated multiple times. None of the identified external validations were performed by researchers independent of those that developed the model. The outcome was related to disease progression in 39 (41%), relapses in 8 (8%), conversion to definite MS in 17 (18%), and conversion to progressive MS in 27 (28%) of the 96 models or validations. The disease and treatment-related characteristics of included participants, and definitions of considered predictors and outcome, were highly heterogeneous amongst the studies. Based on the publication year, we observed an increase in the percent of participants on treatment, diversification of the diagnostic criteria used, an increase in consideration of biomarkers or treatment as predictors, and increased use of machine learning methods over time. Usability and reproducibility All identified models contained at least one predictor requiring the skills of a medical specialist for measurement or assessment. Most of the models (44; 59%) contained predictors that require specialist equipment likely to be absent from primary care or standard hospital settings. Over half (52%) of the developed models were not accompanied by model coefficients, tools, or instructions, which hinders their application, independent validation or reproduction. The data used in model developments were made publicly available or reported to be available on request only in a few studies (two and six, respectively). Risk of bias We rated all but one of the model developments or validations as having high overall risk of bias. The main reason for this was the statistical methods used for the development or evaluation of prognostic models; we rated all but two of the included model developments or validations as having high risk of bias in the analysis domain. None of the model developments that were externally validated or these models' external validations had low risk of bias. There were concerns related to applicability of the models to our research question in over one-third (38%) of the models or their validations. Reporting deficiencies Reporting was poor overall and there was no observable increase in the quality of reporting over time. The items that were unclearly reported or not reported at all for most of the included models or validations were related to sample size justification, blinding of outcome assessors, details of the full model or how to obtain predictions from it, amount of missing data, and treatments received by the participants. Reporting of preferred model performance measures of discrimination and calibration was suboptimal. AUTHORS' CONCLUSIONS: The current evidence is not sufficient for recommending the use of any of the published prognostic prediction models for people with MS in clinical routine today due to lack of independent external validations. The MS prognostic research community should adhere to the current reporting and methodological guidelines and conduct many more state-of-the-art external validation studies for the existing or newly developed models.

Right vs. left ventricular longitudinal strain for mortality prediction after transcatheter aortic valve implantation.

Introduction: This study aims at exploring biventricular remodelling and its implications for outcome in a representative patient cohort with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Methods and results: Pre-interventional echocardiographic examinations of 100 patients with severe AS undergoing TAVI were assessed by speckle tracking echocardiography of both ventricles. Association with mortality was determined for right ventricular global longitudinal strain (RVGLS), RV free wall strain (RVFWS) and left ventricular global longitudinal strain (LVGLS). During a median follow-up of 1,367 [959-2,123] days, 33 patients (33%) died. RVGLS was lower in non-survivors [-13.9% (-16.4 to -12.9)] than survivors [-17.1% (-20.2 to -15.2); P = 0.001]. In contrast, LVGLS as well as the conventional parameters LV ejection fraction (LVEF) and RV fractional area change (RVFAC) did not differ (P = ns). Kaplan-Meier analyses indicated a reduced survival probability when RVGLS was below the -14.6% cutpoint (P < 0.001). Lower RVGLS was associated with higher mortality [HR 1.13 (95% CI 1.04-1.23); P = 0.003] independent of LVGLS, LVEF, RVFAC, and EuroSCORE II. Addition of RVGLS clearly improved the fitness of bivariable and multivariable models including LVGLS, LVEF, RVFAC, and EuroSCORE II with potential incremental value for mortality prediction. In contrast, LVGLS, LVEF, and RVFAC were not associated with mortality. Discussion: In patients with severe AS undergoing TAVI, RVGLS but not LVGLS was reduced in non-survivors compared to survivors, differentiated non-survivors from survivors, was independently associated with mortality, and exhibited potential incremental value for outcome prediction. RVGLS appears to be more suitable than LVGLS for risk stratification in AS and timely valve replacement.

Development and validation of an international preoperative risk assessment model for postoperative delirium.

BACKGROUND: Postoperative delirium (POD) is a frequent complication in older adults, characterised by disturbances in attention, awareness and cognition, and associated with prolonged hospitalisation, poor functional recovery, cognitive decline, long-term dementia and increased mortality. Early identification of patients at risk of POD can considerably aid prevention. METHODS: We have developed a preoperative POD risk prediction algorithm using data from eight studies identified during a systematic review and providing individual-level data. Ten-fold cross-validation was used for predictor selection and internal validation of the final penalised logistic regression model. The external validation used data from university hospitals in Switzerland and Germany. RESULTS: Development included 2,250 surgical (excluding cardiac and intracranial) patients 60 years of age or older, 444 of whom developed POD. The final model included age, body mass index, American Society of Anaesthesiologists (ASA) score, history of delirium, cognitive impairment, medications, optional C-reactive protein (CRP), surgical risk and whether the operation is a laparotomy/thoracotomy. At internal validation, the algorithm had an AUC of 0.80 (95% CI: 0.77-0.82) with CRP and 0.79 (95% CI: 0.77-0.82) without CRP. The external validation consisted of 359 patients, 87 of whom developed POD. The external validation yielded an AUC of 0.74 (95% CI: 0.68-0.80). CONCLUSIONS: The algorithm is named PIPRA (Pre-Interventional Preventive Risk Assessment), has European conformity (ce) certification, is available at http://pipra.ch/ and is accepted for clinical use. It can be used to optimise patient care and prioritise interventions for vulnerable patients and presents an effective way to implement POD prevention strategies in clinical practice.

What proportion of clinical prediction models make it to clinical practice? Protocol for a two-track follow-up study of prediction model development publications.

INTRODUCTION: It is known that only a limited proportion of developed clinical prediction models (CPMs) are implemented and/or used in clinical practice. This may result in a large amount of research waste, even when considering that some CPMs may demonstrate poor performance. Cross-sectional estimates of the numbers of CPMs that have been developed, validated, evaluated for impact or utilized in practice, have been made in specific medical fields, but studies across multiple fields and studies following up the fate of CPMs are lacking. METHODS AND ANALYSIS: We have conducted a systematic search for prediction model studies published between January 1995 and December 2020 using the Pubmed and Embase databases, applying a validated search strategy. Taking random samples for every calendar year, abstracts and articles were screened until a target of 100 CPM development studies were identified. Next, we will perform a forward citation search of the resulting CPM development article cohort to identify articles on external validation, impact assessment or implementation of those CPMs. We will also invite the authors of the development studies to complete an online survey to track implementation and clinical utilization of the CPMs.We will conduct a descriptive synthesis of the included studies, using data from the forward citation search and online survey to quantify the proportion of developed models that are validated, assessed for their impact, implemented and/or used in patient care. We will conduct time-to-event analysis using Kaplan-Meier plots. ETHICS AND DISSEMINATION: No patient data are involved in the research. Most information will be extracted from published articles. We request written informed consent from the survey respondents. Results will be disseminated through publication in a peer-reviewed journal and presented at international conferences. OSF REGISTRATION: (https://osf.io/nj8s9).

Tracking the mental health of home-carers during the first COVID-19 national lockdown: evidence from a nationally representative UK survey.

BACKGROUND: Unpaid carers who look after another member of their household (home-carers) have poorer mental health than the general population. The first COVID-19 national lockdown led to an increasing reliance on home-carers and we investigate the short- and longer-term impacts of lockdown on their mental health. METHODS: Data from 9737 adult participants (aged 16+) from the UK Household Longitudinal Study (Understanding Society) were used to explore changes in 12-item General Health Questionnaire (GHQ-12) score between (a) pre-pandemic (2019) and early lockdowns (April 2020) and (b) early and later (July 2020) lockdowns. RESULTS: GHQ-12 scores among home-carers were higher pre-lockdown and increased more than for non-carers from 2019 to April 2020 with further increases for home-carers compared with non-carers between April and July. Compared with respondents caring for a spouse/partner, those caring for a child under 18 had a particularly marked increase in GHQ-12 score between 2019 and April, as did those caring for someone with a learning disability. Home-carers of children under 18 improved from April to July while those caring for adult children saw a marked worsening of their mental health. Home-carers with greater care burden saw larger increases in GHQ-12 score from 2019 to April and from April to July, and increases through both periods were greater for home-carers who had formal help prior to lockdown but then lost it. CONCLUSIONS: The mental health of home-carers deteriorated more during lockdown than non-carers. Policies that reinstate support for them and their care-recipients will benefit the health of both vulnerable groups.

HautTief Multidisciplinary Educational Program for Patients with Psoriasis or Atopic Dermatitis: A Randomized Controlled Study.

BACKGROUND: Improving health-related quality of life (HRQoL), disease severity, and treatment adherence through patient education is an increasingly important, yet relatively new area in dermatology. This randomized controlled trial aims to contribute to this growing area of research by exploring the effects of a 9-week educational program for patients with chronic skin diseases. OBJECTIVE: The aim of the study was to evaluate the effect of a multidisciplinary educational program on HRQoL and disease severity in patients with psoriasis or atopic dermatitis (AD). METHODS: Sixty-four patients with diagnosed psoriasis or AD were recruited from University Hospital Zurich and randomized (1:1) to the intervention or control group. To assess HRQoL, the following self-reported questionnaires were used: Dermatology Life Quality Index (DLQI), Skindex-29, EuroQol-5D (EQ-5D), RAND 36-Item Short Form Survey (SF-36), and Beck Depression Inventory (BDI) to measure depression symptoms. Psoriasis Area and Severity Index (PASI) and the Eczema Area and Severity Index (EASI) were used to capture disease extent. These scores were assessed at four study visits, which were performed at baseline and 3, 6, and 9 months after the start of the program. RESULTS: At month 6, an improvement of at least 25% in BDI was recorded in 15 (68.2%) of 22 patients in the intervention group and 6 (27.3%) of 22 patients in the control group (difference 40.9%, p = 0.016). 53.3% (16 of 30) of patients achieved an improvement in one subdomain of the SF-36 score (role limitations due to emotional problems) at 6-month follow-up, compared with 23.1% (6 of 26) of those not attending the educational program (difference 30.2%; p = 0.042). No significant differences in DLQI, Skindex-29, EQ-5D, PASI, and EASI between both groups at the three time points were found. CONCLUSION: An educational program may improve HRQoL and depression status of patients with psoriasis or AD.

The incremental value of the contribution of a biostatistician to the reporting quality in health research-A retrospective, single center, observational cohort study.

BACKGROUND: The reporting quality in medical research has recently been critically discussed. While reporting guidelines intend to maximize the value from funded research, and initiatives such as the EQUATOR network have been introduced to advance high quality reporting, the uptake of the guidelines by researchers could be improved. The aim of this study was to assess the contribution of a biostatistician to the reporting and methodological quality of health research, and to identify methodological knowledge gaps. METHODS: In a retrospective, single center, observational cohort study, two groups of publications were compared. The group of exposed publications had an academic biostatistician on the author list, whereas the group of non-exposed publications did not include a biostatistician of the evaluated group. Rating of reporting quality was done in blinded fashion and in duplicate. The primary outcome was a sum score based on six dimensions, ranging between 0 (worst) and 11 (best). The study protocol was reviewed and approved as a registered report. RESULTS: There were 131 publications in the exposed group published between 2017 and 2018. Of these, 95 were either RCTs, observational, or prediction / prognostic studies. Corresponding matches in the group of non-exposed publications were identified in a reproducible manner. Comparison of reporting quality overall revealed a 1.60 (95%CI from 0.92 to 2.28, p <0.0001) units higher reporting quality for exposed publications. A subgroup analysis within study types showed higher reporting quality across all three study types. CONCLUSION: Our study is the first to report an association of a higher reporting quality and methodological strength in health research publications with a biostatistician on the author list. The higher reporting quality persisted through subgroups of study types and dimensions. Methodological knowledge gaps were identified for prediction / prognostic studies, and for reporting on statistical methods in general and missing values, specifically.

Diagnostic delay in moderately/poorly differentiated breast cancer types.

BACKGROUND: Diagnostic delay of breast cancer related to the false-negative assessment of the healthcare provider leads to tumor progression and might worsen the outcome. Previous studies found some factors associated with provider-related diagnostic delay; however, tumor biology has tended not to be considered. The aim of our study was to find differences in diagnostic delay of poorly differentiated breast cancer types. METHODS: Data of 970 patients with newly diagnosed moderately/poorly differentiated (G2/3) breast cancer at the age ≥40 years was retrospectively analyzed regarding breast cancer type, diagnostic delay and its consequence, clinical factors and physician's assessment. Multivariate analysis was used to evaluate associated factors with diagnostic delay. RESULTS: We observed a diagnostic delay in 3.8% (n = 37) of all patients. Mean delay time was 128 days, and clinically relevant tumor growth was observed in 43.2% of these cases. Delay was significantly higher in the group of triple-negative breast cancer (9.9% versus 2.7, 5.3 and 1.8% in hormonal receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR-/Her2+ and HR+/Her2+, respectively; P value <0.001). Age, breast density and reason for presentation were not correlated to diagnostic delay. CONCLUSION: Patients with triple-negative breast cancer are at higher risk of receiving a false-negative assessment and experiencing a diagnostic delay. Our results emphasize the importance of a detailed consideration of clinical risk factors and provider training and suggest a broad indication for a core needle biopsy.

A three-year longitudinal study of retinal function and structure in patients with multiple sclerosis.

BACKGROUND: Researchers have in recent years begun to investigate ophthalmological manifestations of multiple sclerosis (MS) other than optic neuritis (ON), and it is now clear that changes to retinal function (measured using the electroretinogram, ERG) and structure (measured using optical coherence tomography, OCT) are found in MS patients irrespective of prior ON episodes. ERG results are consistent with dysfunctional bipolar cells, as in other autoimmune diseases. To date, studies have presented only cross-sectional data regarding ERG and OCT. We, therefore, studied the longitudinal course of ERG and OCT in patients with MS, as well as the effect of disability changes and non-ON clinical relapses on these functional and structural measures. METHODS: MS patients (n = 23) participating in an ongoing longitudinal observational study were invited to take part in a 3-year ophthalmological substudy. ERG and OCT were performed, and measures of MS-related disability and relapse history were obtained. Study visits were repeated annually. ERG peak times, rod b-wave amplitude, mixed rod/cone and cone b-/a-wave amplitude ratios, thickness of the peripapillary retinal nerve fibre layer, and volumes of the segmented retinal layers/complexes were analysed. Using generalised estimating equation models adjusted for age, ON, and MS treatment status, we assessed changes to ERG and OCT over the study duration, the effect of changes in disability and recent non-ON MS relapses on ERG and OCT, and the effect of selected OCT parameters on corresponding ERG parameters. RESULTS: At the group level, small fluctuations of several ERG peak times were recorded, with OCT values remaining stable. Increased disability between visits was associated with significant prolongation of mixed rod-cone ERG b-wave peak times. No evidence of associations between OCT and ERG parameters was observed. CONCLUSIONS: Retinal bipolar cell function may be affected by changes in disability in patients with MS; however, recent non-ON MS clinical relapses appear not to affect ERG or OCT results. As ERG changes in MS patients over 3 years are likely to be small and of uncertain clinical relevance, longitudinal studies of retinal function in MS should be planned over an extended period.

Incremental Prognostic Value of Coronary Artery Calcium Score for Predicting All-Cause Mortality after Transcatheter Aortic Valve Replacement.

Background Current risk models show limited performances for predicting all-cause mortality after transcatheter aortic valve replacement (TAVR). Purpose To determine the prognostic value of coronary artery calcium (CAC) scoring for predicting 30-day and 1-year mortality in patients undergoing TAVR. Materials and Methods In this single-center institutional review board-approved secondary analysis of prospectively collected data (SwissTAVI Registry), the authors evaluated participants who, before TAVR, underwent CT that included a nonenhanced electrocardiography-gated cardiac scan between May 2008 and September 2019 and who had not undergone previous coronary revascularization. Clinical data, including the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), were recorded. The CAC score was determined, and 30-day and 1-year all-cause mortality were assessed by using Cox regression analyses. Results In total, 309 participants (mean age ± standard deviation, 81 years ± 7; 175 women) were included, with a median CAC score of 334 (interquartile range, 104-987). Seventy-seven of the 309 participants (25%) had a CAC score greater than or equal to 1000. A CAC score of 1000 or greater served as an independent predictor of 30-day (hazard ratio [HR], 4.5 [95% CI: 1.5, 13.6] compared with a CAC score <1000; P = .007) and 1-year (HR, 4.3 [95% CI: 1.5, 12.7] compared with a CAC score of 0-99; P = .008) mortality after TAVR. Similar trends were observed for each point increase of the EuroSCORE II as an independent predictor of 30-day (HR, 1.22 [95% CI: 1.10, 1.36]; P < .001) and 1-year (HR, 1.16 [95% CI: 1.08, 1.25]; P < .001) mortality. Adding the CAC score to the EuroSCORE II provided incremental prognostic value for 1-year mortality after TAVR over the EuroSCORE II alone (concordance index, 0.76 vs 0.69; P = .04). Conclusion In participants without prior coronary revascularization, the coronary artery calcium score represented an independent predictor of 30-day and 1-year mortality after transcatheter aortic valve replacement. ClinicalTrials.gov identifier, NCT01368250 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

Predictors of COVID-19 vaccine hesitancy in the UK household longitudinal study.

Vaccine hesitancy could undermine efforts to control COVID-19. We investigated the prevalence of COVID-19 vaccine hesitancy in the UK and identified vaccine hesitant subgroups. The 'Understanding Society' COVID-19 survey asked participants (n = 12,035) their likelihood of vaccine uptake and reason for hesitancy. Cross-sectional analysis assessed vaccine hesitancy prevalence and logistic regression calculated odds ratios. Overall vaccine hesitancy was low (18% unlikely/very unlikely). Vaccine hesitancy was higher in women (21.0% vs 14.7%), younger age groups (26.5% in 16-24 year olds vs 4.5% in 75 + ) and those with lower education levels (18.6% no qualifications vs 13.2% degree qualified). Vaccine hesitancy was high in Black (71.8%) and Pakistani/Bangladeshi (42.3%) ethnic groups. Odds ratios for vaccine hesitancy were 13.42 (95% CI:6.86, 26.24) in Black and 2.54 (95% CI:1.19, 5.44) in Pakistani/Bangladeshi groups (compared to White British/Irish) and 3.54 (95% CI:2.06, 6.09) for people with no qualifications versus degree. Urgent action to address hesitancy is needed for some but not all ethnic minority groups.

Computed Tomography Angiography of the Aorta-Optimization of Automatic Tube Voltage Selection Settings to Reduce Radiation Dose or Contrast Medium in a Prospective Randomized Trial.

OBJECTIVES: The aim of this study was to compare the image quality of low-kV protocols with optimized automatic tube voltage selection (ATVS) settings to reduce either radiation dose or contrast medium (CM) with that of a reference protocol for computed tomography angiography (CTA) of the thoracoabdominal aorta. MATERIALS AND METHODS: In this institutional review board-approved, single-center, prospective randomized controlled trial, 126 patients receiving CTA of the aorta were allocated to one of three computed tomography protocols: (A) reference protocol at 120 kVp and standard weight-adapted CM dose; (B) protocol at 90 kVp, reduced radiation and standard CM dose; and (C) protocol at 90 kVp, standard radiation and reduced CM dose. All three protocols were performed on a third-generation dual-source computed tomography scanner using the semimode of the ATVS system. The image-task-dependent optimization settings of the ATVS (slider level) were adjusted to level 11 (high-contrast task) for protocols A and B and level 3 (low-contrast task) for protocol C. Radiation dose parameters were assessed. The contrast-to-noise ratios (CNRs) of protocols B and C were tested for noninferiority compared with A. Subjective image quality was assessed using a 5-point Likert scale. RESULTS: Size-specific dose estimate was 34.3% lower for protocol B compared with A (P < 0.0001). Contrast medium was 20.2% lower for protocol C compared with A (P < 0.0001). Mean CNR in B and C was noninferior to protocol A (CNR of 30.2 ± 7, 33.4 ± 6.7, and 30.5 ± 8.9 for protocols A, B, and C, respectively). There was no significant difference in overall subjective image quality among protocols (4.09 ± 0.21, 4.03 ± 0.19, and 4.08 ± 0.17 for protocols A, B, and C, respectively; P = 0.4). CONCLUSIONS: The slider settings of an ATVS system can be adjusted to optimize either radiation dose or CM at noninferior image quality in low-kV CTA of the aorta. This optimization could be used to extend future ATVS algorithms to take clinical risk factors like kidney function of individual patients into account.

Is reporting quality in medical publications associated with biostatisticians as co-authors? A registered report protocol.

BACKGROUND: Quality in medical research has recently been criticized for being low, especially in observational research. Methodology is increasingly difficult, but collaboration between clinical researchers and biostatisticians may improve research and reporting quality. The aim of this study is to quantify the value of a biostatistician in the team of authors. METHODS: Single-center, retrospective observational study following the STROBE reporting guidelines. We will systematically review all medical publications with biostatisticians from our center as co-authors or authors and review corresponding papers without biostatisticians from our center during the same time range. We will compare aspects of reporting quality, overall and for the three study types observational, randomized trial, and prognostic separately. DISCUSSION: We anticipate that the results of the study will raise awareness of the importance of high methodological quality, as well as appropriate reporting quality in clinical research. CONCLUSION: Our study will have a direct impact on our center by making each of us more aware of the reporting guidelines for various research designs. This in turn will enhance reporting quality in future research with our involvement. Our study will also raise awareness of the important role that biostatisticians play in the design and analysis of health research projects.

Clinical Imaging of the Heterogeneous Group of Triple-negative Breast Cancer.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) can be divided into subtypes of basal-like (BL), mesenchymal-like (ML), luminal androgen receptor (LAR), and immunomodulatory (IM). The aim of our study was to assess whether there are distinct radiologic features within the different TNBC subtypes and whether this has potential clinical impact. PATIENTS AND METHODS: Imaging pictures of 135 patients with TNBC were re-evaluated. TNBC subtyping was performed on asservated tumor tissue using a panel of antibodies. RESULTS: Mammographic margins of LAR-TNBC were more often spiculated (24.3% versus 0-4.1%). BL-TNBC presented more frequent a mass without calcification in mammogram than other subtypes (71.4% versus 48.6-57.9%). In ultrasound, ML and LAR were described more often with smooth borders. CONCLUSION: The histopathological subtype of TNBC influences its presentation in ultrasound and mammogram. This can reflect a different growth pattern of the subtypes and may have an impact on the early diagnosis of TNBC.

Extensive Histological Sampling following Focal Therapy of Clinically Significant Prostate Cancer with High Intensity Focused Ultrasound.

PURPOSE: Clinically significant, localized prostate cancer is currently treated with whole gland therapy. This approach is effective but associated with genitourinary and rectal side effects. Focal therapy of prostate cancer has been proposed as an alternative. The aim of this study was to determine the oncologic and functional outcomes of focal high intensity focused ultrasound therapy of prostate cancer. MATERIALS AND METHODS: In this single center, prospective study 75 men were treated between April 2014 and April 2018. Multiparametric magnetic resonance imaging and transperineal template saturation prostate biopsy were performed to localize prostate cancer, followed by focal ablation with high intensity focused ultrasound. The study primary end point was the detection of clinically significant prostate cancer, defined as Gleason score 7 or greater, at 6-month followup transperineal template saturation prostate biopsy. Genitourinary side effects were of secondary interest. RESULTS: Median patient age was 67 years (IQR 60-71) and median prostate specific antigen was 5.87 ng/ml (IQR 4.65-7.44). There were 5 low risk (6.7%) and 70 intermediate risk (93.3%) cancers. Clinically significant prostate cancer was detected in 41% of the men (95% CI 30.3-53.0) who underwent biopsy at 6 months and the median number of sampled cores was 44 (IQR 36-44). Prostate specific antigen (OR 1.17, IQR 0.49-2.85, p=0.71) and multiparametric magnetic resonance imaging (14.3% sensitivity, IQR 6.7-31.5) performed poorly to predict positive biopsies. Pad-free continence and erection sufficient for penetration were preserved in 63 of 64 (98.4%) and 31 of 45 patients (68.9%), respectively. CONCLUSIONS: Focal therapy with high intensity focused ultrasound leads to a low rate of genitourinary side effects. Followup biopsy of treated and untreated prostates remains the only modality to adequately select men in need of early salvage treatment.

CT Angiography of the Aorta: Contrast Timing by Using a Fixed versus a Patient-specific Trigger Delay.

Background Optimal timing of the CT scan relative to the contrast media bolus remains a challenging task given the shorter scan durations of modern CT scanners, as well as interpatient variability. Purpose To compare contrast opacification in CT angiography of the aorta between a cohort with fixed trigger delay and a cohort with patient-specific individualized trigger delay for contrast media timing with bolus tracking. Materials and Methods In this prospective study (January-August 2018), CT angiography of the thoracoabdominal aorta with bolus tracking was performed in two different study cohorts: one with a fixed trigger delay of 4 seconds (fixed cohort) and one with a patient-specific trigger delay (individualized cohort). All CT and contrast media protocol parameters were kept identical among cohorts. Objective image quality was evaluated by one reader; two readers assessed subjective image quality. Student t test was used to test for differences in mean attenuation; the Wilcoxon-Mann-Whitney test was used to test for differences in noise, contrast-to-noise ratio, and subjective image quality. Results The fixed cohort had 108 study participants (16 women; mean age ± standard deviation, 72 years ± 10); the individualized cohort had 108 participants (16 women; mean age, 72 years ± 12). The trigger delay in the individualized cohort ranged from 6.4-11.3 seconds (mean, 9.2 seconds). There was higher overall attenuation in the individualized cohort than in the fixed cohort (486 HU ± 92 for individualized vs 438 HU ± 99 for fixed; P < .001), with increasing differences from the aortic arch (8 HU) to the iliac arteries (95 HU). The regression model indicated uniform attenuation in the individualized cohort and decreasing attenuation in the fixed cohort (decrease of 87 HU by the iliac arteries; P < .001). There was no difference between cohorts for image noise (20 vs 19; P = .41), but contrast-to-noise ratio (21 vs 19; P = .04) and subjective image quality were higher in the individualized cohort than in the fixed cohort (excellent or good image quality, 100% vs 67%; P < .001). Conclusion Compared with a fixed delay time after bolus tracking, a patient-specific individualized trigger delay improves image quality and provides uniform contrast attenuation for CT angiography of the aorta. ©RSNA, 2019.