Can large language models build causal graphs?

Building causal graphs can be a laborious process. To ensure all relevant causal pathways have been captured, researchers often have to discuss with clinicians and experts while also reviewing extensive relevant medical literature. By encoding common and medical knowledge, large language models (LLMs) represent an opportunity to ease this process by automatically scoring edges (i.e., connections between two variables) in potential graphs. LLMs however have been shown to be brittle to the choice of probing words, context, and prompts that the user employs. In this work, we evaluate if LLMs can be a useful tool in complementing causal graph development.Comment: Peer reviewed and accepted for presentation at the Causal Machine Learning for Real-World Impact Workshop (CML4Impact) at NeuRIPs2022 Fixed author lis

Verteilungsbasierte kausale Inferenzmodelle zur Schätzung von Therapieffekten in randomisierten kontrollierten klinischen Studien

In prospective randomized trials differences in population based means can be considered as estimates of mean causal exposure or treatment effects. Nevertheless, occurence of intermediate events in the course of a trial may lead to biased estimates of treatment effects. Particularly this will be the case, if the probability of such an event is not independent of initial treatment allocation and the intermediate event is both a risk factor for the main outcome parameter (e.g. survival) and a predictor of subsequent treatment. This situation was referred as 'treatment by indication problem' by Robins (1992) and is common in epidemiological trials. Robins demonstrated that the usual approach of an adjusted estimation of treatment effect using a time-dependent proportional hazards model may be biased in this situation, whether or not one further adjusts for past confounder history in the analysis. In this thesis a novel inference procedure for randomized trials is introduced which is based on the idea of Robin's G-Estimation principle but particularly consideres specifics of randomized trials. The suggested procedure allows for an unbiased and consistent estimation of a treatment effect parameter (or paremeter vector) which is connected by a real-valued function to the parameters of an underlying distribution of survival times. In fulfilment of the requirements of a causal individual-level based model, a link of a subject's observed and counterfactual survival time is directly achieved by the inverse distribution function of survival times in a reference treatment arm. In this term, causal inference is feasible based on the likelihood function and its corresponding test statistics, even under appropriate consideration of time-dependent confounders

Preoperative/Neoadjuvant Therapy in Pancreatic Cancer: A Systematic Review and Meta-analysis of Response and Resection Percentages

Jörg Kleef and colleagues systematically reviewed studies on neoadjuvant therapy and tumor response, toxicity, resection, and survival percentages in pancreatic cancer and suggest that patients with locally nonresectable tumors should be included in neoadjuvant protocols

Transpulmonary thermodilution using femoral indicator injection: a prospective trial in patients with a femoral and a jugular central venous catheter

INTRODUCTION: Advanced hemodynamic monitoring using transpulmonary thermodilution (TPTD) is established for measurement of cardiac index (CI), global end-diastolic volume index (GEDVI) and extra-vascular lung water index (EVLWI). TPTD requires indicator injection via a central venous catheter (usually placed via the jugular or subclavian vein). However, superior vena cava access is often not feasible due to the clinical situation. This study investigates the conformity of TPTD using femoral access. METHODS: This prospective study involved an 18-month trial at a medical intensive care unit at a university hospital. Twenty-four patients with both a superior and an inferior vena cava catheter at the same time were enrolled in the study. RESULTS: TPTD-variables were calculated from TPTD curves after injection of the indicator bolus via jugular access (TPTDjug) and femoral access (TPTDfem). GEDVIfem and GEDVIjug were significantly correlated (rm = 0.88; P < 0.001), but significantly different (1,034 +/- 275 vs. 793 +/- 180 mL/m2; P < 0.001). Bland-Altman analysis demonstrated a bias of +241 mL/m2 (limits of agreement: -9 and +491 mL/m2). GEDVIfem, CIfem and ideal body weight were independently associated with the bias (GEDVIfem-GEDVIjug). A correction formula of GEDVIjug after femoral TPTD, was calculated. EVLWIfem and EVLWIjug were significantly correlated (rm = 0.93; P < 0.001). Bland-Altman analysis revealed a bias of +0.83 mL/kg (limits of agreement: -2.61 and +4.28 mL/kg). Furthermore, CIfem and CIjug were significantly correlated (rm = 0.95; P < 0.001). Bland-Altman analysis demonstrated a bias of +0.29 L/min/m2 (limits of agreement -0.40 and +0.97 L/min/m2; percentage-error 16%). CONCLUSIONS: TPTD after femoral injection of the thermo-bolus provides precise data on GEDVI with a high correlation, but a self-evident significant bias related to the augmented TPTD-volume. After correction of GEDVIfem using a correction formula, GEDVIfem shows high predictive capabilities for GEDVIjug. Regarding CI and EVLWI, accurate TPTD-data is obtained using femoral access

Safety and efficacy of a lifestyle intervention for pregnant women to prevent excessive maternal weight gain: a cluster-randomized controlled trial

Background: Excessive gestational weight gain (GWG) is associated with short- and long-term health problems among mothers and their offspring. There is a strong need for effective intervention strategies targeting excessive GWG to prevent adverse outcomes. Methods: We performed a cluster-randomized controlled intervention trial in eight gynecological practices evaluating the feasibility and effectiveness of a lifestyle intervention presented to all pregnant women; 250 healthy, pregnant women were recruited for the study. The intervention program consisted of two individually delivered counseling sessions focusing on diet, physical activity, and weight monitoring. The primary outcome was the proportion of pregnant women exceeding weight gain recommendations of the Institute of Medicine (IOM). Secondary outcome variables were maternal weight retention and short-term obstetric and neonatal outcomes. Results: The intervention resulted in a lower proportion of women exceeding IOM guidelines among women in the intervention group (38\%) compared with the control group (60\%) (odds ratio (OR): 0.5; 95\% confidence interval (CI): 0.3 to 0.9) without prompting an increase in the proportion of pregnancies with suboptimal weight gain (19\% vs. 21\%). Participants in the intervention group gained significantly less weight than those in the control group. Only 17\% of the women in the intervention group showed substantial weight retention of more than 5 kg compared with 31\% of those in the control group at month four postpartum (pp) (OR: 0.5; 95\% CI: 0.2 to 0.9). There were no significant differences in obstetric and neonatal outcomes. Conclusions: Lifestyle counseling given to pregnant women reduced the proportion of pregnancies with excessive GWG without increasing suboptimal weight gain, and may exert favorable effects on pp weight retention

Evolving a conceptual framework and developing a new questionnaire for usability evaluation of blended learning programs in health professions education

Background: Blended learning programs (BLPs) have been widely adopted across health professions education (HPE). To bolster their impact on learning outcomes, the usability of BLPs should be rigorously evaluated. However, there is a lack of reliable and validated tools to appraise this dimension of BLPs within HPE. The purpose of this investigation was to evolve a conceptual framework for usability evaluation in order to initially develop the Blended Learning Usability Evaluation – Questionnaire (BLUE-Q). Methods: After the completion of a scoping review, we conducted a qualitative descriptive study with seven purposefully selected international experts in usability and learning program evaluation. Individual interviews were conducted via videoconferencing, transcribed verbatim, and analyzed through thematic analysis. Results: Three themes were identified: (1) Consolidation of the multifaceted ISO definition of usability in BLPs within HPE; (2) Different facets of usability can assess different aspects of BLPs; (3) Quantitative and qualitative data are needed to assess the multifaceted nature of usability. The first theme adds nuance to a previously established HPE-focused usability framework, and introduces two new dimensions: ‘pedagogical usability’ and ‘learner motivation.’ The latter two provide guidance on structuring BLP evaluations within HPE. From this followed the development of the BLUE-Q, a new questionnaire that includes 55 Likert scale items and 6 open-ended questions. Conclusions: Usability is an important dimension of BLPs and must be examined to improve the quality of these interventions in HPE. As such, we developed a new questionnaire, solidly grounded in theory and the expertise of international scholars, currently under validation

Time Period From Onset of Pain to Hospital Admission and Patients' Awareness in Acute Pancreatitis

Objectives: This study aimed to explore the period between onset of pain and hospital-admission (pain-to-admission time) in patients with acute pancreatitis (AP), to investigate the prognostic value and associated factors of this time, and to ascertain the knowledge about the pancreas in these patients. Methods: An analysis of a prospective multicenter study was done, which included 188 patients with AP. Results: Median pain-to-admission time was 27 hours (interquartile range, 6.0-72.0). Median pain-to-admission time was significantly shorter in intensive care unit (ICU) patients (10 hours) compared to non-ICU patients (36 hours) (P = 0.045). Short pain-to-admission time was associated with high pain level. Median pain level (0, no pain; 10, maximal pain) was 8.0 (interquartile range, 7.0-10.0). Older age correlated with lower pain level (r = -0.26; P = 0.002). Multiple logistic regression analysis including the admission values for serum lipase and C-reactive protein and the corresponding interactions to the pain-to-admission time showed substantial discriminative ability regarding ICU admission (concordance index, 0.706; P = 0.006). 86% (112/130) knew that they have a pancreas, 72% (81/112) of these patients knew that AP exists, and 56% (45/81) recognized that AP is potentially fatal. Conclusions: Knowledge about AP in hospitalized AP patients is poor. Serum lipase and C-reactive protein in dependency of the pain-to-admission time might be a suitable predictor for severity of AP

Left ventricular diastolic function is strongly correlated with active emptying of the left atrium: a novel analysis using three-dimensional echocardiography

Background: Increased left atrial (LA) dimensions are known to be a risk factor in predicting cardiovascular events and mortality and to be one key diagnostic tool to assess diastolic dysfunction. Currently, LA measurements are usually conducted using 2D-echocardiography, although there are well-known limitations. Real-time 3D-echocardiography is able to overcome these limitations, furthermore being a valid measurement tool compared to reference standards (e.g. cardiac magnetic resonance imaging). We investigated LA function and volume and their association to left ventricular (LV) diastolic function, using newly designed and validated software for 3D-echocardiographic analysis. This software is the first to allow for a sophisticated analysis of both passive and active LA emptying. Methods: We analyzed 2D- and 3D-echocardiographic measurements of LA volume and function in 56 subjects and compared the results between patients with normal LV diastolic function (NDF) (n = 30, 52 +/- 15 years, BMI 24.7 +/- 2. 6 kg/m(2)) and patients in which diastolic dysfunction (DDF) was suspected (n = 26, 65 +/- 9 years, BMI 26.7 +/- 3.7 kg/m(2)). Results: Volumes during LA active emptying were significantly smaller in DDF compared to NDF (active atrial stroke volume (ASV): 3.0 (0.1-4.5) vs. 5.5 (2.7-7.8) ml, p = 0.005;True-EF: 7.3(0.1-11.5) vs. 16.2 (8.1-25.4) %, p = 0.002). Furthermore, ASV showed a stronger association to E/e'(mean) than all other measured LA volumes (beta = -0.35, p = 0.008). Neither total stroke LA volume, nor maximum or minimum LA volume differed significantly between the groups. Conclusions: Diastolic LV dysfunction results in a reduction in active LA emptying, which is more strongly associated with LV filling pressure than other previously investigated LA parameters