Clinical effectiveness and safety of time-lapse imaging systems for embryo incubation and selection in in-vitro fertilisation treatment (TILT): a multicentre, three-parallel-group, double-blind, randomised controlled trial.

BACKGROUND: Time-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging. METHODS: We conducted a multicentre, three-parallel-group, double-blind, randomised controlled trial in participants undergoing IVF or ICSI at seven IVF centres in the UK and Hong Kong. Embryologists randomly assigned participants using a web-based system, stratified by clinic in a 1:1:1 ratio to the time-lapse imaging system for undisturbed culture and embryo selection (time-lapse imaging group), time-lapse imaging system for undisturbed culture alone (undisturbed culture group), and standard care without time-lapse imaging (control group). Women were required to be aged 18-42 years and men (ie, their partners) 18 years or older. Couples had to be receiving their first, second, or third IVF or ICSI treatment and could not participate if using donor gametes. Participants and trial staff were masked to group assignment, embryologists were not. The primary outcome was live birth. We performed analyses using the intention-to-treat principle and reported the main analysis in participants with primary outcome data available (full analysis set). The trial is registered on the International Trials Registry (ISRCTN17792989) and is now closed. FINDINGS: 1575 participants were randomly assigned to treatment groups (525 participants per group) between June 21, 2018, and Sept 30, 2022. The live birth rates were 33·7% (175/520) in the time-lapse imaging group, 36·6% (189/516) in the undisturbed culture group, and 33·0% (172/522) in the standard care group. The adjusted odds ratio was 1·04 (97·5% CI 0·73 to 1·47) for time-lapse imaging arm versus control and 1·20 (0·85 to 1·70) for undisturbed culture versus control. The risk reduction for the absolute difference was 0·7 percentage points (97·5% CI -5·85 to 7·25) between the time-lapse imaging and standard care groups and 3·6 percentage points (-3·02 to 10·22) between the undisturbed culture and standard care groups. 79 serious adverse events unrelated to the trial were reported (n=28 in time-lapse imaging, n=27 in undisturbed culture, and n=24 in standard care). INTERPRETATION: In women undergoing IVF or ICSI treatment, the use of time-lapse imaging systems for embryo culture and selection does not significantly increase the odds of live birth compared with standard care without time-lapse imaging. FUNDING: Barts Charity, Pharmasure Pharmaceuticals, Hong Kong OG Trust Fund, Hong Kong Health and Medical Research Fund, Hong Kong Matching Fund.

Mental health and drug use in college students: Should we take action?

BACKGROUND: College students are vulnerable to suffering from anxiety and depression. Moreover, mental disorders can contribute to drug consumption or inappropriate use of prescribed drugs. Studies on this topic in Spanish college students are limited. This work analyses anxiety and depression and psychoactive drug intake pattern in the post-COVID era in college students. METHODS: An online survey was conducted among college students from UCM (Spain). The survey collected data including demographic, academic student perception, GAD-7 and PHQ-9 scales, and psychoactive substances consumption. RESULTS: A total of 6798 students were included; 44.1 % (CI95%: 42.9 to 45.3) showed symptoms of severe anxiety and 46.5 % (CI95%: 45.4 to 47.8) symptoms of severe or moderately severe depression. The perception of these symptoms did not change after returning to face-to-face university classes in the post-COVID19 era. Despite the high percentage of cases with clear symptoms of anxiety and depression, most students never had a diagnosis of mental illnesses [anxiety 69.2 % (CI95%: 68.1 to 70.3) and depression 78.1 % (CI95%: 77.1 to 79.1)]. Regarding psychoactive substances, valerian, melatonin, diazepam, and lorazepam were the most consumed. The most worrying issue was the consumption of diazepam, 10.8 % (CI95%: 9.8 to 11.8), and lorazepam, 7.7 % (CI95%: 6.9 to 8.6) without medical prescription. Among illicit drugs, cannabis is the most consumed. LIMITATIONS: The study was based on an online survey. CONCLUSIONS: The high prevalence of anxiety and depression aligned with poor medical diagnosis and high intake of psychoactive drugs should not be underestimated. University policies should be implemented to improve the well-being of students.

Individualized prediction for the occurrence of acute kidney injury during the first postoperative week following cardiac surgery.

STUDY OBJECTIVE: To develop individualized dynamic predictions for the occurrence of acute kidney injury (AKI) during the first postoperative week after cardiac surgery. DESIGN: Observational retrospective cohort study. SETTING: Single university teaching hospital in Madrid, Spain. PATIENTS: 3960 cases of major cardiac surgery performed from January 2002 to December 2013. MEASUREMENTS: Baseline demographic and clinical characteristics, intraoperative risk factors, and repeated postoperative estimated glomerular filtration rates (eGFR). The primary outcome was AKI during the first postoperative week (stage 1 or higher of the Acute Kidney Injury Network). The dataset was split in two random samples (exploratory and validation). By combining time-to-event outcomes (AKI), and longitudinal data (repeated postoperative eGFR), we developed two different joint models for patients with normal and high baseline levels of serum creatinine (sCr). MAIN RESULTS: AKI occurred in 1105 patients (31%, 95% confidence interval [CI] 29.5-32.5) in the exploratory sample and 128 (32.2%, 95% CI 27.6-36.8) in the validation sample. For high baseline sCr patients, the risk of an AKI event was associated with the eGFR trajectory (hazard ratio [HR] 0.91, 95% CI 0.90-0.92), as well as with age, and cardiopulmonary bypass time. The normal baseline sCr model incorporated the same covariates and intraoperative transfusion. In this second model, the risk of an AKI event was associated with both the eGFR trajectory (HR 0.91, 95% CI 0.91-0.92, for the current value of eGFR), and with its slope at that point (HR 0.96, 95% CI 0.94-0.99). So AKI risk decreased when the eGFR values increased, in accordance with the speed of this rise. Internal validation showed good discrimination and calibration of both joint models. The AUCs were always higher than 0.7. CONCLUSIONS: The joint models obtained combining both patient risk factors and postoperative eGFR values, are useful to predict individualized risk of cardiac surgery-associated AKI. Predictions can be updated as new information is gathered.

Bootstrap-based testing approaches for the assessment of the diagnostic accuracy of biomarkers subject to a limit of detection.

Assessment of the diagnostic accuracy of biomarkers through receiver operating characteristic curve analysis frequently involves a limit of detection imposed by the laboratory analytical system precision. As a consequence, measurements below a certain level are undetectable and ignoring these is known to lead to negatively biased estimates of the area under the receiver operating characteristic curve. In this article, we introduce two receiver operating characteristic curve-based parametric approaches that tackle the issue of correct assessment of diagnostic markers in the presence of a limit of detection. Proposed approaches are simulation-based utilising bootstrap methodology. Non-parametric alternatives that are naively used in the literature do not solve the inherent problem of limit of detection values which are treated as censored observations. However, the latter seems to perform adequately well in our simulation study. Nonparametric bootstrap was consistently used throughout, while other bootstrap alternatives performed similarly in our pilot simulation study. The simulation study involves the comparison of parametric and non-parametric options described here versus alternative strategies that are routinely used in the literature. We apply all methods to a study-setting resembling a chemical quasi-standard situation, where compound tumour biomarkers were searched within a multi-variable set of measurements to discriminate between two groups, namely colorectal cancer and controls. We focus in the assessment of glutamine and methionine.