A Real-World Comparison of Drug Trough Levels between Patients Experiencing a Secondary Nonimmune Loss of Response and Those Maintaining a Response to Infliximab on Long-Term Maintenance Therapy for Inflammatory Bowel Disease.

Introduction: A secondary loss of response (LOR) to infliximab (IFX) therapy for inflammatory bowel disease (IBD) is typically associated with low IFX trough levels, often with high levels of neutralizing antibodies to IFX (ATI). A small subset of patients on long-term therapy experience a "nonimmune" LOR, without ATI and with desired IFX trough levels ≥5 μg/mL, regarded as a LOR to the mechanism of action of IFX. However, this currently accepted IFX goal level is largely derived from observations of patients within the first year of therapy and may not apply to those on treatment beyond 1 year.

Back to the drawing board: Overview of the next generation of combination therapy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is entering a potentially new era of combined therapeutics. Triantafillidis provide an insightful review of the current state of combination therapy, with a focus on the use of a combined biologic and immunomodulator, as well as emerging data on the future potential of dual-biologic therapy (DBT). While current evidence for DBT is limited, encouraging safety profiles and ongoing trials suggest a brighter future for this approach.

Brief Report: A Novel Digital Therapeutic that Combines Applied Behavior Analysis with Gaze-Contingent Eye Tracking to Improve Emotion Recognition in Children with Autism Spectrum Disorder.

This study examined the feasibility, acceptability, and efficacy of a video game-based digital therapeutic combining applied behavior analysis techniques and gaze-contingent eye tracking to target emotion recognition in youth with autism spectrum disorder (ASD). Children aged 4-14 years with ASD were randomized to complete Lookware™ (n = 25) or a control video game (n = 29). Results from a 2 × 2 mixed ANOVA revealed that children in the intervention condition demonstrated significant improvements in emotion recognition from pre- to post-intervention compared to children in the control condition, F(1,52) = 17.

Machine Learning Guidance for Connection Tableaux.

Connection calculi allow for very compact implementations of goal-directed proof search. We give an overview of our work related to connection tableaux calculi: first, we show optimised functional implementations of connection tableaux proof search, including a consistent Skolemisation procedure for machine learning. Then, we show two guidance methods based on machine learning, namely reordering of proof steps with Naive Bayesian probabilities, and expansion of a proof search tree with Monte Carlo Tree Search.

A conformational transition observed in single HIV-1 Gag molecules during in vitro assembly of virus-like particles.

Unlabelled: The conformational changes within single HIV-1 Gag molecules that occur during assembly into immature viruses are poorly understood. Using an in vitro assembly assay, it has been proposed that HIV-1 Gag undergoes a conformational transition from a compact conformation in solution to an extended rod-like conformation in virus-like particles (VLPs). Here we used single-molecule Förster resonance energy transfer (smFRET) to test this model by directly probing the conformation of single HIV-1 Gag molecules.

Prospective multicenter trial comparing push-and-pull enteroscopy with the single- and double-balloon techniques in patients with small-bowel disorders.

Objectives: Double-balloon enteroscopy (DBE) is now an established method for diagnostic and therapeutic small-bowel endoscopy. Single-balloon enteroscopy (SBE) has been introduced to simplify the technique. A prospective randomized study was carried out to compare the two methods.

Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

Background: Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [>or=50%] or REF [<50%]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42 418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF.

Methods And Results: HF diagnostic criteria were prespecified in the ALLHAT protocol.

Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate.

Background: Chronic kidney disease is common in older patients with hypertension.

Objective: To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR.

Design: Post hoc subgroup analysis.

Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Background: This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic.

Methods: We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.

Relationship of antihypertensive treatment regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly assigned to doxazosin or chlorthalidone: further analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial.

Background: The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial reported that treatment initiated with doxazosin compared with chlorthalidone doubled the risk for heart failure in high-risk hypertensive patients (relative risk, 2.04 [95% CI, 1.79 to 2.