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Many clinical studies collect longitudinal and survival data concurrently. Joint models combining these two types of outcomes through shared random effects are frequently used in practical data analysis. The standard joint models assume that the coefficients for the longitudinal and survival components are time-invariant. In many applications, the assumption is overly restrictive. In this research, we extend the standard joint model to include time-varying coefficients, in both longitudinal and survival components, and we present a data-driven method for variable selection. Specifically, we use a B-spline decomposition and penalized likelihood with adaptive group LASSO to select the relevant independent variables and to distinguish the time-varying and time-invariant effects for the two model components. We use Gaussian-Legendre and Gaussian-Hermite quadratures to approximate the integrals in the absence of closed-form solutions. Simulation studies show good selection and estimation performance. Finally, we use the proposed procedure to analyze data generated by a study of primary biliary cirrhosis. [ABSTRACT FROM AUTHOR]

Triamterene is a potassium-sparing diuretic, often used in combination with thiazide diuretics for treatment of hypertension. By inhibiting the epithelial sodium channel (ENaC) in collecting duct, it reduces potassium secretion, thus reducing the risk of hypokalemia. But it is unclear whether triamterene also has a blood pressure (BP)-lowering effect. We conducted an observational study to examine the BP effect of triamterene. We extracted medical records of 1723 patients diagnosed with hypertension from an urban hospital. There were 1375 patients on hydrochlorothiazide (HCTZ) alone and 348 patients on a combination of HCTZ and triamterene. We compared the recorded BP using regression analysis and the propensity score method. Patient characteristics of the two treatment groups were largely comparable, except for patients on the combination therapy were more likely to be female (83% vs 66%; p<0.001), slightly older (44.7 vs 42.4 years; p=0.0021), and had more recorded chronic kidney disease diagnosis (1.7% vs 0.5%). Direct comparison showed that mean systolic-BP in the patients on triamterene was lower (132.3 vs 136.8 mmHg; p<0.001). Regression analysis showed that systolic BP was 3.06 mmHg (p=0.0005) lower in patients on combination therapy, after adjusting for patient’s demographic and clinical characteristics. Finally, we estimated the propensity of each patient receiving the combination therapy using a logistic regression model and then classified patients into five homogeneous subgroups based on their estimated propensity values. The combined subgroup analysis showed that mean systolic BP in the triamterene group was 4.66 mmHg lower (p=0.0006). All analyses consistently point to a lower BP in patients who received triamterene, as compared to patients who received HCTZ alone. In conclusion, ENaC inhibition with triamterene at doses that are potassium-sparing also lower BP. The use of triamterene in combination with HCTZ may have antihypertensive properties that heretofore were underappreciated. [ABSTRACT FROM AUTHOR]

In the randomized phase II DREAMM-2 study, single-agent belantamab mafodotin demonstrated deep and durable responses and a manageable safety profile in triple-class refractory relapsed/refractory multiple myeloma (RRMM). We present patient-reported outcomes (PROs) from this study for patients treated with the approved dose of belantamab mafodotin (2.5 mg/kg q3w). Disease and treatment-related symptoms, health-related quality of life (HRQOL), functioning, and patient-reported ocular changes were assessed using questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life questionnaires EORTC-QLQ-C30 and EORTC-QLQ-MY20, Ocular Surface Disease Index [OSDI], and the National Eye Institute Visual Functioning Questionnaire 25 [NEI VFQ-25]) at baseline, during treatment (every 3 or 6 weeks), and at the end of treatment (EOT). Eye examinations were conducted at baseline, prior to each treatment cycle, and at EOT. Patients reported ocular symptoms in the OSDI and NEI VFQ-25 questionnaires, with the median time to worst severity of 45 to 64 days depending on symptoms considered. Some limitations in driving and reading were reported. Ocular symptoms were improved and median time to recovery was 23.5 to 44.0 days. EORTC-QLQ-C30 data suggest core MM symptoms (including fatigue and pain), overall HRQOL, and patient functioning were maintained while patients continued belantamab mafodotin treatment, even if meaningful worsening of vision-related symptoms occurred. These PRO results, together with the clinical efficacy of belantamab mafodotin, support its use in patients with RRMM and further evaluation of its use at earlier lines of therapy., Competing Interests: RP has received consultancy fees from Takeda, AbbVie, GSK, and Celgene, research funding from Takeda, honoraria from Janssen, Takeda, Celgene, and GSK and travel expenses from Janssen, Takeda, and GSK. SL has received research funding from Celgene and Takeda, and personal fees from Celgene, Takeda, Amgen, Bristol-Myers Squibb, GSK, Janssen, Merck, and Novartis. PMV has received personal fees from Abbvie, Bristol-Myers Squibb/Celgene, Janssen, GSK, Karyopharm, Lava therapeutics, Novartis, Pfizer, Oncopeptides, Regeneron, Sanofi, and SecuraBio. SDE has received consultancy fees from GSK, honoraria from AbbVie, speaker fees from Novartis, Roche, GSK, GenSight Biologics and Bayer UK and travel support from Bayer UK, Roche, GenSight Biologics. BG was an employee of GSK at the time of the study, and holds stocks in GSK and Daiichi-Sankyo. IG was an employee of GSK at the time of the study and reports an ownership interest (including stock options but excluding indirect investments) in GSK and Novartis. JO, SS, TP, and ZH are employees of GSK and report an ownership interest (including stock options but excluding indirect investments) in GSK. DK reports consultancy fees from Emergent Product Development, Ascidian Therapeutics, Inc., Helixmith USA, Kala Pharmaceuticals, ONL Therapeutics, Inc., Opus Genetics, Parsons Medical Communications, Prime Medicine, Blueprint Medicines, AGTC, Editas Medicine, Inc., Aprea Therapeutics, Cleave Biosciences and Synergy Research Inc, holds stocks in ONL Therapeutics, Inc., has leadership or fiduciary role in Eyeon Therapeutics, Inc., Calm Water Therapeutics LLC and Cataract Innovations LLC and has participated in a data safety monitoring board or advisory board for Apellis Pharmaceuticals, Inc. DS reports consultancy fees from GSK, Novaliq, and SilkTech. AR and JM are employees of Modus Outcomes. LE was an employee of GSK at the time of the study., (© 2023 Harborside™.)