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Introduction: We aimed to assess the validity and reproducibility of a wearable hydration device in a cohort of maintenance dialysis patients. Methods: We conducted a prospective, single-arm observational study on 20 haemodialysis patients between January and June 2021 in a single centre. A prototype wearable infrared spectroscopy device, termed the Sixty device, was worn on the forearm during dialysis sessions and nocturnally. Bioimpedance measurements were performed 4 times using the body composition monitor (BCM) over 3 weeks. Measurements from the Sixty device were compared with the BCM overhydration index (litres) pre- and post-dialysis and with standard haemodialysis parameters. Results: 12 out of 20 patients had useable data. Mean age was 52 ± 12.4 years. The overall accuracy for predicting pre-dialysis categories of fluid status using Sixty device was 0.55 [K = 0.00; 95% CI: -0.39-0.42]. The accuracy for the prediction of post-dialysis categories of volume status was low [accuracy = 0.34, K = 0.08; 95% CI: -0.13-0.3]. Sixty outputs at the start and end of dialysis were weakly correlated with pre- and post-dialysis weights (r = 0.27 and r = 0.27, respectively), as well as weight loss during dialysis (r = 0.31), but not ultrafiltration volume (r = 0.12). There was no difference between the change in Sixty readings overnight and the change in Sixty readings during dialysis (mean difference 0.09 ± 1.5 kg), [t(39) = 0.38, p = 0.71]. Conclusion: A prototype wearable infrared spectroscopy device was unable to accurately assess changes in fluid status during or between dialysis sessions. In the future, hardware development and advances in photonics may enable the tracking of interdialytic fluid status.
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BACKGROUND: Fluid overload has a high prevalence in haemodialysis patients and is an important risk factor for excess mortality and hospitalisations. Despite the risks associated with chronic fluid overload, it is clinically difficult to assess and maintain fluid status adequately. Current methods of fluid status assessment are either imprecise or time intensive. In particular, to date, no method exists to accurately assess fluid status during the interdialytic interval. OBJECTIVES: This pilot study aimed to evaluate whether a prototype wearable hydration monitor can accurately and reproducibly detect fluid overload in the haemodialysis population when compared to haemodialysis and bioimpedance data. METHODS: A prospective, open-label, single-arm observational trial of 20 patients commenced in January 2021 in a single haemodialysis centre in Ireland, with a wearable hydration monitor, the Sixty device. The Sixty device uses diffuse reflectance spectroscopy to measure fluid levels at the level of the subdermis and uses machine learning to develop an algorithm that can determine fluid status. The Sixty device was worn at every dialysis session and nocturnally over a three-week observational period. Haemodialysis parameters including interdialytic weight gain, ultrafiltration volume, blood pressure, and relative blood volume were collected from each session, and bioimpedance measurements using the Fresenius body composition monitor were performed on 4 occasions as a comparator. The primary objective of this trial was to determine the accuracy and reproducibility of the Sixty device compared to bioimpedance measurements. CONCLUSION: If the accuracy of the wearable hydration monitor is validated, further studies will be conducted to integrate the device output into a multi-parameter machine learning algorithm that can provide patients with actionable insights to manage fluid overload in the interdialytic period. TRIAL REGISTRATION: www.clinicaltrials.gov NCT04623281 . Registered November 10th, 2020.
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BACKGROUND AND OBJECTIVES: Dutasteride is currently marketed by GlaxoSmithKline (GSK), either as monotherapy or as a fixed-dose combination with tamsulosin. As part of the project to develop the fixed-dose combination product, alternative formulations of dutasteride were prepared by GSK, and their pharmacokinetic properties were investigated. METHODS: Two single-centre, open-label, active-comparator, randomised, three-period crossover studies were performed. The first study evaluated the relative bioavailability of dutasteride 0.5 mg soft gelatin capsule (marketed formulation, reference) versus a dutasteride 0.5 mg hard gelatin capsule and a dutasteride 0.5 mg tablet. The second assessed the relative bioavailability of dutasteride 0.5 mg from soft gelatin capsules containing 300 or 100 mg of mono- and diglycerides of caprylic acid/capric acid (MDC8, an emulsifying agent) versus the marketed formulation. RESULTS: In the first study (n = 36), compared with the marketed soft gelatin capsule formulation, the bioavailability (least squares [LS] means ratio) of the tablet formulation was 76 % (90 % CI 0.68-0.84), and that of the hard gelatin capsule was 73 % (90 % CI 0.66-0.82). Peak exposures were also lower for the tablet (73 %; 90 % CI 0.66-0.81) and hard capsule (71 %; 90 % CI 0.64-0.79) relative to the marketed soft gelatin capsule. In the second study (n = 37), compared with the marketed soft gelatin formulation, the bioavailability (LS means ratio) of the 300 mg MDC8 capsule formulation was 95 % (90 % CI 0.88-1.03), and that of the 100 mg MDC8 capsule formulation was 93 % (90 % CI 0.86-1.00). Peak exposures were also lower for the 300 mg MDC8 (90 %; 90 % CI 0.81-0.99) and 100 mg MDC8 (87 %; 90 % CI 0.79-0.96) formulations. CONCLUSIONS: The bioavailability of, and peak exposure to, dutasteride are influenced by the formulation of the administered medication. These studies demonstrate the importance of formulation for obtaining the optimal pharmacokinetic properties of dutasteride.
