Patient Centric Microsampling to Support Paxlovid Clinical Development: Bridging and Implementation.

Nirmatrelvir is a potent and selective severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease inhibitor. Nirmatrelvir co-packaged with ritonavir (as PAXLOVID) received US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) on December 22, 2021, as an oral treatment for coronavirus disease 2019 (COVID-19) and subsequent new drug application approval on May 25, 2023. Pharmacokinetic (PK) capillary blood sampling at-home using Tasso-M20 micro-volumetric sampling device was implemented in the program, including three phase II/III outpatient and several clinical pharmacology studies supporting the EUA. The at-home sampling complemented venous blood sampling procedures to enrich the PK dataset, to decrease the need for patients' site visit for PK sampling, and to allow different sampling approaches for flexibility and convenience. To demonstrate concordance/equivalence, bridging between venous plasma and Tasso dried blood results was conducted by comparing concentrations and derived PK parameters from both sampling approaches. In addition, a two-compartment population PK model was utilized to bridge the plasma and Tasso data by estimating the PK parameters using blood-to-plasma ratio as a slope parameter. Operational challenges were successfully managed to implement at-home PK sampling in global phase II/III trials. Sample quality was generally very good with less than 3% samples deemed as "not usable" from over 800 samples collected in all the studies. Experience gained from sites and patients will guide future broader implementations.

Continuous bedside pressure mapping and rates of hospital-associated pressure ulcers in a medical intensive care unit.

BACKGROUND: Critically ill patients are vulnerable to the development of hospital-associated pressure ulcers (HAPUs). Positioning of patients is an essential component of pressure ulcer prevention because it off-loads areas of high pressure. However, the effectiveness of such positioning is debatable. A continuous bedside pressure mapping (CBPM) device can provide real-time feedback of optimal body position though a pressure-sensing mat that displays pressure images at a patient's bedside, allowing off-loading of high-pressure areas and possibly preventing HAPU formation. METHODS: A prospective controlled study was designed to determine if CBPM would reduce the number of HAPUs in patients treated in our medical intensive care unit. In 2 months, 422 patients were enrolled and assigned to beds equipped with or without a CBPM device. Patients' skin was assessed daily and weekly to determine the presence and progress of HAPUs. All patients were turned every 2 hours. CBPM patients were repositioned to off-load high-pressure points during turning, according to a graphic display. The number of newly formed HAPUs was the primary outcome measured. A χ(2) test was then used to compare the occurrence of HAPUs between groups. RESULTS: HAPUs developed in 2 of 213 patients in the CBPM group (0.9%; both stage II) compared with 10 of 209 in the control group (4.8%; all stage II; P = .02). CONCLUSION: Significantly fewer HAPUs occurred in the CBPM group than the control group, indicating the effectiveness of real-time visual feedback in repositioning of patients to prevent the formation of new HAPUs.

A Continuous Bedside Pressure Mapping System for Prevention of Pressure Ulcer Development in the Medical ICU: A Retrospective Analysis.

OBJECTIVE: Patient repositioning to offload high-pressure areas is an essential component of pressure ulcer prevention for bed-bound patients. In most settings, the quantity and quality of offloading and repositioning are difficult to measure. Real-time continuous bedside pressure mapping (CBPM) offers an opportunity to do so. MATERIAL AND METHODS: Data was collected on 627 patients being treated in a medical intensive care unit (MICU): 307 patients placed on beds with a CBPM system and 320 historical controls placed on the same beds without the CBPM system 1 year prior to the study participants. A pressure ulcer prevention bundle was enhanced by the addition of a CBPM system that provides real-time digital imaging of the patient on the support surface to National Pressure Ulcer Advisory Panel guidelines. RESULTS: During the 2-month study period, 1 (0.3%) patient in the CBPM cohort developed a pressure ulcer compared with 16 (5%) patients in the historical cohort (P = 0.001). In a survey of the MICU care providers, 90% of respondents reported that the CBPM contributed to improved pressure detection and relief, 88% indicated the CBPM assisted them with repositioning protocols, and 84% reported the pressure map provided for more efficient and effective patient repositioning. CONCLUSION: Real-time, ongoing pressure measurement using a pressure-sensing mat may be a useful tool to help care providers effectively reposition patients within the context of existing standardized protocols for the prevention and minimization of pressure ulcers. .