Development of 3D-printed dual-release fixed-dose combination through double-melt extrusion.

This study aimed to develop a 3D-printed fixed-dose combination tablet featuring differential release of two drugs using double-melt extrusion (DME). The hot-melt extrusion (HME) process was divided into two steps to manufacture a single filament containing the two drugs. In Step I, a sustained-release matrix of acetaminophen (AAP) was obtained through HME at 190 °C using Eudragit® S100, a pH-dependent polymer with a high glass transition temperature. In Step II, a filament containing both sustained-release AAP from Step I and solubilized ibuprofen (IBF) was fabricated via HME at 110 °C using a mixture of hydroxy propyl cellulose (HPC-LF) and Eudragit® EPO, whose glass transition temperatures make them suitable for use in a 3D printer. A filament manufactured using DME was used to produce a cylindrical 3D-printed fixed-dose combination tablet with a diameter and height of 9 mm. To evaluate the release characteristics of the manufactured filament and 3D-printed tablet, dissolution tests were conducted for 10 h under simulated gastrointestinal tract conditions using the pH jump method with the United States Pharmacopeia apparatus II paddle method at 37 ± 0.5 °C and 50 rpm. Dissolution tests confirmed that both the sustained-release and solubilized forms of AAP and IBF within the filament and 3D-printed tablet exhibited distinct drug-release behaviors. The physicochemical properties of the filament and 3D-printed tablet were confirmed by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. HME transforms crystalline drugs into amorphous forms, demonstrating their physicochemical stability. Scanning electron microscopy and confocal laser scanning microscopy indicated the presence of sustained AAP granules within the filament, confirming that the drugs were independently separated within the filament and 3D-printed tablets. Finally, sustained-release AAP and solubilized IBF were independently incorporated into the filaments using DME technology. Therefore, a dual-release 3D-printed fixed-dose combination was prepared using the proposed filament.

Nurse Practitioner Care, Scope of Practice, and End-of-Life Outcomes for Nursing Home Residents With Dementia.

Importance: Nursing home residents with Alzheimer disease and related dementias (ADRD) often receive burdensome care at the end of life. Nurse practitioners (NPs) provide an increasing share of primary care in nursing homes, but how NP care is associated with end-of-life outcomes for this population is unknown. Objectives: To examine the association of NP care with end-of-life outcomes for nursing home residents with ADRD and assess whether these associations differ according to state-level NP scope of practice regulations. Design, Setting, and Participants: This cohort study using fee-for-service Medicare claims included 334 618 US nursing home residents with ADRD who died between January 1, 2016, and December 31, 2018. Data were analyzed from April 6, 2015, to December 31, 2018. Exposures: Share of nursing home primary care visits by NPs, classified as minimal (<10% of visits), moderate (10%-50% of visits), and extensive (>50% of visits). State NP scope of practice regulations were classified as full vs restrictive in 2 domains: practice authority (authorization to practice and prescribe independently) and do-not-resuscitate (DNR) authority (authorization to sign DNR orders). Main Outcomes and Measures: Hospitalization within the last 30 days of life and death with hospice. Linear probability models with hospital referral region fixed effects controlling for resident characteristics, visit volume, and geographic factors were used to estimate whether the associations between NP care and outcomes varied across states with different scope of practice regulations. Results: Among 334 618 nursing home decedents (mean [SD] age at death, 86.6 [8.2] years; 69.3% female), 40.5% received minimal NP care, 21.4% received moderate NP care, and 38.0% received extensive NP care. Adjusted hospitalization rates were lower for residents with extensive NP care (31.6% [95% CI, 31.4%-31.9%]) vs minimal NP care (32.3% [95% CI, 32.1%-32.6%]), whereas adjusted hospice rates were higher for residents with extensive (55.6% [95% CI, 55.3%-55.9%]) vs minimal (53.6% [95% CI, 53.3%-53.8%]) NP care. However, there was significant variation by state scope of practice. For example, in full practice authority states, adjusted hospice rates were 2.88 percentage points higher (95% CI, 1.99-3.77; P < .001) for residents with extensive vs minimal NP care, but the difference between these same groups was 1.77 percentage points (95% CI, 1.32-2.23; P < .001) in restricted practice states. Hospitalization rates were 1.76 percentage points lower (95% CI, -2.52 to -1.00; P < .001) for decedents with extensive vs minimal NP care in full practice authority states, but the difference between these same groups in restricted practice states was only 0.43 percentage points (95% CI, -0.84 to -0.01; P < .04). Similar patterns were observed in analyses focused on DNR authority. Conclusions and Relevance: The findings of this cohort study suggest that NPs appear to be important care providers during the end-of-life period for many nursing home residents with ADRD and that regulations governing NP scope of practice may have implications for end-of-life hospitalizations and hospice use in this population.

Advanced practice clinician care and end-of-life outcomes for community- and nursing home-dwelling Medicare beneficiaries with dementia.

INTRODUCTION: Older adults with Alzheimer's disease and related dementias (ADRD) often face burdensome end-of-life care transfers. Advanced practice clinicians (APCs)-which include nurse practitioners and physician assistants-increasingly provide primary care to this population. To fill current gaps in the literature, we measured the association between APC involvement in end-of-life care versus hospice utilization and hospitalization for older adults with ADRD. METHODS: Using Medicare data, we identified nursing home- (N=517,490) and community-dwelling (N=322,461) beneficiaries with ADRD who died between 2016 and 2018. We employed propensity score-weighted regression methods to examine the association between different levels of APC care during their final 9 months of life versus hospice utilization and hospitalization during their final month. RESULTS: For both nursing home- and community-dwelling beneficiaries, higher APC care involvement associated with lower hospitalization rates and higher hospice rates. DISCUSSION: APCs are an important group of providers delivering end-of-life primary care to individuals with ADRD. HIGHLIGHTS: For both nursing home- and community-dwelling Medicare beneficiaries with ADRD, adjusted hospitalization rates were lower and hospice rates were higher for individuals with higher proportions of APC care involvement during their final 9 months of life. Associations between APC care involvement and both adjusted hospitalization rates and adjusted hospice rates persisted when accounting for primary care visit volume.

Enhancement in Power Conversion Efficiency of Perovskite Solar Cells by Reduced Non-Radiative Recombination Using a Brij C10-Mixed PEDOT:PSS Hole Transport Layer.

Interface properties between charge transport and perovskite light-absorbing layers have a significant impact on the power conversion efficiency (PCE) of perovskite solar cells (PSCs). Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is a polyelectrolyte composite that is widely used as a hole transport layer (HTL) to facilitate hole transport from a perovskite layer to an anode. However, PEDOT:PSS must be modified using a functional additive because PSCs with a pristine PEDOT:PSS HTL do not exhibit a high PCE. Herein, we demonstrate an increase in the PCE of PSCs with a polyethylene glycol hexadecyl ether (Brij C10)-mixed PEDOT:PSS HTL. Photoelectron spectroscopy results show that the Brij C10 content becomes significantly high in the HTL surface composition with an increase in the Brij C10 concentration (0-5 wt%). The enhanced PSC performance, e.g., a PCE increase from 8.05 to 11.40%, is attributed to the reduction in non-radiative recombination at the interface between PEDOT:PSS and perovskite by the insulating Brij C10. These results indicate that the suppression of interface recombination is essential for attaining a high PCE for PSCs.