Pharmacist Interventions in a Palliative PLUS Program at a Veterans Affairs Medical Center.

Background: Palliative PLUS (PP) at the Minneapolis Veterans Affairs Health Care System (MVAHCS) is an interdisciplinary team that seeks to improve veteran access to palliative and hospice resources. Palliative care pharmacists were incorporated to increase patient access to palliative specialties. Objective: To identify and categorize pharmacist interventions within an outpatient PP team at the MVAHCS. Methods: This quality improvement project was a retrospective analysis of the electronic health record. Results: A total of 84 patients were participating in the PP program over 13 months. Among those patients, 25 had pharmacist involvement and a total of 56 interventions were identified. Of those interventions, 29 (51.8%) were direct interventions and 27 (48.2%) were curbside consults. Most interventions involved medication counseling and medication adherence. Conclusion: Pharmacists made an impact on the PP team through direct patient interventions involving medication counseling and aided the interdisciplinary team by facilitating patient medication adherence.

Evaluation of sealants to mitigate the release of per- and polyfluoroalkyl substances (PFAS) from AFFF-impacted concrete: Characterization and forecasting.

Per- and polyfluoroalkyl substances (PFAS) within concrete pads impacted by historical firefighting training using aqueous film-forming foam (AFFF) may be potential secondary sources of PFAS due to surficial leaching. This study aimed to (i) characterize the effectiveness of two commercially available sealants (Product A and Product B) in mitigating leaching of five PFAS (e.g., PFOS, PFOA, PFHxS, PFHxA, 6:2 FTS) from concrete surfaces at the laboratory-scale, and (ii) develop a model to forecast cumulative leaching of the same five PFAS over 20 years from sealed and unsealed concrete surfaces. Laboratory trials demonstrated that both sealants reduced the surficial leaching of the five PFAS studied, and Product B demonstrated a comparatively greater reduction in surface leaching than Product A as measured against unsealed controls. The cumulative PFOS leaching from an unsealed concrete surface is estimated by the model to be about 400 mg/m2 over 20 years and reached asymptotic conditions after 15 years. In contrast, the model output suggests asymptotic conditions were not achieved within the modeled time of 20 years after sealing with Product A and 85% of PFOS was predicted to have leached (∼340 mg/m2). Negligible leaching of PFOS after sealing with Product B was observed ( < 5 × 10-9 mg/m2). Results from modeled rainfall scenarios suggest PFAS leachability is reduced from sealed versus unsealed AFFF-impacted concrete surfaces.

Trajectory of blood pressure after initiating anti-calcitonin gene-related peptide treatment of migraine: a target trial emulation from the veterans health administration.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is involved in migraine pathophysiology and blood pressure regulation. Although clinical trials have established the cardio-cerebrovascular safety profile of anti-CGRP treatment, limited high-quality real-world evidence exists on its long-term effects on blood pressure (BP). To address this gap, we examined the safety of anti-CGRP treatment on BP in patients with migraine headache in the Veterans Health Administration (VHA). METHODS: We emulated a target trial of patients who initiated anti-CGRP treatment or topiramate for migraine prevention between May 17th, 2018 and February 28th, 2023. We calculated stabilized inverse probability weights to balance between groups and then used weighted linear mixed-effect models to estimate the systolic and diastolic BP changes over the study period. For patients without hypertension at baseline, we estimated the cumulative incidence of hypertension using Kaplan-Meier curve. We also used weight mixed-effect Poisson model to estimate the number of antihypertension medications for patients with hypertension at baseline. RESULTS: This analysis included 69,589 patients and 554,437 blood pressure readings. of these, 18,880 patients received anti-CGRP treatment, and they were more likely to be women, have a chronic migraine diagnosis and higher healthcare utilization than those received topiramate. Among patients without hypertension at baseline, we found no significant differences in systolic BP changes over the four-year follow-up between anti-CGRP (slope [standard error, SE] = 0.48[0.06]) and topiramate treated patients (slope[SE] = 0.39[0.04]). The incidence of hypertension was similar for anti-CGRP and topiramate group (4.4 vs 4.3 per 100 person-years). Among patients with hypertension at baseline who initiated anti-CGRP treatment, we found a small but persistent effect on exacerbating hypertension during the first four years of treatment, as evidenced by a significant annual 3.7% increase in the number of antihypertensive medications prescribed (RR = 1.037, 95%CI 1.025-1.048). CONCLUSIONS: Our findings suggest that anti-CGRP treatment is safe regarding blood pressure in patients without hypertension. However, for those with baseline hypertension, anti-CGRP treatment resulted in a small but persistent increase in the number of antihypertensives, indicating an exacerbation of hypertension. Future studies are needed to evaluate the cardio-cerebrovascular safety of anti-CGRP treatment beyond the first four years.

Calcitonin Gene-Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder.

Importance: Calcitonin gene-related peptide (CGRP), a neuropeptide involved in migraine pathophysiology, is also a key neuroimmune modulator. CGRP antagonists may help mitigate the hyperinflammatory response observed in patients with COVID-19; however, findings from the literature are contradictory, and to date, no study has investigated the safety and effectiveness of CGRP antagonists against COVID-19. Objective: To evaluate the association between CGRP monoclonal antibody (mAb) treatment and risk of SARS-CoV-2 infection and sequela hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death. Design, Setting, and Participants: This retrospective cohort study analyzed the electronic health records of US veterans aged 18 to 65 years who were diagnosed with migraine disorder and were at risk of COVID-19 between January 20, 2020, and May 19, 2022. Exposure: Initiation of CGRP mAbs. Main Outcomes and Measures: The main outcome was cumulative incidence of SARS-CoV-2 infection. Odds of 30-day hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death were secondary outcomes. Results: Among 8 178 652 eligible person-trials (354 294 veterans), 9992 (mean [SD] age, 46.0 [9.5] years; 53.9% male) initiated CGRP mAbs and 8 168 660 (mean [SD] age, 46.6 [10.2] years; 65.7% male) did not initiate CGRP mAbs. Over a 28-month follow-up period, 1247 initiators (12.5%) and 780 575 noninitiators (9.6%) tested positive for SARS-CoV-2. After censoring persons who deviated from treatment, the incidence was 7.4 cases per 1000 person-months among initiators and 6.9 per 1000 person-months among noninitiators. The inverse probability-weighted observational analogs of intention-to-treat and per-protocol hazard ratios were 0.95 (95% CI, 0.89-1.01) and 0.93 (95% CI, 0.86-1.02), respectively. No significant differences in the likelihood of hospitalization (odds ratio [OR], 0.93; 95% CI, 0.62-1.41), requiring supplemental oxygen (OR, 0.77; 95% CI, 0.45-1.30), use of mechanical ventilation (OR, 0.85; 95% CI, 0.26-2.84), or death (OR, 0.67; 95% CI, 0.09-5.23) were observed between CGRP mAb initiators and noninitiators who tested positive for SARS-CoV-2. Conclusions and Relevance: In this cohort study, CGRP mAb treatment was not associated with positive SARS-CoV-2 test results or risk of severe COVID-19 outcomes, suggesting that CGRP mAbs may be used for migraine prevention during the COVID-19 pandemic. Given the few events of requiring supplemental oxygen, use of mechanical ventilation, and death, replication analysis in a larger sample of patients later in the course of disease is warranted.

Beyond EGFR inhibitors in advanced colorectal cancer: Targeting BRAF and HER2.

The addition of antiepidermal growth factor receptor (EGFR) monoclonal antibodies, cetuximab or panitumumab, to conventional chemotherapy has improved clinical outcomes for rat sarcoma virus (RAS) wild-type advanced colorectal cancer patients, however, durable responses and 5-year overall survival rates remain limited. BRAF V600E somatic mutation and human epidermal growth factor receptor (HER2) amplification/overexpression have been separately implicated in primary resistance to anti-EGFR therapeutic strategies via aberrant activation of the mitogen-activated protein kinase (MAPK) signaling pathway, resulting in poorer outcomes. In addition to being a negative predictive biomarker for anti-EGFR therapy, BRAF V600E mutation and HER2 amplification/overexpression serve as positive predictors of response to therapies targeting these respective tumor promoters. This review will highlight key clinical studies that support the rational use of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and HER2-targeted therapies, often in combination with other targeted agents, cytotoxic chemotherapy, and immune checkpoint inhibitors. We discuss current challenges with BRAF and HER2-targeted therapies in metastatic colorectal cancer and potential opportunities for improvement.

Rib spur causing a hemothorax, pneumothorax, and diaphragmatic injury in a pediatric patient.

Pleural effusion is a relatively common condition encountered in the pediatric emergency department. Evaluation of pleural effusion in the emergency department typically includes advanced imaging such as computer tomography or ultrasound, as well as diagnostic thoracocentesis. We report a case of a 10-year-old female with a rib spur at the anterolateral left sixth rib that caused a hemothorax, pneumothorax, and diaphragmatic injury. The patient underwent video-assisted thoracoscopic surgery and resection of the rib spur. The procedure was well-tolerated without any complications.

Immune organoids: from tumor modeling to precision oncology.

Cancer immunotherapies, particularly immune checkpoint inhibitors, are rapidly becoming standard-of-care for many cancers. The ascendance of immune checkpoint inhibitor treatment and limitations in the accurate prediction of clinical response thereof have provided significant impetus to develop preclinical models that can guide therapeutic intervention. Traditional organoid culture methods that exclusively grow tumor epithelium as patient-derived organoids are under investigation as a personalized platform for drug discovery and for predicting clinical efficacy of chemotherapies and targeted agents. Recently, the patient-derived tumor organoid platform has evolved to contain more complex stromal and immune compartments needed to assess immunotherapeutic efficacy. We review the different methodologies for developing a more holistic patient-derived tumor organoid platform and for modeling the native immune tumor microenvironment.

A Review of Platelet-Activating Factor As a Potential Contributor to Morbidity and Mortality Associated with Severe COVID-19.

The precise mechanisms of pathology in severe COVID-19 remains elusive. Current evidence suggests that inflammatory mediators are responsible for the manifestation of clinical symptoms that precedes a fatal response to infection. This review examines the nature of platelet activating factor and emphasizes the similarities between the physiological effects of platelet activating factor and the clinical complications of severe COVID-19.

Over 30% efficiency bifacial 4-terminal perovskite-heterojunction silicon tandem solar cells with spectral albedo.

We developed and designed a bifacial four-terminal perovskite (PVK)/crystalline silicon (c-Si) heterojunction (HJ) tandem solar cell configuration albedo reflection in which the c-Si HJ bottom sub-cell absorbs the solar spectrum from both the front and rear sides (reflected light from the background such as green grass, white sand, red brick, roofing shingle, snow, etc.). Using the albedo reflection and the subsequent short-circuit current density, the conversion efficiency of the PVK-filtered c-Si HJ bottom sub-cell was improved regardless of the PVK top sub-cell properties. This approach achieved a conversion efficiency exceeding 30%, which is higher than those of both the top and bottom sub-cells. Notably, this efficiency is also greater than the Schockley-Quiesser limit of the c-Si solar cell (approximately 29.43%). The proposed approach has the potential to lower industrial solar cell production costs in the near future.

IFNα Augments Clinical Efficacy of Regulatory T-cell Depletion with Denileukin Diftitox in Ovarian Cancer.

PURPOSE: Immunotherapy treats some cancers, but not ovarian cancer. Regulatory T cells (Tregs) impede anti-ovarian cancer immunity but effective human Treg-directed treatments are lacking. We tested Treg depletion with denileukin diftitox (DD) ± IFNα as ovarian cancer immunotherapy. PATIENTS AND METHODS: Mice with syngeneic ID8 ovarian cancer challenge were treated with DD, IFNα, or both. The phase 0/I trial tested one dose-escalated DD infusion for functional Treg reduction, safety, and tolerability. The phase II trial added IFNα2a to DD if DD alone failed clinically. RESULTS: DD depleted Tregs, and improved antitumor immunity and survival in mice. IFNα significantly improved antitumor immunity and survival with DD. IFNα did not alter Treg numbers or function but boosted tumor-specific immunity and reduced tumor Treg function with DD by inducing dendritic cell IL6. DD alone was well tolerated, depleted functional blood Tregs and improved immunity in patients with various malignancies in phase 0/I. A patient with ovarian cancer in phase 0/I experienced partial clinical response prompting a phase II ovarian cancer trial, but DD alone failed phase II. Another phase II trial added pegylated IFNα2a to failed DD, producing immunologic and clinical benefit in two of two patients before a DD shortage halt. DD alone was well tolerated. Adding IFNα increased toxicities but was tolerable, and reduced human Treg numbers in blood, and function through dendritic cell-induced IL6 in vitro. CONCLUSIONS: Treg depletion is clinically useful but unlikely alone to cure ovarian cancer. Rational treatment agent combinations can salvage clinical failure of Treg depletion alone, even when neither single agent provides meaningful clinical benefit.

Transparent Stacked Photoanodes with Efficient Light Management for Solar-Driven Photoelectrochemical Cells.

Solar-driven hydrogen generation is one of the most promising approaches for building a sustainable energy system. Photovoltaic-assisted photoanodes can help to reduce the overpotential of water splitting in photoelectrochemical (PEC) cells. Transparent photoanodes can improve light-conversion efficiency by absorbing high-energy photons while transmitting lower energy photons to the photocathode for hydrogen production. In this work, transparent photoanodes were implemented by forming metal-oxide junctions of NiO/TiO2 heterostructures for creating the photovoltaic effect. The photovoltaic-induced transparent photoelectrode (PTPE) provides the photovoltage (0.7 V), which efficiently reduces the onset potential voltage by -0.38 V versus the reversible hydrogen electrode (RHE), as compared to 0.17 V versus RHE for a single-TiO2 photoanode. The PEC cell has a high photocurrent of 1.68 mA at 1.23 V with respect to the RHE. The chemical endurance of metal-oxides maintains the stability of the PTPE for over 100 h in an alkaline electrolyte of 0.1 M KOH. The results of this study reveal that combining multiple PTPE cells to create a stacked photoanode enhances the photocurrent roughly in proportion to the number of PTPE cells. This design scheme for optimizing the light-conversion efficiency in a PTPE-photoanode system is promising for creating robust systems for on-site energy producers.

Creation and propagation of a single magnetic domain wall in 2D nanotraps with a square injection pad.

Polycrystalline permalloy 2D nanotraps with a thickness of 20 nm were studied using a Lorentz microscope associated with micro-magnetic simulations. Each trap was designed to create a single head-to-head domain wall. The traps consist of a few nanowires with an in-plane dimension of w nm × 1000 nm (w = 150, 200 and 250 nm). Some structures with an injection pad were also designed to create a single domain wall and propagate it through the structure with the said injection pad. A few of them were patterned to study the nucleation and propagation behavior of such nucleated domain walls using both horizontal magnetic field and injection pad approaches. The case of a domain wall created at the first corner of the trap with a wire width of 200 nm was systematically studied, while single and multiple domain walls can also be created and propagated with or without an injection structure. The characteristics of such movements were exploited with an emphasis on a single head-to-head domain wall.

High-Efficiency Photo-Generated Charges of ZnO/TiO2 Heterojunction Thin Films for Photocatalytic and Antibacterial Performance.

Forming heterostructures based on hybrid photocatalysts has been considered as one of the most effective techniques for improving the photocatalytic efficacy of semiconductor photocatalysts. To address this issue, this article describes ZnO/TiO2 heterojunction thin films that were produced via the direct current reaction magnetron sputtering technique and with varying thickness of TiO2 coating. The structural, morphological, and optical features were thoroughly characterized by X-ray diffraction, scanning electron microscope, photoluminescence, and ultra-violet-visible transmission spectra. The photocatalytic and antibacterial ability were assessed by the photo-degradation of methyl orange (MO) aqueous solution and count method of E. coli bacteria. The results demonstrated that the photocatalytic and antimicrobial efficacy of the ZnO/TiO2 heterojunction was found to vary depending on the morphology of the TiO2 layer. In addition, their photocatalytic (91% MO degradation within 150 min) and antimicrobial efficacy (92.7% antibacterial efficiency within 90 min) were higher than the efficiency of either material alone. This could can be ascribed to the photogenerated charge carrier efficiency and hierarchical nanostructure with a large surface area. The mechanism for the improved photocatalytic performance has been discussed in detail.

Scaling Up Testing for Human Immunodeficiency Virus Infection Among Contacts of Index Patients - 20 Countries, 2016-2018.

In 2017, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that worldwide, 36.9 million persons were living with human immunodeficiency virus (HIV) infection, the virus infection that causes acquired immunodeficiency syndrome (AIDS). Among persons with HIV infection, approximately 75% were aware of their HIV status, leaving 9.4 million persons with undiagnosed infection (1). Index testing, also known as partner notification or contact tracing, is an effective case-finding strategy that targets the exposed contacts of HIV-positive persons for HIV testing services. This report summarizes data from HIV tests using index testing in 20 countries supported by CDC through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) during October 1, 2016-March 31, 2018. During this 18-month period, 1,700,998 HIV tests with 99,201 (5.8%) positive results were reported using index testing. The positivity rate for index testing was 9.8% among persons aged ≥15 years and 1.5% among persons aged <15 years. During the reporting period, HIV positivity increased 64% among persons aged ≥15 years (from 7.6% to 12.5%) and 67% among persons aged <15 years (from 1.2% to 2.0%). Expanding index testing services could help increase the number of persons with HIV infection who know their status, are initiated onto antiretroviral treatment, and consequently reduce the number of persons who can transmit the virus.

Insight into the adsorption mechanisms of methylene blue and chromium(iii) from aqueous solution onto pomelo fruit peel.

In this study, the biosorption mechanisms of methylene blue (MB) and Cr(iii) onto pomelo peel collected from our local fruits are investigated by combining experimental analysis with ab initio simulations. Factors that affect the adsorption such as pH, adsorption time, adsorbent dosage and initial adsorbate concentration, are fully considered. Five isotherm models-Langmuir, Freundlich, Sips, Temkin, and Dubinin-Radushkevich-are employed to estimate the capacity of pomelo peel adsorption, whereas four kinetic models-pseudo-first-order, pseudo-second-order, Elovich and intra-diffusion models-are also used to investigate the mechanisms of the uptake of MB and Cr(iii) onto the pomelo fruit peel. The maximum biosorption capacities calculated from the Langmuir models for MB and Cr(iii) at 303 K are, 218.5 mg g-1 and 11.3 mg g-1, respectively. In particular, by combining, for the first time, the experimental FT-IR spectra with those obtained from ab initio calculations, we are able to demonstrate that the primary adsorption mechanisms of the uptake of MB onto pomelo fruit peel are electrostatic attraction and hydrogen-bond formations, whereas the adsorption mechanisms for Cr(iii) are electrostatic attraction and n-d interactions.

High Efficiency Inorganic/Inorganic Amorphous Silicon/Heterojunction Silicon Tandem Solar Cells.

We investigated high-efficiency two-terminal tandem photovoltaic (PV) devices consisting of a p/i/n thin film silicon top sub-cell (p/i/n-TFS) and a heterojunction with an intrinsic thin-layer (HIT) bottom sub-cell. We used computer simulations and experimentation. The short-circuit current density (Jsc) of the top sub-cell limits the Jsc of the p/i/n-TFS/HIT tandem PV device. In order to improve the Jsc of the top sub-cell, we used a buffer-layer at the p/i and i/n interface and a graded forward-profile (f-p) band gap hydrogenated amorphous silicon germanium active layer, namely i-layer, in the top sub-cell. These two approaches showed a remarkable raise of the top sub-cell's Jsc, leading to the increase of the Jsc of the PV tandem device. Furthermore, in order to minimize the optical loss, we employed a double-layer anti-reflective coating (DL-ARC) with a magnesium fluoride/indium tin oxide double layer on the front surface. The reduction in broadband reflection on the front surface (with the DL-ARC) and the enhanced optical absorption in the long wavelength region (with the graded f-p band gap) resulted in the high Jsc, which helped achieve the efficiency up to 16.04% for inorganic-inorganic c-Si-based tandem PV devices.

Field-driven single domain wall motion in ferromagnetic nanowires.

We present a Lorentz microscopy study of polycrystalline permalloy 2D nanostructures with a thickness of 20 nm. Each structure was designed as a single domain wall trap. The trap comprises two horizontal nanowires with an in-plane dimension of 200 × 1000 nm2, and three tilted pads with different shapes. These structures allow us to create head-to-head domain walls, and these created walls can propagate in the structures by an external magnetic field. These designed traps were simulated using the micro-magnetic OOMMF simulation software. Those nanostructures were also patterned using electron beam lithography and focussed-ion beam techniques. This aims to determine the geometric parameters required to propagate a single magnetic domain wall in these structures reproducibly. Among the studied structures with one and two field directions, we found that the motion of a domain wall can be reproducibly driven by two alternative field directions in a trap which consists of the two horizontal nanowires and three 90°-tilted ones. We investigated systematically the viability of both single field and sequential switching of two field directions. Lorentz microscopy and micro-magnetic simulation results indicate that the propagation of a domain wall is strongly affected by the precise shape of the corner sections linking the trap elements, and the angles of the horizontal nanowires and tilted pads. Domain wall pinning and transformation of wall chirality are strongly correlated to the trap geometries. Our results are vital to design an optimal trap which supports a reproducible domain wall motion. This might also support a greater understanding of domain wall creation and propagation in magnetic nanowires which are of interest for concepts of high-density and ultrafast nonvolatile data storage devices, including racetrack memory and magnetic logic gates.

Exploring characteristics of the corner sections of a domain wall trap nanostructure with the two-field direction method.

A 2D polycrystalline permalloy domain wall trap nanostructure with a thickness of 20 nm was studied. The structure was alternatively designed and patterned using QCAD/L-Edit software and focused-ion beam technique. With this design, a magnetic domain wall can be created and propagated with a sequence of two-field directions in a Lorentz microscopy. The trap consists of two horizontal nanowires and three 90°-tilted ones. Each nanowire has an in-plane dimension of 200 × 1000 nm2. The trap corners were curved to allow a created domain wall that easily moves through the structure. A head-to-head domain-wall aims to create using a continuous field, this created wall can be propagated in the trap using a sequence of two-field directions. The designed trap was simulated using the Object Oriented Micro-Magnetic Framework software. Lorentz microscopy and simulation results indicate that the propagation of a domain wall is strongly affected by the precise roughness behavior of the trap elements. Domain wall pinning and transformation of wall chirality are sensitively correlated to the corner sections of the trap structure and field directions at a certain regime. Using the two-field direction method enables us to explore characteristics of the corner sections of the patterned trap nanostructure. This study is vital to fabricate an optimal nano-trap which supports a reproducible domain wall motion. This also suggests a useful method for the domain wall propagation using sequences of two-field directions. This work provides a better understanding of wall creation and propagation in polycrystalline permalloy curved nanowires which are of interest for concepts of nonvolatile data storage devices.