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BackgroundSickle cell disease (SCD) is an inherited blood disorder causing acute complications and chronic progressive end organ damage. SCD is associated with significant morbidity, early mortality, impaired health-related quality of life, and increased acute health care utilization. Hydroxyurea is a US Food and Drug Administration–approved medication that reduces disease complications, acute health care utilization, and costs. However, adherence to hydroxyurea is suboptimal. Mobile health (mHealth) interventions have the potential to improve hydroxyurea adherence, but few examples exist that are specific to the SCD population. ObjectiveThis study aimed to design a mHealth intervention for individuals with SCD to improve adherence to hydroxyurea, using a user-centered design that was informed by specific barriers to hydroxyurea adherence and utilization in this population. MethodsThis study consisted of 4 phases. In phase 1, individuals with SCD and health care providers participated in an optimization digital workshop. In phase 2, patients completed surveys pertaining to their interest in mHealth use, barriers and facilitators to hydroxyurea use, and health literacy. Phases 3 and 4 involved semistructured interviews and focus groups, respectively, and used the Health Belief Model (HBM) as the framework to investigate drivers of poor hydroxyurea adherence and to inform the development of an app prototype. In addition, in phase 4, we have incorporated the patients’ feedback on the preliminary app prototype and its features. ResultsBarriers to hydroxyurea adherence were consistent with the literature and included forgetfulness and several specific thoughts and emotions associated with hydroxyurea use (eg, fear of side effects, depression, stigma, and hopelessness). In addition, more than half of the participants reported potentially low health literacy. Preferred patient app features included 7 key components, namely (1) medication reminders and tracker, (2) disease education, (3) communication, (4) personalization, (5) motivation, (6) support during pain episodes, and (7) social support. Utilizing a user-centered design approach, data obtained from patients and providers were translated into features within the app, mapping to components of the HBM and the specific drivers of hydroxyurea adherence and matching the literacy level of the population, resulting in the development of a novel mobile app called InCharge Health. ConclusionsThe InCharge Health app is an mHealth intervention developed with substantial input from users and by mapping the HBM as the framework that guided the choice for its components. InCharge Health is a customized product for the SCD population aimed at optimizing medication adherence, with the end goal of improving quality of life and health outcomes among patients with SCD. The efficacy and implementation of the InCharge Health app as an mHealth intervention to promote hydroxyurea adherence will be tested in a future stepped-wedge multicenter trial for adolescents and adults with SCD.

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.

Hydroxyurea is an efficacious treatment for sickle cell disease (SCD), but adoption is low among individuals with SCD. The objective of this study was to examine barriers to patients' adherence to hydroxyurea use regimens by using the intentional and unintentional medication nonadherence framework. We interviewed individuals with SCD age 15 to 49.9 years who were participants in the Sickle Cell Disease Implementation Consortium (SCDIC) Needs Assessment. The intentional and unintentional medication nonadherence framework explains barriers to using hydroxyurea and adds granularity to the understanding of medication adherence barriers unique to the SCD population. In total, 90 semi-structured interviews were completed across 5 of the 8 SCDIC sites. Among interviewed participants, 57.8% (n = 52) were currently taking hydroxyurea, 28.9% (n = 26) were former hydroxyurea users at the time of the interview, and 13.3% (n = 12) had never used hydroxyurea but were familiar with the medication. Using a constructivist grounded theory approach, we discovered important themes that contributed to nonadherence to hydroxyurea, which were categorized under unintentional (eg, Forgetfulness, External Influencers) and intentional (Negative Perceptions of Hydroxyurea, Aversion to Taking Any Medications) nonadherence types. Participants more frequently endorsed adherence barriers that fell into the unintentional nonadherence type (70%) vs intentional nonadherence type (30%). Results from this study will help SCD health care providers understand patient choices and decisions as being either unintentional or intentional, guide tailored clinical discussions regarding hydroxyurea therapy, and develop specific, more nuanced interventions to address nonadherence factors.

Nanotechnology is considered a successful approach for cancer diagnosis and treatment. Preferentially, cancer cell recognition and drug targeting via nano‐delivery system include the penetration of anticancer agents into the cell membrane to damage the cancer cell by protein modification, DNA oxidation, or mitochondrial dysfunction. The past research on nano‐delivery systems and their target has proven the beneficial achievement in a malignant tumor. Modern perceptions using inventive nanomaterials for cancer management have been offered by a multifunctional platform based on various nano‐carriers with the probability of imaging and cancer therapy simultaneously. Emerging nano‐delivery systems in cancer therapy still lack knowledge of the biological functions behind the interaction between nanoparticles and cancer cells. Since the potential of engineered nanoparticles addresses the various challenges, limiting the success of cancer therapy subsequently, it is a must to review the molecular targeting of a nano‐delivery system to enhance the therapeutic efficacy of cancer. This review focuses on using a nano‐delivery system, an imaging system, and encapsulated nanoparticles for cancer therapy. [ABSTRACT FROM AUTHOR]

Seeking optimal material distribution in a nuclear system to maximize a response function of interest has been a subject of considerable interest in nuclear engineering. Examples are the optimal fuel distribution in a nuclear reactor core to achieve uniform burnup using minimum critical mass and the use of composite materials with an optimal mix of constituent elements in detection systems and radiation shielding. For such studies, variational methods have been found to be useful but, they have been used for standalone analyses often restricted to idealized models, while more elaborate design studies have required computationally expensive Monte Carlo simulations ill-suited to iterative schemes for optimization. Such an inherent disadvantage of Monte Carlo methods changed with the development of perturbation algorithms but, their efficiency is still dependent on the reference configuration for which a hit-and-trial approach is often used. In the first illustrative example, this paper explores the computational speedup for a bare cylindrical reactor core, achievable by using a variational result to enhance the computational efficiency of Monte Carlo design optimization simulation. In the second example, the effect of non-uniform material density in a fixed-source problem, applicable to optimal moderator and radiation shielding, is presented. While applications of this work are numerous, the objective of this paper is to present preliminary variational results as inputs to elaborate stochastic optimization by Monte Carlo simulation for large and realistic systems.

This paper carries out a Monte Carlo simulation of a landmine detection system, using the MCNP5 code, for the detection of concealed explosives such as trinitrotoluene and cyclonite. In portable field detectors, the signal strength of backscattered neutrons and gamma rays from thermal neutron activation is sensitive to a number of parameters such as the mass of explosive, depth of concealment, neutron moderation, background soil composition, soil porosity, soil moisture, multiple scattering in the background material, and configuration of the detection system. In this work, a detection system, with BF3 detectors for neutrons and sodium iodide scintillator for g-rays, is modeled to investigate the neutron signal-to-noise ratio and to obtain an empirical formula for the photon production rate Ri(n,γ)= SfGfMf(d,m) from radiative capture reactions in constituent nuclides of trinitrotoluene. This formula can be used for the efficient landmine detection of explosives in quantities as small as ~200 g of trinitrotoluene concealed at depths down to about 15 cm. The empirical formula can be embedded in a field programmable gate array on a field-portable explosives' sensor for efficient online detection.

Background: Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. Objective: We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. Methods: The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients' daily app use. Adherence to hydroxyurea was calculated as the proportion of days covered (PDC) from prescription records over the first 12 and 24 weeks after implementation. A linear model examined the relationship between app usage and PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured interviews with patients, health care providers, administrators, and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed methods approach to investigate the convergence of qualitative and quantitative findings. Results: The percentage of patients accessing the app decreased after March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: -8.2%; P=.14; 24 weeks: -10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B's closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. Conclusions: We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may "insulate" the implementation of interventions to increase medication adherence. [ABSTRACT FROM AUTHOR]