Healthcare Utilization and Advance Care Planning among Older Adults Across Cognitive Levels.

This study examined the impact of advance care planning (ACP) on healthcare utilization among older adults with normal cognition and impaired cognition/dementia. Using datasets from the Health and Retirement Study, we conducted a cross-sectional study on 17,698 participants aged 51 years and older. Our analyses included survey descriptive and logistic regression procedures. ACP measures included a living will and durable power of attorney for healthcare. Healthcare utilization was measured using the days spent in hospitals, hospice care, nursing homes, and home care. Of the participants, 77.8% had normal cognition, and 22% had impaired cognition/dementia. The proportion of impaired cognition/dementia was higher among racially minoritized participants, single/widowed participants, and those who lived alone and were less educated. The results showed that having an ACP was associated with longer stays in hospitals, nursing homes, and home healthcare in all participants.

Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1/2 trial.

BACKGROUND: Outcomes for patients with blast-phase chronic myeloid leukaemia are poor. Long-term survival depends on reaching a second chronic phase, followed by allogeneic haematopoietic stem-cell transplantation (HSCT). We investigated whether the novel combination of the tyrosine-kinase inhibitor ponatinib with fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) could improve response and optimise allogeneic HSCT outcomes in patients with blast-phase chronic myeloid leukaemia. The aim was to identify a dose of ponatinib, which combined with FLAG-IDA, showed clinically meaningful activity and tolerability. METHODS: MATCHPOINT was a seamless, phase 1/2, multicentre trial done in eight UK Trials Acceleration Programme-funded centres. Eligible participants were adults (aged ≥16 years) with Philadelphia chromosome-positive or BCR-ABL1-positive blast-phase chronic myeloid leukaemia, suitable for intensive chemotherapy. Participants received up to two cycles of ponatinib with FLAG-IDA. Experimental doses of oral ponatinib (given from day 1 to day 28 of FLAG-IDA) were between 15 mg alternate days and 45 mg once daily and the starting dose was 30 mg once daily. Intravenous fludarabine (30 mg/m2 for 5 days), cytarabine (2 g/m2 for 5 days), and idarubicin (8 mg/m2 for 3 days), and subcutaneous granulocyte colony-stimulating factor (if used), were delivered according to local protocols. We used an innovative EffTox design to investigate the activity and tolerability of ponatinib-FLAG-IDA; the primary endpoints were the optimal ponatinib dose meeting prespecified thresholds of activity (inducement of second chronic phase defined as either haematological or minor cytogenetic response) and tolerability (dose-limiting toxicties). Analyses were planned on an intention-to-treat basis. MATCHPOINT was registered as an International Standard Randomised Controlled Trial, ISRCTN98986889, and has completed recruitment; the final results are presented. FINDINGS: Between March 19, 2015, and April 26, 2018, 17 patients (12 men, five women) were recruited, 16 of whom were evaluable for the coprimary outcomes. Median follow-up was 41 months (IQR 36-48). The EffTox model simultaneously considered clinical responses and dose-limiting toxicities, and determined the optimal ponatinib dose as 30 mg daily, combined with FLAG-IDA. 11 (69%) of 16 patients were in the second chronic phase after one cycle of treatment. Four (25%) patients had a dose-limiting toxicity (comprising cardiomyopathy and grade 4 increased alanine aminotransferase, cerebral venous sinus thrombosis, grade 3 increased amylase, and grade 4 increased alanine aminotransferase), fulfilling the criteria for clinically relevant activity and toxicity. 12 (71%) of 17 patients proceeded to allogeneic HSCT. The most common grade 3-4 non-haematological adverse events were lung infection (n=4 [24%]), fever (n=3 [18%]), and hypocalcaemia (n=3 [18%]). There were 12 serious adverse events in 11 (65%) patients. Three (18%) patients died due to treatment-related events (due to cardiomyopathy, pulmonary haemorrhage, and bone marrow aplasia). INTERPRETATION: Ponatinib-FLAG-IDA can induce second chronic phase in patients with blast-phase chronic myeloid leukaemia, representing an active salvage therapy to bridge to allogeneic HSCT. The number of treatment-related deaths is not in excess of what would be expected in this very high-risk group of patients receiving intensive chemotherapy. The efficient EffTox method is a model for investigating novel therapies in ultra-orphan cancers. FUNDING: Blood Cancer UK and Incyte.

Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia.

Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level <1% to 2% with a <1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD-; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction <4.4-log) at EOT.

Predictors of Feelings of Anxiety in Graduate Allied Health Students: An Exploratory Study.

The objective of this study was to take a multi-domain approach to predict feelings of anxiety among graduate allied health students. Participants (n=77) from a small university in upstate New York completed a series of questionnaires [International Physical Activity Questionnaire-short form (IPAQ-SF), Rapid Eating Assessment of Participants-Short Form (REAP-S), Pittsburgh Sleep Quality Inventory (PSQI), Profile of Mood Survey-Short Form (POMS-SF), Trait and State Mental and Physical Energy and Fatigue Survey], and their resting metabolic rate, fat free mass and muscle oxygen saturation levels were measured. A backwards linear regression was used to identify predictors of anxiety. Our model predicted 28.1% of variance with women reporting greater feelings of anxiety. Poor sleep quality, increased sedentary behavior, and low trait physical energy were all significant predictors of increased feelings anxiety. Our results suggest that educators should attempt to reduce in class sitting time and promote better sleep hygiene. Additionally, researchers should examine barriers and burdens female students face that increase feelings of anxiety.

Suicide Distribution and Trends Among Male Older Adults in the U.S., 1999-2018.

INTRODUCTION: This study examines the distribution and trends in suicide death rates among male adults aged ≥65 years in the U.S. from 1999 to 2018. METHODS: Suicide mortality data were derived from Multiple Cause of Death from the Center for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research database. Suicides were identified from the underlying causes of death. Joinpoint regression examined the distribution and shift in suicide age-adjusted death rates overall and by age groups, race/ethnicity, method of suicide, and urbanicity. Analyses were conducted in 2020. RESULTS: Between 1999 and 2018, a total of 106,861 male adults aged ≥65 years died of suicide (age-adjusted rate=31.4 per 100,000 population, 95% CI=31.2, 31.6). Suicide rates showed a V-shaped trend. They were declining annually by 1.8% (95% CI= -2.4, -1.2); however, starting in 2007, there was a shift upward, increasing significantly by 1.7% per year for the next decade (95% CI=1.0, 1.6). Suicide rates were highest among those aged ≥85 years (48.8 per 100,000 population with an upward shift in 2008), Whites (35.3 per 100,000 population with an upward shift in trend in 2007), and the most rural communities (39.0 per 100,000 population). Most suicides were due to firearms (78.3% at a rate of 24.7 per 100,000 population), especially in rural areas, and shifted upward after 2007. CONCLUSIONS: Increases in suicide rates among male older adults in the U.S., particularly after the 2007-2008 economic recession, are concerning. Tailored suicide prevention intervention strategies are needed to address suicide-related risk factors.

Translating CDSMP to the Workplace: Results of the Live Healthy Work Healthy Program.

PURPOSE: Report the results of a randomized, controlled trial of Live Healthy, Work Healthy (LHWH), a worksite translation of the Chronic Disease Self-Management Program (CDSMP). DESIGN: 14 worksites were randomly assigned to LHWH, standard CDSMP (usual care) or no-intervention (control) group. SETTING: The diverse set of work organizations centered around a rural community in SE US. SUBJECTS: 411 participants completed baseline data with 359 being included in the final analyses. INTERVENTION: LHWH had been adapted to fit the unique characteristics of work organizations. This translated program consists of 15 sessions over 8 weeks and was facilitated by trained lay leaders. MEASURES: The primary outcomes including health risk, patient-provider communication, quality of life, medical adherence and work performance were collected pretest, posttest (6 mos.) and follow-up (12 mos.). ANALYSIS: Analyses were conducted using latent change score models in a structural equation modeling framework. RESULTS: 79% of participants reported at least one chronic condition with an average of 2.7 chronic conditions reported. Results indicated that LHWH program demonstrated positive changes in a most outcomes including significant exercise (uΔ = 0.89, p < .01), chronic disease self-efficacy (uΔ = 0.63, p < .05), fatigue (uΔ = -1.45, p < .05), stress (uΔ = -0.98, p < .01) and mentally unhealthy days (uΔ = -3.47, p < .001). CONCLUSIONS: The translation of LHWH is an effective, low cost, embeddable program that has the potential to improve the health and work life of employees.

Biosurfactants: A Covid-19 Perspective.

The recent outbreak in severe acute respiratory syndrome - coronavirus-2 (SARS-CoV-2) has demonstrated the complete inability of nations across the world to cope with the pressures of a global pandemic, especially one in which the only current feasible treatments are those which deal with the symptoms alone and not the viral cause. As the death toll rises, scientists begin to fall toward new avenues of research, with novelty showing itself to be an incredible and so far, underrated resource. In this case, the use of biosurfactants in dealing with this pandemic justifies extensive study with their potential applications being in the prevention of viral spread; dealing with the symptoms that develop after the incubation period; directly targeting viral infected cells and preventing the spread of the virus throughout the host, all in addition to also acting as potential drug delivery systems and cleaning agents. This extensive avenue of biosurfactants owes to the simplicity in their amphiphilic structure which permits them to interact directly with the lipid membrane of the coronavirus, in a way which wouldn't be of significant threat to the host. Although it could possibly interact and affect the virus, it could also affect human internal organs/cells by interacting with lipid membrane, if (biosurfactant is) ingested, and it still needs further studies in human models. The structure of the coronavirus, in this case SARS-CoV-2, is detrimentally dependent on the integrity of its lipid membrane which encloses its vital proteins and RNA. Biosurfactants possess the innate ability to threaten this membrane, a result of their own hydrophobic domains across their amphiphilic structure. With biosurfactants additionally being both natural and sustainable, while also possessing a remarkably low cytotoxicity, it is of no doubt that they are going to be of increasing significance in dealing with the current pandemic.

Advances in upstream and downstream strategies of pectinase bioprocessing: A review.

This review aims to highlight the bioprocessing strategies behind one of the most commercially produced enzymes in the biotechnological market, pectinase. Significant steps in the upstream processing of this enzyme include its source, the selection of the substrate, the reaction conditions and the overall reactor design, all of which will be discussed in great detail. Past literature which has contributed to the viability of this design will be highlighted with the intention of generating a comparative review that accounts not only for the contributions of previous research but also for what needs to be done in the future to further increase the productivity of this vital industrial process. There is an incredibly wide net of application based research and industry which currently depends on the bioprocessing of pectinase, these will thereby benefit greatly from the concepts of process intensification and optimisation which are at the forefront of this review and will likely be inspired by the outlined steps that need to be taken to further improve this process.

Health Differences in Didactic Versus Clinical Stage Graduate Allied Health Students.

AIMS: Graduate education in the healthcare professions can be stressful and mentally taxing. The objective of this study was to identify differences in health and health-related behaviors among graduate allied health students based on sex and curriculum stage (i.e., didactic or clinical education). METHODS: Participants (n=77) were assessed for body fat, BMI, resting metabolic rate (RMR), and peripheral arterial-venous O2 (AVO2), as well as a series of cognitive tasks and self-reported health and health-related behaviors. Independent sample t-tests and tests of proportions were used to assess differences between groups. RESULTS: There was no evidence that the didactic and clinical students were meaningfully different upon entering their programs. Didactic students reported significantly higher tension/anxiety, depression, anger, confusion, fatigue, total mood disturbance, trait mental fatigue, total intensity of mental work performed, and time spent sitting (p<0.05). Didactic students also reported significantly lower RMR (p=0.033), but not after normalizing for fat-free mass. Males reported lower intensity of mental work performed on non-work days compared to females (p=0.009). CONCLUSIONS: Findings indicate students in didactic stages have worse mood and decreased health relative to their counterparts in clinical stages. Opportunities exist to integrate physical and mental health-related education, resources, and self-management programming into graduate allied health curricula to improve wellness among students.

Expansion Of Telestroke Services Improves Quality Of Care Provided In Super Rural Areas.

Telestroke is a telemedicine intervention that facilitates communication between stroke centers and lower-resourced facilities to optimize acute stroke management. Using administrative claims data, we assessed trends in telestroke use among fee-for-service Medicare beneficiaries with acute ischemic stroke and the association between providing telestroke services and intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy use, mortality, and medical expenditures, by urban versus rural county of residence in the period 2008-15. The proportion of ischemic stroke cases receiving telestroke increased from 0.4 to 3.8 per 1,000 cases, with usage highest among younger, male, non-Hispanic white, and patients in rural or super rural areas (super rural is the bottom quartile of rural areas. Compared with patients receiving usual care, those receiving telestroke had greater IV tPA and mechanical thrombectomy use regardless of county type, while those in super rural counties had lower thirty-day all-cause mortality. Despite increased telestroke use, rural patients remained less likely than urban patients to receive IV tPA. The findings suggest that telestroke service expansion efforts have increased, especially in rural and super rural counties, and have improved outcomes.

Otago Exercise Program in the United States: Comparison of 2 Implementation Models.

Background: The Otago Exercise Program (OEP) is an evidence-based fall prevention program delivered by a physical therapist in 6 visits over a year. Despite documented effectiveness, there has been limited adoption of the OEP by physical therapists in the United States. To facilitate dissemination, 2 models have been developed: (1) the US OEP provided by a physical therapist or physical therapist assistant in the home or outpatient setting and (2) the community OEP provided by a non­physical therapist and a physical therapist consultant. It is unknown whether such modifications result in similar outcomes. Objective: The aims of this study were to identify the components of these 2 models, to compare participant characteristics for those components reached by each model, and to examine outcome changes by model and between models. Design: This was a translational cohort study with physical therapists implementing the US OEP and trained providers implementing the community OEP. Methods: Data for physical performance, sociodemographic characteristics, and self-perception of function were collected at baseline and at 8 weeks. Results: Participants in the community OEP were significantly younger and reported more falls compared with those in US OEP. Both sites reported significant improvements in most physical and self-reported measures of function, with larger effect sizes reported by the community OEP for the Timed "Up & Go" Test. There was no significant difference in improvements in outcome measures between sites. Limitations: This was an evaluation of a translational research project with limited control over delivery processes. The sample was 96% white, which may limit application to a more diverse population. Conclusion: Alternative, less expensive implementation models of the OEP can achieve results similar to those achieved with traditional methods, especially improvements in Timed "Up & Go" Test scores. The data suggest that the action of doing the exercises may be the essential element of the OEP, providing opportunities to develop and test new delivery models to ensure that the best outcomes are achieved by participants.

Photomechanical Deformation of Azobenzene-Functionalized Polyimides Synthesized with Bulky Substituents.

Photomechanical effects realized in azobenzene-functionalized polyimides have shown large deformation and an exceptional increase in photogenerated force output. Here, we synthesize and characterize the photomechanical output of a series of linear polyimide materials prepared with a bulky substituent, incorporated via the development of a new bis(azobenzene-diamine) monomer containing a 9,9-diphenylfluorene cardo structure (azoCBODA). All six azoCBODA-containing polyimides are amorphous and exhibit high glass transition temperatures (Tg) ranging from 298 to 358 °C, storage moduli ranging from 2.27 to 3.81 GPa (at 30 °C), and good thermal stability. The magnitude of the photoinduced mechanical response of the azobenzene-functionalized polyimide is correlated to the rotational freedom of the polyimide chains (resulting in extensive segmental mobility) and fractional free volume (FFV > 0.1).

Factors Associated With Intentions to Engage in Vaginal Intercourse Among Sexually Abstinent Missouri High School Freshmen.

BACKGROUND: We examine personal characteristics, alcohol consumption, normative beliefs, household factors, and extracurricular engagement associated with intentions to have intercourse before marriage among abstinent students. METHODS: Data were analyzed from 245 freshmen enrolled in a school-based abstinence-only-until-marriage program. Two binary logistic regression analyses identified factors associated with intentions to engage in intercourse before marriage and within the next year. RESULTS: Approximately 21% and 14% of participants reported intentions to have intercourse. Respondents participated in 2.2 (standard deviation [SD] = 1.2) extracurricular activities. Freshmen who were male, perceived their friends to approve of premarital sex, and consumed alcohol were more likely to report intentions to have intercourse. For every additional extracurricular activity in which freshmen participated, they were less likely to report intentions to have intercourse within the next year (odds ratio [OR] = 0.56). CONCLUSIONS: Factors such as extracurricular activities provide youth with opportunities to build supportive relationships, connect with peers and role models, and positively engage in schools and communities. Extracurricular activities typically already exist, have funding, and are generally well-supported. School-based strategies can increase teenagers' autonomy by providing a variety of activities to participate in and reduce unsupervised time. This, in turn, has the potential to decrease sexual risk taking behaviors.

The Dietary Flavonoid Fisetin Causes Cell Cycle Arrest, Caspase-Dependent Apoptosis, and Enhanced Cytotoxicity of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells.

Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonoid found in a number of fruits and vegetables, has diverse biological activities, including cytotoxic effects on cancer cells. In this study, we investigated the effect of fisetin on triple-negative breast cancer (TNBC) cells. TNBC has a poorer prognosis than other types of breast cancer and treatment options for this disease are limited. Fisetin inhibited the growth of MDA-MB-468 and MDA-MB-231 TNBC cells, as well as their ability to form colonies, without substantially affecting the growth of non-malignant cells. In addition, fisetin inhibited the growth of estrogen receptor-bearing MCF-7 breast cancer cells and human epidermal growth factor receptor 2-overexpressing SK-BR-3 breast cancer cells. Fisetin inhibited TNBC cell division and induced apoptosis, which was associated with mitochondrial membrane permeabilization and the activation of caspase-9 and caspase-8, as well as the cleavage of poly(ADP-ribose) polymerase-1. Induction of caspase-dependent apoptosis by fisetin was confirmed by reduced killing of TNBC cells in the presence of the pan-caspase inhibitors Z-VAD-FMK and BOC-D-FMK. Decreased phosphorylation of histone H3 at serine 10 in fisetin-treated TNBC cells at G2/M phase of the cell cycle suggested that fisetin-induced apoptosis was the result of Aurora B kinase inhibition. Interestingly, the cytotoxic effect of cisplatin, 5-fluorouracil, and 4-hydroxycyclophosphamide metabolite of cyclophosphamide on TNBC cells was increased in the presence of fisetin. These findings suggest that further investigation of fisetin is warranted for possible use in the management of TNBC. J. Cell. Biochem. 117: 1913-1925, 2016. © 2016 Wiley Periodicals, Inc.

Leveraging Administrative Data for Program Evaluations: A Method for Linking Data Sets Without Unique Identifiers.

In community-based wellness programs, Social Security Numbers (SSNs) are rarely collected to encourage participation and protect participant privacy. One measure of program effectiveness includes changes in health care utilization. For the 65 and over population, health care utilization is captured in Medicare administrative claims data. Therefore, methods as described in this article for linking participant information to administrative data are useful for program evaluations where unique identifiers such as SSN are not available. Following fuzzy matching methodologies, participant information from the National Study of the Chronic Disease Self-Management Program was linked to Medicare administrative data. Linking variables included participant name, date of birth, gender, address, and ZIP code. Seventy-eight percent of participants were linked to their Medicare claims data. Linking program participant information to Medicare administrative data where unique identifiers are not available provides researchers with the ability to leverage claims data to better understand program effects.

Design of polarization-dependent, flexural-torsional deformation in photo responsive liquid crystalline polymer networks.

Light responsive materials that exhibit wirelessly actuated, multidimensional deformation are excellent candidates for programmable matter applications such as morphing structures or soft robotics. A central challenge to designing adaptive structures from these materials is the ability accurately predict three dimensional deformations. Previous modeling efforts have focused almost exclusively on pure bending. Herein we examine key material parameters affecting light driven flexural-torsional response in azobenzene functionalized liquid crystal polymer networks. We show that a great deal of control can be obtained by specifying material alignment and actuating the material with polarized light. Insight gained from the theoretical framework here lays the foundation for more extensive modeling efforts to combine polarization controlled flexural-torsional deformations with complex geometry, boundary conditions, and loading conditions.

Contactless, photoinitiated snap-through in azobenzene-functionalized polymers.

Photomechanical effects in polymeric materials and composites transduce light into mechanical work. The ability to control the intensity, polarization, placement, and duration of light irradiation is a distinctive and potentially useful tool to tailor the location, magnitude, and directionality of photogenerated mechanical work. Unfortunately, the work generated from photoresponsive materials is often slow and yields very small power densities, which diminish their potential use in applications. Here, we investigate photoinitiated snap-through in bistable arches formed from samples composed of azobenzene-functionalized polymers (both amorphous polyimides and liquid crystal polymer networks) and report orders-of-magnitude enhancement in actuation rates (approaching 10(2) mm/s) and powers (as much as 1 kW/m(3)). The contactless, ultra-fast actuation is observed at irradiation intensities <<100 mW/cm(2). Due to the bistability and symmetry of the snap-through, reversible and bidirectional actuation is demonstrated. A model is developed to elucidate the underlying mechanics of the snap-through, specifically focusing on isolating the role of sample geometry, mechanical properties of the materials, and photomechanical strain. Using light to trigger contactless, ultrafast actuation in an otherwise passive structure is a potentially versatile tool to use in mechanical design at the micro-, meso-, and millimeter scales as actuators, as well as switches that can be triggered from large standoff distances, impulse generators for microvehicles, microfluidic valves and mixers in laboratory-on-chip devices, and adaptive optical elements.

Barriers to health care among Bell County residents with health insurance medical aid.

Barriers to high-quality health care are associated with negative consequences, not only for the uninsured but also for persons with adequate health insurance or medical aid. Understanding barriers encountered by community residents can improve the outcomes of community interventions designed to address unmet health care needs. The Bell County Needs Assessment was conducted to understand the needs of residents in Bell County, Texas. The current study examined residents' (n = 1422) self-reported barriers to health care and factors associated with reporting one or more such barriers. The most common barriers reported were issues related to health care access and socioeconomic barriers. Residents reporting use of urgent care, emergency room, and walk-in clinics as a regular source of care were significantly more likely to experience two or more barriers to health care (OR = 2.543). Community health interventions may be improved by focusing on reducing barriers among patients who rely on urgent or emergency services as their usual source of care.