Purpose
Inherent structural and functional properties of biotechnology-derived therapeutic biologics make them susceptible to light- and temperature-induced degradation and consequently can influence ...their quality. Photosensitivity of therapeutic proteins continues to be examined, but the commonalities and trends of storage conditions and information about light and temperature sensitivity among currently licensed therapeutic proteins has not been previously surveyed.
Methods
Using a comprehensive and relational database approach, we conducted a scientific survey of all licensed biotechnology-derived drug products with the goal of providing evidence-based information about recommended storage conditions of formulations sorted by light- and temperature-related attributes as described for each product at licensure.
Results
We report the prevalence of indications for light and temperature sensitivity in formulations categorized by their presentation type, number of doses, container type, dosage form and active molecule type. We also report the storage temperature range across formulations and diluents for reconstitution and dilution. Formulations with excipients that potentially facilitate light-induced and thermal degradation were also noted.
Conclusions
The result of our analysis indicates that light and temperature sensitivity are prevalent across therapeutic protein formulations. However, when a formulation is reconstituted or diluted, both light and temperature sensitivity are less clear. In addition, light and temperature sensitivity are more well defined in liquid formulations than lyophilized powder formulations, and more well defined in products manufactured in autoinjectors, prefilled-syringes, and pens than products in vials. Overall, our report provides a data-driven summary of storage conditions among therapeutic protein formulations to support the development of future biologic drug products.
Essentials
It is not clear if patients are less adherent to low molecular weight heparin (LMWH) compared to direct oral anticoagulants (DOACs) for cancer‐associated thrombosis (CAT).
We evaluated ...medication adherence among two propensity‐matched groups of patients with CAT by comparing the proportion of days covered (PDC).
Median treatment persistence on DOACs was more than 80 days longer than LMWH.
Medication adherence was high (~95%) and was similar with LMWH compared to DOACs.
Background
Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) are used to treat cancer‐associated thrombosis (CAT). It is not clear if patients are less adherent to LMWH compared to DOACs.
Objectives
To compare medication persistence and adherence between LMWH and DOACs.
Patients/Methods
We analyzed Optum's de‐identified Clinformatics® Data Mart Database of privately insured adults with cancer diagnosed between January 2009 and October 2015 who were undergoing chemotherapy, immunotherapy, targeted or hormonal therapies; developed CAT; and were treated with an outpatient anticoagulant. The proportion of days covered (PDC) was calculated from the date of anticoagulant prescription until the anticoagulant was switched, stopped, or the study end. Medication adherence was defined as PDC ≥ 80%, ≥95%, and by comparing the mean PDC.
Results
Two propensity‐matched groups of 1128 patients were identified. Patient persistence was higher with DOACs compared to LMWH (median 116 days versus 34 days). With adherence defined as PDC ≥ 80%, we found no significant difference (95.6% versus 94.6% adherence with DOACs versus LMWH, P = .33). The mean difference of PDC between the two groups was also similar. With medication adherence defined as PDC ≥ 95%, adherence was evident in 73% of DOAC users and 81% of patients on LMWH (P < .001). Prescription copayments were higher on average for LMWH compared to DOACs (mean $153.61 versus 40.67; standard deviation $306.74 versus $33.11).
Conclusion
Patients remain on DOACs longer than LMWH, but medication adherence is similar with LMWH.
The innovation of rapid influenza polymerase chain reaction (XT-PCR) has allowed quick, highly sensitive test results. Consequently, physicians can differentiate influenza from other respiratory ...illnesses and rapidly initiate treatment. We examined the effect of implementing XT-PCR on antimicrobial use, admission rates, and length of stay at a tertiary healthcare system.
Goal 1 of the National Plan to Address Alzheimer’s Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease–related dementias by 2025. To help inform the research agenda ...toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimerʼs Disease–Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.
The events underlying senescence induced by critical telomere shortening are not fully understood. Here we provide evidence that TERRA, a non-coding RNA transcribed from subtelomeres, contributes to ...senescence in yeast lacking telomerase (tlc1Δ). Levels of TERRA expressed from multiple telomere ends appear elevated at senescence, and expression of an artificial RNA complementary to TERRA (anti-TERRA) binds TERRA in vivo and delays senescence. Anti-TERRA acts independently from several other mechanisms known to delay senescence, including those elicited by deletions of EXO1, TEL1, SAS2, and genes encoding RNase H enzymes. Further, it acts independently of the senescence delay provided by RAD52-dependent recombination. However, anti-TERRA delays senescence in a fashion epistatic to inactivation of the conserved histone methyltransferase Dot1. Dot1 associates with TERRA, and anti-TERRA disrupts this interaction in vitro and in vivo. Surprisingly, the anti-TERRA delay is independent of the C-terminal methyltransferase domain of Dot1 and instead requires only its N-terminus, which was previously found to facilitate release of telomeres from the nuclear periphery. Together, these data suggest that TERRA and Dot1 cooperate to drive senescence.
Hematologic toxicity frequently complicates chimeric antigen receptor (CAR) T-cell therapy, resulting in significant morbidity and mortality. In an effort to standardize reporting, the European ...Hematology Association (EHA) and European Society of Blood and Marrow Transplantation (EBMT) devised the immune effector cell-associated hematotoxicity (ICAHT) grading system, distinguishing between early (day 0-30) and late (after day +30) events based on neutropenia depth and duration. However, manual implementation of ICAHT grading criteria is time-consuming and susceptible to subjectivity and error. To address these challenges, we introduce a novel computational approach, utilizing the R programming language, to automate early and late ICAHT grading. Given the complexities of early ICAHT grading, we benchmarked our approach both manually and computationally in two independent cohorts totaling 1251 patients. Our computational approach offers significant implications by streamlining grading processes, reducing manual time and effort, and promoting standardization across varied clinical settings. We provide this tool to the scientific community alongside a comprehensive implementation guide, fostering its widespread adoption and enhancing reporting consistency for ICAHT.
Social vulnerabilities increase the risk of developing hypertension and lower life expectancy, but the effect of an individual's overall vulnerability burden is unknown. Our objective was to ...determine the association of social vulnerability count and the risk of developing hypertension or dying over 10 years and whether these associations vary by race. We used the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) and included participants without baseline hypertension. The primary exposure was the count of social vulnerabilities defined across economic, education, health and health care, neighborhood and built environment, and social and community context domains. Among 5425 participants of mean age 64±10 SD years of which 24% were Black participants, 1468 (31%) had 1 vulnerability and 717 (15%) had ≥2 vulnerabilities. Compared with participants without vulnerabilities, the adjusted relative risk ratio for developing hypertension was 1.16 (95% CI, 0.99-1.36) and 1.49 (95% CI, 1.20-1.85) for individuals with 1 and ≥2 vulnerabilities, respectively. The adjusted relative risk ratio for death was 1.55 (95% CI, 1.24-1.93) and 2.30 (95% CI, 1.75-3.04) for individuals with 1 and ≥2 vulnerabilities, respectively. A greater proportion of Black participants developed hypertension and died than did White participants (hypertension, 38% versus 31%; death, 25% versus 20%). The vulnerability count association was strongest in White participants (
value for vulnerability count×race interaction: hypertension=0.046, death=0.015). Overall, a greater number of socially determined vulnerabilities was associated with progressively higher risk of developing hypertension, and an even higher risk of dying over 10 years.
The purpose of this study was to explore the effect of vocalic behavior in resolving high-conflict situations. A quantitative study was employed using 277 university students from California and ...Florida. We experimentally tested a vocal coding system using passive, aggressive, and assertive audio clips presented to research subjects, which included volume, pitch, rate, pausing, and vocal variety. Participants rated these audio clips based on vocal qualities, relational outcomes, appropriateness, and resolving conflict. Results revealed that the assertive vocal style was associated with higher ratings to resolve conflict and perceptions of verbal assertiveness and appropriateness than were passive or aggressive vocal styles. Implications and applications are discussed to stimulate future research among researchers and practitioners when addressing conflict situations.
Public Significance Statement
This study tested the effects of different vocal qualities on perceptions of conflict. The results found that the assertive vocal style (as opposed to aggressive or passive) was most conducive to resolving conflict and wanting to work with a partner in the future.
This prospective study seeks to examine the utility of subjective cognitive decline (SCD) as a marker of future progression to dementia in a community-based cohort of non-Latinx White, non-Latinx ...Black, and Latinx individuals. Debate surrounds the utility of SCD, the subjective perception of decline in one's cognition before such impairment is evident in traditional neuropsychological assessments, as an early indicator of impending Alzheimer disease. Unfortunately, most studies examining SCD have been conducted in non-Latinx White samples and commonly exclude groups of individuals shown to be most vulnerable to dementia.
Participants were enrolled into this cohort study from the Washington Heights-Inwood Columbia Aging Project if they were cognitively unimpaired, had baseline measurement of SCD, and self-identified as non-Latinx White, non-Latinx Black, or Latinx. SCD was measured as a continuous sum of 10 items assessing cognitive complaints. Competing risk models tested the main effects of baseline SCD on progression to dementia. Models were adjusted for age, sex/gender, years of education, medical comorbidity burden, enrollment cohort, and baseline memory test performance with death jointly modelled as a function of race/ethnicity.
A total of 4,043 (1,063 non-Latinx White, 1,267 non-Latinx Black, and 1,713 Latinx) participants were selected for this study with a mean age of 75 years, 67% women, and with a mean follow-up of 5 years. Higher baseline SCD was associated with increased rates of incident dementia over time in the full sample (hazard ratio HR 1.085, CI 1.047-1.125,
< 0.001) and within Latinx (HR 1.084, CI 1.039-1.130,
< 0.001) and non-Latinx Black individuals (HR 1.099, CI 1.012-1.194,
= 0.024).
Overall results of this study support SCD as a prodromal marker of dementia in a multiracial community sample, and in Latinx and non-Latinx Black individuals in particular. Because models examining the risk of dementia were adjusted for baseline memory test performance, the results support the idea that SCD, a subjective reflection of one's own current cognitive functioning, contributes information above and beyond standard memory testing. Current findings highlight the importance of carefully evaluating any memory concerns raised by older adults during routine visits and underscore the potential utility of screening older adults for SCD.
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