This exploratory study examined older rural women's health decision making. Thirty-three rural women were recruited to participate in semistructured qualitative interviews. Major themes emerged that ...focused on rural women's comments regarding their concerns about not worrying or bothering their children with personal health matters. Themes were discussed in the context of an ethic of care. Results suggest that it is important for mental health professionals, family physicians, social workers, and other practitioners to be aware of the sense of worry and concern for others that older rural women bring to bear in decision making about personal health issues.
Glioblastoma is the most common and most aggressive primary brain malignancy. The current initial standard of care consists of maximal safe surgical resection followed by radical radiotherapy and ...adjuvant temozolomide. Despite optimal therapy, median survival is ~15 months from diagnosis in molecularly unselected patients, and <6 months for patients with recurrent disease. Therefore, clinical treatments are currently palliative, not curative. Collectively, current knowledge suggests that the continued tumor growth and recurrence is in part due to the presence of glioma stem-like cells, which display self-renewal and tumorigenic potential. They differ from their more differentiated progeny, as they are more resistant to current treatments. Recurrent disease may be a consequence of the enhancement and/or gain of stem cell-like characteristics during disease progression, together with preferential death of more differentiated tumor cells during treatment, signifying that the cancer stem cell phenotype is a crucial therapeutic target. The limited knowledge of the characteristics of these cells and their response to current clinical treatments warrants intensive investigation with the aim to improve patient survival and/or develop a cure for this disease.
•Because of its ability to prevent and treat hypoglycemia, glucagon shows great promise in closed loop treatment of diabetes.•However, glucagon degrades in liquid solution, and the mechanisms of ...degradation are not well understood.•We found that deamidation and isomerization were common, and in many cases, impair the bioactivity of glucagon.•Glucagon also undergoes spontaneous oxidation, but oxidized glucagon retains its bioactivity.•An understanding of glucagon's inactivating degradation mechanisms might help in the search for stabilizing excipients.
Glucagon is unstable and undergoes degradation and aggregation in aqueous solution. For this reason, its use in portable pumps for closed loop management of diabetes is limited to very short periods. In this study, we sought to identify the degradation mechanisms and the bioactivity of specific degradation products. We studied degradation in the alkaline range, a range at which aggregation is minimized. Native glucagon and analogs identical to glucagon degradation products were synthesized. To quantify biological activity in glucagon and in the degradation peptides, a protein kinase A-based bioassay was used. Aged, fresh, and modified peptides were analyzed by liquid chromatography with mass spectrometry (LCMS). Oxidation of glucagon at the Met residue was common but did not reduce bioactivity. Deamidation and isomerization were also common and were more prevalent at pH 10 than 9. The biological effects of deamidation and isomerization were unpredictable; deamidation at some sites did not reduce bioactivity. Deamidation of Gln 3, isomerization of Asp 9, and deamidation with isomerization at Asn 28 all caused marked potency loss. Studies with molecular-weight-cutoff membranes and LCMS revealed much greater fibrillation at pH 9 than 10. Further work is necessary to determine formulations of glucagon that minimize degradation and fibrillation.
Atmospheric methane directly affects surface temperatures and indirectly affects ozone, impacting human welfare, the economy, and environment. The social cost of methane (SC‐CH4) metric estimates the ...costs associated with an additional marginal metric ton of emissions. Current SC‐CH4 estimates do not consider the indirect impacts associated with ozone production from changes in methane. We use global model simulations and a new BenMAP webtool to estimate respiratory‐related deaths associated with increases in ozone from a pulse of methane emissions in 2020. By using an approach consistent with the current SC‐CH4 framework, we monetize and discount annual damages back to present day values. We estimate that the methane‐ozone mechanism is attributable to 760 (95% CI: 330–1200) respiratory‐related deaths per million metric tons of methane globally, for a global net present damage of $1800/mT (95% CI: $760–$2800/mT CH4; 2% Ramsey discount rate); this would double the current SC‐CH4 if included. These physical impacts are consistent with recent studies, but comparing direct costs is challenging. Economic damages are sensitive to uncertainties in the exposure and health risks associated with tropospheric ozone, assumptions about future projections of NOx emissions, socioeconomic conditions, and mortality rates, monetization parameters, and other factors. Our estimates are highly sensitive to uncertainties in ozone health risks. We also develop a reduced form model to test sensitivities to other parameters. The reduced form tool runs with a user‐supplied emissions pulse, as well as socioeconomic and precursor projections, enabling future integration of the methane‐ozone mechanism into the SC‐CH4 modeling framework.
Plain Language Summary
The social cost of methane is used to assess the costs and benefits associated with emissions mitigation in U.S. regulations, in addition to other decision‐making applications. The current social cost of methane used by the U.S. Government is $1500/metric ton of methane emissions. This estimate does not include damages related to deaths associated with changes in exposure to background ozone, resulting from increases in atmospheric methane. Using an approach consistent with the social cost of methane framework, we estimate that damages from the methane‐ozone mechanism are $1800/metric ton, which, if included, would double the current social cost of methane. These costs have uncertainties related to the health risks associated with exposure to ozone, assumptions about future NOx emissions, choice of discount rates, and other factors. We also develop a reduced form model that allows rapid estimation of many of these sensitivities and enables consideration of this mechanism in the social cost methodology.
Key Points
Increases in mortality attributable to ozone produced from methane are not currently considered in the government's social cost of methane
Ozone from a 2020 methane emissions pulse results in 760 deaths per million metric ton and a net present value of $1800 per metric ton
A reduced form tool is developed to assess uncertainties and facilitate additional social cost of methane calculations
Small doses of glucagon given subcutaneously in the research setting by an automated system prevent most cases of hypoglycemia in persons with diabetes. However, glucagon is very unstable and cannot ...be kept in a portable pump. Glucagon rapidly forms amyloid fibrils, even within the first day after reconstitution. Aggregation eventually leads to insoluble gels, which occlude pump catheters. Fibrillation occurs rapidly at acid pH, but is absent or minimal at alkaline pH values of ~10. Glucagon also degrades over time; this problem is greater at alkaline pH. Several studies suggest that its primary degradative pathway is deamidation, which results in a conversion of asparagine to aspartic acid. A cell-based assay for glucagon bioactivity that assesses glucagon receptor (GluR) activation can screen promising glucagon formulations. However, mammalian hepatocytes are usually problematic as they can lose GluR expression during culture. Assays for cyclic AMP (cAMP) or its downstream effector, protein kinase A (PKA), in engineered cell systems, are more reliable and suitable for inexpensive, high-throughput assessment of bioactivity.
Multiple digital data sources can capture moment-to-moment information to advance a robust understanding of opioid use disorder (OUD) behavior, ultimately creating a digital phenotype for each ...patient. This information can lead to individualized interventions to improve treatment for OUD.
The aim is to examine patient engagement with multiple digital phenotyping methods among patients receiving buprenorphine medication for OUD.
The study enrolled 65 patients receiving buprenorphine for OUD between June 2020 and January 2021 from 4 addiction medicine programs in an integrated health care delivery system in Northern California. Ecological momentary assessment (EMA), sensor data, and social media data were collected by smartphone, smartwatch, and social media platforms over a 12-week period. Primary engagement outcomes were meeting measures of minimum phone carry (≥8 hours per day) and watch wear (≥18 hours per day) criteria, EMA response rates, social media consent rate, and data sparsity. Descriptive analyses, bivariate, and trend tests were performed.
The participants' average age was 37 years, 47% of them were female, and 71% of them were White. On average, participants met phone carrying criteria on 94% of study days, met watch wearing criteria on 74% of days, and wore the watch to sleep on 77% of days. The mean EMA response rate was 70%, declining from 83% to 56% from week 1 to week 12. Among participants with social media accounts, 88% of them consented to providing data; of them, 55% of Facebook, 54% of Instagram, and 57% of Twitter participants provided data. The amount of social media data available varied widely across participants. No differences by age, sex, race, or ethnicity were observed for any outcomes.
To our knowledge, this is the first study to capture these 3 digital data sources in this clinical population. Our findings demonstrate that patients receiving buprenorphine treatment for OUD had generally high engagement with multiple digital phenotyping data sources, but this was more limited for the social media data.
RR2-10.3389/fpsyt.2022.871916.
Quantitative studies indicate that the COVID-19 pandemic has contributed to increased rates of prenatal cannabis use. However, little is known about how the pandemic has impacted cannabis use from ...the perspective of pregnant individuals themselves. Our objective was to characterize COVID-19-related changes in cannabis use among pregnant individuals who used cannabis during the pandemic.
We conducted 18 focus groups (from 11/17/2021 to 12/17/2021) with Black and White pregnant individuals aged 18+ who self-reported prenatal cannabis use during universal screening at entrance to prenatal care (at ~8 weeks gestation) in Kaiser Permanente Northern California. Virtual focus groups were transcribed and analyzed using thematic analysis.
The sample of 53 pregnant individuals (23 Black, 30 White) was 30.3 years old (SD = 5.2) on average, and most (70%) self-reported daily versus weekly or monthly prenatal cannabis use. Major themes regarding the impact of the pandemic on cannabis use included increases in use (resulting from depression, anxiety, stress, boredom), and changes in social use (less sharing of smoked cannabis products), modes of use (from smoking to other modes due to respiratory concerns) and source (from storefront retailers to delivery).
Coping with mental health symptoms and stress were identified drivers of perceived pandemic-related increases in prenatal cannabis use in 2021. Pregnant individuals adapted their use in ways consistent with public health recommendations to decrease social contact and reduce or quit smoking to mitigate COVID-19 transmission and harms. Proactive, mental health outreach for pregnant individuals during future pandemic waves may reduce prenatal cannabis use.
For patients with type 1 diabetes mellitus, a bihormonal artificial endocrine pancreas system utilizing glucagon and insulin has been found to stabilize glycemic control. However, commercially ...available formulations of glucagon cannot currently be used in such systems because of physical instability characterized by aggregation and chemical degradation. Storing glucagon at pH 10 blocks protein aggregation but results in chemical degradation. Reductions in pH minimize chemical degradation, but even small reductions increase protein aggregation. We hypothesized that common pharmaceutical excipients accompanied by a new excipient would inhibit glucagon aggregation at an alkaline pH.
As measured by tryptophan intrinsic fluorescence shift and optical density at 630 nm, protein aggregation was indeed minimized when glucagon was formulated with curcumin and albumin. This formulation also reduced chemical degradation, measured by liquid chromatography with mass spectrometry. Biological activity was retained after aging for 7 days in an in vitro cell-based bioassay and also in Yorkshire swine.
Based on these findings, a formulation of glucagon stabilized with curcumin, polysorbate-80, l-methionine, and albumin at alkaline pH in glycine buffer may be suitable for extended use in a portable pump in the setting of a bihormonal artificial endocrine pancreas.
Across the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have ...been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid data from individuals in MOUD treatment to extend our understanding of factors that impact treatment engagement and outcomes.
This paper describes the protocol (including the study design and methodological considerations) from a novel study supported by the National Drug Abuse Treatment Clinical Trials Network at the National Institute on Drug Abuse (NIDA). This study (D-TECT) primarily seeks to evaluate the feasibility of collecting ecological momentary assessment (EMA), smartphone and smartwatch sensor data, and social media data among patients in outpatient MOUD treatment. It secondarily seeks to examine the utility of EMA, digital sensing, and social media data (separately and compared to one another) in predicting MOUD treatment retention, opioid use events, and medication adherence as captured in electronic health records (EHR) and EMA data. To our knowledge, this is the first project to include all three sources of digitally derived data (EMA, digital sensing, and social media) in understanding the clinical trajectories of patients in MOUD treatment. These multiple data streams will allow us to understand the relative and combined utility of collecting digital data from these diverse data sources. The inclusion of EHR data allows us to focus on the utility of digital health data in predicting objectively measured clinical outcomes.
Results may be useful in elucidating novel relations between digital data sources and OUD treatment outcomes. It may also inform approaches to enhancing outcomes measurement in clinical trials by allowing for the assessment of dynamic interactions between individuals' daily lives and their MOUD treatment response.
Identifier: NCT04535583.
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