Recent advancements in the role of histone acetylation dynamics to improve stress responses in plants.

In eukaryotes, transcriptional regulation is determined by the DNA sequence and is facilitated through sophisticated and complex chromatin alterations and histone remodelling. Recent research has shown that the histone acetylation dynamic, an intermittent and reversible substitution, constitutes a prerequisite for chromatin modification. These changes in chromatin structure modulate genome-wide and specific changes in response to external and internal cues like cell differentiation, development, growth, light temperature, and biotic stresses. Histone acetylation dynamics also control the cell cycle. HATs and HDACs play a critical role in gene expression modulation during plant growth and response to environmental circumstances. It has been well established that HATs and HDACs interact with various distinct transcription factors and chromatin-remodelling proteins (CRPs) involved in the transcriptional regulation of several developmental processes. This review explores recent research on histone acyltransferases and histone deacetylases, mainly focusing on their involvement in plant biotic stress responses. Moreover, we also emphasized the research gaps that must be filled to fully understand the complete function of histone acetylation dynamics during biotic stress responses in plants. A thorough understanding of histone acetylation will make it possible to enhance tolerance against various kinds of stress and decrease yield losses in many crops.

Molecular aspects of regeneration in insects.

Regeneration is a fascinating phenomenon observed in various organisms across the animal kingdom. Different orders of class Insecta are reported to possess comprehensive regeneration abilities. Several signalling molecules, such as morphogens, growth factors, and others trigger a cascade of events that promote wound healing, blastema formation, growth, and repatterning. Furthermore, epigenetic regulation has emerged as a critical player in regulating the process of regeneration. This report highlights the major breakthrough research on wound healing and tissue regeneration. Exploring and reviewing the molecular basis of regeneration can be helpful in the area of regenerative medicine advancements. The understanding gathered from this framework can potentially contribute to hypothesis designing with implications in the field of synthetic biology and human health.

Conversations and Reactions Around Severe Hypoglycemia (CRASH) Study: Results From People With Diabetes and Caregivers in the United States.

A survey was conducted in eight countries to examine conversations around, and experiences and treatments during, severe hypoglycemia among people with diabetes and caregivers of people with diabetes. This article reports a subgroup analysis from the United States involving 219 people with diabetes and 210 caregivers. Most respondents (79.7%) did not use professional health care services during their most recent severe hypoglycemic event, and 40.3% did not report the event to their health care providers at a subsequent follow-up visit. Hypoglycemic events left respondents feeling scared (70.9%), unprepared (42.7%), and helpless (46.9%). These clinically important psychosocial impacts on people with diabetes and caregivers underscore the need for conversations about hypoglycemia prevention and management.

Development of a Measure to Assess Attitudes Towards Nasal versus Autoinjector Glucagon Delivery Devices for Treatment of Severe Hypoglycemia.

Background: For individuals managing diabetes, the administration of glucagon for severe hypoglycemia can be lifesaving, yet, until recently, there were no easy-to-use devices for these stressful emergencies. New products have emerged to meet this need, including nasal glucagon (NG) and auto-injector glucagon (AI). This study evaluated the psychometric properties of a new measure, the Glucagon Device Attitudes Questionnaire (GDAQ), in assessing attitudes toward NG and AI from the perspectives of persons with diabetes on insulin (PWDs), caregivers, and acquaintances. Methods: Developed based on qualitative research, the GDAQ consists of 38 rating items for each device and 16 direct-elicitation of attitudes of device relative to each other. It was administered to participants via a cross-sectional online survey. Twenty-six rating items were included in principal component analysis and confirmatory factor analysis. Items comprising each factor were averaged to form scales. Additionally, 12 direct elicitation items were averaged to form an overall "Attitudes" scale. Reliability and validity analyses were conducted. Descriptive statistics were provided for the rating items not included in the factor analysis. Results: A total of 405 PWDs, 313 caregivers, and 305 acquaintances participated. Three factors were identified: "Prepared and Protected" (7 items), "Hesitation" (12 items), and "Device Perceptions by Others" (7 items); factor loadings ranged from 0.13 to 0.92, 0.50 to 0.89, and 0.16 to 0.92, respectively. Cronbach's alpha for the four scales ranged from 0.76 to 0.96. Correlations of the scales with their global item ranged from 0.30 to 0.90. The items outside of the factor analysis showed good distribution in responses and differentiation between the two devices. Discussion: This study supports the validity and reliability of the GDAQ, which successfully conceptualizes attitudes towards devices for administering glucagon among different respondent groups. Use of the GDAQ can help guide the development and testing of new glucagon drug/device combinations.

Nasal Glucagon Is Easier to Use and More Preferred and Needs Less Effort to Administer Than Injectable Glucagon: User Perceptions of Glucagon Administration During Severe Hypoglycemia Simulation.

OBJECTIVE: To evaluate ease of use, user preference, and effort required to use nasal glucagon (NG) versus injectable glucagon needing reconstitution (IG) in simulations of severe hypoglycemia (SH)-a challenge for caregivers of a person with diabetes (PWD) in real-life. METHODS: In this randomized, crossover study, high-fidelity manikins placed in mock representative high-stress environments were used to simulate an SH rescue. Thirty-two trained (by PWDs) and 33 untrained participants attempted NG and IG administrations and then completed questionnaires regarding ease of use, preference, and workload for each device. RESULTS: More trained users agreed that NG was easy to use (87.1% vs 54.8%) and prepare (80.6% vs 51.6%) and had confidence to use NG correctly (93.5% vs 54.8%) than those who agreed the same for IG (P < .05). Untrained users reported similar differences, favoring NG in all parameters. In direct device comparison across all simulations, 80.6% of trained users and 93.5% of untrained users preferred NG over IG-a preference largely sustained regardless of the success or failure of administration. Among PWDs, 90.3% considered NG device as safer than IG during an SH event. In the assessment of workload required to administer glucagon, the weighted mean National Aeronautics and Space Administration Task Load Index scores were 37.8 for NG and 48.4 for IG (P = .0020). CONCLUSION: Participants in this study considered NG easier, more preferred, required less effort for administration, and more intuitive to use than reconstitutable IG, irrespective of whether there was prior training. NG improves the potential for successful administration of glucagon, better preparedness, and increased adoption of glucagon for SH rescue.

Health care resource utilization and cost of severe hypoglycemia treatment in insulin-treated patients with diabetes in the United States.

BACKGROUND: Hypoglycemia is a major limiting factor in achieving glycemic control in persons with diabetes. In some instances, recovery from a severe hypoglycemia event may require health care resource utilization (HCRU), including the use of emergency medical services (EMS), visits to the emergency department (ED), and inpatient hospitalization. OBJECTIVES: To (a) describe the profiles of patients who experience severe hypoglycemic events and (b) characterize HCRU and the associated cost related to severe hypoglycemia treatment. METHODS: This retrospective, observational cohort study used administrative claims data from IBM MarketScan Research Databases. The study examined a cohort of subjects who experienced severe hypoglycemic events that involved HCRU during the 1-year index period. Baseline patient demographic data were collected according to patient profiles, such as payer type, type of diabetes, age, and type of insulin. HCRU and the associated cost data categorized by the patient profiles and care progression scenarios were described. RESULTS: 9,563 patients from the IBM MarketScan Research Databases experienced a severe hypoglycemic event during the index period and were included in the study; approximately 75% of those patients did not experience a severe hypoglycemic event in the previous year. Of the 9,563 patients in the cohort, the largest patient profile (n = 1,767, 18.5%) consisted of those who were on Medicaid, had type 2 diabetes, and used basal/bolus or premixed-only insulins. Overall, more than 90% of the index severe hypoglycemic events involved visits to the ED. EMS claims in the 24 hours before the ED visit were found for half of the severe hypoglycemic events (51.5%). CONCLUSIONS: Differences in HCRU and the associated costs for the treatment of severe hypoglycemia were observed among patients based on insurance, diabetes, and insulin types. Clinicians need to be aware of these differences. Optimizing treatment of severe hypoglycemia, specifically EMS care, and examining patient profiles to develop targeted interventions could potentially provide benefits to patients and reduce cost and resource utilization. DISCLOSURES: This study was funded by Eli Lilly and Company. All authors are employees and shareholders of Eli Lilly and Company. The data presented here have been presented in poster form at AMCP Nexus 2020 Virtual, October 19-23, 2020; ADCES Virtual Conference 2020, August 13-16, 2020; and Virtual ISPOR 2020, May 18-20, 2020.

The Association Between Adherence to Insulin Therapy and Health Care Costs for Adults with Type 2 Diabetes: Evidence from a U.S. Retrospective Claims Database.

BACKGROUND: Research has shown that many patients with type 2 diabetes (T2D) are not adherent to their medication regimen. OBJECTIVE: To examine the association between adherence to insulin therapy and all-cause health care costs for patients with T2D. METHODS: This study used the IQVIA PharMetrics Plus Linkable to Ambulatory Electronic Medical Record data from January 1, 2012, through September 30, 2017. Patients were included if they were identified with T2D and initiated therapy on basal insulin (BAS) or basal-bolus (BAS-BOL) combination at any time from January 1, 2013, through October 1, 2016. Patients aged < 18 years, who used an insulin pump, identified as pregnant, or did not have continuous insurance coverage from 1 year before initiation on insulin therapy through 1 year after initiation were excluded. Descriptive statistics compared patient characteristics and costs (in U.S. 2017 dollars) between patients who were adherent or nonadherent to their insulin therapy in the 1-year postperiod, where adherence was defined as having proportion of days covered (PDC) of at least 80%. In addition, generalized linear models were used to compare costs between adherent and nonadherent patients, while controlling for patient characteristics, previous general health and comorbidities, resource utilization, medication use and type of insulin. RESULTS: 13,296 patients were included in the BAS cohort (5,502 adherent; 7,794 nonadherent) and 10,069 in the BAS-BOL cohort (2,006 adherent; 8,063 nonadherent). Adherent patients had significantly lower all-cause total unadjusted costs following initiation on BAS ($29,322 vs. $31,888, P = 0.0134) and BAS-BOL combination ($36,229 vs. $40,147, P = 0.0078). Drug costs comprised 39.5%-45.4% of costs among adherent patients and 23.0%-25.9% of costs among nonadherent patients. Multivariable analyses revealed that adherent patients had significantly lower adjusted all-cause total costs than nonadherent patients in the BAS cohort ($30,127 vs. $37,049, 95% CI for difference -$8,460 to -$5,384) and the BAS-BOL cohort ($36,603 vs. $44,702, 95% CI for difference -$9,129 to -$6,980). CONCLUSIONS: In patients with T2D who initiated BAS or BAS-BOL combination therapy, adherence was associated with significantly lower all-cause total health care costs, despite significantly higher drug costs. These results illustrate the potential economic benefits associated with adherence to insulin therapy. DISCLOSURES": Eli Lilly and Company funded this study and was responsible for study design and execution. Bajpai, Eby, Faries, and Haynes are employees and own stock in Eli Lilly and Company. Lage received compensation from Eli Lilly and Company for her work on this research project.

Perceptions About Glucagon Delivery Devices for Severe Hypoglycemia: Qualitative Research With Patients, Caregivers, and Acquaintances.

PURPOSE: People with diabetes taking insulin are at risk of severe hypoglycemia, an unpredictable, life-threatening event that requires assistance from others. Outside the clinical setting, glucagon is indicated for the treatment of hypoglycemia. However, there is significant unmet medical need to improve successful administration of glucagon by caregivers and acquaintances. This study assesses perceptions about glucagon delivery and potential effects of 2 glucagon delivery devices for severe hypoglycemia. METHODS: Qualitative interviews were conducted with people with diabetes (patients), caregivers, and acquaintances from a general population panel composed of individuals across the United States who have agreed to be recruited for research studies. Participants were recruited via email with a link to an online screener to determine eligibility. Experienced qualitative researchers conducted telephone interviews after a semistructured discussion guide, developed by the authors, that focused on aspirational device features and perceptions about the 2 devices: nasal glucagon and autoinjector glucagon; visuals of the instructions for use were displayed. Verbatim transcripts were developed, and a qualitative analysis software program, MaxQDA, was used to code responses and themes that emerged from the data. FINDINGS: A total of 45 (15 patients, 15 caregivers, and 15 acquaintances) interviews were conducted (mean ages, 55, 40, and 51, respectively). The most frequently spontaneously identified aspirational features for a new glucagon device were ease of use (29 [64%]), including being uncomplicated, premixed/ready to use, and ability to use quickly; small/easy to carry (9 [20%]); needle-free/no long needles (8 [18%]); and easy instructions (4 [9%]). In general, participants indicated that having a glucagon delivery device on hand would make them feel prepared, protected, and confident that others could assist in the event of severe hypoglycemia. More participants across all subgroups preferred nasal glucagon versus autoinjector glucagon (33 [73%] vs 12 [27%]). Favorable comments about nasal glucagon included that it appeared to be easy to carry, easy to use, and lacked a needle, that one does not need to remove clothing to use it, and that others likely would be more comfortable using it. Favorable comments about autoinjector glucagon included that it was familiar as a rescue device and that patients felt confident that the full dose would be delivered with it. There may be more hesitation using autoinjector glucagon versus nasal glucagon because of anxiety about needles and locating an injection site. Participants indicated that they would feel more comfortable socially using nasal glucagon because it was viewed as more discreet and less embarrassing than using autoinjector glucagon; it was also considered less traumatic for use in children. IMPLICATIONS: This research suggests that patients with diabetes, caregivers, and acquaintances prefer a device that is simple, compact, and ready to use. Nasal glucagon was generally preferred over autoinjector glucagon primarily because it lacks a needle and it appears to be less complicated.

Nasal Glucagon Versus Injectable Glucagon for Severe Hypoglycemia: A Cost-Offset and Budget Impact Analysis.

BACKGROUND: Severe hypoglycemic events (SHEs) in patients with diabetes are associated with substantial health care costs in the United States (US). Injectable glucagon (IG) is currently available for treatment of severe hypoglycemia but is associated with frequent handling errors. Nasal glucagon (NG) is a novel, easier-to-use treatment that is more often administered successfully. The economic impact of this usability advantage was explored in cost-offset and budget impact analyses for the US setting. METHODS: A health economic model was developed to estimate mean costs per SHE for which treatment was attempted using NG or IG, which differed only in the probability of treatment success, based on a published usability study. The budget impact of NG was projected over 2 years for patients with type 1 diabetes (T1D) and type 2 diabetes treated with basal-bolus insulin (T2D-BB). Epidemiologic and cost data were sourced from the literature and/or fee schedules. RESULTS: Mean costs were $992 lower if NG was used compared with IG per SHE for which a user attempted treatment. NG was estimated to reduce SHE-related spending by $1.1 million and $230 000 over 2 years in 10 000 patients each with T1D and T2D-BB, respectively. Reduced spending resulted from reduced professional emergency services utilization as successful treatment was more likely with NG. CONCLUSIONS: The usability advantage of NG over IG was projected to reduce SHE-related treatment costs in the US setting. NG has the potential to improve hypoglycemia emergency care and reduce SHE-related treatment costs.