Objectives: To compare characteristics of patients with type 2 diabetes mellitus (T2DM) who did/did not achieve short-term (3-12 months) and/or long-term (24-36 months) glycemic control (HbA1c < 7%) ...following treatment with metformin (MET) monotherapy and determine factors associated with glycemic control.
Methods: This was a retrospective study using administrative claims from a national health plan. Patients with T2DM on MET monotherapy for ≥1 year, HbA1c ≥7% and initiating a new glucose lowering medication between January 2010-December 2014 were eligible for this study with date of the first prescription set as index date. Patients were required to have ≥1 HbA1c between 24-36 months post-index; a subset of patients with HbA1c values between 3-12 months was identified. Descriptive analyses were used to compare patients by achievement of glycemic control. Multivariable analyses were used to evaluate factors associated with glycemic control.
Results: A total of 7,416 patients were eligible of which 6,561 had data for short-term assessment. Mean A1c (%) during pre-index was 8.2+/-1.3 which decreased to 7.3+/- 1.1 in the short-term and 7.5+/-1.3 in long term, with 39.8% achieving long-term glycemic control. Among patients achieving glycemic control in the short-term (44.4%), 58.2% maintained glycemic control in long-term. For every 1.0% higher HbA1c at baseline, odds of attaining glycemic control decreased by 16% in the short-term and 12% in the long-term. Treatments associated with greater odds ratio (OR) (95% CI) of achieving HbA1c <7% in long-term were SGLT2 inhibitors OR= 2.45 (1.93-3.12), GLP-1 RA OR= 1.95 (1.60-2.36) and Thiazolidinediones OR= 1.73 (1.52-1.96).
Conclusion: Although the majority of patients intensifying treatment after MET monotherapy did not achieve optimal glycemic goals in the long term, understanding how to facilitate treatments that encourage better glycemic control can aid in treatment selection.
Disclosure
S.K. Bajpai: Employee; Self; Eli Lilly and Company. R. Nair: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., GlaxoSmithKline plc. T. Changamire: Employee; Self; Humana. R. Sheer: None. Q. Wang: None. H. Patel: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
AbstractPurposePeople 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. MethodsQualitative 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. FindingsA 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. ImplicationsThis 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.
Injectable glucagon (IG) is challenging to use for caregivers of a person with diabetes (PWD) in stressful severe hypoglycemia (SH) rescue. We evaluated user preference for nasal glucagon (NG) and IG ...devices after treating simulated SH. The PWD trained arm was adult PWDs trained to use NG or IG, then PWDs trained their caregivers how to use it; 1 week later, caregivers administered the device to a life-like manikin exhibiting SH in a simulated real life setting with distractions creating urgency. The untrained arm was adults not associated with a PWD, but willing to assist - not trained, but shown the device just presimulation. After 1 week, the process was repeated with the other device. We assessed perceptions of simulation participants and PWDs via comparative device questionnaires, completed after videos of both simulations were viewed after the 2nd simulation (no confirmation of success provided). NG was rated more preferred by those with successful doses of NG or IG. PWDs indicated that they felt safer with NG even with successful IG dosing (Table). Untrained users were as successful as PWD-trained in dosing NG, while there were no IG successes without training. None of the few who preferred IG gave a successful IG dose, whereas the few successful IG-users preferred NG or stated no preference. Being PWD-trained was not critical for success with NG, and ease of preparation and use likely contributed to overall preference.
Disclosure
J. Settles: Employee; Self; Eli Lilly and Company. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. S.K. Bajpai: Employee; Self; Eli Lilly and Company. E. Spaepen: Consultant; Self; Eli Lilly and Company. J.G. Suico: Employee; Self; Eli Lilly and Company.
Funding
Eli Lilly and Company
Objective: This study assessed preference, hesitation using, perceived ease of use, and feeling prepared and protected for nasal glucagon (NG) vs. autoinjector glucagon (AI) for rescue treatment of ...severe hypoglycemia (SH) among people with diabetes (PWDs), caregivers (CGs) and acquaintances (AQs).
Methods: US PWDs (type 1 or 2, on insulin; n=405), CGs (n=313) and AQs (n=305) completed an online survey, after viewing a description of SH and graphics and descriptions of NG and AI (based on publicly available information at the time of study; prior to access to the final commercial device or their instructions for use). Respondents rated strength of preference for NG vs. AI on 16 attributes using direct elicitation (7-point scale; 1 = ‘very strongly prefer AI‘ and 7 = ‘very strongly prefer NG’, 4 = neutral); 4 items focused on overall preference, being less likely to hesitate using, perceived ease of use, and feeling prepared and protected, and 12 items were averaged to create a preference scale (e.g., size of device, less complicated). This measure was developed using established guidelines for instrument development, including qualitative research and assessment of the measure’s psychometric properties. One sample t-tests evaluated whether mean preference ratings differed from a neutral score.
Results: Across PWDs, CGs, and AQs, NG was preferred over AI (all P<0.001 compared to neutral) on overall preference (4.5, 4.9, and 5.4, respectively), being less likely to hesitate using (4.8, 5.1, and 5.4, respectively), perceived ease of use (4.8, 5.1, and 5.4, respectively) and the preference scale (4.7, 5.0, and 5.3, respectively). CGs and AQs preferred NG vs. AI on feeling prepared and protected (4.6 and 4.8, respectively; both P<0.001 compared to neutral); PWDs were neutral (4.1, P=0.376).
Conclusions: This study provides insights on PWDs’, CGs’ and AQs’ attitudes towards new glucagon devices, which may be considered when making product choices among the glucagon delivery systems.
Disclosure
S.K. Bajpai: Employee; Self; Eli Lilly and Company. J. Cambron-Mellott: Other Relationship; Self; Eli Lilly and Company. N.K. Raibulet: Employee; Self; Eli Lilly and Company. E.Y. Peck: None. J. Poon: Employee; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. B. Mitchell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. O. Will: Other Relationship; Self; Eli Lilly and Company. J. Babrowicz: Other Relationship; Self; Eli Lilly and Company. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. K. Beusterien: Other Relationship; Self; Eli Lilly and Company.
The CRASH study examines the experience and treatment of a severe hypoglycemia event (SHE) among people with T1DM (ppl w/T1DM) or insulin-treated ppl w/T2DM and caregivers. The online survey was ...conducted in 8 countries. To be eligible in the global study, ppl had experienced or cared for a person who had ≥1 SHE in the last 3 years. SHE was defined as low blood glucose requiring assistance for recovery. Here, we report U.S. data for 220 ppl with diabetes (n=110 T1DM; n=110 T2DM). Sixty-five (59.1%) ppl w/T2DM used insulin for >5 years, while mean (SD) duration of diabetes was 30.6 (16.6) years for ppl w/T1DM and 16.0 (8.7) years for ppl w/T2DM. Forty (36.4%) ppl w/T1DM and 22 (20.0%) ppl w/T2DM reported impaired awareness (Gold score ≥4). During the last SHE, glucagon use was low (T1DM 8.2%; T2DM 3.6%); reasons for not using glucagon were not having a prescription (T1DM 40.0%; T2DM 59%) or it was unavailable (T1DM 20.0%; T2DM 17.1%). Also, ppl w/T1DM (75.5%) and ppl w/T2DM (83.6%) reported using oral glucose only for treatment; use of healthcare provider assistance was low. The main causes reported for a SHE were eating less than planned (T1DM 27.3%; T2DM 47.3%) or exercising more than planned (T1DM 21.8%; T2DM 20.0%). Results indicate that treatment of a SHE mainly occurred outside the healthcare system with fewer ppl having glucagon as an option for recovery.
Disclosure
F.J. Snoek: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Research Support; Self; Sanofi. Speaker's Bureau; Self; Lilly Diabetes. A. Jiletcovici: Employee; Self; Eli Lilly and Company. D.M. Bushnell: None. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. S.K. Bajpai: Employee; Self; Eli Lilly and Company. E. Spaepen: Consultant; Self; Eli Lilly and Company. J. Thomas: Employee; Self; Eli Lilly and Company. Z. Balantac: Other Relationship; Self; Eli Lilly and Company. M. Peyrot: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Calibra Medical. Research Support; Spouse/Partner; Eli Lilly and Company. B. Mitchell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
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. Keywords: diabetes, severe hypoglycemic events, glucagon delivery device, patient attitudes
Background: SURMOUNT-4 was a Phase 3 clinical trial evaluating the safety and efficacy of tirzepatide in adults living with obesity or overweight. The method of delivery for tirzepatide was via a ...weekly, single-use injection pen device. The aim of this qualitative interview study was to better understand the ease-of-use of the pen device used to administer the study medication. Methods: Exit interviews were conducted with a random sample of US-based participants who had completed their Week 88 primary endpoint and Week 92 safety follow-up visits in SURMOUNT-4. A semi-structured discussion guide was used to understand the participant experience of the study, including use of the single-use pen device. Participants also completed an Injection Device Experience Questionnaire (ID-EQ) during their interview. As of May 30, 2023, interviews are on-going; n = 79 have been completed. The intended total sample size is n = 90 interviews. Results: Most participants reported that the single-use pen device was easy to use, and this was reflected in their responses to the IDEQ item "Overall, the device is easy to use": 91% responded "Strongly Agree", and 9% responded "Agree." Participants commented that the device was convenient due to being pre-filled and packaged as an allin-one device, that administration was simple and required minimal steps to inject each dose, that using the device took very little time, and that the needle was small and caused little to no pain. The requirement for the drug (and therefore the device) to be kept refridgerated was the key limitation mentioned. Conclusions: Qualitative exit interview methodology was utilized to understand participants' overall experience during SURMOUNT-4. Participants in the SURMOUNT-4 clinical trial found the single-use injection pen device to be easy to use and convenient.
Molecular aspects of regeneration in insects Pandita, Shivali; Singh, Sanchita; Bajpai, Sanjay Kumar ...
Developmental biology,
March 2024, 2024-Mar, 2024-03-00, 20240301, Letnik:
507
Journal Article
Recenzirano
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.
•Insects’ regenerative capabilities is governed at molecular level.•Phases of regeneration: Wound healing/blastema formation, growth, re-patterning.•Signalling pathways such as JNK, JAK/STAT, Wnt etc. are involved in regeneration.•Epigenetics also plays a vital role in regeneration.
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.
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.
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.
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).
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.
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